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Why do‘OFF’periods still occur during continuous drug delivery in Parkinson’s disease?

Translational Neurodegeneration 2022年第1期11卷 280-293页

作者： Silvia Rota Daniele Urso Daniel J.van Wamelen Valentina Leta Iro Boura per odin Alberto J.Espay Peter Jenner K.Ray Chaudhuri Department of Basic and Clinical Neurosciences Institute of PsychiatryPsychology and NeuroscienceKing’s College LondonLondonUK Parkinson’s Foundation Centre of Excellence King’s College HospitalLondonUK Department of Neuroimaging Institute of PsychiatryPsychology and NeuroscienceKing’s College LondonLondonUK Centre for Neurodegenerative Diseases and the Aging Brain Department of Clinical Research in NeurologyUniversity of Bari‘Aldo Moro“Pia Fondazione Cardinale G.Panico”73039 TricaseItaly Donders Institute for Brain Cognition and BehaviourDepartment of NeurologyRadboud University Medical CentreNijmegenThe Netherlands School of Medicine University of CreteCreteGreece Department of Neurology University Hospital of HeraklionCreteGreece Division of Neurology Department of Clinical Sciences LundLund UniversityLundSweden University of Cincinnati Gardner Neuroscience Institute Gardner Family Center for Parkinson’s Disease and Movement DisordersDepartment of NeurologyUniversity of CincinnatiCincinnatiOHUSA Institute of Pharmaceutical Sciences Faculty of Life Science and MedicineKing’s College LondonLondonUK.

Continuous drug delivery(CDD)is used in moderately advanced and late-stage Parkinson’s disease(PD)to control motor and non-motor fluctuations(‘OFF’periods).Transdermal rotigotine is indicated for early fluctuations,while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD.All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD.A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of‘OFF’periods.However,data suggest that despite their efficacy in reducing the number and duration of‘OFF’periods,these strategies still do not prevent‘OFF’periods in the middle to late stages of PD,thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation.Why these emergent‘OFF’periods still occur is unknown.In this review,we analyse the potential reasons for their persistence.The contribution of drug-and device-related involvement,and the problems related to site-specific drug delivery are analysed.We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent‘OFF’periods unresponsive to dopaminergic therapy delivered via CDD.

关键词： ‘OFF’periods Continuous drug delivery Continuous dopaminergic stimulation Rotigotine patch Subcutaneous apomorphine infusion Levodopa-carbidopa intestinal gel

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鸟类形态特征的同质性比较

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动物学杂志 2024年第3期59卷 321-336页

作者：郑雪星 per G.P.Ericson 屈延华中国科学技术大学生命科学与医学部中国科学院动物研究所动物进化与系统学院重点实验室瑞典自然历史博物馆

鸟类作为脊椎动物中的主要类群之一，其内部演化关系一直是动物学研究的重点。形态特征及分子特征在推断鸟类内部类群间的系统发育关系时被广泛应用，但长久以来受制于同质性的影响，不同形态特征难以得到一致的系统发育关系。随着基因... 详细信息

鸟类作为脊椎动物中的主要类群之一，其内部演化关系一直是动物学研究的重点。形态特征及分子特征在推断鸟类内部类群间的系统发育关系时被广泛应用，但长久以来受制于同质性的影响，不同形态特征难以得到一致的系统发育关系。随着基因组测序技术及分析方法的快速发展，基于大量DNA序列数据所建的物种树成为领域内普遍认可的鸟类系统发育关系。在此基础之上，重新挖掘形态特征的研究价值成为可能。本研究基于Prum发表于2015年的鸟类科级水平系统发育树，比较了不同形态特征同质性水平的差异，讨论了形态特征对于提高分子特征系统发育信号及分子树支持率的作用。研究发现，不同种类形态特征的同质性水平存在显著的差异，以一致性指数为标准，杂项特征（包括神经、肌腱及肠道的特征）的得分显著高于骨学特征和肌学特征（P<0.01），颅骨特征的得分显著高于非颅骨、躯干及腿部特征的得分（P<0.05）；加入形态特征能够显著提高分子特征的系统发育信号（P<0.05），也提高了分子树的支持率。综上所述，不同的形态特征在同质性水平的得分上具有显著差异，在分子特征上加入形态特征既能够提高分子特征的系统发育信号，也能够提高分子树的支持率。

关键词：形态特征同质性水平一致性指数系统发育信号支持率

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Oxidized organic molecules in the tropical free troposphere over Amazonia

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National Science Review 2024年第1期11卷 174-184页

作者： Qiaozhi Zha Diego Aliaga Radovan Krejci Victoria A.Sinclair Cheng Wu Giancarlo Ciarelli Wiebke Scholz Liine Heikkinen Eva Partoll Yvette Gramlich Wei Huang Markus Leiminger Joonas Enroth Otso per?kyl? Runlong Cai Xuemeng Chen Alkuin Maximilian Koenig Fernando Velarde Isabel Moreno Tuukka Pet?j? Paulo Artaxo Paolo Laj Armin Hansel Samara Carbone Markku Kulmala Marcos Andrade Douglas Worsnop Claudia Mohr Federico Bianchi Agrarian Sciences Institute Federal University of Uberl?ndia Beijing Advanced Innovation Center for Soft Matter Science and Engineering Beijing University of Chemical Technology Department of Atmospheric and Oceanic Sciences University of Maryland Aerodyne Research Inc. Department of Environmental System Science ETH Zürich Switzerland and Laboratory of Atmospheric Chemistry Paul Scherrer Institute Institute for Atmospheric and Earth System Research/Physics University of Helsinki Joint International Research Laboratory of Atmospheric and Earth System Sciences Nanjing University Department of Environmental Science & Bolin Centre for Climate Research Stockholm University Department of Chemistry and Molecular Biology University of Gothenburg Institute for Ion and Applied Physics University of Innsbruck Ionicon Analytik GmbH Laboratory for Atmospheric Physics Institute for Physics Research Universidad Mayor de San Andrés Institute of Physics University of Sao Paulo Institute for Geosciences and Environmental Research (IGE) University of Grenoble Alpes

New particle formation(NPF) in the tropical free troposphere(FT) is a globally important source of cloud condensation nuclei, affecting cloud properties and climate. Oxidized organic molecules(OOMs)produced from biogenic volatile organic compounds are believed to contribute to aerosol formation in the tropical FT, but without direct chemical observations. We performed in situ molecular-level OOMs measurements at the Bolivian station Chacaltaya at 5240 m above sea level, on the western edge of Amazonia. For the first time, we demonstrate the presence of OOMs, mainly with 4–5 carbon atoms, in both gas-phase and particle-phase(in terms of mass contribution) measurements in tropical FT air from Amazonia. These observations, combined with air mass history analyses, indicate that the observed OOMs are linked to isoprene emitted from the rainforests hundreds of kilometers away. Based on particle-phase measurements, we find that these compounds can contribute to NPF, at least the growth of newly formed nanoparticles, in the tropical FT on a continental scale. Thus, our study is a fundamental and significant step in understanding the aerosol formation process in the tropical FT.

关键词： oxidized organic molecules tropical aerosol formation Amazon free troposphere

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May Traditional Chinese Medicine Reduce the Risk of Developing Rheumatoid Arthritis?An One-armed Prospective Study

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Clinical Complementary Medicine and Pharmacology 2024年第1期4卷 10-18页

作者： Kaixin Gao Qi Liang Dongyun Li Chuanning Li Maojie Wang Xiumin Chen Qingchun Huang Zehuai Wen per-Johan Jakobsson Runyue Huang The Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine) Guangzhou 510006GuangdongChina The Second Clinical Medical College Guangzhou University of Chinese MedicineGuangzhou 510006GuangdongChina State Key Laboratory of Dampness Syndrome of Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120GuangdongChina Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases Guangzhou 510403GuangdongChina Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research Guangzhou 510000GuangdongChina The key unit of methodology of clinical research The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510000GuangdongChina Rheumatology Unit Department of Medicine SolnaKarolinska InstituteKarolinska University HospitalStockholm 17177Sweden Department of Doctor-Patient Relationship The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630GuangdongChina

Background:Rheumatoid arthritis(RA)is a worldwide public health problem.Intervention and prevention before the onset of rheumatic diseases is a new direction in current research.Objective:The aim of this study was to evaluate the potential and feasibility of traditional Chinese medicine(TCM)in the prevention of RA.Methods:This was a single-armed prospective clinical trial.All participants were recruited from a single center in Guangdong,China.Adults who were tested positive for anti-cyclic citrullinated peptide antibody(anti-CCP)and/or rheumatoid factor(RF),had no synovitis and never been treated with disease-modifying anti-rheumatic drugs(DMARDs),were enrolled to take the Huayu-Qiangshen-Tongbi(HQT)decoction orally twice daily,200 mL each time for 24 weeks.Primary outcome was the proportion of patients who met 2010 ACR(American College of Rheumatology)/EULAR(European League Against Rheumatism)classification criteria of RA during observation.Secondary outcomes included levels of anti-CCP,RF,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),assessment of signs and symptoms,and radiographic progression by magnetic resonance imaging(MRI).Results:19 individuals were enrolled in the study,4 of which withdrew because of the epidemic of COVID-19.During the observation period,3 individuals(20%)developed RA and they had longer morning stiffness(P=0.009)and more obvious synovial enhancement in MRI(P=0.041)at baseline when compared with those who did not develop RA.After 24 weeks of intervention,there were improvements in 28-swollen joint count(SJC28)(P=0.046),Visual Analog Scale(VAS)(P=0.019),Patient’s Global Assessment(PtGA)(P=0.019)and Physician’s Global Assessment(PGA)(P=0.031),but no statistical significance was observed in the levels of anti-CCP,RF,ESR,CRP,morning stiffness,28-tender joint count(TJC28),Health Assessment Questionnaire(HAQ)and magnetic resonance imaging(MRI)analysis(P>0.05).Conclusion:The HQT formula is safe and could improve joint symptoms and signs in these at-risk individuals,but it remains

关键词： Rheumatoid arthritis(RA) Prevention Traditional Chinese medicine(TCM) Huayu-Qiangshen-Tongbi decoction(HQT) Clinical trial

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湿型砂铸铝:打开新的视角

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铸造 2024年第1期73卷 135-138页

作者： per Larsen Tim J.Baron 陈之伟(译) 刘溢(译) DISA Industries A/S 迪砂中国

许多汽车零部件已经用铸铝件替代以前的铸铁件。铸铝件在电动汽车的过渡中至关重要。随着汽车行业的成功转型,大批量的新型电动汽车传动系统铝部件应运而生,如电机壳和机盖。众所周知,湿型砂工艺能高效,可低成本生产出高质量的铸铁件。... 详细信息

许多汽车零部件已经用铸铝件替代以前的铸铁件。铸铝件在电动汽车的过渡中至关重要。随着汽车行业的成功转型,大批量的新型电动汽车传动系统铝部件应运而生,如电机壳和机盖。众所周知,湿型砂工艺能高效,可低成本生产出高质量的铸铁件。随着全球对铸铝件的需求不断上升,降低成本的压力不断加大,越来越多的铸造厂和制造商开始探索湿型砂生产铸铝件的运用。铸铁厂用湿型砂生产的优势成功转移到铸铝件,带来低成本、快速成形和灵活性等优点。

关键词：铸铝件湿型砂铸铁件低成本生产快速成形汽车零部件汽车传动系统电机壳

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Comparative analysis of planted and unplanted controls for assessment of rhizosphere priming effect

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Pedosphere 2022年第6期32卷 884-892页

作者： Jian LI per BENGTSON Department of Biology Microbial Ecology GroupLund UniversitySölvegatan 37Lund 22362(Sweden) Key Laboratory of Urban Environment and Health Institute of Urban EnvironmentChinese Academy of Sciences1799 Jimei RoadXiamen 361021(China)

The rhizosphere priming effect(RPE)is increasingly being considered to be an important regulator of soil organic matter(SOM)decomposition and nutrient turnover,with potential importance for the global CO_(2) budget.As a result,studies on the RPE have rapidly increased in number over the last few years.Most of these experiments have been performed using unplanted soil as the control,which could potentially lead to incorrect assessment of the RPE.Therefore,we performed a greenhouse experiment to investigate how the choice of control(i.e.,unplanted control and planted control)influenced the quantification of RPE on SOM decomposition and gross nitrogen(N)mineralization,and to link this to differences in microbial and abiotic soil properties between the two controls.In the planted control,planted seedlings were cut at soil surface 5 d before measurement of the RPE.The RPE on SOM decomposition was positive in pine soil and almost 2-fold higher when calculated from the planted control than from the unplanted control.In spruce soil,a negative RPE on SOM decomposition was found when calculated from the planted control,while the RPE was positive when calculated from the unplanted control.No RPE on gross N mineralization was found when calculated from the planted control,while a positive RPE of more than 100%was found when calculated from the unplanted control.The microbial biomass and growth rate were lower,while the inorganic N content was higher in the unplanted control than in the planted control.The microbial community composition and potential enzyme activity in the planted treatment and planted control were similar,but they differed significantly from those in the unplanted control.The results showed that the RPE varied widely depending on the choice of control;thus,we suggest that a planted control,in which the aboveground plant parts are removed only a few days before the measurement of RPE,should be used as the control when elucidating the RPE on belowground C and N cycling responses to environmental change.

关键词： enzyme activity gross nitrogen mineralization microbial community composition nitrogen availability soil organic matter decomposition

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Are ATXN2 variants modifying our understanding about neural pathogenesis,phenotypes,and diagnostic?

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Neural Regeneration Research 2022年第11期17卷 2445-2447页

作者： Jose Miguel Laffita-Mesa Martin Paucar per Svenningsson Department of Clinical Neuroscience(CNS) Karolinska Universitetssjukhuset

ATXN2 one gene with multiple phenotype effects:ATXN2 gene encodes a cytosolic protein(ataxin-2)with pleiotropic functions(see below).This gene contains a number of exonic Cytosine-Adenine-Guanine(CAG)-repeats which encodes a polyglutamine tract(polyQ)in the N-terminal intrinsically disordered region(IDR)of the protein.ATXN2CAG repeats are interrupted by CAA codons which is relevant only for DNA and RNA but not for protein since CAA also encodes glutamine(Q).

关键词： pathogenesis neural interrupted

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Comparative population genomics reveals glacial cycles to drive diversifications in tropical montane birds(Aves,Timaliidae)

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Avian Research 2022年第4期13卷 399-406页

作者： per G.P.Ericson Martin Irestedt Department of Bioinformatics and Genetics Swedish Museum of Natural HistoryP.O.Box 50007SE-10405StockholmSweden

Many bird species are specialized to live in the broadleaved,evergreen forests in the mountain regions in Southeast Asia.These mountain habitats are not continuously distributed as the different mountain areas are separated by lowlands,which has restricted gene flow and thus contributed to the high biological diversity in this region.The degree of connectivity between mountain areas has fluctuated with the Pleistocene glacial cycles,being largest during the glaciations when the mountain forests spread to lower elevations.Here we study how the intermittent periods of restricted gene flow and connectivity between the populations of five montane species of babblers(Aves,Timaliidae)in Vietnam may be traced in their genomes.The results suggest that the babbler species in the Central Highlands have been isolated from their sister-populations in northern Vietnam for between ca.585 and 380 ky.For two species with populations in both the Central Highlands and the Da Lat region,we found that these split at more or less the same time(440–340 kya).We also found a significant statistical correlation between the time of the splits of these populations and the lowest altitude at which they are known to occur(no similar correlation was found with the geographic distances between populations).The populations in northern Vietnam show higher genetic variation than their counterparts in South-Central Vietnam,supporting the postulate that smaller populations may have lower genetic variation than larger.In accordance with this,we found the lowest genetic variation in the two species with the smallest populations in the Central Highlands.These two populations also show low levels of genomic heterozygosity.Our results show that the south-central populations of the studied babbler species are genetically distinct from their sister-populations in northern Vietnam,providing additional argument for the long-term protection of the evergreen mountain forests in Southeast Asia.

关键词： Aves Timaliidae Babblers Demographic history Fragmented distributions Pleistocene glacial cycles Population genomics Tropical mountain forests

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Self-Powered,Long-Durable,and Highly Selective Oil-Solid Triboelectric Nanogenerator for Energy Harvesting and Intelligent Monitoring

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Nano-Micro Letters 2022年第10期14卷 95-107页

作者： Jun Zhao Di Wang Fan Zhang Jinshan Pan per Claesson Roland Larsson Yijun Shi Division of Machine Elements Department of Engineering Sciences and MathematicsLuleåUniversity of Technology97187 LuleåSweden Department of Engineering and Design School of Engineering and InformaticsUniversity of SussexBrighton BN19RHUK Division of Surface and Corrosion Science Department of ChemistryKTH Royal Institute of Technology10044 StockholmSweden

Triboelectric nanogenerators(TENGs)have potential to achieve energy harvesting and condition monitoring of oils,the“lifeblood”of industry.However,oil absorption on the solid surfaces is a great challenge for oil-solid TENG(O-TENG).Here,oleophobic/superamphiphobic O-TENGs are achieved via engineering of solid surface wetting properties.The designed O-TENG can generate an excellent electricity(with a charge density of 9.1μC m^(−2) and a power density of 1.23 mW m^(−2)),which is an order of magnitude higher than other O-TENGs made from polytetrafluoroethylene and polyimide.It also has a significant durability(30,000 cycles)and can power a digital thermometer for self-powered sensor applications.Further,a superhigh-sensitivity O-TENG monitoring system is successfully developed for real-time detecting particle/water contaminants in oils.The O-TENG can detect particle contaminants at least down to 0.01 wt%and water contaminants down to 100 ppm,which are much better than previous online monitoring methods(particle>0.1 wt%;water>1000 ppm).More interesting,the developed O-TENG can also distinguish water from other contaminants,which means the developed O-TENG has a highly water-selective performance.This work provides an ideal strategy for enhancing the output and durability of TENGs for oil-solid contact and opens new intelligent pathways for oil-solid energy harvesting and oil condition monitoring.

关键词： Oil Triboelectric nanogenerator Energy harvesting Intelligent monitoring

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Saussure’s Prolegomena——Toward a Semiotics of the Mind

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Language and Semiotic Studies 2022年第1期8卷 91-104页

作者： per Aage Brandt 不详

The study of language is based either on the word or on the sentence as basic units.Ferdinand de Saussure opted for the word;other linguists later preferred the sentence or chose to ignore the difference between word and sentence.Words,however,have extra-linguistic functions related to the topologies of thought,the spontaneous geometrical imageries of meaningful mental figuration,as we know them from sign posts,from verbal descriptions,and from the semiotics of diagrams.If words,rather than sentences,are in this sense the essential connectors of language and thought,then the general architecture of linguistic structures,including semantics and syntax,should be centered around this lexical“window”into the thinking mind,and the semiotic modes of language and signs may then be described by similar architectures directly connected to the figurative mind itself.This paper offers tentative connected models of the architectures of language,signs,and the figurative mind,and suggests the possibility of interpreting Ferdinand de Saussure’s semiological intuitions in the sense of a semiotics of the mind along these cognitive-semiotic lines.

关键词： word-based linguistics mental architecture cognitive semiotics sign categories

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