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A chemoenzymatic cascade system (GA&GOx@Au–SiO2) was fabricated by immobilizing Au nanoparticles onto silica (SiO2) followed by the co-immobilization of glucoamylase (GA) and glucose oxidase (GOx) for the production of gluconic acid from starch.

We report on studying tunnel junctions and an optical cavity structure for developing epitaxially-stacked high-efficiency 905 nm high-power laser diodes. The GaAs tunnel junctions were explored via simulations and experiments to realize a high peak current density of 7.7 × 104 A/cm2 and a low specific resistance of 1.5 × 10-5 Ωcm2 with a high n-doping concentration of 6 × 1019 cm-3. Employing a low-loss epitaxial structure design, single-, double-, and triple-cavity structure laser diodes demonstrated power scaling by epitaxial stacking. Triple-cavity laser diodes have a low optical loss (0.42 cm-1) and generate a peak power of 83 W with a short cavity length of 750 μm at a limited current of 30 A. © 2009-2012 IEEE.

In natural photosynthesis, photosynthetic organisms such as green plants realize efficient solar energy conversion and storage by integrating photosynthetic components on the thylakoid membrane of chloroplasts. Inspired by natural photosynthesis, researchers have developed many artificial photosynthesis systems (APS's) that integrate various photocatalysts and biocatalysts to convert and store solar energy in the fields of resource, environment, food, and energy. To improve the system efficiency and reduce the operation cost, reaction platforms are introduced in APS's since they allow for great stability and continuous processing. A systematic understanding of how a reaction platform affects the performance of artificial photosynthesis is conducive for designing an APS with superb solar energy utilization. In this review, we discuss the recent APS's researches, especially those confined on/in platforms. The importance of different platforms and their influences on APS's performance are emphasized. Generally, confined platforms can enhance the stability and repeatability of both photocatalysts and biocatalysts in APS's as well as improve the photosynthetic performance due to the proximity effect. For functional platforms that can participate in the artificial photosynthesis reactions as active parts, a high integration of APS's components on/in these platforms can lead to efficient electron transfer, enhanced light-harvesting, or synergistic catalysis, resulting in superior photosynthesis performance. Therefore, the integration of APS's components is beneficial for the transfer of substrates and photoexcited electrons in artificial photosynthesis. We finally summarize the current challenges of APS's development and further efforts on the improvement of APS's.

Sustainable and efficient production of chiral amines was realized with an oriented co-immobilized dual-enzyme system via SiBP-tag.

Objective Recent data have shown that regular exercise may ameliorate motor symptoms in Parkinson’s disease (PD). This study aims to investigate how intended exercise impacts motor and non-movement symptoms of PD. Methods 88 patients were randomly assigned to an early exercise group (E-EG), late exercise group (L-EG), or a control group (CG) using a randomized delayed-start design. The E-EG carried out a rigorous, formal exercise program for one hour, twice per week, for 18 months (May 2018 - November 2019). The L-EG took part in the exercise program in the final 6–12 months of the study. We assessed outcomes using the Unified Parkinson’s Disease Rating Scale (UPDRS), PDQ-39 Questionnaire, Line A test, Line B test, Nine-hole column test, 30 seconds squat and stand-up test (30s SST), 10m Walk test(10mW), Balance Evaluation Systems Mini Test (MiniBESTest), FAB and Time Up and Go Test(TUG). Results The patients with PD in the E-EG had lower performance in the UPDRS and Line B test compared to those in the L-EG at post-exercise(p

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor symptoms and non-motor symptoms, and affects millions of people worldwide. Growing evidence implies β-Hydroxybutyrate (BHB), one of the ketone bodies generated by ketogenesis, plays a neuroprotective role in neurodegenerative diseases. We aimed to verify the anti-inflammatory effect of BHB on PD and further explore potential molecular mechanisms.We performed the experiments on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model in vivo and 1-methyl-4-phenylpyridinium (MPPBHB treatment reversed motor deficits, loss of dopaminergic neurons and glial cell activation in PD mice induced by MPTP. Moreover, BHB inhibited microglia pyroptosis by negatively regulating STAT3/NLRP3/GSDMD signal pathway, resulting in downregulation of proinflammatory cytokines (IL-1β and IL-18) in vivo and vitro.These data suggested BHB supplement inhibited pyroptosis by down-regulating STAT3-mediated NLRP3 inflammasome activation for PD models in vivo and in vitro. Our findings provided novel insights and available interventions for the prevention and treatment of PD, and highlighted pyroptosis as a potential therapeutic target for PD.

Background: Synaptic abnormalities in synaptic proteins are the initial hallmarks of Alzheimer’s disease (AD). The higher level of palmitoylation of synaptic proteins was closely associated with amyloid-β (Aβ) in AD. Cattle encephalon glycoside and ignotin (CEGI) have been shown to act as multitarget neurotrophic agents in APPswe/PS1dE9 (APP/PS1) transgenic AD mice. However, it is not clear whether CEGI can influence Aβ deposition or whether it does so by the regulation of protein palmitoylation and expression of synaptic proteins in transgenic AD mice. Objective: In this study, we investigated the roles of CEGI in modulating postsynaptic density protein 95 (PSD-95) palmitoylation, Aβ pathologies, and expression of synaptic-associated proteins in APP/PS1 mice. Methods: Five-month-old APP/PS1 mice were treated intraperitoneally with 6.6 mL/kg of CEGI for 6 weeks. At the end of the treatment period, APP/PS1 mice were subjected to Morris water maze to test their cognitive functions. Acyl-biotinyl exchange (ABE) for PSD-95 palmitoylation, immunofluorescent staining for expression of PSD-95, N-methyl-D-aspartic acid receptor subunit 2B (NR2B), and synaptotagmin 1 (SYT1) were assessed in mouse brain sections. Results: CEGI treatment in APP/PS1 mice significantly reduced Aβ deposition, relieved memory deficits, and decreased PSD-95 palmitoylation while markedly increasing the expression of PSD-95, NR2B, and SYT1 in the frontal cortex. There was a significant correlation between Aβ expression and PSD-95 palmitoylation in APP/PS1 mice. Conclusion: Our findings demonstrate that CEGI improved AD-like neuropathology, possibly by inhibiting PSD-95 palmitoylation, improving learning memory, and enhancing expression of synaptic-associated proteins, representing a potential therapy for AD treatment.

Background and objective Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson’s disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD). Methods A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG (n = 100) or placebo (n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks. Results After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (− 1.43 scores [− 2.50, − 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (− 3.56 scores [− 5.77, − 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated. Conclusion ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432

Nemaline myopathy (NM) is a congenital myopathy of great heterogeneity, characterized by the presence of rods in the cytoplasm of muscle fibers. The samples of 16 nemaline myopathy patients diagnosed by characteristically pathological features went through whole exon sequencing. Clinico-pathological and genetic features of the cases were systematically analyzed. According to the classification of nemaline myopathy by ENMC, 8 cases are typical congenital subtype, 6 cases are childhood/juvenile onset subtype and 2 case are adult onset subtype. In histological findings, characteristic purple-colored rods are discovered under modified gömöri trichrome staining (MGT). Electron microscopy revealed the presence of high electron-dense nemaline bodies around the submucosa and the nucleus nine patients (9/16 56.3%) were detected pathogenic causative mutations, among whom mutations in the NEB gene were the most frequent (6 patients, 66.7%). KBTBD13 gene mutation was discovered in two patients and ACTA1 gene mutation was discovered in 1 patient. Nemaline myopathy is a congenital myopathy with highly clinico-pathological and genetic heterogeneity. NEB gene mutation is the most common mutation, in which splicing change c.21522 +3A > G is hotspot mutation in Chinese NM patients.

High-power, broad-area, semiconductor lasers are attractive sources for material processing, aerospace, and laser pumping. The design of the active region is crucial to achieve the required high power and electro-optical conversion efficiency, since the temperature significantly affects the performance of the quantum well, including the internal quantum efficiency and mode gain. In this work, the temperature effects on the active region of a 808 nm high-power semiconductor laser were investigated theoretically and experimentally. The simulations were performed with a Quasi-3D model, which involved complete steady-state semiconductor and carrier confinement efficiency combined with a new mathematical method. The critical aluminum content of the quantum barrier was proposed and the relationship between temperature and various loss sources was disclosed in the temperature range of 213 to 333 K, which provides a reliable reference for the design of epitaxial structures of high-power semiconductor lasers in different operating conditions. Subsequently, the optimized epitaxial structure was determined and used to fabricate standard laser bar chips with a cavity length of 2 mm. The experimental electro-optical conversion efficiency of 71% was demonstrated with a slope efficiency of 1.34 W/A and an injection current of 600 A at the heatsink temperature of 223 K. A record high electro-optical conversion efficiency of 73.5% was reached at the injection current of 400 A, while the carrier confinement efficiency was as high as 98%.

Myotonia congenita (MC) is a rare genetic disease caused by mutations in the skeletal muscle chloride channel gene (

This is the document corresponding to the talk the first author gave at IHES for the Laurent Schwartz seminar on November 19, 2019. It concerns our recent introduction of a modulated free energy in mean-field theory in BrJaWa [4]. This physical object may be seen as a combination of the modulated potential energy introduced by S. Serfaty [See Proc. Int. Cong. Math. (2018)] and of the relative entropy introduced in mean field limit theory by P.-E. Jabin, Z. Wang [See Inventiones 2018]. It allows to obtain, for the first time, a convergence rate in the mean field limit for Riesz and Coulomb repulsive kernels in the presence of viscosity using the estimates in Du [8] and Se1 [20]. The main objective in this paper is to explain how it is possible to cover more general repulsive kernels through a Fourier transform approach as announced in BrJaWa [4] first in the case σN → 0 when N → +∞ and then if σ > 0 is fixed. Then we end the paper with comments on the particle approximation of the Patlak-Keller-Segel system which is associated to an attractive kernel and refer to [C.R.

In order to solve the toxic and hazardous issues of the agents in the chemical reduction process of graphene oxide (GO), disodium guanosine 5′-monophosphate (GMP-2Na) was used as an ideal reducing agent for the synthesis of functionalized GO (FGO) for lipase immobilization. At the condition of low amount adsorption of GMP-2Na indicated by the N1s spectra of X-ray photoelectron spectroscopy (XPS), the C/O atomic ratio of the FGO increased from 2.09 to 3.12, indicating the reduction of GO. As the amount of GMP-2Na increased, the intensity of the characteristic peak of GO in the XRD pattern decreased, and the I D /I G peak intensity of Raman spectra increased during the functionalization process. It was found that when the concentration of GMP-2Na is 0.20 mg/mL, the degree of hydrophobicity of FGO is conducive to the formation of optimal conformation of lipase. After immobilization, the activity of the immobilized enzyme reaches twice the value of free enzyme. At the same time, the protein loading reaches to 600 mg/g. The immobilized enzyme showed enhanced durability since no obvious decrease was observed after incubation for 8 h at pH 6.0 and pH 7.0. After storage for 35 days, the activity of GO-G@ enzyme was 54.47% higher than that of free enzyme. GO reduced by GMP-2Na provides a possibility to obtain a highly efficient lipase immobilization carrier.

The ketogenic diet (KD) is a low-carbohydrate, high-fat and adequate-protein diet. As a diet mimicking fasting, it triggers the production of ketone bodies (KBs) and brings the body into a state of ketosis. Recent and accumulating studies on humans and animal models have shown that KD is beneficial to neurodegenerative diseases through modulating central and peripheral metabolism, mitochondrial function, inflammation, oxidative stress, autophagy, and the gut microbiome. Complicated interplay of metabolism, gut microbiome, and other mechanisms can regulate neuroinflammation in neurodegenerative diseases by activating multiple molecular and cellular pathways. In this review, we detail the physiological basis of the KD, its functions in regulating neuroinflammation, and its protective role in normal brain aging and neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). We aimed to elucidate the underlying neuroinflammatory mechanisms of KD therapies in neurodegenerative diseases and provide novel insights into their application for neurodegenerative disease prevention and treatment.

As an autoimmune central nervous system disease characterized by inflammation and demyelination, neuromyelitis optica (NMO) has been extensively investigated. A specific antigenic target, astrocytic water channel aquaporin-4 (AQP4) has already been identified, and it can be recognized explicitly by the autoantibody marker NMO-IgG. Along with the immune attacks, clinical disabilities would gradually accumulate. As there has been no validated and well-recognized therapy for NMO till now, preventing and postponing attack using immunosuppressive therapies is the primary treatment option. In the current retrospective study, the effect of immunosuppressive agents was investigated through a long-term follow-up. To assess the long-term effectiveness and safety of rituximab (RTX), azathioprine (AZA), and mycophenolate mofetil (MMF) therapies, all 129 patients with NMO spectrum disorders (NMOSD) who received at least one of these treatments were studied, including 55 seropositive for AQP4-Ab and 74 seronegative for AQP4-Ab. The median post-treatment annualized relapse rate (ARR) was lower than the pre-treatment rates in all AQP4+Ab groups (from 1.0 to 0.7 in RTX, from 0.8 to 0.3 in AZA, and from 0.85 to 0.35 in MMF). Meanwhile, the ARR also decreased in all AQP4−Ab groups (from 0.3 to 0.2 in RTX, from 0.9 to 0.5 in AZA, and from 0.9 to 0.4 in MMF). Disability condition improved in the Expanded Disability Status Scale (EDSS) in all AQP4+Ab groups (from 4.0 to 2.75 in RTX, from 3.5 to 2.5 in AZA, and from 3.0 to 2.0 in MMF) and in all AQP4−Ab groups (from 3.0 to 2.5 in RTX, from 3.0 to 2.5 in AZA, and from 3.5 to 2.0 in MMF). There was no statistically significant difference between the post-treatment and pre-treatment changes of EDSS and ARR in the RTX, AZA, and MMF groups (P > 0.05). However, according to Kaplan–Meier survival analysis, RTX-treated patients were more likely to be relapse-free after long-term follow-up than those who received AZA or MMF therapy. Meanwhile, adverse effects were noted in three out of 23 patients with RTX treatment, five of 32 with AZA treatment, and three of 21 with MMF treatment. No serious adverse events were observed in all treatment groups during the study. RTX, AZA, and MMF therapies efficiently lowered the relapse frequency and disability in both of the AQP4-Ab seropositive or seronegative patients with NMO. Furthermore, low dosage of RTX is recommended for the patients with NMO owing to its long-term effectiveness and safety.

Parkinson’s disease (PD) is a common neurodegenerative disease, and the mechanism underlying PD pathogenesis is not completely understood. Increasing evidence indicates that microRNAs (miRNAs) play a critical regulatory role in the pathogenesis of PD. This study aimed to explore the miRNA-mRNA regulatory network for PD. The differentially expressed miRNAs (DEmis) and genes (DEGs) between PD patients and healthy donors were screened from the miRNA dataset GSE16658 and mRNA dataset GSE100054 downloaded from the Gene Expression Omnibus (GEO) database. Target genes of the DEmis were selected when they were predicted by three or four online databases and overlapped with DEGs from GSE100054. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID) and Metascape analytic tools. The correlation between the screened genes and PD was evaluated with the online tool Comparative Toxicogenomics Database (CTD), and protein-protein interaction (PPI) networks were built by the STRING platform. We further investigated the expression of genes in the miRNA-mRNA regulatory network in blood samples collected from PD patients and healthy donors via qRT-PCR. We identified 1505 upregulated and 1302 downregulated DEGs, and 77 upregulated and 112 downregulated DEmis were preliminarily screened from the GEO database. Further functional enrichment analysis identified 10 PD-related hub genes, including RAC1, IRS2, LEPR, PPARGC1A, CAMKK2, RAB10, RAB13, RAB27B, RAB11A, and JAK2, which were mainly involved in Rab protein signaling transduction, AMPK signaling pathway, and signaling by Leptin. A miRNA-mRNA regulatory network was then constructed with 10 hub genes, and their interacting miRNAs overlapped with DEmis, including miR-30e-5p, miR-142-3p, miR-101-3p, miR-32-3p, miR-508-5p, miR-642a-5p, miR-19a-3p, and miR-21-5p. Analysis of clinical samples verified significant upregulation of LEPR and downregulation of miR-101-3p and miR-30e-5p in PD patients as compared with healthy donors. Thus, the miRNA-mRNA regulatory network was initially constructed and has the potential to provide novel insights into the pathogenesis and treatment of PD.

Combination of enzymatic and chemical reactions provides tremendous possibilities for chemoenzymatic cascade processes. However, constructing efficient hybrid catalysts still faces great challenges. Herein, we develop a hybrid catalyst by in situ encapsulating organophosphorus hydrolase (OPH) into a Zn-doped Co-based ZIF (0.8CoZIF) via biomimetic mineralization for the chemoenzymatic cascade conversion of methyl parathion to 4-nitrophenol and then 4-aminophenol. The exsolved Co nanoclusters in Zn/Co-ZIF are found to catalyze 4-nitrophenol reduction into 4-aminophenol in the presence of sodium borohydride (NaBH4). The as-synthesized OPH@0.8CoZIF catalyzes the complete conversion of 95 μM methyl parathion at nearly 100% 4-aminophenol production in the presence of 50 mM NaBH4 within 15 min, which is 1/4 that of the physical mixture of OPH and 0.8CoZIF, benefiting from the MP accumulation and substrate channeling in the hybrid catalyst. The maximum cascade conversion rate of MP to 4-AP reaches 8.07 μmol·min-1·g-catalyst-1, which is higher than most of the reported chemoenzymatic cascade catalysts. Therefore, the hybrid nanocatalyst containing Co-ZIF-based catalyst and OPH is successfully fabricated and enables to catalyze the complete conversion of a toxic pollutant like methyl parathion into a non-toxic resource like 4-aminophenol for recycling in useful chemical synthesis through efficient one-pot cascade reactions.

We report on the development of a 940-nm diode laser bar based on epitaxially stacked active regions by employing a tunnel junction structure. The tunnel junction and the device parameters were systematically optimized to achieve high output and power conversion efficiency. A record quasi-continuous wave (QCW) peak power of 1.91 kW at 25 °C was demonstrated from a 1-cm wide bar with a 2-mm cavity length at 1 kA drive current (200 μs pulse width and 10 Hz repetition rate). Below the onset of the thermal rollover, the slope efficiency was as high as 2.23 W/A. The maximum power conversion efficiency of 61.1% at 25 °C was measured at 300 A. Reducing the heatsink temperature to 15 °C led to a marginal increase in the peak power to 1.95 kW.

In this note, we propose a modulated free energy combination of the methods developed by P.-E. Jabin and Z. Wang [Inventiones (2018)] and by S. Serfaty [Proc. Int. Cong. Math. (2018) and references therein] to treat more general kernels in mean-field limit theory. This modulated free energy may be understood as introducing appropriate weights in the relative entropy developed by P.-E. Jabin and Z. Wang (in the spirit of what has been recently developed by D. Bresch and P.-E. Jabin [Ann. of Math. (2) (2018)]) to cancel the most singular terms involving the divergence of the flow. Our modulated free energy allows us to treat singular potentials that combine large smooth part, small attractive singular part, and large repulsive singular part. As an example, a full rigorous derivation (with quantitative estimates) of some chemotaxis models, such as the Patlak–Keller–Segel system in subcritical regimes, is obtained.

We prove the uniqueness of weak solutions to the spatially homogeneous special relativistic Landau equation under the conditional assumption that the solution satisfies $(p^0)^7 F(t,p) \in L^1 ([0,T]; L^\infty)$. The existence of standard weak solutions to the relativistic Landau equation has been shown recently in (arXiv:1806.08720), Comment: 37 pages, published version

To achieve efficient one-step production of gluconic acid, cascade reactions of glucose oxidase (GOD) and catalase (CAT) have been advocated in the biocatalysis system. In this work, the methodology of co-immobilization of GOD and CAT was investigated in details for obtaining improved enzyme loading and activity. The maximum adsorption capability of GOD and CAT was 24.18 and 14.33 mg·g−1, respectively. The matching between dimensions of enzymes and hierarchical pore sizes of carriers are critical to the success of immobilization process. The simultaneous self-assembly on glutaraldehyde cross-linked mesoporous carriers exhibited favorable properties in comparison with sequential immobilization of GOD and CAT. The conversion of glucose under adequate air by co-localized GOD&CAT sustained the activity more than 90% after repeated utilization in the production of sodium gluconate and gluconic acid, suggesting that the co-immobilized GOD&CAT could be a promising catalyst for gluconate and gluconic acid production in some chemical and food industries.

Surface amine modification could not only improve the microenvironment near the active sites of enzyme, but also enhance the multi-point chemical crosslinking between the enzyme and carrier. The linear structured polymer of e-poly- l -lysine (EPL) is an ideal donor of amino with much more exposed on the surface for enzyme attachment. Analysis of the result of dynamic light scattering (DLS) and circular dichroism (CD) demonstrated the favorable electrostatic interactions and negligible impact on the conformation of enzymes, Glucose Oxidase and Catalase (GOx&CAT). Titration and dissociation curve together with Zeta-potential characterization revealed that enzymes (EPL@GOx&CAT) under the protection of EPL had more stable structure and better activity and stability in acidic reaction environment. Meanwhile, the activity recovery of immobilized EPL@GOx&CAT increased to 1.56 times higher than that of GOx&CAT, and the acid resistance was improved by 1.44 times with the optimum pH shifting to acidic by 0.50 unit. The substrate affinity was raised with the decrease of Km from 5.98 to 4.35 mg mL−1. Thus, the gluconic acid production in low pH system could be increased by pH-engineering of the enzyme microenvironment via conjugation with positively charged polyelectrolyte.

Recent data have shown that regular exercise may ameliorate motor symptoms in Parkinson's disease (PD). This study aims to investigate how intended exercise impacts motor and non-movement symptoms of PD.Eighty-eight patients were randomly assigned to an early exercise group (E-EG), late exercise group (L-EG), or a control group (CG) using a randomized delayed-start design. The E-EG carried out a rigorous, formal exercise program for 1 h, twice per week, for 18 months (May 2018-November 2019). The L-EG took part in the exercise program in the final 6-12 months of the study. We assessed outcomes using the Unified Parkinson's Disease Rating Scale (UPDRS), PDQ-39 Questionnaire, Line A test, Line B test, Nine-hole column test, 30 s squat and stand-up test (30 s SST), 10-m walk test (10mW), Balance Evaluation Systems Mini Test (MiniBESTest), FAB, and Time Up and Go Test (TUG).The patients with PD in the E-EG had lower performance in the UPDRS and Line B test compared to those in the L-EG at post-exercise (p 0.05). Moreover, the patients with PD in the E-EG had much lower performance in the PDQ-39 and 9-Hole Peg test compared to those in the L-EG at post-exercise (p 0.01).Implementation of an exercise regimen improved the movement abilities and quality of life in PD patients, especially in the E-EG. This data supports the idea that intended exercise should be implemented as part of the treatment strategy for PD patients as early as possible.

Anti-Sry-like high mobility group box (SOX) 1 antibodies (abs) are partly characterized onconeural autoantibodies (autoabs) due to their correlation with neoplastic diseases. Anti-SOX1 abs are associated with various clinical manifestations, including Lambert-Eaton myasthenic syndrome (LEMS) and paraneoplastic cerebellar degeneration (PCD). However, the clinical characteristics of patients with anti-SOX1 abs have not been described in detail. This review systematically explores the reported patients with anti-SOX1 abs and analyzes these cases for demographic characteristics, clinical features, coexisting neuronal autoabs, neuroimaging findings, treatment, and clinical outcomes. In addition, considering that PCD is the most common paraneoplastic neurological syndrome and that the association between PCD and anti-SOX1 abs remains unclear, we focus on the presence of autoabs in relation to PCD and associated tumors. PCD-associated autoabs include various intracellular autoabs (e.g., anti-Hu, anti-Yo, anti-Ri, and anti-SOX1) and cell-surface autoabs (anti-P/Q-type voltage-gated calcium channel). Commonly involved tumors in PCD are small-cell lung cancer (SCLC), gynecological, and breast tumors. LEMS is the most common clinical symptom in patients with anti-SOX1 abs, followed by PCD, and multiple neuronal autoabs coexist in 47.1% of these patients. SCLC is still the predominant tumor in patients with anti-SOX1 abs, while non-SCLC is uncommon. No consistent imaging feature is found in patients with anti-SOX1 abs, and there is no consensus on either the therapy choice or therapeutic efficacy. In conclusion, the presence of anti-SOX1 abs alone is a potential predictor of an uncommon paraneoplastic neurological disorder, usually occurring in the setting of LEMS, PCD, and SCLC. The detection of anti-SOX1 abs contributes to an early diagnosis of underlying tumors, given the diversity of clinical symptoms and the absence of characteristic neuroimaging features.

We derive quantitative estimates proving the propagation of chaos for large stochastic systems of interacting particles. We obtain explicit bounds on the relative entropy between the joint law of the particles and the tensorized law at the limit. We have to develop for this new laws of large numbers at the exponential scale. But our result only requires very weak regularity on the interaction kernel in the negative Sobolev space $\dot W^{-1,\infty}$, thus including the Biot-Savart law and the point vortices dynamics for the 2d incompressible Navier-Stokes., 59 pages

Thermomechanical behavior has an important effect on reliability and lifetime of high-power diode lasers (HPDLs). Finite-element analysis (FEA) model and analytical solution model of the conduction-cooled package (CS) HPDL are established to analyze the thermomechanical behavior including normal stress, shearing stress, and displacement in reflowing process and working process. Moreover, in order to simulate and analyze the thermomechanical behavior in total process, reflowing thermal stress and displacement are considered as the residual stress and the initial condition of working process. We find that shearing stress is the origin of other thermomechanical behavior due to coefficient thermal expansion (CTE) mismatch, while both CTE mismatch and temperature gradient cause the thermal stress and displacement in working process. Although thermal stresses and displacement induced in reflowing process are larger than working process, the working process has great impact on smile and causes much worse total smile. The influence of different working temperatures on smile is also studied in total process with analytical solution, FEA, and experiment. For analytical solution, the total smile value is inversely proportional to the working temperature, while for FEA the smile value is proportional to the working temperature and FEA result accords with experimental result.

Objective Dementia with Lewy bodies (DLB) is a common type of neurodegenerative dementia. Molecular neuroimaging using dopamine transporter (DaT), Pittsburgh compound B (PIB), and fluorodeoxyglucose (FDG) positron emission tomography (PET) has advantages in detecting dopaminergic neuron loss, abnormal amyloid β-protein deposition, and glucose metabolism changes in patients with neurodegenerative disorders. However, the multi-modality molecular imaging features of patients with DLB have rarely been reported. Methods Five patients with a probable diagnosis of DLB were enrolled. PET/magnetic resonance imaging was performed with three tracers: 11C-β-CFT, 11C-PIB, and 18F-FDG. Clinical and imaging characteristics were analyzed. Results All patients with DLB showed reduced uptake in the bilateral putamen on DaT PET, increased uptake throughout the cerebral cortex on PIB PET, and intact metabolism of the posterior cingulate gyrus on FDG PET. Conclusion Multimodal molecular imaging is helpful for early diagnosis of DLB. Studies with larger sample sizes are needed to confirm the molecular imaging differences between DLB and Alzheimer’s disease and Parkinson’s disease dementia.

Developing targeted delivery nanosystems for delivering chemotherapeutic anticancer drugs specifically to cancerous tissues with improvement in the specificity of drugs for different cancer cells can result in high therapeutic efficacy and low toxicity in healthy tissues. Herein, we proposed the synthesis of a multifunctional nanodelivery system, folic acid (FA) decorating nanographene oxide (nGO) functionalized with poly(ethylene glycol) (PEG), called pGO-FA, with good biocompatibility and good delivering performance of a hydrophobic water-insoluble anticancer drug of paclitaxel (PTX). 4-br-PEG-NH2, FA, and PTX were attached to PEG-functionalized nGO (pGO) through a combined chemical and physical force to form a nanosized complex, pGO-FA-PTX, defined as the nanodrug system. WST-8 assay in vitro illustrated that pGO-FA-PTX inhibited A2780 cells in a concentration-dependent manner. Cell viability was kept high to 60% when treated with 200 nM of free PTX. However, pGO-FA-PTX with the same dose of PTX (cell viability less than 30%) had double the cytotoxicity effect compared to free PTX. Furthermore, fluorescence observation demonstrated that pGO-FA-PTX exhibited an improved efficiency in killing A2780 cells due to the special affinity between FA and FA receptor, which has high expression in cancer cells. The strategy and method used in this study could be effective in improving both the bioavailability of PTX and therapy efficiency.

Background Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been reported to exhibit therapeutic effects in various animal models of neurological diseases, such as stroke and hypoxic-ischemic brain injury. Objective The present study investigated the potential beneficial effect of MSC-derived EVs in an animal model of Alzheimer's disease (AD). Methods APP/PS1 mice and their non-transgenic littermates (WT) received intracerebroventricle injection of MSC-derived EVs once per two days for two weeks. Then novel object recognition and water maze tasks were carried out to measure the cognitive behaviors. Electrophysiological tests were carried out to measure hippocampal synaptic plasticity. Inducible nitric oxide synthase (iNOS) mRNA and protein levels were measured by qRT-PCR and western blotting in primary cultured neurons treated with amyloid-β peptide (Aβ) or prepared from APP/PS1 mice. Results Treatment with MSC-derived EVs alleviates exogenous Aβ-induced iNOS mRNA and protein expression. In cultured primary neurons prepared from APP/PS1 pups, iNOS mRNA and protein levels were significantly reduced when treated with MSC-derived EVs. MSC-derived EVs improved cognitive behavior, rescued impairment of CA1 synaptic transmission, and long-term potentiation in APP/PS1 mice. Conclusion MSC-derived EVs possessed beneficial effects in a mouse model of AD, probably by suppressing Aβ induced iNOS expression.

The continuous-wave 100 W-class 808 nm laser diode arrays with extremely high power conversion efficiency of 68% were reported at the heatsink temperature of 25 °C. To the best of our knowledge, this was the highest power conversion efficiency at continuous-wave 106 W 808 nm laser diode array with 50% fill factor so far. An asymmetric broad waveguide epitaxial structure with very low internal optical loss of 0.5 cm −1 was presented. In order to improve the efficiency, various fill factor devices were studied. The 50 W laser diode array with 30% fill factoir and 1.0 mm cavity length demonstrated power conversion efficiency of 71% at heatsink temperature of 15 °C.

Semiconductor lasers with high power conversion efficiency (PCE) and output power are heavily investigated driven by more energy-efficient commercial applications. In this paper, an asymmetric broad area laser (A-BAL) design is studied and compared with a conventional symmetric broad area laser (S-BAL) design for 808 nm single emitter laser diodes. We present a comparative theoretical and experimental investigation by studying the thermal effects on the laser parameters. The output characteristics and efficiency loss paths for the designs were analyzed. The leakage of carriers was identified as the primary source of the PCE reduction with temperature. Suppressing this leakage by optimization of the A-BAL design, a record continuous-wave PCE of 68% at 25 °C and 60.4% at 75 °C were achieved for a single emitter laser with 10 W output power. These devices deliver high efficiency at high temperatures with reliable operation achieving 2000 h of an accelerated aging lifetime without failures.

Broad-area diode lasers with high output power and low lateral divergence angle are highly desired for extensive scientific and industrial applications. Here, we report on the epitaxial design for higher output power and a flared waveguide design for reduced divergence, which leads to high power operation with a low lateral divergence angle. A vertically asymmetric epitaxial structure was employed and optimized for low internal optical loss and high efficiency to realize high output power operation. Using a flared waveguide design, the lateral divergence angle was efficiently reduced by decreasing the number of high-order lateral optical modes significantly. The flared waveguide design introduces a smooth modification of the ridge width along the cavity without deteriorating laser performance. Based on the optimized epitaxial and waveguide design, we scaled the waveguide width to realize high continuous-wave power of 34.5 W at 25 °C. A low lateral divergence angle of 8° and high power conversion efficiency of 60% were achieved at the operating power level of 25 W. The life test data (30 A at 45 °C for 39 units, 0 failures in 1000 h) demonstrated reliable operation illustrating the efficient design for reduced lateral divergence angle and high operating power.

A novel black phosphorus (BP) solution saturable absorber (SA) is fabricated by the liquid-phase-exfoliated method and successfully used for passively Q-switched (QS) Nd:YVO4 laser. Compared with a traditional solid SA, a BP solution SA possesses more excellent optical transparency and higher damage resistance. The shortest pulse duration and highest average output power are measured to be 119 ns and 1.23 W, respectively. To the best of our knowledge, both of them are the best results among QS solid-state lasers with BP-based absorbers so far. The repetition rate is in the range of 533.2 to 722 kHz. The results indicate the potential application of the BP solution SA into high-power solid-state pulse lasers.

The report presents the high power mode-locking operation in an anomalous-dispersion fiber laser with a novel WS 2 saturable absorber (SA) based on fluorine mica (FM) substrate. Compared to organic host material such as polymer, FM has higher softening temperature, heat dissipation and laser damage threshold. By employing the SA, a stable mode-locked fiber laser is achieved. The duration of the pulse broadens from 2.816 ns to 3.654 ns almost linearly with increasing pump power. The average output power and single pulse energy can increase up to 33.5 mW and 4 nJ at the maximum pump power respectively. The results indicate that WS 2 /FM material is an ideal SA for high power Er-doped fiber (EDF) lasers.

High-power GaAs-based semiconductor lasers are the most efficient source of energy for converting electrical into optical power. 940nm diode lasers are used directly or as pump sources for Yb:YAG solid-state lasers, and are widely used in laser cladding and other fields. Improving electro-optic conversion efficiency and reliable output power are urgent requirements for current research hotspots and industrial laser systems. In this paper, we use an asymmetric epitaxial structure of InGaAs/AlGaAs, which reduces the optical loss and resistance, and adopt better cavity surface technology to present 940nm 1-cm quasi-continuous micro-channel cooling (MCC) laser bars. The lasers are tested under a high duty cycle of 9.6% (600us,160Hz) at 25°C with output power of 660.05W, electro-optic conversion efficiency of 64.71% at 600A and slope efficiency of 1.16 W/A. The peak efficiency reaches 72.4%. The increased efficiency results from a lower threshold current and a lower series resistance. Furthermore, the output power of 1025W (1000A) has been confirmed at a duty cycle of 4% (400us,100Hz).

Graphene oxide (GO) with oxygen containing functional groups can be selectively modified by small biomolecules to achieve heterogeneous surface properties. To achieve a hyper-enzymatic activity, the surface functionality of GO should be tailored to the orientation adsorption of the Thermomyces lanuginosus (TL) lipase, and the active center can be covered by a relatively hydrophobic helical lid for protection. In this work, amino acids were used to interact with GO through reduction reaction, hydrophobic forces, electrostatic forces, or hydrogen bonding to alter the surface hydrophobicity and charge density. Characterization of the structure and surface properties confirmed that the GO samples decorated with phenylalanine (Phe) and glutamic acid (Glu) exhibited superior hydrophobicity than other modifications, whereas tryptophan (Trp) and cysteine (Cys) provided weaker reduction effects on GO. Moreover, the zeta potential of the samples modified by amino acids of lysine (Lys) and arginine (Arg) is higher than other modified samples. The adsorption amount of lipase on Glu-GO reached 172 mg/g and the relative enzymatic activity reached up to 200%. The thermodynamic data and the Freundlich isotherm model fitting showed that the lipase adsorption process on modified samples was spontaneous, endothermic and entropy increase.

The wide array of clinical manifestations of dopa-responsive dystonia (DRD) or Segawa disease and the prevalence of numerous DRD-associated mutations in guanosine triphosphate cyclohydrolase 1 (GCH1) gene makeDRD diagnosis challenging. Methods: In this study, we assessed the clinical and genetic characteristics of two Chinese families with 3 DRD probands. Clinical assessment of DRD-related symptoms was conducted for all participants. All 6 exons of GCH1 were assessed by genetic analyses for individuals with heteroduplex DNA as compared that of controls. Results: The median DRD-onset age was 24 years and the female to male ratio of DRD patients was 8:1. Six out of eight (75%) patients responded to levodopa therapy. The data indicated that the GCH1 sequence had a novel point mutation resulting in T to C transition at position 80 in exon 1 of the cDNA sequence (c.80T>C), which resulting in an amino acid change (L27P) of GCH1 in the probands and their mother in the first DRD family. Conclusion: A novel GCH1 mutation (c.80T>C) was identified in the DRD patients in the first family. Our findings indicate that both clinical symptom assessment and genetic testing should be employed for improving DRD diagnosis.

Summary Background Acute kidney injury (AKI) has become a worldwide public health problem, but little information is available about the disease burden in China. We aimed to evaluate the burden of AKI and assess the availability of diagnosis and treatment in China. Methods We launched a nationwide, cross-sectional survey of adult patients who were admitted to hospital in 2013 in academic or local hospitals from 22 provinces in mainland China. Patients with suspected AKI were screened out on the basis of changes in serum creatinine by the Laboratory Information System, and we reviewed medical records for 2 months (January and July) to confirm diagnoses. We assessed rates of AKI according to two identification criteria: the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition and an increase or decrease in serum creatinine by 50% during hospital stay (expanded criteria). We estimated national rates with data from the 2013 report by the Chinese National Health and Family Planning Commission and National Bureau of Statistics. Findings Of 2 223 230 patients admitted to the 44 hospitals screened in 2013, 154 950 (7·0%) were suspected of having AKI by electronic screening, of whom 26 086 patients (from 374 286 total admissions) were reviewed with medical records to confirm the diagnosis of AKI. The detection rate of AKI was 0·99% (3687 of 374 286) by KDIGO criteria and 2·03% (7604 of 374 286) by expanded criteria, from which we estimate that 1·4–2·9 million people with AKI were admitted to hospital in China in 2013. The non-recognition rate of AKI was 74·2% (5608 of 7555 with available data). Renal referral was done in 21·4% (1625 of 7604) of the AKI cases, and renal replacement therapy was done in 59·3% (531 of 896) of those who had the indications. Delayed AKI recognition was an independent risk factor for in-hospital mortality, and renal referral was an independent protective factor for AKI under-recognition and mortality Interpretation AKI has become a huge medical burden in China, with substantial underdiagnosis and undertreatment. Nephrologists should take the responsibility for leading the battle against AKI. Funding National 985 Project of China, National Natural Science Foundation of China, Beijing Training Program for Talents, International Society of Nephrology Research Committee, and Bethune Fund Management Committee.

Compared to the traditional chemical reduction method, a green and efficient strategy was successfully applied to regulate the surface heterogeneity of graphene oxide (GO). In this work, different kinds of amino acids were used to reduce and modify GO. The reduction and adsorption disparities of amino acids contributed to the difference of structural heterogeneity in terms of density, thermal tolerance and disorder of the oxygen-containing groups of GO. The modification also resulted in discrepancies in surface properties of the GO samples, such as hydrophobicity and surface charge. The functionalized GO was employed as a carrier for the immobilization of lipase from Thermomyces lanuginosus (lipase TL). The storage stability, the temperature and pH sensitivity of the immobilized biocatalysts and the free lipase TL were studied. Lipase immobilized on functionalized GO demonstrates superior enzymatic loading and relative activity compared to GO, with a maximum increase of 70% and 47%, respectively. The relative activity of lipase immobilized on functionalized GO was 19.21 times more than that of commercial immobilized lipase TLIM. Through molecular dynamics simulations we concluded that the increase in the relative activity of lipase TL is mainly related to its adsorption orientation and slight conformational change. Thus, our research offered a green and effective strategy to regulate the heterogeneity of nanomaterials for a suitable microenvironment to enhance the performance of immobilized lipase.

Cerebral microbleeds (CMBs) and lacunar infarcts are common manifestations of cerebral small vessel disease. However, the association between the location of CMBs and lacunar infarcts is unclear. Our study aimed to clarify the relationship between the location of CMBs and lacunar infarcts.This study retrospectively analyzed 166 patients with ischemic stroke or transient ischemic attacks admitted in the Geriatric Neurology Department of Chinese PLA General Hospital between February 2010 and December 2012. We collected clinical characteristics and risk factors of CMBs. The location of CMBs on T2*-weighted angiography was assessed by the Microbleed Anatomical Rating Scale. The number of lacunar infarcts and the severity of white matter hyperintensities were also recorded. The association between the location of CMBs and lacunar infarcts parameters was examined.CMBs were present in 77 (46.4%) patients. The presence [odds ratios (OR), 2.14; 95% confidence interval (CI), 1.02-4.48], number (OR, 1.17; 95% CI, 1.02-1.36 per lesion), severity (OR, 1.61; 95% CI, 1.07-2.42) of lacunar infarcts, and hypertension (OR, 5.76; 95% CI, 2.01-16.55) were independent risk factors for CMBs. Stratified by the location of CMBs, lobar CMBs and infratentorial CMBs did not show significant association with lacunar infarcts. Deep CMBs were significantly associated with the number (OR 1.18, 95% CI 1.03-1.36) and severity (OR 1.71, 95% CI 1.11-2.63) of lacunar infarcts. Moreover, the percentage of deep CMBs increased with the increased severity of lacunar infarcts (P = .003).Deep CMBs rather than lobar and infratentorial CMBs are associated with lacunar infarcts.

We review some classical and more recent results for the derivation of mean field equations from systems of many particles, focusing on the stochastic case where a large system of SDEs leads to a McKean–Vlasov PDE as the number N of particles goes to infinity. Classical mean field limit results require that the interaction kernel be essentially Lipschitz. To handle more singular interaction kernels is a long-standing and challenging question but which has had some recent successes.

The package structure critically influences the major characteristics of semiconductor lasers, such as thermal behavior, output power, wavelength, and far-field distribution. In this paper, a new single emitter package structure called F-mount is designed and compared with the conventional package structure C-mount. The influence of package structure on their performances is characterized and analyzed. The thermal resistances of lasers with different package structures are calculated through simulation, and are contrasted with experimental results. Some devices are also tested for the maximum output power level. Under the continuous wave (CW) condition, the maximum power of F-mount reaches 12.6 W at 808 nm while the output power only reaches 10.9 W for C-mount. Under the condition of 0.5% duty cycle (100 μs, 50 Hz), the catastrophic optical mirror damage level reaches 58.7 W at 74 A for F-mount, and 54.8 W at 57 A for C-mount are reported for the first time. It is experimentally found that there is an obvious wavelength difference between the two type structure lasers: about 1.37 nm in CW mode and 2.89 nm in quasi CW mode. Theoretical analysis shows that red-shift and blue-shift is a result of external strain in the package process of F-mount and C-mount, respectively. It is also found that the package structure has an effect on the divergence angle of slow axis far fields, but little impact on that of fast axis far fields. The analysis shows that package structure has a strong influence on the performance of the laser; therefore, the package should be optimized to achieve better performance for some special applications.

Thermal stress is an influential factor for the reliability of HPDL and their optical properties. Two packages of conduction-cooled-packaged 60W HPDL were selected as the study samples. In order to investigate what reflow factors influence thermo-mechanical of HPLD, a COS model is established. In reflow process and working process, hard solder package suffers higher thermal stress. Thermal stress mainly comes from reflow process. In reflow process, copper mount will deteriorate thermo-mechanical of hard solder package. There exists shear stress in HPLD and it will convert TE-polarized power to TM-polarized power. In working process, uniaxial normal stress along the width direction of QW is mainly influenced by coefficient expansion thermal. The displacement of HCS along growth direction is larger than that of CS, whereas the “smile” value is smaller. “Smile” is mainly impacted by CTE of solder and submount.

We consider large systems of particles interacting through rough but bounded interaction kernels. We are able to control the relative entropy between the $N$-particle distribution and the expected limit which solves the corresponding Vlasov system. This implies the Mean Field limit to the Vlasov system together with Propagation of Chaos through the strong convergence of all the marginals. The method works at the level of the Liouville equation and relies on precise combinatorics results., 37 pages

The whispering-gallery-mode (WGM) photonic crystal microcavity can be potentially used for miniaturized photonic devices, such as thresholdless lasers. In this paper, we use plane wave expansion (PWE) method and study the WGM of H2 photonic crystal microcavities which are formed by removing seven center air holes in a photonic crystal. The WGM in these large-size cavities has some advantages compared with single defect WGM in the view of real device applications. We analyze the nearby air hole effect on WGM and conclude that WGM is more sensitive to moving towards the outside rather than moving towards the inside of a nearby air hole. In our case, if a nearby air hole is moved 0.1a away from the center, the WGM will disappear. If a nearby air hole is moved 0.6a towards the center, however, the WGM will still exit. We also analyze the structure with an air hole (rm= 0.2a) in the center of the microcavity, and we find that the WGM is not affected by the central hole sensitively. As we increase rm, the WGM remains unchanged until rm is 0.64 times greater than period a. It is found that the tolerance of WGM to the displacement of nearby air holes and the occurance of central holes is large enough to fabricate electrical injection structure.