Upregulation of immunoproteasome PSMB8 is associated with Parkinson's disease.

BACKGROUND: Immunoproteasome, a part of ubiquitin-proteasome system, is involved in immune response as well as protein degradation. However, the relationship between immunoproteasome and Parkinson's disease (PD) was not evaluated clearly. We hypothesized that the shift of immunoproteasome attributes to PD pathogenesis due to its role in inflammation and protein homeostasis. OBJECTIVE: To determine whether immunoproteasome in peripheral blood mononuclear cells (PBMC) and brain is expressed differently between patients with PD and healthy controls (HC). METHODS: Blood samples were collected from 19 HC to 40 patients with PD of comparable ages. Peripheral blood mononuclear cells were isolated and followed by RT-qPCR to measure the mRNA levels of three catalytic subunits of immunoproteasome, namely, PSMB8, PSMB9, and PSMB10. Then, the protein levels of each subunit were measured by western blot. Finally, we confirmed the altered immunoproteasome subunit in the post-mortem human brain of PD. RESULTS: In PBMCs, PSMB8 mRNA expression of PD group significantly increased compared to HC (p = 0.004), whereas PSMB9 and PSMB10 mRNA were not different between the PD and HC. The ratio of PSMB10 and PSMB8 mRNA (PSMB10/8 ratio) also reflected the significant difference between the PD and HC (p = 0.002). The PSMB10/8 ratio was well correlated with the UPDRS total and Part III score in the early stage of PD (Hoehn and Yahr ≤2.5) or drug-naïve PD subgroups. In terms of the protein level of immunoproteasome subunits in PBMCs, the increase of PSMB8 protein was observed in PD compared to HC (p = 0.0009), while PSMB9 and PSMB10 were not different between groups. Finally, we confirmed that immunoproteasome PSMB8 was expressed abundantly in the postmortem PD brain compared with normal control. CONCLUSION: Our novel findings implicate that immunoproteasome PSMB8 is engaged in PD pathomechanism.

Role of NLRP3 Inflammasome in Parkinson's Disease and Therapeutic Considerations.

Parkinson's disease (PD) is the second most common neurodegenerative disease, with two main pathological features: misfolded α-synuclein protein accumulation and neurodegeneration. Inflammation has recently been identified as a contributor to a cascade of events that may aggravate PD pathology. Inflammasomes, a group of intracellular protein complexes, play an important role in innate immune responses to various diseases, including infection. In PD research, accumulating evidence suggests that α-synuclein aggregations may activate inflammasomes, particularly the nucleotide-binding oligomerization domain-leucine-rich repeat-pyrin domain-containing 3 (NLRP3) type, which exacerbates inflammation in the central nervous system by secreting proinflammatory cytokines like interleukin (IL)-18 and IL-1ß. Afterward, activated NLRP3 triggers local microglia and astrocytes to release additional IL-1ß. In turn, the activated inflammatory process may contribute to additional α-synuclein aggregation and cell loss. This review summarizes current research evidence on how the NLRP3 inflammasome contributes to PD pathogenesis, as well as potential therapeutic strategies targeting the NLRP3 inflammasome in PD.

Influence of Polymer Backbone Fluorination on the Electrochemical Behavior of Single-Ion Conducting Multiblock Copolymer Electrolytes.

The presence of fluorine, especially in the electrolyte, frequently has a beneficial effect on the performance of lithium batteries owing to, for instance, the stabilization of the interfaces and interphases with the positive and negative electrodes. However, the presence of fluorine is also associated with reduced recyclability and low biodegradability. Herein, we present a single-ion conducting multiblock copolymer electrolyte comprising a fluorine-free backbone and compare it with the fluorinated analogue reported earlier. Following a comprehensive physicochemical and electrochemical characterization of the copolymer with the fluorine-free backbone, the focus of the comparison with the fluorinated analogue was particularly on the electrochemical stability toward oxidation and reduction as well as the reactions occurring at the interface with the lithium-metal electrode. To deconvolute the impact of the fluorine in the ionic side chain and the copolymer backbone, suitable model compounds were identified and studied experimentally and theoretically. The results show that the absence of fluorine in the backbone has little impact on the basic electrochemical properties, such as the ionic conductivity, but severely affects the electrochemical stability and interfacial stability. The results highlight the need for a very careful design of the whole polymer for each desired application, essentially, just like for liquid electrolytes.

Effect of Rehmannia glutinosa Libosch extract on proliferation and cardiogenic pre-differentiation of human mesenchymal stem cells.

Background: Vietnamese medicine tried and tested certain bioactive compounds from plants to increase the rate of tissue immunomodulation, regeneration, and differentiation. Although there are many research papers discovered about phytochemicals of Rehmannia glutinosa Libosch and differentiation induction potential of some substances purified from this herbal, it finds difficult to seek research that investigated the effect of hot water-extracted R. glutinosa Libosch (RGE) on proliferation and cardiogenic differentiation of mesenchymal stem cells, even though it has commonly been used for a long time because of its function as a restorative and as a critical role in cardiovascular treatment in traditional. Results: Our research indicated that RGE has many predicted bio-pharmacological effects, and the RGE is demonstrated that it is non-toxic to UC-MSCs (IC50 = 1274 ppm). It also stimulates the proliferation and migration of UC-MSCs at various concentrations, especially at the RGE concentration of 50 ppm, during four days of treatment. On the other hand, the RGE can induce the cardiac pre-differentiation process from the fifth day to the fifteenth day after treatment, which was proven through both molecular and cellular (morphology evidence) levels like the up-regulation of GATA4, Nkx2.5, cTnT α-MHC, Desmin genes; the expression of Desmin protein, the appearance of two-nuclei cells, connecting process of adjoining cells, the cytoplasmic striations. Conclusion: The RGE could either stimulate proliferation-migration of MSCs or induce the cardiac pre-differentiation process. This extract can be classified as non-toxic to the UC-MSCs.

Super-efficient drilling of metals with ultrafast non diffractive laser beams.

A highly efficient drilling process is found in non-transparent metallic materials enabled by the use of non-diffractive ultrafast Bessel beams. Applied for deep drilling through a 200 µm-thick steel plate, the Bessel beam demonstrates twofold higher drilling efficiency compared to a Gaussian beam of similar fluence and spot size. Notwithstanding that surface ablation occurs with the same efficiency for both beams, the drilling booster results from a self-replication and reconstruction of the beam along the axis, driven by internal reflections within the crater at quasi-grazing incidence, bypassing potential obstacles. The mechanism is the consequence of an oblique wavevectors geometry with low angular dispersion and generates a propagation length beyond the projection range allowed by the geometry of the channel. With only the main lobe being selected by the channel entrance, side-wall reflection determines the refolding of the lobe on the axis, enhancing and replicating the beam multiple times inside the channel. The process is critically assisted by the reduction of particle shielding enabled by the intrinsic self-healing of the Bessel beam. Thus the drilling process is sustained in a way which is uniquely different from that of the conventional Gaussian beam, the latter being damped within its Rayleigh range. These mechanisms are supported and quantified by Finite Difference Time Domain calculations of the beam propagation. The results show key advantages for the quest towards efficient laser drilling and fabrication processes.

Influence of Piper betle L. extract on umbilical cord cells in vitro and potential treating cutaneous wound.

This research aimed to test the effects of Piper betle L. from Vietnam on fibroblasts and UC-derived mesenchymal stem cells (UC-MSCs) from human umbilical cord (UC) on the scratch assay. We tested the extract at different concentrations and then assessed the level of expression of the factors involved in the inflammatory process on fibroblasts including IL-33, VCAM, CD248 by assay real time qPCR. At the concentrations of 0.025 µL/mL and 0.03 µL/mL, the extracts positively affected fibroblast proliferation and UC-MSCs. By contrast, the concentration of 0.058 µL/mL, the extract was toxic to UC-MSCs and fibroblast cell lines, the cells were no longer able to survive. qPCR results show that Piper betle L. extract has the ability to reduce the expression levels of IL-33 (50.8%), VCAM (32.1%), CD248 (46.13%) which trigger inflammatory processes, thereby reducing cellular stress and promoting the process of healing scratches. Our study revealed the proliferation capabilities of Piper betle L. extract from Vietnam In vitro. Hence, Piper betle L. could be recommended as a potential source of wound healing agents.

Non-Diffractive Bessel Beams for Ultrafast Laser Scanning Platform and Proof-Of-Concept Side-Wall Polishing of Additively Manufactured Parts.

We report the potential use of non-diffractive Bessel beam for ultrafast laser processing in additive manufacturing environments, its integration into a fast scanning platform, and proof-of-concept side-wall polishing of stainless steel-based additively fabricated parts. We demonstrate two key advantages of the zeroth-order Bessel beam: the significantly long non-diffractive length for large tolerance of sample positioning and the unique self-reconstruction property for un-disrupted beam access, despite the obstruction of metallic powders in the additive manufacturing environment. The integration of Bessel beam scanning platform is constructed by finely adapting the Bessel beam into a Galvano scanner. The beam sustained its good profile within the scan field of 35 × 35 mm2. As a proof of concept, the platform showcases its advanced capacity by largely reducing the side-wall surface roughness of an additively as-fabricated workpiece from Ra 10 µm down to 1 µm. Therefore, the demonstrated Bessel-Scanner configuration possesses great potential for integrating in a hybrid additive manufacturing apparatus.

Perfluorosulfonyl Imide versus Perfluorosulfonic Acid Ionomers in Proton-Exchange Membrane Fuel Cells at Low Relative Humidity.

Designing highly conductive ionomers at high temperature and low relative humidity is challenging in proton-exchange membrane fuel cells. Perfluorosulfonyl imide ionomers were believed to achieve this goal, owing to their exceptional acidity and excellent thermal stability. Perfluorosulfonyl imide ionomers are less conductive than the analogous perfluorosulfonic acids despite similar membrane microstructure. In this study, the distinct behavior is rationalized by in situ synchrotron infrared spectroscopy during hydration. The protonation mechanism, formation of the protonic moiety and water clustering are totally different for the two different families of membranes. The ionization mediated by trans-to-cis conformational transition of the perfluorosulfonyl imide ionomer is not accompanied by the formation of hydronium ions. In contrast, Zundel-ion entities were identified as the elementary protonic complex, which is stable over the hydration range. The H-bond network of surrounding water molecules appears to be less connected and the protons remain highly localized and unavailable for efficient structural transport. The delocalization of protons and their mitigated interaction with the surrounding medium are prominent effects that negatively impact conductivity.

Mapping Temperature Distribution Generated by Photothermal Conversion in Graphene Film Using Er,Yb:NaYF4 Nanoparticles Prepared by Microwave-Assisted Solvothermal Method.

This study analyzes the mapping of temperature distribution generated by graphene in a glass slide cover after illumination at 808 nm with a good thermal resolution. For this purpose, Er,Yb:NaYF4 nanoparticles prepared by a microwave-assisted solvothermal method were used as upconversion luminescent nanothermometers. By tuning the basic parameters of the synthesis procedure, such as the time and temperature of reaction and the concentration of ethanol and water, we were able to control the size and the crystalline phase of the nanoparticles, and to have the right conditions to obtain 100% of the ß hexagonal phase, the most efficient spectroscopically. We observed that the thermal sensitivity that can be achieved with these particles is a function of the size of the nanoparticles and the crystalline phase in which they crystallize. We believe that, with suitable changes, these nanoparticles might be used in the future to map temperature gradients in living cells while maintaining a good thermal resolution.

Low-loss 3D-laser-written mid-infrared LiNbO3 depressed-index cladding waveguides for both TE and TM polarizations.

We report mid-infrared LiNbO3 depressed-index microstructured cladding waveguides fabricated by three-dimensional laser writing showing low propagation losses (~1.5 dB/cm) at 3.68 µm wavelength for both the transverse electric and magnetic polarized modes, a feature previously unachieved due to the strong anisotropic properties of this type of laser microstructured waveguides and which is of fundamental importance for many photonic applications. Using a heuristic modeling-testing iteration design approach which takes into account cladding induced stress-optic index changes, the fabricated cladding microstructure provides low-loss single mode operation for the mid-IR for both orthogonal polarizations. The dependence of the localized refractive index changes within the cladding microstructure with post-fabrication thermal annealing processes was also investigated, revealing its complex dependence of the laser induced refractive index changes on laser fabrication conditions and thermal post-processing steps. The waveguide modes properties and their dependence on thermal post-processing were numerically modeled and fitted to the experimental values by systematically varying three fundamental parameters of this type of waveguides: depressed refractive index values at sub-micron laser-written tracks, track size changes, and piezo-optic induced refractive index changes.

Controlling Microstructure-Transport Interplay in Highly Phase-Separated Perfluorosulfonated Aromatic Multiblock Ionomers via Molecular Architecture Design.

Proton-conducting multiblock polysulfones bearing perfluorosulfonic acid side chains were designed to encode nanoscale phase-separation, well-defined hydrophilic/hydrophobic interfaces, and optimized transport properties. Herein, we show that the superacid side chains yield highly ordered morphologies that can be tailored by best compromising ion-exchange capacity and block lengths. The obtained microstructures were extensively characterized by small-angle neutron scattering (SANS) over an extended range of hydration. Peculiar swelling behaviors were evidenced at two different scales and attributed to the dilution of locally flat polymer particles. We evidence the direct correlation between the quality of interfaces, the topology and connectivity of ionic nanodomains, the block superstructure long-range organization, and the transport properties. In particular, we found that the proton conductivity linearly depends on the microscopic expansion of both ionic and block domains. These findings indicate that neat nanoscale phase-separation and block-induced long-range connectivity can be optimized by designing aromatic ionomers with controlled architectures to improve the performances of polymer electrolyte membranes.

Heuristic modelling of laser written mid-infrared LiNbO3 stressed-cladding waveguides.

Mid-infrared lithium niobate cladding waveguides have great potential in low-loss on-chip non-linear optical instruments such as mid-infrared spectrometers and frequency converters, but their three-dimensional femtosecond-laser fabrication is currently not well understood due to the complex interplay between achievable depressed index values and the stress-optic refractive index changes arising as a function of both laser fabrication parameters, and cladding arrangement. Moreover, both the stress-field anisotropy and the asymmetric shape of low-index tracks yield highly birefringent waveguides not useful for most applications where controlling and manipulating the polarization state of a light beam is crucial. To achieve true high performance devices a fundamental understanding on how these waveguides behave and how they can be ultimately optimized is required. In this work we employ a heuristic modelling approach based on the use of standard optical characterization data along with standard computational numerical methods to obtain a satisfactory approximate solution to the problem of designing realistic laser-written circuit building-blocks, such as straight waveguides, bends and evanescent splitters. We infer basic waveguide design parameters such as the complex index of refraction of laser-written tracks at 3.68 µm mid-infrared wavelengths, as well as the cross-sectional stress-optic index maps, obtaining an overall waveguide simulation that closely matches the measured mid-infrared waveguide properties in terms of anisotropy, mode field distributions and propagation losses. We then explore experimentally feasible waveguide designs in the search of a single-mode low-loss behaviour for both ordinary and extraordinary polarizations. We evaluate the overall losses of s-bend components unveiling the expected radiation bend losses of this type of waveguides, and finally showcase a prototype design of a low-loss evanescent splitter. Developing a realistic waveguide model with which robust waveguide designs can be developed will be key for exploiting the potential of the technology.

Low-repetition rate femtosecond laser writing of optical waveguides in KTP crystals: analysis of anisotropic refractive index changes.

We report on the direct low-repetition rate femtosecond pulse laser microfabrication of optical waveguides in KTP crystals and the characterization of refractive index changes after the thermal annealing of the sample, with the focus on studying the potential for direct laser fabricating Mach-Zehnder optical modulators. We have fabricated square cladding waveguides by means of stacking damage tracks, and found that the refractive index decrease is large for vertically polarized light (c-axis; TM polarized) but rather weak for horizontally polarized light (a-axis; TE polarized), this leading to good near-infrared light confinement for TM modes but poor for TE modes. However, after performing a sample thermal annealing we have found that the thermal process enables a refractive index increment of around 1.5x10(-3) for TE polarized light, while maintaining the negative index change of around -1x10(-2) for TM polarized light. In order to evaluate the local refractive index changes we have followed a multistep procedure: We have first characterized the waveguide cross-sections by means of Raman micro-mapping to access the lattice micro-modifications and their spatial extent. Secondly we have modeled the waveguides following the modified region sizes obtained by micro-Raman with finite element method software to obtain a best match between the experimental propagation modes and the simulated ones. Furthermore we also report the fabrication of Mach-Zehnder structures and the evaluation of propagation losses.

Effects of Block Length and Membrane Processing Conditions on the Morphology and Properties of Perfluorosulfonated Poly(arylene ether sulfone) Multiblock Copolymer Membranes for PEMFC.

Perfluorosulfonated poly(arylene ether sulfone) multiblock copolymers have been shown to be promising as proton exchange membranes. The commonly used approach for preparation of the membrane is solvent casting; the properties of the resulting membranes are very dependent on the membrane processing conditions. In this paper, we study the effects of block length, selectivity of the solvent, and thermal treatment on the membrane properties such as morphology, water uptake, and ionic conductivity. DiMethylSulfOxide (DMSO), and DiMethylAcetamide (DMAc) were selected as casting solvents based on the Flory-Huggins parameter calculated by inversion gas chromatography (IGC). It was found that the solvent selectivity has a mild impact on the mean size of the ionic domains and the expansion upon swelling, while it dramatically affects the supramolecular ordering of the blocks. The membranes cast from DMSO exhibit more interconnected ionic clusters yielding higher conductivities and water uptake as compared to membranes cast from DMAc. A 10-fold increase in proton conductivity was achieved after thermal annealing of membranes at 150 °C, and the ionomers with longer block lengths show conductivities similar to Nafion at 80 °C and low relative humidity (30%).