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Background: Sequential working memory refers to the cognitive ability to maintain and/or manipulate a set of ordered representations within a short period. It remains unclear whether sequential working memory is impaired in patients with young onset Parkinson's disease (YOPD)., Objectives: The aim of this study is to evaluate the sequential working memory in patients with YOPD., Methods: Sixty-three YOPD patients (29 women) and one hundred age- and education-matched healthy controls participated in three well-established sequential working memory tests. The YOPD patients were categorized into akinetic rigid type (PD-ART) and non-akinetic rigid type (PD-NART). Participants were asked to maintain digit sequences in mind in the digit span forward (DST-F) and to maintain and manipulate digit sequences in mind in the digit span backward (DST-B) and adaptive digit ordering tests (DOT-A)., Results: The PD-ART group scored lower and had higher ordering costs (difference between the DST-F and DOT-A scores) than the healthy control group in the DOT-A. Moreover, in the PD-ART group, the daily levodopa equivalent dose for dopamine D2/3 receptor agonists positively correlated with the DOT-A score and negatively correlated with the DOT-A ordering cost, suggesting that patients who took a greater dose of dopamine D2/3 receptor agonists tended to have higher DOT-A scores and lower DOT-A ordering costs., Conclusions: These results indicated that the impaired sequential working memory may be one of markers of identifying early cognitive impairment in patients with YOPD, especially in PD-ART patients. The dopamine D2/3 receptor agonists can recover this impairment to some extent., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

The traditional fabrication of opal-structured photonic crystals is constrained by the rate of solvent evaporation, a process that is not only time-consuming but also labor-intensive. This study introduces a paradigm shift by incorporating silica nanoparticles (SiNPs) with high zeta potentials and hydrogen bonding capabilities into an elastomeric matrix, resulting in a novel non-close-packed structure. This innovation circumvents the limitations of conventional methods by enabling the rapid formation of photonic inks (PI) into vibrant and luminous photonic elastomers (PEs) within seconds. These PEs demonstrate remarkable mechanochromic properties, exhibiting dynamic color changes across the visible spectrum in response to tensile and compressive deformations. Furthermore, the presence of hydroxyl groups endows the PEs with superior water-responsiveness, which can be finely tuned through the ink formulation. The elimination of solvent evaporation dependency facilitates the fabrication of macroscopic photonic crystal devices with complex geometries using digital light processing (DLP)-based 3D printing. This approach ensures exceptional optical performance and high customization potential. The resulting PEs hold significant promise for applications in smart wearables, soft robotics, and advanced human-machine interface technologies., (© 2024 Wiley‐VCH GmbH.)

Brodifacoum, a long-acting anticoagulant rodenticide, exerts inhibitory effects on blood coagulation factor synthesis, leading to abnormal clotting function and potential fatality. Poisoning of accidental exposure to brodifacoum is not rare, but death from brodifacoum poisoning can be largely avoided with timely and long-term effective treatments, consequently, forensic data on fatalities due to brodifacoum poisoning may be limited. This paper presents a case of brodifacoum-induced homicide, detailing the medial records and pathological changes observed in multiple organs. Furthermore, t liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to measure the concentrations of brodifacoum in blood, hydropericardium, and urine 40 days post-poisoning (1 day post-mortem), yielding values of 0.097 μg/mL, 0.089 μg/mL, and 0.007 μg/mL respectively. The aim of this article is to contribute towards forensic identification of fatalities resulting from brodifacoum poisoning while also serving as a reference for clinical diagnosis in similar cases., Competing Interests: Declaration of competing interest All authors have agreed and declared that there was no conflict of interest., (Copyright © 2024 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Heavy metals, including chromium, are extensively employed in industrial processes, leading to human poisoning and environmental contamination. Chronic exposure to chromium commonly occurs through skin contact and inhalation of airborne particles. The bioaccumulation of chromium can result in toxicity and harm to various biological systems. However, it is quite rare to come across reports of acute fatal cases resulting from oral ingestion of chromium. Here we report a case of the accidental ingestion of electroplating water containing chromium by the female worker resulted in multiple organ failure and ultimately died. The initial symptoms of nausea and abdominal pain are consistent with chromium toxicity. The sequential impairment of various organ systems, starting with the kidneys and progressing damage to the liver, digestive system, cardiovascular system, and immune system, indicates the widespread toxic effects of chromium on the body. Interestingly, the yellow-green changes observed in multiple organs during the autopsy and it have not been previously documented in the literature. The histopathological examination further confirmed the extensive damage. Toxicological analysis substantiated the presence of chromium in various body fluids and organs, both qualitatively and quantitatively. This confirms the absorption and distribution of chromium throughout the body following oral ingestion. These findings highlight the acute and severe toxic effects of orally ingested chromium, leading to fatal consequences in this case., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Vibrotactile stimulation has been studied in its efficacy of reducing freezing of gait (FOG) in patients with Parkinson's disease (PD). However, the results are still controversial. We evaluated the efficacy of a newly developed vibrotactile foot device on freezing severity and gait measures in PD patients with FOG., Objective: To evaluate the efficacy of vibrotactile foot device on PD patients with FOG., Methods: Thirty-three PD patients with FOG were examined during their "off" medication state. The efficacy of the vibrotactile foot device was evaluated using a gait protocol comprising walking trials with vibrotactile stimulation "off" and "on." Walking trials were videotaped for the offline rating by two movement disorder specialists. The Opal inertial sensor unit (128 Hz; Mobility Lab; APDM Inc., Portland, OR, USA) was used for quantitative gait analysis., Results: The results demonstrated 33.1% reduction in number of FOG episodes (P < 0.001) and 32.6% reduction of freezing episodes (P < 0.001). Quantitative gait analysis showed a significant increase in step length (P = 0.033). A moderate negative correlation was observed between the change of percent time frozen and age (r = -0.415, P = 0.016). 73% of participants reported minimal to substantial improvement in walking with this vibrating stimulation delivered by the vibrotactile foot device., Conclusions: The vibrotactile foot device is an efficient device that could significantly reduce freezing severity and provide gait regulation to patients with PD experiencing frequent freezing. It could potentially be used in the home environment for improving the quality of life., (© 2024 International Parkinson and Movement Disorder Society.)

Background: Stem cell-based therapy is a promising strategy for treating Parkinson's disease (PD) characterized by the loss of dopaminergic neurons. Recently, induced neural stem cell-derived dopaminergic precursor cells (iNSC-DAPs) have been emerged as a promising candidate for PD cell therapy because of a lower tumor-formation ability. Designer receptors exclusively activated by designer drugs (DREADDs) are useful tools for examining functional synaptic connections with host neurons., Methods: DREADD knock-in human iNSCs to express excitatory hM3Dq and inhibitory hM4Di receptors were engineered by CRISPR. The knock-in iNSCs were differentiated into midbrain dopaminergic precursor cells (DAPs) and transplanted into PD mice. The various behavior test such as the Apomorphine-induced rotation test, Cylinder test, Rotarod test, and Open field test were assessed at 4, 8, or 12 weeks post-transplantation with or without the administration of CNO. Electrophysiology were performed to assess the integrated condition and modulatory function to host neurons., Results: DREADD expressing iNSCs were constructed with normal neural stem cells characteristics, proliferation ability, and differentiation potential into dopaminergic neuorns. DAPs derived from DREADD expressing iNSC showed matched function upon administration of clozapine N-oxide (CNO) in vitro. The results of electrophysiology and behavioral tests of transplanted PD mouse models revealed that the grafts established synaptic connections with downstream host neurons and exhibited excitatory or inhibitory modulation in response to CNO in vivo., Conclusion: iNSC-DAPs are a promising candidate for cell replacement therapy for Parkinson's disease. Remote DREADD-dependent activation of iNSC-DAP neurons significantly enhanced the beneficial effects on transplanted mice with Parkinson's disease., (© 2024. The Author(s).)

While numerous single nucleotide variants and small indels have been identified in Parkinson's disease (PD), the contribution of structural variants (SVs), copy number variants (CNVs), and short tandem repeats (STRs) remains poorly understood. Here we investigated the association using the high-depth whole-genome sequencing data from 466 Chinese PD patients and 513 controls. Totally, we identified 29,561 SVs, 32,153 CNVs, and 174,905 STRs, and found that CNV deletions were significantly enriched in the end-proportion of autosomal chromosomes in PD. After genome-wide association analysis and replication in an external cohort of 352 cases and 547 controls, we validated that the 1.6 kb-deletion neighboring MUC19, 12.4kb-deletion near RXFP1 and GGGAAA repeats in SLC2A13 were significantly associated with PD. Moreover, the MUC19 deletion and the SLC2A13 5-copy repeat reduced the penetrance of the LRRK2 G2385R variant. Moreover, genes with these variants were dosage-sensitive. These data provided novel insights into the genetic architecture of PD., (© 2024. The Author(s).)

Brodifacoum exerts its antagonistic effect against the metabolism of vitamin K, an essential component in the synthesis of blood coagulation factors. This effect ultimately hinders the blood's capacity to clot effectively, rendering it a commonly employed rodenticide. Instances of lethal poisonings are exceedingly rare owing to expeditious medical intervention and treatment. Within this report, we present a case of brodifacoum-induced homicide, wherein the patient exhibited distinct clinical examinations and symptoms. Moreover, the patient's blood sample exhibited a noteworthy brodifacoum concentration of 0.681 µg/mL even after a period of 43 days following the incident of poisoning. Although an autopsy was not conducted due to religious restrictions, we endeavor to reasonably deduce the cause of death and furnish corroborative evidence for clinical diagnosis, treatment, and forensic examination in instances involving brodifacoum poisoning., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function. Similar to patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) scored lower than healthy adults in the well-established semantic fluency test. However, it is unclear how unique are the produced words. This study examined the relationship between semantic fluency and words' uniqueness in patients with PSP., Methods: Twenty-seven patients with PSP Richardson's syndrome (PSP-RS), 37 patients with PD, and 41 healthy controls (HC) performed a standard semantic fluency test (animals), and their verbal responses were audio-recorded. We used the uniqueness to reflect the ability to produce both original and effective work, that is, creativity., Results: The PSP-RS group produced fewer correct words and fewer unique words than the PD and HC groups. Moreover, the correlation between fluency and uniqueness was positive in the HC and PD groups but negative in the PSP-RS group. Importantly, the actual levodopa dose was positively correlated with the fluency but negatively correlated with the uniqueness in PSP-RS. The PSP-RS patients who took a greater dose of levodopa tended to produce more correct words but fewer unique words., Conclusions: These results suggested that levodopa may modulate semantic fluency and uniqueness in the early stages of PSP-RS., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Asymptomatic Leucine-Rich Repeat Kinase 2 Gene (LRRK2) carriers are at risk for developing Parkinson's disease (PD). We studied presymptomatic substantia nigra pars compacta (SNc) regional neurodegeneration in asymptomatic LRRK2 carriers compared to idiopathic PD patients using neuromelanin-sensitive MRI technique (NM-MRI). Fifteen asymptomatic LRRK2 carriers, 22 idiopathic PD patients, and 30 healthy controls (HCs) were scanned using NM-MRI. We computed volume and contrast-to-noise ratio (CNR) derived from the whole SNc and the sensorimotor, associative, and limbic SNc regions. An analysis of covariance was performed to explore the differences of whole and regional NM-MRI values among the groups while controlling the effect of age and sex. In whole SNc, LRRK2 had significantly lower CNR than HCs but non-significantly higher volume and CNR than PD patients, and PD patients significantly lower volume and CNR compared to HCs. Inside SNc regions, there were significant group effects for CNR in all regions and for volumes in the associative region, with a trend in the sensorimotor region but no significant changes in the limbic region. PD had reduced volume and CNR in all regions compared to HCs. Asymptomatic LRRK2 carriers showed globally decreased SNc volume and CNR suggesting early nigral neurodegeneration in these subjects at risk of developing PD., (© 2024. The Author(s).)

Purpose: Sequential working memory is the ability to maintain and manipulate sequential information at a second time scale. Patients with progressive supranuclear palsy (PSP) or Parkinson's disease (PD) perform poorly in tests that require the flexible arrangement of thoughts or actions. This study investigated whether sequential working memory is differently impaired in patients with PSP versus PD., Method: Twenty-nine patients with PSP Richardson's syndrome (PSP-RS), 36 patients with PD, and 36 healthy controls (HC) completed 3 well-established neuropsychological tests, including digit span forward (DST-F), digit span backward (DST-B), and adaptive digit ordering tests (DOT-A). The DST-F required maintaining digit sequences, and the DST-B and DOT-A required maintaining and manipulating digit sequences., Finding: The PSP-RS group scored lower than the PD and HC groups in the DST-B and DOT-A but not in the DST-F, indicating that the ability to manipulate sequences was impaired, but the maintenance ability was preserved in PSP-RS patients. Moreover, in PSP-RS, the DST-B score negatively correlated with the severity of motor symptoms. The actual levodopa dose positively correlated with the DST-B ordering cost (DST-F score vs. DST-B score). The PSP patients who took a greater dose of levodopa tended to have higher DST-B ordering cost. There was no effect of levodopa on DST-B or DOT-A in PD., Conclusion: These results suggested that the ability to manipulate sequence was already reduced in patients with PSP-RS and was worse than in patients with PD., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Dimethyl sulfate (DMS) is a highly toxic chemical that appears innocuous and is commonly used as a methylating agent in industry. It can be readily absorbed leading to poisoning or death through the skin or mucous membranes of the respiratory tract in the process of production or transportation. Although there are some articles on treatment for DMS poisoning, reports of death resulting from acute fatal DMS poisoning are very rare. Here, we present a case of a 50-year-old Chinese man who died accidentally from DMS poisoning after he broke a plastic storage tank full of DMS during transportation. The patient complained of eye irritation. In addition, the corrosive damage could be seen in his corneas and skin. The autopsy revealed erosions and ulcers in the respiratory tract, as well as massive congestion, necrosis, edema, and pseudomembrane formation on the mucous layer of the trachea and main bronchi. Histopathological examination confirmed extensive pulmonary edema, multifocal hemorrhages, whole-cell swelling in the brain, as well as disintegration of the neuronal cell. We inferred that DMS poisoning caused the symptoms resulting from the production of methanol and sulfate through hydrolysis, including respiratory toxicity and neurotoxicity, and these symptoms had temporal continuity. Toxicological analysis revealed no DMS or methanol, but formic acid was detected in the brain, both qualitatively and quantitatively. In this report, we also present a retrospective study of 8 similar cases of DMS poisoning in literature in China, including some clinical data and autopsy information., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Recent animal model studies have suggested that the parafascicular nucleus has the potential to be an effective deep brain stimulation target for Parkinson's disease. However, our knowledge on the role of the parafascicular nucleus in Parkinson's disease patients remains limited., Objective: We aimed to investigate the functional alterations of the parafascicular nucleus projections in Parkinson's disease patients., Methods: We enrolled 72 Parkinson's disease patients and 60 healthy controls, then utilized resting-state functional MRI and spectral dynamic causal modeling to explore the effective connectivity of the bilateral parafascicular nucleus to the dorsal putamen, nucleus accumbens, and subthalamic nucleus. The associations between the effective connectivity of the parafascicular nucleus projections and clinical features were measured with Pearson partial correlations., Results: Compared with controls, the effective connectivity from the parafascicular nucleus to dorsal putamen was significantly increased, while the connectivity to the nucleus accumbens and subthalamic nucleus was significantly reduced in Parkinson's disease patients. There was a significantly positive correlation between the connectivity of parafascicular nucleus-dorsal putamen projection and motor deficits. The connectivity from the parafascicular nucleus to the subthalamic nucleus was negatively correlated with motor deficits and apathy, while the connectivity from the parafascicular nucleus to the nucleus accumbens was negatively associated with depression., Conclusion: The present study demonstrates that the parafascicular nucleus-related projections are damaged and associated with clinical symptoms of Parkinson's disease. Our findings provide new insights into the impaired basal ganglia-thalamocortical circuits and give support for the parafascicular nucleus as a potential effective neuromodulating target of the disease., Competing Interests: Declaration of Competing Interest All authors declared that there are no competing financial interests., (Copyright © 2023. Published by Elsevier Inc.)

The well-established semantic fluency test measures the ability to produce a sequence of spoken words from a particular category within a limited period of time. Like patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) tend to produce fewer correct words than age-matched healthy adults. This study further examined the difference between patients with PSP and PD in their semantic fluency performance using a graph theory-based approach. Twenty-nine patients with PSP Richardson's syndrome (PSP-RS), thirty-eight patients with PD, and fifty-one healthy controls (HC) were recruited. All participants completed a standard semantic fluency test (animals). Their verbal responses were recorded, transcripted, and transformed into directed speech graphs. The speech graphs of the PSP-RS group showed higher density, shorter diameter, and shorter average shortest path than those of the PD and HC groups. It indicates that the PSP-RS group produced smaller and denser speech graphs than the PD and HC groups. In the PSP-RS group, moreover, the average shortest paths of the speech graphs correlated with the severity of motor symptoms. This study shows the potential of the graph theory-based approach in distinguishing the semantic fluency performance of nondemented patients with PSP-RS and PD., Competing Interests: The authors declared no conflict of interest., (Copyright © 2023 Jinghong Ma et al.)

Locus coeruleus (LC) is severely affected in Parkinson's Disease (PD). However, alterations in LC-related resting-state networks (RSNs) in PD remain unclear. We used resting-state functional MRI to investigate the alterations in functional connectivity (FC) of LC-related RSNs and the associations between RSNs changes and clinical features in idiopathic rapid eye movement sleep behavior disorder (iRBD) and PD patients with (PD RBD+ ) and without RBD (PD RBD- ). There was a similarly disrupted FC pattern of LC-related RSNs in iRBD and PD RBD+ patients, whereas LC-related RSNs were less damaged in PD RBD- patients than that in patients with iRBD and PD RBD+ . The FC of LC-related RSNs correlated with cognition and duration in iRBD, depression in PD RBD- , and cognition and severity of RBD in patients with PD RBD+ . Our findings demonstrate that LC-related RSNs are significantly disrupted in the prodromal stage of α-synucleinopathies and proposed body-first PD (PD RBD+ ), but are less affected in brain-first PD (PD RBD- )., (© 2023. The Author(s).)

Genome-wide association studies (GWASs) have identified numerous susceptibility loci for Parkinson's disease (PD), but its genetic architecture remains underexplored in populations of non-European ancestry. To identify genetic variants associated with PD in the Chinese population, we performed a GWAS using whole-genome sequencing (WGS) in 1,972 cases and 2,478 controls, and a replication study in a total of 8209 cases and 9454 controls. We identified one new risk variant rs61204179 (P combined  = 1.47 × 10 -9 ) with low allele frequency, four previously reported risk variants (NUCKS1/RAB29-rs11557080, SNCA-rs356182, FYN-rs997368, and VPS13C-rs2251086), as well as three risk variants in LRRK2 coding region (A419V, R1628P, and G2385R) with genome-wide significance (P < 5 × 10 -8 ) for PD in Chinese population. Moreover, of the reported genome-wide significant risk variants found mostly in European ancestry populations, the correlation coefficient (r b ) of effect size accounting for sampling errors was 0.91 between datasets and 63.6% attained P < 0.05 in Chinese population. Accordingly, we estimated a heritability of 0.14-0.18 for PD, and a moderate genetic correlation between European ancestry and Chinese populations (r g  = 0.47, se = 0.21). Polygenic risk score (PRS) analysis revealed that individuals with PRS values in the highest quartile had a 3.9-fold higher risk of developing PD than the lowest quartile. In conclusion, the present GWAS identified PD-associated variants in Chinese population, as well as genetic factors shared among distant populations. Our findings shed light on the genetic homogeneity and heterogeneity of PD in different ethnic groups and suggested WGS might continue to improve our understanding of the genetic architecture of PD., (© 2023. The Author(s).)

Background: Neuroimaging studies have shown that the functional connectivity (FC) of corticostriatal circuits in nonmanifesting leucine-rich repeat kinase 2 (LRRK2) G2019S mutation carriers mirrors neural changes in idiopathic Parkinson's disease (PD). In contrast, neural network changes in LRRK2 G2385R and R1628P mutations are unclear. We aimed to investigate the FC of corticostriatal circuits in nonmanifesting LRRK2 G2385R and R1628P mutation carriers (NMCs)., Methods: Twenty-three NMCs, 28 PD patients, and 29 nonmanifesting noncarriers (NMNCs) were recruited. LRRK2 mutation analysis was performed on all participants. Clinical evaluation included MDS-UPDRS., Results: When compared to NMNCs, NMCs showed significantly reduced FC between the caudate nucleus and superior frontal gyrus and cerebellum, and between the nucleus accumbens and parahippocampal gyrus, amygdala, and insula. We also found increased striatum-cortical FC in NMCs., Conclusions: Although the corticostriatal circuits have characteristic changes similar to PD, the relatively intact function of the sensorimotor striatum-cortical loop may result in less possibility of developing parkinsonian motor symptoms for the NMCs. This study helps explain why LRRK2 G2385R and R1628P mutations are risk factors rather than pathogenic mutations for PD and suggests that various LRRK2 mutations have distinct effects on neural networks., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

The chromosome 9 open reading frame 72 (C9ORF72) has been proposed as the causative gene of frontotemporal dementia with parkinsonism (FTDP), but its pathophysiological mechanism of parkinsonism is poorly understood. To explore the roles of striatal motor subdivisions in the pathogenesis of parkinsonism resulting from C9ORF72 repeat expansions in the FTDP, two patients with FTDP from one pedigree and seventeen healthy controls were enrolled. The participants received clinical interviews, physical examinations, genetic testing, [ 18 F]-fluorodeoxyglucose PET/MRI, and [ 18 F]-dihydrotetrabenazine PET/CT. Voxel-wise and region of interest analysis were conducted with respect to gray matter volume, metabolism, and dopamine transport function between patients and controls, focusing on the motor part of the striatum according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Patient 1 presented with parkinsonism as the initial symptom, while patient 2 exhibited behavior disturbance as the first symptom, followed by parkinsonism within one year. Both patients had the hexanucleotide expansion detected in C9ORF72(>52 repeats). Gray matter volume atrophy, hypometabolism and dopamine dysfunction were observed in the motor areas of the striatum. Of the two patients, marked glucose hypometabolism within the striatal motor subregion was observed in patient 1, with corresponding gray matter atrophy. In addition, presynaptic dopaminergic integrity of patient 2 was deteriorated in the motor subregions which was consistent with gray matter atrophy. These findings imply that parkinsonism in FTDP may be associated with the degeneration and dopaminergic dysfunction of the striatal motor subregion, which might be attributed to C9orf72 repeat expansions., (© 2022. The Author(s).)

Organic molecules are widely used as structure directing agents, mesopore generating agents or zeolite growth modifiers in the synthesis of various zeolites. However, the organic molecules used in zeolite synthesis are mostly positively charged cationic molecules, since the cationic group can balance the negative charge in the zeolite structure. Here we attempt for the first time to apply an anionic surfactant fatty alcohol polyoxyethylene ether ammonium sulfate (AESA) in the crystallization of zeolite Beta. It is found that both the crystallization process and the characteristics of the product were affected by the addition of AESA into the synthesis. Compared with that without AESA, it shows that the induction period was significantly prolonged for the synthesis of zeolite Beta with AESA, and the crystallinity and the completeness of the crystal were improved. The yield of the product was increased when AESA was used in the synthesis. The framework Si/Al ratio was increased when AESA was added into the synthesis gel, which could be due to the fact that the anionic surfactant AESA facilitated the formation of Si-O-Si bonds and hindered the combination of the negatively charged aluminum species to silicon species to form Si-O-Al bonds, thus increasing the incorporation of Si and reducing the incorporation of Al into the framework. Moreover, we demonstrate an ability to enrich chiral polymorph-A in zeolite Beta by using AESA in the crystallization, with the proportion of polymorph-A in the as synthesized zeolite Beta reaching 77.9%. It is reported that AESA did not remain in the structure of zeolite Beta when the crystallization was completed, which implies that AESA plays a role of zeolite growth modifiers during the crystallization. The results of this study suggest that anionic surfactants can be used in zeolite synthesis to optimize the crystallization process and achieve zeolites with the desired properties.

Endocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations in 2-AG synthase diacylglycerol lipase β (DAGLB) to an early onset autosomal recessive Parkinsonism. DAGLB is the main 2-AG synthase in human and mouse substantia nigra (SN) dopaminergic neurons (DANs). In mice, the SN 2-AG levels were markedly correlated with motor performance during locomotor skill acquisition. Genetic knockdown of Daglb in nigral DANs substantially reduced SN 2-AG levels and impaired locomotor skill learning, particularly the across-session learning. Conversely, pharmacological inhibition of 2-AG degradation increased nigral 2-AG levels, DAN activity and dopamine release and rescued the locomotor skill learning deficits. Together, we demonstrate that DAGLB-deficiency contributes to the pathogenesis of Parkinsonism, reveal the importance of DAGLB-mediated 2-AG biosynthesis in nigral DANs in regulating neuronal activity and dopamine release, and suggest potential benefits of 2-AG augmentation in alleviating Parkinsonism., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic memory, working memory, and executive function. Semantic disfluency is a common problem in Parkinson's disease (PD) and Alzheimer's disease (AD). We demonstrated a graph theoretical analysis of semantic fluency in patients with PD ( N = 86), patients with AD ( N = 40), and healthy controls (HC, N = 88). All participants completed a standard animal fluency test. Their verbal responses were recorded, transcripted, and transformed into directed speech graphs. Patients with PD generated fewer correct words than HC and more correct words than patients with AD. Patients with PD showed higher density, shorter diameter, and shorter average shortest path length than HC, but lower density, longer diameter, and longer average shortest path length than patients with AD. It suggests that patients with PD produced relatively smaller and denser speech graphs. Moreover, in PD, the densities of speech graphs correlated with the severity of non-motor symptoms, but not the severity of motor symptoms. The graph theoretical analysis revealed new features of semantic disfluency in patients with PD., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Guanyu Zhang et al.)

Objective: To explore the roles of striatal subdivisions in the pathogenesis of frontotemporal dementia with parkinsonism (FTDP) in a patient resulting from prion protein gene (PRNP) mutation., Methods: This patient received clinical interviews and underwent neuropsychological assessments, genetic testing, [ 18 F]-fluorodeoxyglucose positron emission tomography ([ 18 F]-FDG PET)/MRI, and [ 18 F]-dihydrotetrabenazine positron emission tomography ([ 18 F]-DTBZ PET)/CT. Region-of-interest analysis was conducted concerning metabolism, and dopamine transport function between this patient and 12 controls, focusing on the striatum subregions according to the Oxford-GSK-Imanova Striatal Connectivity Atlas., Results: A 64-year-old man initially presented with symptoms of motor dysfunction and subsequently behavioral and personality changes. FTDP was initially suspected. Sequence analysis disclosed a valine to isoleucine at codon 180 in PRNP . Compared to controls, this patient had a severe reduction (> 2SD) of standard uptake value ratio (SUVR) in the limbic and executive subregions but relative retention of metabolism in rostral motor and caudal motor subregions using [ 18 F]-FDG PET/MRI, and the SUVR decreased significantly across the striatal in [ 18 F]-DTBZ PET/CT, especially in the rostral motor and caudal motor subregions., Conclusion: The alteration of frontal striatal loops may be involved in cognitive impairment in FTDP, and the development of parkinsonism in FTDP may be primarily due to the involvement of the presynaptic nigrostriatal loops in PRNP V180I mutation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Ma, Liu, Liu, Zhang, Chu, Wang, Chan and Wu.)

Background: Parkinson's disease (PD) pathological changes begin before motor symptoms appear. Rapid eye movement sleep behavior disorder (RBD) has the highest specificity and predictive value of any marker of prodromal PD. Tumor necrosis factor α (TNF-α) plays a part in the pathology of PD and disease conversion in isolated RBD (iRBD). TNF can also directly impair the hypocretin system in mice in vivo . As a result, we intend to investigate the effect of TNF-α on orexin levels in PD patients with RBD., Method: Participants were recruited from the Department of Neurology of Xuanwu Hospital, Capital Medical University to engage in assessments on motor symptoms, sleep, cognition, etc. Then we collected blood and cerebrospinal fluid of all patients and 10 controls' cerebrospinal fluid. The levels of TNF-α in the serum and cerebrospinal fluid, as well as the level of orexin in the cerebrospinal fluid, were measured in the patients., Results: The difference in TNF- levels in cerebrospinal fluid and serum between the three groups were not statistically significant. The levels of orexin in the three groups were not significantly lower than in the control group. UPDRS-III scores were significantly higher in the PD+RBD and PD-RBD groups than in the iRBD group. There was no statistically significant difference in H-Y stages, PSQI, or ESS scores between the PD+RBD and PD-RBD groups., Conclusion: Our findings suggest that TNF-α may not have a significant effect on the orexinergic system in patients with Parkinson's disease and iRBD. As a result, it is necessary to investigate the changes in TNF-α and orexin levels in different disease stages and to enlarge the sample size to determine whether TNF-α affects the function of the orexin system, which may be related to the occurrence of RBD and disease progression in Parkinson's disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yuan, Zhang, Cheng, Hou, Huang, Ma, Li and Zhan.)

Background: The utility of imaging methods to detect iron content in the substantia nigra pars compacta (SNc) and free water imaging in the posterior substantia nigra (pSN) has the potential to be imaging markers for the detection of Parkinson's disease (PD)., Objective: This study aimed to compare the discriminative power of above methods, and whether the combination can improve the diagnostic potential of PD., Methods: Quantitative susceptibility mapping (QSM) and diffusion-weighted data were obtained from 41 healthy controls (HC), 37 patients with idiopathic REM sleep behavior disorder (RBD), and 65 patients with PD. Mean QSM values of bilateral SNc and mean isotropic volume fraction (Viso) values of bilateral pSN (mean QSM|Viso values of bilateral SNc|pSN) were separately calculated and compared among the groups., Results: Mean QSM|Viso values of bilateral SNc|pSN were significantly higher for RBD and PD patients compared to HC and were significantly higher in PD patients than in RBD patients. The power of the mean QSM|Viso values of bilateral SNc|pSN and combined mean QSM and Viso values was 0.873, 0.870, and 0.961 in discriminating PD and HC, 0.779, 0.719, and 0.864 in discriminating RBD from HC, 0.634, 0.636, and 0.689 in discriminating PD and RBD patients., Conclusion: QSM and free water imaging have similar discriminative power in the detection of prodromal and clinical PD, while combination of these two methods increases discriminative power. Our findings suggest that the combination of QSM and free water imaging has the potential to become an imaging marker for the diagnosis of PD.

Objectives: The literature regarding the use of diffusion-tensor imaging-derived metrics in the evaluation of Parkinson's disease (PD) is controversial. This study attempted to assess the feasibility of a deep-learning-based method for detecting alterations in diffusion kurtosis measurements associated with PD., Methods: A total of 68 patients with PD and 77 healthy controls were scanned using scanner-A (3 T Skyra) (DATASET-1). Meanwhile, an additional five healthy volunteers were scanned with both scanner-A and an additional scanner-B (3 T Prisma) (DATASET-2). Diffusion kurtosis imaging (DKI) of DATASET-2 had an extra b shell compared to DATASET-1. In addition, a 3D-convolutional neural network (CNN) was trained from DATASET-2 to harmonize the quality of scalar measures of scanner-A to a similar level as scanner-B. Whole-brain unpaired t test and Tract-Based Spatial Statistics (TBSS) were performed to validate the differences between the PD and control groups using the model-fitting method and CNN-based method, respectively. We further clarified the correlation between clinical assessments and DKI results., Results: An increase in mean diffusivity (MD) was found in the left substantia nigra (SN) in the PD group. In the right SN, fractional anisotropy (FA) and mean kurtosis (MK) values were negatively correlated with Hoehn and Yahr (H&Y) scales. In the putamen (Put), FA values were positively correlated with the H&Y scales. It is worth noting that these findings were only observed with the deep learning method. There was neither a group difference nor a correlation with clinical assessments in the SN or striatum exceeding the significance level using the conventional model-fitting method., Conclusions: The CNN-based method improves the robustness of DKI and can help to explore PD-associated imaging features., (© 2021. The Author(s).)

Background: Cognitive impairment is one of the most prominent non-motor symptoms in Parkinson's disease (PD), due in part to known cerebellar dysfunctions. Furthermore, previous studies have reported altered cerebellar functional connectivity (FC) in PD patients. Yet whether these changes are also due to the cognitive deficits in PD remain unclear. Methods: A total of 122 non-dementia participants, including 64 patients with early PD and 58 age- and gender-matched elderly controls were stratified into four groups based on their cognitive status (normal cognition vs. cognitive impairment). Cerebellar volumetry and FC were investigated by analyzing, respectively, structural and resting-state functional MRI data among groups using quality control and quantitative measures. Correlation analysis between MRI metrics and clinical features (motor and cognitive scores) were performed. Results: Compared to healthy control subjects with no cognitive deficits, altered cerebellar FC were observed in early PD participants with both motor and cognitive deficits, but not in PD patients with normal cognition, nor elderly subjects showing signs of a cognitive impairment. Moreover, connectivity between the "motor" cerebellum and SMA was positively correlated with motor scores, while intracerebellar connectivity was positively correlated with cognitive scores in PD patients with cognitive impairment. No cerebellar volumetric difference was observed between groups. Conclusions: These findings show that altered cerebellar FC during resting state in early PD patients may be driven not solely by the motor deficits, but by cognitive deficits as well, hence highlighting the interplay between motor and cognitive functioning, and possibly reflecting compensatory mechanisms, in the early PD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dan, Hu, Sun, Gao, Zhou, Ma, Doyon, Wu and Chan.)

Background: We aimed to address the knowledge gap that exists regarding the epidemiological, demographic, and clinical characteristics of nontuberculous mycobacterial pulmonary diseases (NTM-PDs) among smear-positive patients with symptoms suggestive of pulmonary tuberculosis (PTB) in China., Methods: Prospective and national surveillance of NTM-PD was performed from 17 hospitals within the China Nontuberculous Mycobacteria Surveillance Study (CNTMS). Patients were eligible for inclusion if they had positive smears during hospitalization. Sputum specimens were collected for molecular species identification., Results: 6,766 patients with valid results were included, consisting of 6,236 (92.2%) with PTB, 458 (6.8%) with NTM-PD, and 72 (1.0%) with colonization. The proportion of NTM-PD in PTB patients exhibited significant geographic diversity, ranging from 3.2% in the northwest to 9.2% in the south. The most prevalent species was Mycobacterium intracellulare, followed by Mycobacterium abscessus complex. Females, elderly people, and patients with bronchiectasis or COPD are at high risk for developing NTM-PD, while patients with diabetes have a lower risk of NTM-PD when compared with non-diabetic patients. Regarding clinical symptoms, lower rates of persistent cough and weight loss were noted in NTM-PD patients than in PTB patients., Conclusions: Approximately one-fifteenth of PTB patients are afflicted with nontuberculous mycobacterial infections in China. The prevalence of NTM shows geographic diversity across the country, and it showed a gradual increase from north to south and from west to east. NTM-PD patients are prone to exhibit less severe clinical symptoms than PTB patients, highlighting the importance of raising awareness of NTM diseases to improve decision making on how to best screen, diagnose, and treat NTM in TB-endemic settings., Competing Interests: Declaration of Competing Interests We declare no competing interests., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Lower urinary tract symptoms are one of the most common groups of non-movement symptoms in patients with Parkinson's disease (PD). Storage symptoms are well-acknowledged, but neurogenic voiding dysfunction caused by PD remains a knowledge gap. This study aimed to evaluate the neurogenic bladder outlet obstruction in male patients with PD and its clinical significance., Methods: Male patients who were diagnosed with PD and underwent urodynamic studies were retrospectively reviewed. The patients with prostate size < 30 ml and bladder outlet obstruction index ≥40 were included in the study. Lower urinary tract symptoms were evaluated by International Prostate Symptom Score (IPSS). Free flowmetry was performed and post void residual (PVR) volume was measured by ultrasound at follow-up., Results: Six patients were included in the final analysis. The mean age was 68.2 and the mean movement symptom duration was 70.7 months. The patients had a mean IPSS of 12.5 and mean PVR volume of 70.8 ml. All patients had slow stream but none of them reported significant voiding difficulty. Urodynamic studies showed the delayed urinary sphincter relaxation and the special trace pattern. After a mean follow-up of 20 months, they had a mean IPSS of 12.5 and mean PVR volume of 73.3 ml. None of them complained of significant voiding difficulty at follow-up., Conclusion: The delayed urinary sphincter relaxation is a rare but repeatable phenomenon in male patients with PD. It is unlikely to cause disturbing voiding dysfunction, as reported by the patients, and does not progress prominently during the course of PD. Further studies are needed to investigate the nature of this special type of neurogenic BOO and whether it is peculiar to PD in a larger patient cohort.

Emerging evidence indicates that gut dysbiosis may play a regulatory role in the onset and progression of Huntington's disease (HD). However, any alterations in the fecal microbiome of HD patients and its relation to the host cytokine response remain unknown. The present study investigated alterations and host cytokine responses in patients with HD. We enrolled 33 HD patients and 33 sex- and age- matched healthy controls. Fecal microbiota communities were determined through 16S ribosomal DNA gene sequencing, from which we analyzed fecal microbial richness, evenness, structure, and differential abundance of individual taxa between HD patients and healthy controls. HD patients were evaluated for their clinical characteristics, and the relationships of fecal microbiota with these clinical characteristics were analyzed. Plasma concentrations of interferon gamma (IFN-γ), interleukin 1 beta (IL-1β), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor alpha were measured by Meso Scale Discovery (MSD) assays, and relationships between microbiota and cytokine levels were analyzed in the HD group. HD patients showed increased α-diversity (richness), β-diversity (structure), and altered relative abundances of several taxa compared to those in healthy controls. HD-associated clinical characteristics correlated with the abundances of components of fecal microbiota at the genus level. Genus Intestinimonas was correlated with total functional capacity scores and IL-4 levels. Our present study also revealed that genus Bilophila were negatively correlated with proinflammatory IL-6 levels. Taken together, our present study represents the first to demonstrate alterations in fecal microbiota and inflammatory cytokine responses in HD patients. Further elucidation of interactions between microbial and host immune responses may help to better understand the pathogenesis of HD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Du, Dong, Yang, Yu, Ma, Gu and Huang.)

The ability to sequence thoughts and actions is impaired in Parkinson's disease (PD). In PD, a distinct error pattern has been found in the offline performance of sequential working memory. This study examined how PD's performance of sequential working memory unfolds over time using mouse tracking techniques. Non-demented patients with mild PD ( N = 40) and healthy controls ( N = 40) completed a computerized digit ordering task with a computer mouse. We measured response dynamics in terms of the initiation time, ordering time, movement time, and area under the movement trajectory curve. This approach allowed us to distinguish between the cognitive processes related to sequence processing before the actual movement (initiation time and ordering time) and the execution processes of the actual movement (movement time and area under the curve). PD patients showed longer initiation times, longer movement times, and more constrained movement trajectories than healthy controls. The initiation time and ordering time negatively correlated with the daily exposure to levodopa and D2/3 receptor agonists, respectively. The movement time positively correlated with the severity of motor symptoms. We demonstrated an altered temporal profile of sequential working memory in PD. Stimulating D1 and D2/3 receptors might speed up the maintenance and manipulation of sequences, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Ma, Chan and Ye.)

The citrate-based tissue adhesive, synthesized by citric acid, diol, and dopamine, is a kind of mussel-inspired adhesive. The adhesion of mussel-inspired adhesive is not completely dependent on 3, 4-dihydroxyphenylalanine (Dopa) groups. The backbone structure of the adhesive also greatly affects the adhesion. In this study, to explore the effects of hydrophobicity and hydrophilicity of the backbone structure on adhesion, we prepared a series of citrate-based tissue adhesives (POEC-d) by changing the molar ratio of two diols, 1, 8-octanediol (O) and poly(ethylene oxide) (E), which formed hydrophobic segment units and hydrophilic segment units, respectively, in the molecule structure. The properties of cured adhesives showed that the adhesive with high E units had high swelling, rapid degradation, and low cohesion. In the adhesion strength measurement on the porcine skin, the adhesive with higher hydrophobicity was more likely to perform better. For the interfacial adhesion, hydrophilicity was conducive to the diffusion and penetration on the skin surface, but hydrophobic interaction showed a stronger effect to adhere with skin and hydrophobic association increased the adhesive concentration on the interface; for the bulk cohesion, hydrophobicity led to coacervation, promoting the Dopa-quinone coupling for cross-linking. In this amphipathic, citrate-based, soft-tissue adhesive system, when the feed ratio of hydrophilic segment was lower than 0.7, the coacervation could be formed through hydrophobic interaction, forming an efficient underwater adhesion system similar to that of mussels.

Polyvinylpyrrolidone (PVP) nanofilms prepared by spin-coating have vast applications in biological and microdevice fields. However, detailed knowledge of processing induced nonequilibrium behavior of PVP nanofilms and solutions for minimizing residual stresses toward high-quality films has still been lacking. In the present study, we first explored the rapid film formation process via statistics on nascent holes. Next, by employing dewetting as a major probe, we revealed that many processing conditions, particularly previously overlooked variables like the atmosphere, substrates, and immersion time, were correlated substantially with the degree of nonequilibrium of nanofilms. Proper aging temperature and time were demonstrated essential for releasing residual stresses and achieving more equilibrium nanofilms. This work offered abundant experimental evidence in the building relationship between the processing and nonequilibrium nature of polymer nanofilms, which were crucial for their preparation and application.

Although chlorinated polyfluoroalkyl ether sulfonic acid (Cl-PFESA) has been reported to be widespread in different environmental matrices of China, its exposure data in the general Chinese population are very limited. In the present study, the serum-to-whole-blood ratio was first assessed for 6:2 Cl-PFESA (mean/median: 2.07/1.82) based on its paired concentrations (n = 36), which allows a comparison in different blood matrices. The exposure levels of Cl-PFESAs in the general population were investigated by collecting blood samples (n = 1516) from residents of seven cities in central and eastern China. 6:2 Cl-PFESA was observed as the third-highest contributing polyfluoroalkyl substance (PFAS) (8.69%), with the median concentration at 2.18 ng/mL, indicating its importance for assessing the human exposure risks of PFASs. The regional difference between 6:2 Cl-PFESA and perfluorooctane sulfonate (PFOS) can be explained by their use pattern in China. Overall, similar to PFOS, 6:2 Cl-PFESA displays significantly increasing levels with increasing age for both males and females, with significantly higher levels in males. However, a significant sex dependence was found for 6:2 Cl-PFESA in one specific age group (41-60), while there was no significance in the other groups although males display higher levels than females. Our study provides robust data regarding human exposure to 6:2 Cl-PFESA in the general population in central and eastern China., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Systematic autopsy and comprehensive pathological analyses of COVID-19 decedents should provide insights into the disease characteristics and facilitate the development of novel therapeutics. In this study, we report the autopsy findings from the lungs and lymphatic organs of 12 COVID-19 decedents-findings that evaluated histopathological changes, immune cell signature and inflammatory factor expression in the lungs, spleen and lymph nodes. Here we show that the major pulmonary alterations included diffuse alveolar damage, interstitial fibrosis and exudative inflammation featured with extensive serous and fibrin exudates, macrophage infiltration and abundant production of inflammatory factors (IL-6, IP-10, TNFα and IL-1β). The spleen and hilar lymph nodes contained lesions with tissue structure disruption and immune cell dysregulation, including lymphopenia and macrophage accumulation. These findings provide pathological evidence that links injuries of the lungs and lymphatic organs with the fatal systematic respiratory and immune malfunction in critically ill COVID-19 patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Here, we report a novel thermo-triggered-releasing microcapsule for liposoluble drug delivery. Monodisperse microcapsules with a poly(N-isopropylacrylamide- co -methacrylic acid) hydrogel shell and an oil core were successfully fabricated by a double coaxial microfluidic device. Fluorescent dye Lumogen Red F300 as a model liposoluble drug was dissolved in the oil core with controllable loading capacity. The volume phase transition temperature (VPTT) of the microcapsule was adjusted by copolymerizing with the hydrophilic methacrylic acid. The in vitro release study demonstrates that the shells shrink, leading to the thermo-triggered release of the model drug from the microcapsules at the environmental temperature above the VPTT, while the swollen hydrogel shells can protect the encapsulated drug from leakage and contamination below the VPTT. The proposed microcapsule is a promising liposoluble drug delivery system with controllable loading and smart thermo-triggered release.

Purpose: To evaluate whether neurogenic lower urinary tract dysfunction and urodynamic parameters predict the outcomes of patients with multiple system atrophy (MSA)., Methods: A retrospective study was performed in patients who were diagnosed with MSA and underwent urodynamic studies simultaneously from September 2014 to July 2018. The urodynamic traces were reviewed by urologists. Detrusor contractility was evaluated by the bladder contractility index (BCI) and Schäfer nomogram. Telephone follow-up was conducted in July 2019 to acquire survival data. Clinical and urodynamic parameters were analyzed for survival using Cox regression analysis., Results: Overall, 70 MSA patients were eligible for analysis, and 61 of them underwent urodynamic study within 3 years of initial symptom onset. The parkinsonian subtype of MSA (MSA-P) had a smaller proportion of men as well as longer motor and lower urinary tract symptom durations than the cerebellar subtype (MSA-C). MSA-P also had a lower mean BCI than MSA-C (32.0 ± 27.0 versus 53.6 ± 33.4, p = 0.025). The mean MSA survival time was 5.4 [95% confidence interval (CI) 4.8-6.3] years. Cox regression analysis showed that survival from baseline was correlated only with BCI [hazard ratio (HR) 0.983, 95% CI 0.969-0.997, p = 0.020]. Overall survival was correlated with BCI (HR 0.982, 95% CI 0.966-0.999, p = 0.039) and the presence of urinary incontinence (HR 3.007, 95% CI 0.993-9.220, p = 0.052)., Conclusion: Detrusor contractility can be a prognostic marker in MSA patients. A high BCI value is a protective factor for survival from baseline and overall survival. The presence of urinary incontinence predicts shortened overall survival.

Background: Idiopathic rapid eye movement sleep behavior disorder is an early sign of neurodegenerative disease. This study aimed to quantitatively evaluate iron content in idiopathic rapid eye movement sleep behavior disorder patients using quantitative susceptibility mapping and to examine the potential of this technique to identify the prodromal stage of α-synucleinopathies., Methods: Twenty-five idiopathic rapid eye movement sleep behavior disorder patients, 32 Parkinson's disease patients, and 50 healthy controls underwent quantitative susceptibility mapping. The mean magnetic susceptibility values within the bilateral substantia nigra, globus pallidus, red nucleus, head of the caudate nucleus, and putamen were calculated and compared among groups. The relationships between the values and the clinical features of idiopathic rapid eye movement sleep behavior disorder and Parkinson's disease were measured using correlation analysis., Results: Idiopathic rapid eye movement sleep behavior disorder patients had elevated iron in the bilateral substantia nigra compared with healthy controls. Parkinson's disease patients had increased iron in the bilateral substantia nigra, globus pallidus, and left red nucleus compared with healthy controls and had elevated iron levels in the bilateral substantia nigra compared with idiopathic rapid eye movement sleep behavior disorder patients. Mean magnetic susceptibility values were positively correlated with disease duration in the left substantia nigra in idiopathic rapid eye movement sleep behavior disorder patients., Conclusions: Quantitative susceptibility mapping can detect increased iron in the substantia nigra in idiopathic rapid eye movement sleep behavior disorder, which becomes more significant as the disorder progresses. This technique has the potential to be an early objective neuroimaging marker for detecting α-synucleinopathies. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

A long-standing mystery shrouds the mechanism by which catalytically repressed receptor tyrosine kinase domains accomplish transphosphorylation of activation loop (A-loop) tyrosines. Here we show that this reaction proceeds via an asymmetric complex that is thermodynamically disadvantaged because of an electrostatic repulsion between enzyme and substrate kinases. Under physiological conditions, the energetic gain resulting from ligand-induced dimerization of extracellular domains overcomes this opposing clash, stabilizing the A-loop-transphosphorylating dimer. A unique pathogenic fibroblast growth factor receptor gain-of-function mutation promotes formation of the complex responsible for phosphorylation of A-loop tyrosines by eliminating this repulsive force. We show that asymmetric complex formation induces a more phosphorylatable A-loop conformation in the substrate kinase, which in turn promotes the active state of the enzyme kinase. This explains how quantitative differences in the stability of ligand-induced extracellular dimerization promotes formation of the intracellular A-loop-transphosphorylating asymmetric complex to varying extents, thereby modulating intracellular kinase activity and signaling intensity.

The early detection of Parkinson's disease (PD) still remains a challenge to date. Although studies have previously reported subtle motor function abnormalities in early PD patients, it is unclear whether such clinical signs can be better detected while patients are concurrently performing a cognitive task, and whether they can be useful in predicting patients' clinical conversion state. Seventy-two right-handed participants (40 drug-naive patients with idiopathic unilateral PD and 32 age-matched healthy controls) were enrolled in this study. All participants were asked to perform the Purdue Pegboard test (PPT) either alone (single-task condition) or during a concurrent mental subtraction-by-3 task (dual-task condition). A 4-year telephone follow-up was later conducted to determine whether PD patients converted to bilateral signs. We found that PD patients showed a significant reduction in dexterity on the PPT compared to the controls in both single- and dual-task conditions. Yet patients' performance in the dual-task condition revealed a greater interference effect when patients performed the task with their right hand than with their left hand. PPT also revealed reasonable discriminative ability for prediagnosing PD. However, dual-tasking did not have added value in differentiating early patients and controls. At follow-up, the baseline PPT performance of the asymptomatic hands was positively correlated with time to convert from unilaterally to bilaterally affected states ( r = 0.62, P = 0.031). Together, these findings suggest that PPT can serve as a useful auxiliary tool in evaluating early PD, and shed light on the neuroplasticity mechanism of fine motor deficit at this very early stage., (Copyright © 2019 Dan, Liu, Doyon, Zhou, Ma and Chan.)

Objective: Visual dysfunction is a common feature in α-synucleiopathies but rarely assessed in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). The current study is set to investigate the comprehensive visual function in iRBD as compared to patients of Parkinson's disease (PD) with RBD., Methods: Eighty-three iRBD subjects diagnosed with polysomnograph (PSG), 52 early PD patients (Hoehn-Yahr stages<3) with RBD symptom prior to onset of motor symptoms and 79 healthy controls without RBD diagnosed based on RBD Questionnaire-Hong Kong (RBDQ-HK) were enrolled in this study. Visual function including color discrimination, stereopsis function, visual illusion (VI) or hallucination (VH) were assessed in addition to UPDRS, Purdue Pegboard test (PPT) and cognitive tests., Results: Abnormal color discrimination and stereopsis were presented significantly higher in both iRBD and PD patients as compared to controls and more severe in PD than in iRBD. Color discrimination was decreased in all four color in PD patients but not green color in iRBD subjects. Stereopsis test was abnormal in both iRBD and PD, but the proportion of subjects with abnormal stereopsis was significantly higher in PD patients (69.6% vs 42%). Similar number of subjects with iRBD and PD were presented with illusion but only PD patients reported more hallucination. Changes of visual function were associated with age and cognition in both iRBD and PD subjects but was also affected independently by disease duration and clinical stage or fine motor function in PD. In addition, decreased fine motor function demonstrated by PPT was also observed in some iRBD subjects., Conclusion: Our results demonstrated comprehensively that visual dysfunction was present in iRBD subjects similar but in a less degree of severity to PD patients, and associated with age, cognition and motor deficit. Whether or not it can be useful in predicting iRBD conversion to PD warrants further investigation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Determining the locations and distributions of Al substitution in zeolite-based catalysts and catalysis is always very challenging. Despite advanced experimental characterization techniques and improved theoretical models, this issue is not reasonably solved and this is because the locations and distributions of Al substitution in zeolites are more kinetically than thermodynamically controlled. In this work, we computed one Al substitution in the orthorhombic form of MFI (HZSM-5) which contains 12 distinct tetrahedral (T) centers on the basis of a periodic slab model containing 96 T centers including van der Waals dispersion correction (GGA-PBE-D3). For all 12 T centers, there are 48 acidic sites and each site can be considered for the adsorption of probe molecules. Thermodynamically, the energy span of the twelve most stable acidic sites is less than 15 kJ mol-1, and such a small energy difference enables all adjustable possibilities for the locations and distributions of Al substitution under suitable conditions. Excellent agreement between experiment and theory in the adsorption enthalpies of pyridine, methylamine, dimethylamine and trimethylamine shows that the location of Al substitution is most likely at T1, T3, T5, T7 and T11, while much less likely at the often used T12 site. These results provide the basis for identifying Al substitution in new synthesized HZSM-5 catalysts and for studying the acidic site-dependent catalytic activity of HZSM-5 in cracking and hydrogenation reactions.

Introduction: The sequence effect (SE) is a reason contributing to freezing of gait (FOG) in Parkinson's disease (PD) patients. There is no effective treatment for the SE. The objective of the current study is to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the SE in PD patients with FOG., Methods: 28 PD patients with FOG received either real or sham 10-Hz rTMS over the supplementary motor area (SMA). The effects of rTMS on the SE, FOG, and some gait parameters were evaluated., Results: rTMS did not improve the SE. Real rTMS had beneficial effects on FOG and some gait parameters, and this effect lasted for at least four weeks., Conclusions: High-frequency rTMS over the SMA cannot alleviate the SE in PD patients with FOG. rTMS has a long-lasting beneficial effect on FOG; however, this effect is not achieved by improving the SE but may be through improving some other gait parameters.

CO is a toxic gas discharged as a byproduct in tail gases from different industrial flue gases, which needs to be taken care of urgently. In this study, a CuCl/AC adsorbent was made by a facile route of physically mixing CuCl 2 and Cu(HCOO) 2 powder with activated carbon (AC), followed by heating at 533 K under vacuum. The samples were characterized by X-ray powder diffraction (XRD), inductively coupled plasma optical emission spectrometry (ICP-OES), N 2 adsorption/desorption, and scanning electron microscopy (SEM). It was shown that Cu(II) can be completely reduced to Cu(I), and the monolayer dispersion threshold of CuCl on AC support is 4 mmol·g -1 AC. The adsorption isotherms of CO, CO 2 , CH 4 , and N 2 on CuCl/AC adsorbents were measured by the volumetric method, and the CO/CO 2 , CO/CH 4 , and CO/N 2 selectivities of the adsorbents were predicted using ideal adsorbed solution theory (IAST). The obtained adsorbent displayed a high CO adsorption capacity, high CO/N 2 , CO/CH 4 , and CO/CO 2 selectivities, excellent ad/desorption cycle performance, rapid adsorption rate, and appropriate isosteric heat of adsorption, which made it a promising adsorbent for CO separation and purification.

During the 1990s, we estimated the genetic contribution to Parkinson's disease risk in a large, population-based twin registry. Because many unaffected twins were still alive, previous concordance estimates were based on incomplete information. Ninety-five percent of twins are now deceased. Here, we update concordance and heritability through 2015 using National Death Index data. In total, we identified 30 concordant and 193 discordant pairs. Proband-wise concordance was 0.20 in monozygotic and 0.13 in dizygotic pairs. Heritability was 0.27 overall, 0.83 in pairs diagnosed ≤50, and 0.19 in pairs diagnosed >50. High concordance in dizygotic twins suggests shared effects of early childhood environment. Ann Neurol 2019;85:600-605., (© 2019 American Neurological Association.)