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Introduction: Parkinson’s disease (PD) and Alzheimer’s disease (AD) are common neurodegenerative diseases with multifaceted etiology. Nutritional and metabolic abnormalities are frequently implicated in PD and AD. In this observational study, we analyzed a series of nutritional markers, and aimed to understand their association with AD and PD risk. Methods: A total of 424 PD patients, 314 AD patients, and 388 healthy controls were included. Nutritional markers including Hemoglobin A1c, vitamin B12, folate, apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), low-density lipoprotein (LDL), high-density lipoprotein, triglyceride, total cholesterol (TC), uric acid and homocysteine (HCY) were measured. Significance for odds ratios examining was P

Abstract Background Cognitive impairment is a common non-motor symptom of Parkinson’s disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer’s disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. Methods A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson’s Progression Marker Initiative (PPMI). Results No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aβ42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. Conclusions APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aβ42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.

IntroductionFreezing of gait (FOG) is a disabling and heterogeneous symptom in patients with Parkinson’s disease (PD). Among them, dopamine-induced FOG is rare and difficult to identify. The treatment of dopamine-induced FOG is complex.Case presentationWe herein presented a case of PD patient who complicated with refractory FOG. It was identified as dopamine-induced FOG during levodopa challenge test. Her symptoms were alleviated after we reduced the total equivalent dosage of levodopa.ConclusionOur report emphasizes the importance of levodopa challenge test in identifying different types of FOG, which is very important for further adjusting treatment.

BackgroundCognitive impairment (CI) is common in Parkinson’s disease (PD). Multiple brain regions and their interactions are involved in PD associated CI. Magnetic resonance imaging (MRI) technology is a non-invasive method in investigating brain structure and inter-regional connections. In this study, by comparing cortical thickness, subcortical volume, and brain network topology properties in PD patients with and without CI, we aimed to understand the changes of brain structure and structural covariance network properties in PD associated CI.MethodsA total of 18 PD patients with CI and 33 PD patients without CI were recruited. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Hoehn and Yahr stage, Mini Mental State Examination Scale, Non-motor Symptom Rating Scale, Hamilton Anxiety Scale, and Hamilton Depression Scale were assessed. All participants underwent structural 3T MRI. Cortical thickness, subcortical volume, global and nodal network topology properties were measured.ResultsCompared with PD patients without CI, the volumes of white matter, thalamus and hippocampus were lower in PD patients with CI. And decreased whole-brain local efficiency is associated with CI in PD patients. While the cortical thickness and nodal network topology properties were comparable between PD patients with and without CI.ConclusionOur findings support the alterations of brain structure and disruption of structural covariance network are involved in PD associated CI, providing a new insight into the association between graph properties and PD associated CI.

Abstract Background Gait impairment is common in Parkinson’s disease (PD) patients, which greatly reduces their quality of life. Executive dysfunction is associated with gait impairment. Compensatory strategies, including visual cues, have been shown to be effective in improving PD gait. In this study, we aimed to understand whether carpets with visual cues could improve PD gait, and how the improvement varies across patients with different executive function state. Methods We designed carpets with chessboard and stripe cues. A total of 65 Chinese PD patients were recruited. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, L-dopa equivalent daily dosage, Hoehn & Yahr stage, Frontal Assessment Battery, Mini Mental State Examination Scale, Hamilton Anxiety Scale, and Hamilton Depression Scale were evaluated. Gait parameters including stride length, gait speed and fall risk were recorded by a wearable electronic device. Results The stride length and gait speed were significantly improved and the fall risk was significantly mitigated when PD patients walked on carpets with chessboard and stripe patterns. Further analysis showed the amelioration of gait parameters was independent of executive dysfunction. Conclusions Our study demonstrates that carpets with visual cues can improve the gait of PD patients even in those with mild executive dysfunction.

The multilinear variable separation (MLVS) approach has been proven to be very useful in solving (2 + 1)-dimensional integrable systems. Taking the (3 + 1)-dimensional Burgers hierarchy as an example, we extend the MLVS approach to a whole family of (3 + 1)-dimensional Burgers hierarchy. New exact solutions and universal formulas are obtained, which lead to abundant (3 + 1)-dimensional coherent structures. In particular, two ring-type soliton molecules and their interactions are shown in detail. We also generalize the MLVS results of the (3 + 1)-dimensional Jimbo–Miwa (JM) equation and modified JM equation.

Background: DNA methylation plays an important role in Parkinson’s disease (PD) pathogenesis. DNA methyltransferase 1 (DNMT1) is critical for maintaining DNA methylation in mammals. The link between DNMT1 polymorphisms and PD remains elusive.Methods: The DNMT1 gene contained a total of 28 single nucleotide polymorphisms (SNPs). Four representing tag-SNPs (rs16999593, rs2162560, rs11880553, and rs9305012) were identified and genotyped in a Han Chinese population comprising 712 PD patients and 696 controls. Association analyses were performed at gene-wide significance (p < 1.8 × 10−3).Results: Rs9305012, but not the other 3 tag-SNPs, was gene-wide significantly associated with PD risk (p = 0.8 × 10−3). The rs9305012/C was a protective allele against PD (p = 1.5 × 10−3, OR 0.786, 95% CI 0.677–0.912). No significant association was observed in individual genders or PD subtypes. Haplotypes of the 4 tag-SNPs showed a significant overall distribution difference between PD patients and controls (p < 1 × 10−4). The 3-allele ACC module in the order of rs2162560, rs11880553, and rs9305012 was the highest-risk haplotype associated with PD (p < 1 × 10−4, OR 2.439, 95% CI 1.563–3.704). Rs9305012 displayed certain probability to affect transcription factor binding and target gene expression based on functional annotation analyses.Conclusion: The DNMT1 variant rs9305012 together with its haplotypes may gene-wide significantly modulate PD susceptibility. Our results support a role of DNMT1 in PD pathogenesis and provide novel insights into the genetic connection in between.

Abstract This paper aims to develop a position tracking algorithm by which a rat in a radial arm maze can be accurately located in real time. An infrared (IR) night-vision camera was hung above the maze to capture IR images of the rat. The IR images were binarized and then duplicated for subsequent intersection and opening operations. Due to simple operations and a high robustness against the noise spots formed by the droppings of the rat, it took just minutes to process more than 9000 frames, and an accuracy above 99% was reached as well. The maze was intruded by an experimenter to further test the robustness, and the accuracy slightly fell to 98%. For comparison purposes, the same experiments were carried out using a pre-trained YOLO v2 model. The YOLO counterpart gave an accuracy beyond 97% in the absence and in the presence of the intruder. In other words, this work slightly outperformed the YOLO counterpart in terms of the accuracy in both cases, which indicates the robustness of this work. However, it took the YOLO counterpart an hour or so to locate a rat contained in the frames, which highlights the contribution of this work.

IntroductionBlepharospasm is uncommon in Parkinson's disease, especially in the peak-dose dyskinesia period.Case presentationWe herein present the case of a patient with PD who developed blepharospasm in the peak-dose dyskinesia period. The symptom was improved by taking amantadine.ConclusionThe current report expands the phenomenology of peak-dose dykinesia in PD to include dystonic blepharospasm. This complication of levodopa therapy may respond to amantadine despite the dystonic appearance of movements.

Lipid droplets (LDs) are simple intracellular storage sites for neutral lipids and exhibit important impact on many physiological processes. For example, the changes in the polar microenvironment inside LDs could affect physiological processes, such as lipid metabolism and storage, protein degradation, signal transduction, and enzyme catalysis. Herein, a new fluorescent chemo-sensor (Couoxo-LD) was formulated by our molecular design strategy. The probe could be applied to effectively label intracellular lipid droplets. Intriguingly, Couoxo-LD demonstrated positive sensitivity to both polarity and viscosity, which might be attributed to its D-π-A structure and the twisted rotational behavior of the carbon–carbon double bond (TICT). Additionally, Couoxo-LD was successfully implemented in cellular imaging due to its excellent selectivity, pH stability, and low biotoxicity. In HeLa cells, the co-localization curve between Couoxo-LD and commercial lipid droplet dyes overlapped at 0.93. The results indicated that the probe could selectively sense LDs in HeLa cells. Meanwhile, Couoxo-LD can be applied for in vivo imaging of zebrafish.

Diethyl malonate-based fluorescent probe NE-N2H4 was constructed for monitoring hydrazine (N2H4). The novel probe NE-N2H4 exhibits good properties, such as large Stokes shift (about 125 nm), good selectivity, and low cytotoxicity. This sensing probe NE-N2H4 can be operated to detect hydrazine in living HeLa cells. Especially after soaking in probe solution, the thin-layer chromatography (TLC) plate could detect the vapor of hydrazine. Therefore, the probe NE-N2H4 might be used to monitor hydrazine in biosamples and environmental problem.

Introduction: Autonomic dysfunction is a common and disabling non-motor symptom of Parkinson's disease (PD). We aimed to understand autonomic dysfunction in PD motor subtypes, the pattern of sympathetic skin response (SSR) to motor asymmetry, and the association of SSR with autonomic and motor dysfunctions.Methods: A total of 101 PD patients of Han Chinese were included. Unified PD rating scale (UPDRS), scales for outcomes in PD-autonomic symptoms (SCOPA-AUT), orthostatic hypotension, and SSR were evaluated.Results: SCOPA-AUT and incidences of orthostatic hypotension and absent SSR were worse in the subtype of postural instability gait disorder (PIGD) than the subtypes of tremor dominant and intermediate. SSR latency and amplitude were asymmetrical corresponding to the accentuation of motor severity. Patients with absent SSR had worse UPDRS and SCOPA-AUT scores. SSR parameters of the severe side in patients with SSR showed no independent association with the scores.Conclusion: Our results support that autonomic dysfunction is more severe in the PIGD than other subtypes and demonstrate an asymmetry of SSR in PD patients. Absent SSR may indicate worse autonomic and motor symptoms, but SSR parameters are not sufficient to evaluate the severity of the dysfunctions.

Density functional theory was employed to investigate the (111), (200), (210), (211) and (220) surfaces of CoS2. The surface energies were calculated with a sulfur environment using first-principle-based thermodynamics. It is founded that surfaces with metal atoms at their outermost layer have higher energy. The stoichiometric (220) surface terminated by two layer of sulfur atoms is most stable under the sulfur-rich condition, while the non-stoichiometric (211) surface terminated by a layer of Co atoms has the lower energy under the sulfur-poor environment. The electric structure results show that the front valence electrons of (200) surface are active, indicating that there may be some active sites on this face. There is an energy gap between the stoichiometric (220) and (211), which has low Fermi energy, indicating that their electronic structures are dynamically stable. Spin-polarized bands are calculated on the stoichiometric surfaces, and these two (200) and (210) surfaces are predicted to be noticeably spin-polarized. The Bravais–Friedel–Donnay–Harker (BFDH) method is adopted to predict crystal growth habit. The results show that the most important crystal planes for the CoS2 crystal growth are (111) and (200) planes, and the macroscopic morphology of CoS2 crystal may be spherical, cubic, octahedral, prismatic or plate-shaped, which have been verified by experiments.

Abstract Yield-phenology relation is a critical issue affecting rainfed maize field productivity in semiarid east African Plateau (EAP). We first introduced Chinese ridge-furrow mulching (RFM) system to EAP, using three maize cultivars with early-, mid- and late-maturing traits as test materials. A two-year field experiment was conducted in a semiarid farm of Kenya from 2012 to 2013. Three treatments were designed: alternative ridge and furrow with transparent plastic mulching (FT), with black plastic mulching (FB) and without mulching (CK). We found that FT and FB significantly increased soil moisture and accelerated crop maturity across two growing seasons. Leaf area and shoot biomass were increased by 30.2% and 67.5% in FT, 35.2% and 73.5% in FB, respectively, compared with CK. Grain yield, water use efficiency and economic output were increased by 55.6%, 57.5% and 26.7% in FT, and 50.8%, 53.3% and 19.8% in FB, respectively. Optimal yield and economic benefit were observed in late-maturing cultivar due to increased topsoil temperature in FT in 2012 (cool), and in early-maturing cultivar owing to cooling effect in FB in 2013 (warm). Our study suggested RFM system, combined with crop phenology selection, be a promising strategy to boost maize productivity and profitability in semiarid EAP.

Abstract A novel turn-on two-photon fluorescent probe NS-N 2 H 4 was developed with the 2-benzothiazoleacetonitrile as a new recognition site for the detection of hydrazine (N2H4). The two-photon probe exhibited favorable properties including high selectivity, low cytotoxicity and almost 16-fold fluorescence enhancement in the presence of N2H4 in solution. The probe could be used to image hydrazine in the living cells. Notably, we also used the two-photon fluorescent probe to image hydrazine in the tissue imaging for the first time. Furthermore, by the way of probe-loaded TLC plate, we further monitored vapor of hydrazine. Therefore, the novel two-photon probe is expected to be employed to detect N2H4 in biosamples and environmental pollution and the new recognition site will be widely applied to construct fluorescent probes for the detection of N2H4.

Abstract Introduction Leukodystrophy is a group of hereditary leukoencephalopathies predominantly affecting the white matter. Multiple genes and mutations have been reported to be associated with this disorder. Identification of pathogenic genes can facilitate diagnosis of leukodystrophy and development of therapeutic strategies. Methods A case was presented with clinical examinations. Exome sequencing was applied to identify potential mutations. Sanger sequencing of blood DNA was applied to confirm the mutation and to examine additional members. Results We reported a Chinese male patient of adult‐onset leukodystrophy. Genetic examinations identified a homozygous mutation, c. 452T>C (p. M151T), in alanyl‐tRNA synthetase 2 (AARS2) in the patient. The disease was autosomal recessive as suggested by the genotypic analyses of his family members. We also reviewed phenotypic spectra of AARS2 mutation‐associated leukodystrophies from a total of 16 reported cases. Conclusions Our data provide further evidence that mutations of AARS2 are implicated in adult‐onset leukodystrophy.

Introduction: Level of serotonin is mainly regulated by the serotonin reuptake transporter encoded by SLC6A4. The promoter region of SLC6A4 bears a repeat polymorphism 5-HTTLPR and a single nucleotide polymorphism rs25531. We have previously studied the association between these two variants and sporadic PD. The objective of the current study was to determine whether the SLC6A4 polymorphisms were associated with key motor and non-motor symptoms of PD.Methods: A total of 370 PD patients of Han Chinese were included. Associations between the SLC6A4 polymorphisms and PD symptoms including depression, intellectual impairment, tremor and rigidity were analyzed.Results: 5-HTTLPR was associated with depression in PD patients and presence of the LL genotype was protective against the depression risk. The rs25531 was associated with rest tremor in PD and the A allele serves as a recessive risk allele. No associations were found in the two polymorphisms with respect to intellectual impairment and rigidity in the cohort.Conclusion: The current study reveals two PD symptoms associated with SLC6A4 polymorphisms, and provides new insight into how serotonergic system genetically participates in the symptomatic progression of PD. Further study is warranted in additional populations.

AIM: To investigate the mechanism underlying the anti-inflammatory effects of epigallocatechin-3-gallate (EGCG) in lipopolysaccharide (LPS)-stimulated human retinal endothelial cells (HRECs).METHODS: HRECs pre-treated with EGCG (0-100 μmol/L) were stimulated with LPS (250 ng/mL). Levels of tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) and nitric oxide (NO) in the supernatants were determined by enzyme-linked immunosorbent assay (ELISA) and Griess assay. The protein expression of phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinases (p38) were determined by Western blot analysis.RESULTS: EGCG pre-treatment significantly inhibited the secretion of TNF-α, VEGF, MCP-1 and NO in LPS-stimulated HRECs. Moreover, EGCG effectively attenuated LPS-induced activation and phosphorylation of ERK1/2 and p38 in HRECs in a dose-dependent manner.CONCLUSION: EGCG exhibited inhibitory effects on LPS-induced pro-inflammatory cytokines production by modulating ERK1/2 and p38 pathways in HRECs, suggesting EGCG as a potential candidate for anti-inflammatory intervention.

The finite-time consensus problem in the networks of multiple mobile agents is comprehensively investigated. In order to resolve this problem, a novel nonlinear information exchange protocol is proposed. The proposed protocol ensures that the states of the agents are converged to a weighted-average consensus in finite time if the communication topology is a weighted directed graph with a spanning tree and each strongly connected component is detail-balanced. Furthermore, the proposed protocol is also able to solve the finite-time consensus problem of networks with a switching topology. Finally, computer simulations are presented to demonstrate and validate the effectiveness of the theoretical analysis under the proposed protocol.

We examined three different-ploidy wheat species to elucidate the development of aboveground architecture and its domesticated mechanism under environment-controlled field conditions. Architecture parameters including leaf, stem, spike and canopy morphology were measured together with biomass allocation, leaf net photosynthetic rate and instantaneous water use efficiency (WUE(i)). Canopy biomass density was decreased from diploid to tetraploid wheat, but increased to maximum in hexaploid wheat. Population yield in hexaploid wheat was higher than in diploid wheat, but the population fitness and individual competition ability was higher in diploid wheats. Plant architecture was modified from a compact type in diploid wheats to an incompact type in tetraploid wheats, and then to a more compact type of hexaploid wheats. Biomass accumulation, population yield, harvest index and the seed to leaf ratio increased from diploid to tetraploid and hexaploid, associated with heavier specific internode weight and greater canopy biomass density in hexaploid and tetraploid than in diploid wheat. Leaf photosynthetic rate and WUEi were decreased from diploid to tetraploid and increased from tetraploid to hexaploid due to more compact leaf type in hexaploid and diploid than in tetraploid. Grain yield formation and WUEi were closely associated with spatial stance of leaves and stems. We conclude that the ideotype of dryland wheats could be based on spatial reconstruction of leaf type and further exertion of leaf photosynthetic rate.

Trace elements have been recognized to play an important role in the development of Parkinson's disease (PD). However, it is difficult to precisely identify the relationship between these elements and the progression of PD because of an insufficient number of patients. In this study, quantifications of selenium (Se), copper (Cu), iron (Fe) and zinc (Zn) by atomic absorption spectrophotometry were performed in plasma from 238 PD patients and 302 controls recruited from eastern China, which is so far the largest cohort of PD patients and controls for measuring plasma levels of these elements. We found that plasma Se and Fe concentrations were significantly increased whereas Cu and Zn concentrations decreased in PD patients as compared with controls. Meanwhile, these four elements displayed differential changes with regard to age. Linear and logistic regression analyses revealed that both Fe and Zn were negatively correlated with age in PD patients. Association analysis suggests that lower plasma Se and Fe levels may reduce the risk for PD, whereas lower plasma Zn is probably a PD risk factor. Finally, a model was generated to predict PD patients based on the plasma concentrations of these four trace elements as well as other features such as sex and age, which achieved an accuracy of 80.97±1.34% using 10-fold cross-validation. In summary, our data provide new insights into the roles of Se, Cu, Fe and Zn in PD progression.

The asymmetric unit of the title compound, C19H16O2S2, contains two independent molecules with slightly different conformations. In the crystal structure, weak intermolecular C—H...O hydrogen bonds [C...O = 3.279 (15) and 3.407 (16) Å] link the molecules into chains extended along the c axis.

In the title molecule, C18H21ClN2O3S, the pyrimidine ring exhibits a half-chair conformation. The ethyl group is disordered between two positions in a ratio 0.74:0.26. In the crystal structure, the molecules are linked into chains along the a axis by N—H...O hydrogen bonds.