Stable Photoelectrochemical Reactions at Solid/Solid Interfaces toward Solar Energy Conversion and Storage.

Electrochemistry has extended from reactions at solid/liquid interfaces to those at solid/solid interfaces. However, photoelectrochemistry at solid/solid interfaces has been hardly reported. In this study, we achieve a stable photoelectrochemical reaction at the semiconductor-electrode/solid-electrolyte interface in a Nb-doped anatase-TiO2 (a-TiO2:Nb)/Li3PO4 (LPO)/Li all-solid-state cell. The oxidative currents of a-TiO2:Nb/LPO/Li increase upon light irradiation when a-TiO2:Nb is located at a potential that is more positive than its flat-band potential. This is because the photoexcited electrons migrate to the current collector due to the bending of the conduction band minimum toward the negative potential. The photoelectrochemical reaction at the semiconductor/solid-electrolyte interface is driven by the same principle as those at semiconductor/liquid-electrolyte interfaces. Moreover, oxidation under light irradiation exhibits reversibility with reduction in the dark. Thus, we extend photoelectrochemistry to all-solid-state systems composed of solid/solid interfaces. This extension would enable us to investigate photoelectrochemical phenomena uncleared at solid/liquid interfaces because of low stability and durability.

Periosteum-derived podoplanin-expressing stromal cells regulate nascent vascularization during epiphyseal marrow development.

Bone marrow development and endochondral bone formation occur simultaneously. During endochondral ossification, periosteal vasculatures and stromal progenitors invade the primary avascular cartilaginous anlage, which induces primitive marrow development. We previously determined that bone marrow podoplanin (PDPN)-expressing stromal cells exist in the perivascular microenvironment and promote megakaryopoiesis and erythropoiesis. In this study, we aimed to examine the involvement of PDPN-expressing stromal cells in postnatal bone marrow generation. Using histological analysis, we observed that periosteum-derived PDPN-expressing stromal cells infiltrated the cartilaginous anlage of the postnatal epiphysis and populated on the primitive vasculature of secondary ossification center. Furthermore, immunophenotyping and cellular characteristic analyses indicated that the PDPN-expressing stromal cells constituted a subpopulation of the skeletal stem cell lineage. In vitro xenovascular model cocultured with human umbilical vein endothelial cells and PDPN-expressing skeletal stem cell progenies showed that PDPN-expressing stromal cells maintained vascular integrity via the release of angiogenic factors and vascular basement membrane-related extracellular matrices. We show that in this process, Notch signal activation committed the PDPN-expressing stromal cells into a dominant state with basement membrane-related extracellular matrices, especially type IV collagens. Our findings suggest that the PDPN-expressing stromal cells regulate the integrity of the primitive vasculatures in the epiphyseal nascent marrow. To the best of our knowledge, this is the first study to comprehensively examine how PDPN-expressing stromal cells contribute to marrow development and homeostasis.

Reaction Mechanism of Li2MnO3 Electrodes in an All-Solid-State Thin-Film Battery Analyzed by Operando Hard X-ray Photoelectron Spectroscopy.

Li2MnO3 is a promising cathode candidate for Li-ion batteries because of its high discharge capacity; however, its reaction mechanism during cycling has not been sufficiently explicated. Observations of Mn and O binding energy shifts in operando hard X-ray photoelectron spectroscopy measurements enabled us to determine the charge-compensation mechanism of Li2MnO3. The O 1s peak splits at an early stage during the first charge, and the concentration of lower-valence O changes reversibly with cycling, indicating the formation of a low-valence O species that intrinsically participates in the redox reaction. The O 1s peak-splitting behavior, which indicates the number of valences of O in Li2MnO3, is supported by the computational results for an O3 to O1 structural transition. This is in agreement with the results of our previous study, wherein we confirmed this O3 to O1 transition based on in situ surface X-ray diffraction analysis, X-ray photoelectron spectroscopy, and first-principles formation energy calculations.

Anomalously High Ionic Conductivity of Li2SiS3-Type Conductors.

Solid-state electrolytes that exhibit high ionic conductivities at room temperature are key materials for obtaining the next generation of safer, higher-specific-energy solid-state batteries. However, the number of currently available crystal structures for use as superionic conductors remains limited. Here, we report a lithium superionic conductor, Li2SiS3, with tetragonal crystal symmetry, which possesses a new three-dimensional framework structure consisting of isolated edge-sharing tetrahedral dimers. This species exhibits an anomalously high ionic conductivity of 2.4 mS cm-1 at 298 K, which is 3 orders of magnitude higher than the reported ionic conductivity for its orthorhombic polymorph. The framework of this conductor consists mainly of silicon, which is abundant in natural resources, and its further optimization may lead to the development of new solid-state electrolytes for large-scale applications.

Wearable sensor device-based detection of decreased heart rate variability in Parkinson's disease.

The evidence that heart rate variability (HRV) decreases during early Parkinson's disease (PD) largely depends on electrocardiogram data. In this study, we examined HRV in PD using wearable sensors and assessed various evaluation methods for detecting disease-related alterations. We evaluated 27 patients with PD and 23 disease controls. The wearable sensors POLAR V800 HR and POLAR H10 were used for the HRV measurements. The participants wore the two sensors for approximately 24 h, and long-term HRV data were acquired. We analyzed the standard deviation of normal R-R intervals (SDNN) and coefficient of variation of R-R intervals (CVRR) for every 100 consecutive beats. Focusing on the fluctuation of SDNN and CVRR, we extracted the minimum, first decile, first quartile, and median values of SDNN and CVRR. The area under the receiver operating characteristic curve (AUC) for each HRV parameter was calculated to differentiate PD from the disease controls. The minimum values of SDNN and CVRR had the highest AUC (SDNN: AUC 0.90, 95% confidence interval [CI] 0.78-0.96; CVRR: AUC 0.90, CI 0.76-0.96) among the evaluation methods tested. The minimum values of SDNN and CVRR were significantly decreased in PD (SDNN: 9.5 ± 4.0 ms vs. 4.4 ± 2.0 ms, p < 0.0001; CVRR: 1.15 ± 0.33% vs. 0.65 ± 0.24%, p < 0.0001). We detected decreased HRV in PD using wearable sensors. Analyzing the minimum values of the HRV parameter in long-term recordings appears to be appropriate for detecting the decrease in HRV in PD.

Li10GeP2S12-Type Structured Solid Solution Phases in the Li9+δP3+δ'S12-kOk System: Controlling Crystallinity by Synthesis to Improve the Air Stability.

Understanding the fast Li ionic conductors of oxygen-substituted thiophosphates is useful for developing all-solid-state batteries because these compounds possess a high electrochemical stability and thus may be applied as solid electrolytes. In this study, we synthesized the Li9+δP3+δ'S12-kOk series of solid solution phases with the same structure as the Li10GeP2S12 superionic conductor and characterized their crystallinity, solid solution range, and chemical stabilities. Two methods (mechanochemical and melt quenching) were used for sample synthesis. Mechanochemical synthesis was used to obtain samples within a wide range of sulfur/oxygen substitution degrees, and the solid solution range was determined to be 0 < k ≤ 3.6 based on their lattice parameter variation. Meanwhile, the melt-quenched Li9P3S9O3 phase exhibited a high degree of crystallinity up to its particle surface and was thus selected for neutron crystal structure analysis, which revealed the oxygen distribution related to the solubility limit. The highly crystalline melt-quenched Li9P3S9O3 showed better stability in the air atmosphere compared to the mechanochemically synthesized counterpart with a low crystallinity, implying that sample crystallinity is an important parameter in evaluating the air stability of thiophosphates. The promising electrochemical properties of the solid solution series were demonstrated by the stable charge-discharge cycling of an all-solid-state lithium metal cell using the Li9+δP3+δ'S12-kOk electrolyte with k = 0.9 and a conductivity of >1 × 10-3 S cm-1 at 300 K.

Hierarchical non-negative matrix factorization using clinical information for microbial communities.

BACKGROUND: The human microbiome forms very complex communities that consist of hundreds to thousands of different microorganisms that not only affect the host, but also participate in disease processes. Several state-of-the-art methods have been proposed for learning the structure of microbial communities and to investigate the relationship between microorganisms and host environmental factors. However, these methods were mainly designed to model and analyze single microbial communities that do not interact with or depend on other communities. Such methods therefore cannot comprehend the properties between interdependent systems in communities that affect host behavior and disease processes. RESULTS: We introduce a novel hierarchical Bayesian framework, called BALSAMICO (BAyesian Latent Semantic Analysis of MIcrobial COmmunities), which uses microbial metagenome data to discover the underlying microbial community structures and the associations between microbiota and their environmental factors. BALSAMICO models mixtures of communities in the framework of nonnegative matrix factorization, taking into account environmental factors. We proposes an efficient procedure for estimating parameters. A simulation then evaluates the accuracy of the estimated parameters. Finally, the method is used to analyze clinical data. In this analysis, we successfully detected bacteria related to colorectal cancer. CONCLUSIONS: These results show that the method not only accurately estimates the parameters needed to analyze the connections between communities of microbiota and their environments, but also allows for the effective detection of these communities in real-world circumstances.

Impaired pain processing and its association with attention disturbance in patients with amyotrophic lateral sclerosis.

BACKGROUND: Cognitive dysfunction characterized by executive dysfunction and persistent attention function has been reported in patients with amyotrophic lateral sclerosis (ALS); however, it is unclear if this contributes to the pain processing deficits associated with the disease. OBJECTIVE: We clarified the relationship between pain processing and both cognitive function and sensory symptoms in patients with ALS. METHODS: We enrolled 23 patients with ALS and 14 healthy control subjects. We examined pain-related somatosensory evoked potentials (SEPs) using an intra-epidermal needle electrode. We evaluated cognitive function and the clinical characteristics of sensation and analyzed their relationships with pain-related SEPs. RESULTS: Pain-related SEP amplitudes were significantly lower, while the rate of amplitude attenuation due to habituation or change in attention was significantly greater in patients with ALS than in control subjects. There were no significant differences in pain-related SEP parameters between patients with or without sensory symptoms. Instead, pain-related SEP amplitude and its rate of attenuation were correlated with cognitive dysfunction, particularly with attention domains. CONCLUSIONS: Our results suggest that attention deficit, but not sensory nerve involvement, is a major cause of the alterations in pain-related SEP in patients with ALS.

Parkinson's Disease and Gut Microbiota.

BACKGROUND: Parkinson's disease (PD) is caused by abnormal aggregation of α-synuclein fibrils, called the Lewy bodies, in the central nervous system. Accumulating knowledge points to the notion that α-synuclein fibrils start from the dorsal vagal nucleus and ascend to the locus ceruleus and the substantia nigra (SN). Even in healthy elderly subjects without motor or cognitive impairment, α-synuclein fibrils are frequently observed in the brain and sometimes in the intestinal neural plexus. Enteroendocrine cells have a direct synapse to the vagal afferents, and the vagal nucleus has synaptic pathways to the SN and the striatum. Intestinal bacteria are likely to be involved in the formation of intestinal α-synuclein fibrils. SUMMARY: A nonparametric meta-analysis of intestinal microbiota in PD in 5 countries, as well as scrutinization of the other reports from the other countries, indicates that mucin-degrading Akkermansia is increased in PD and that short-chain fatty acid (SCFA)-producing bacteria are decreased in PD. Both dysbiosis should increase the intestinal permeability, which subsequently facilitates exposure of the intestinal neural plexus to toxins like lipopolysaccharide and pesticide, which should lead to abnormal aggregation of α-synuclein fibrils. Decreased SCFA also downregulates regulatory T cells and fails to suppress neuronal inflammation. Key Messages: Therapeutic intervention may be able to be established against these mechanisms. Additional biochemical, cellular, and animal studies are required to further dissect the direct association between intestinal microbiota and PD.

Syntheses and Characterization of Novel Perovskite-Type LaScO3-Based Lithium Ionic Conductors.

Perovskite-type lithium ionic conductors were explored in the (LixLa1-x/3)ScO3 system following their syntheses via a high-pressure solid-state reaction. Phase identification indicated that a solid solution with a perovskite-type structure was formed in the range 0 ≤ x < 0.6. When x = 0.45, (Li0.45La0.85)ScO3 exhibited the highest ionic conductivity and a low activation energy. Increasing the loading of lithium as an ionic diffusion carrier expanded the unit cell volume and contributed to the higher ionic conductivity and lower activation energy. Cations with higher oxidation numbers were introduced into the A/B sites to improve the ionic conductivity. Ce4+ and Zr4+ or Nb5+ dopants partially substituted the A-site (La/Li) and B-site Sc, respectively. Although B-site doping produced a lower ionic conductivity, A-site Ce4+ doping improved the conductive properties. A perovskite-type single phase was obtained for (Li0.45La0.78Ce0.05)ScO3 upon Ce4+ doping, providing a higher ionic conductivity than (Li0.45La0.85)ScO3. Compositional analysis and crystal-structure refinement of (Li0.45La0.85)ScO3 and (Li0.45La0.78Ce0.05)ScO3 revealed increased lithium contents and expansion of the unit cell upon Ce4+ co-doping. The highest ionic conductivity of 1.1 × 10-3 S cm-1 at 623 K was confirmed for (Li0.4Ce0.15La0.67)ScO3, which is more than one order of magnitude higher than that of the (LixLa1-x/3)ScO3 system.

Meta-Analysis of Gut Dysbiosis in Parkinson's Disease.

BACKGROUND: PD may begin with the intestinal accumulation of α-synuclein fibrils, which can be causally associated with gut dysbiosis. The variability of gut microbiota across countries prevented us from identifying shared gut dysbiosis in PD. OBJECTIVES: To identify gut dysbiosis in PD across countries. METHODS: We performed 16S ribosomal RNA gene sequencing analysis of gut microbiota in 223 patients with PD and 137 controls, and meta-analyzed gut dysbiosis by combining our dataset with four previously reported data sets from the United States, Finland, Russia, and Germany. We excluded uncommon taxa from our analyses. For pathway analysis, we developed the Kyoto Encyclopedia of Genes and Genomes orthology set enrichment analysis method. RESULTS: After adjusting for confounding factors (body mass index, constipation, sex, age, and catechol-O-methyl transferase inhibitor), genera Akkermansia and Catabacter, as well as families Akkermansiaceae, were increased, whereas genera Roseburia, Faecalibacterium, and Lachnospiraceae ND3007 group were decreased in PD. Catechol-O-methyl transferase inhibitor intake markedly increased family Lactobacillaceae. Inspection of these bacteria in 12 datasets that were not included in the meta-analysis revealed that increased genus Akkermansia and decreased genera Roseburia and Faecalibacterium were frequently observed across countries. Kyoto Encyclopedia of Genes and Genomes orthology set enrichment analysis revealed changes in short-chain fatty acid metabolisms in our dataset. CONCLUSIONS: We report that intestinal mucin layer-degrading Akkermansia is increased and that short-chain fatty acid-producing Roseburia and Faecalibacterium are decreased in PD across countries. © 2020 International Parkinson and Movement Disorder Society.

Freeze-drying enables homogeneous and stable sample preparation for determination of fecal short-chain fatty acids.

BACKGROUND: The analysis methods for fecal short-chain fatty acids (SCFAs) have evolved considerably. Recently, the role of SCFAs in gastrointestinal physiology and their association with intestinal microbiota and disease were reported. However, the intra-fecal variability and storage stability of SCFAs have not been extensively investigated. The aim of this study was to understand the limitations of the measurement of SCFAs in crude feces and develop a useful pre-examination procedure using the freeze-drying technique. METHODS: SCFAs in crude feces, obtained from healthy volunteers, and freeze-dried feces were determined by derivatization with isobutyl chloroformate, followed by liquid-liquid extraction with hexane, and separation and analysis using gas chromatography-mass spectrometry. RESULTS: Among the SCFAS, the maximum intra-fecal variability was observed for iso-butyrate (coefficient of variation of 37.7%), but the freeze-drying procedure reduced this variability (coefficient of variation of 7.9%). Similar improvements were also observed for other SCFAs. Furthermore, significant decreases in the SCFA amounts were observed with storage at 4 °C for 24 h. CONCLUSIONS: The freeze-drying procedure affords fecal SCFA stability, even with storage at room temperature for 3 d. The freeze-drying procedure allows reliable SCFA measurements without labour-intensive processes. Therefore, the freeze-drying procedure can be applied in basic, clinical, and epidemiological studies.

Difference in cardiovascular response during orthostatic stress in Parkinson's disease and multiple system atrophy.

Although orthostatic hypotension is more prominent in multiple system atrophy (MSA) than in Parkinson's disease (PD), there is no study comparing the degree of decrease in total peripheral resistance and cardiac response during orthostatic stress between both diseases. In this study, we examined whether there is a difference in cardiovascular response between MSA and PD. We examined the results of the head-up tilt test in 68 patients with MSA, 28 patients with cardiac non-denervated PD, and 70 patients with cardiac denervated PD whose total peripheral resistance after 60° tilting was lower than the value at 0°. Differences in cardiac output and blood pressure changes were compared against the decrease in total peripheral resistance. There was no difference in the degree of decrease in total peripheral resistance among the three groups. However, the slope of the regression line revealed that the increase in cardiac output against the change in total peripheral resistance was significantly lower in the MSA group than in the cardiac non-denervated and denervated PD groups, and that the decrease in systolic blood pressure against the change in total peripheral resistance was significantly greater in the MSA group than in the cardiac non-denervated and denervated PD groups. In MSA, the cardiac response during orthostatic stress is lower than that in PD, possibly underlying the fact that orthostatic hypotension is more prominent in MSA than in PD.

Impact of orthostatic hypotension on wheelchair use in patients with Parkinson's disease.

Wheelchair use is an important indicator of disease progression in Parkinson's disease (PD). Here, we investigated whether orthostatic hypotension (OH) affects the time to wheelchair use. We examined 33 PD patients with OH and 95 without OH. Median time to start using a wheelchair calculated from the time of disease onset was significantly shorter in patients with OH than in those without OH (12.0 vs 19.0 years; p < 0.001). Thus, appropriate management of OH and motor function is necessary.

Relationship between cardiac parasympathetic dysfunction and the anteroposterior diameter of the medulla oblongata in multiple system atrophy.

PURPOSE: Neurodegeneration of the nucleus ambiguus and the dorsal vagal motor nucleus has been implicated in cardiac parasympathetic dysfunction in multiple system atrophy (MSA). The nucleus ambiguus and the dorsal vagal motor nucleus, which are located in the medulla oblongata (MO), control the autonomic-specifically, the parasympathetic-functions of the body. The aim of our study was to investigate the relationship between cardiac parasympathetic dysfunction and the anteroposterior diameter of the MO in MSA by quantitatively analyzing magnetic resonance imaging (MRI) outcome measures. METHODS: We retrospectively assessed 40 consecutive patients with probable MSA and 25 age- and sex-matched controls. The anteroposterior diameter of the MO at two locations (MO diameter-A and -B) and the diameters of the midbrain and pons were measured by conventional MRI. A cardiac parasympathetic function score (CP-score) and cardiac sympathetic function score (CS-score) were generated by calculating the z-scores of multiple autonomic function tests. The relationship between the scores and the measured diameters of the brainstem was also investigated. RESULTS: The CP-score and CS-score were significantly lower in the patients with MSA than in the controls (CP-score: 0.61 ± 0.75 vs. - 0.38 ± 0.52, p < 0.001; CS-score: 0.91 ± 1.06 vs. - 0.57 ± 1.07, p < 0.001). Also, in the patients with MSA, the CP-score was significantly correlated with MO diameter-A (r = 0.40, p = 0.010), and the CS-score was significantly correlated with the diameter of the midbrain (r = 0.33, p = 0.038). CONCLUSION: The anteroposterior diameter of the MO is a potential imaging marker of parasympathetic dysfunction in MSA.

ENIGMA: an enterotype-like unigram mixture model for microbial association analysis.

BACKGROUND: One of the major challenges in microbial studies is detecting associations between microbial communities and a specific disease. A specialized feature of microbiome count data is that intestinal bacterial communities form clusters called as "enterotype", which are characterized by differences in specific bacterial taxa, making it difficult to analyze these data under health and disease conditions. Traditional probabilistic modeling cannot distinguish between the bacterial differences derived from enterotype and those related to a specific disease. RESULTS: We propose a new probabilistic model, named as ENIGMA (Enterotype-like uNIGram mixture model for Microbial Association analysis), which can be used to address these problems. ENIGMA enabled simultaneous estimation of enterotype-like clusters characterized by the abundances of signature bacterial genera and the parameters of environmental effects associated with the disease. CONCLUSION: In the simulation study, we evaluated the accuracy of parameter estimation. Furthermore, by analyzing the real-world data, we detected the bacteria related to Parkinson's disease. ENIGMA is implemented in R and is available from GitHub ( https://github.com/abikoushi/enigma ).

A latent allocation model for the analysis of microbial composition and disease.

BACKGROUND: Establishing the relationship between microbiota and specific diseases is important but requires appropriate statistical methodology. A specialized feature of microbiome count data is the presence of a large number of zeros, which makes it difficult to analyze in case-control studies. Most existing approaches either add a small number called a pseudo-count or use probability models such as the multinomial and Dirichlet-multinomial distributions to explain the excess zero counts, which may produce unnecessary biases and impose a correlation structure taht is unsuitable for microbiome data. RESULTS: The purpose of this article is to develop a new probabilistic model, called BERnoulli and MUltinomial Distribution-based latent Allocation (BERMUDA), to address these problems. BERMUDA enables us to describe the differences in bacteria composition and a certain disease among samples. We also provide a simple and efficient learning procedure for the proposed model using an annealing EM algorithm. CONCLUSION: We illustrate the performance of the proposed method both through both the simulation and real data analysis. BERMUDA is implemented with R and is available from GitHub ( https://github.com/abikoushi/Bermuda ).

Association between changes in visual evoked magnetic fields and non-motor features in Parkinson's disease.

Visual dysfunction can be caused by several abnormalities, including dysfunctions in the visual cortex and retina. Our aim was to investigate changes in visual evoked brain responses in the primary visual cortex associated with Parkinson's disease (PD). Sixteen healthy control subjects and ten patients with PD participated in this study. We assessed the visual evoked magnetic field (VEF) using magnetoencephalography (MEG). Checkerboard pattern reversal (CPR) and monotonous grating pattern (MGP) stimulations were used. Magnetic resonance imaging (MRI) was performed to analyze brain volume and generate a tractogram. Cognitive and olfactory function, and Unified Parkinson's Disease Rating Scale (UPDRS) scores were evaluated in patients with PD. Four components of the VEF (1M, 2M, 3M, 4M) were observed following stimulation. For both stimuli, results from the 1M and 2M components were significantly greater and the latency of the 1M component was increased markedly in the PD group compared with the healthy control group. In the PD group, 1M latency correlated with the UPDRS score of 1 for both stimuli, and a correlation was observed between olfactory function and the UPDRS score of 3 for the CPR stimulation alone. We suggest that the conduction delay observed following visual stimulation occurs peripherally rather than in the primary visual cortex. Degeneration of selective elements of the visual system in the retina, possibly midget cells, may be involved.

Association of leptin with orthostatic blood pressure changes in Parkinson's disease.

INTRODUCTION: Leptin is involved in the regulation of blood pressure; however, no studies have evaluated the role of leptin in blood pressure changes during orthostatic stress in PD patients. The aim of this study was to determine whether plasma leptin levels influence orthostatic blood pressure changes in PD patients. METHODS: We enrolled 55 patients and 25 age-matched healthy controls in this study. Associations between head-up tilt test measurements and leptin levels were evaluated. RESULTS: Systolic blood pressure changes during the head-up tilt tests were strongly correlated with leptin levels at baseline and at a 60-degree head-up tilt in PD patients, but not in control subjects. Multiple regression analysis also demonstrated that leptin levels were associated with orthostatic blood pressure changes. CONCLUSION: These observations suggest that low leptin levels may be associated with orthostatic hypotension during the head-up tilt test in patients with PD. © 2016 International Parkinson and Movement Disorder Society.