Parkinson's disease (PD) is the most common movement disorder with motor and nonmotor signs. The current therapeutic regimen for PD is mainly symptomatic as the etio-pathophysiology has not been ...fully elucidated. A variety of animal models has been generated to study different aspects of the disease for understanding the pathogenesis and therapeutic development. The disease model can be generated through neurotoxin-based or genetic-based approaches in a wide range of animals such as non-human primates (NHP), rodents, zebrafish,
(
)
, and drosophila. Cellular-based disease model is frequently used because of the ease of manipulation and suitability for large-screen assays. In neurotoxin-induced models, chemicals such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat are used to recapitulate the disease. Genetic manipulation of PD-related genes, such as α-Synuclein(SNCA), Leucine-rich repeat kinase 2 (LRRK2), Pten-Induced Kinase 1 (PINK1), Parkin(PRKN), and Protein deglycase (DJ-1) Are used in the transgenic models. An emerging model that combines both genetic- and neurotoxin-based methods has been generated to study the role of the immune system in the pathogenesis of PD. Here, we discuss the advantages and limitations of the different PD models and their utility for different research purposes.
Multiple lines of evidence indicate that immune system dysfunction has a role in Parkinson disease (PD); this evidence includes clinical and genetic associations between autoimmune disease and PD, ...impaired cellular and humoral immune responses in PD, imaging evidence of inflammatory cell activation and evidence of immune dysregulation in experimental models of PD. However, the mechanisms that link the immune system with PD remain unclear, and the temporal relationships of innate and adaptive immune responses with neurodegeneration are unknown. Despite these challenges, our current knowledge provides opportunities to develop immune-targeted therapeutic strategies for testing in PD, and clinical studies of some approaches are under way. In this Review, we provide an overview of the clinical observations, preclinical experiments and clinical studies that provide evidence for involvement of the immune system in PD and that help to define the nature of this association. We consider autoimmune mechanisms, central and peripheral inflammatory mechanisms and immunogenetic factors. We also discuss the use of this knowledge to develop immune-based therapeutic approaches, including immunotherapy that targets α-synuclein and the targeting of immune mediators such as inflammasomes. We also consider future research and clinical trials necessary to maximize the potential of targeting the immune system.
Lithium‐ion batteries (LIBs) are in great demand for their impressive successes in serving people's daily life. Concomitantly, recycling the retired LIBs has also aroused the enthusiasm of widespread ...studies due to its great significance in the sustainable development of LIBs. Among the spent LIBs, LiFePO4 (LFP) is the main force because of its widespread use in electric vehicles and grids due to its stability and favorable price. However, considering the low cost of LFP manufacture as well as the abundance of Fe and P, traditional metallurgy processes are not economically feasible for recycling LFP because of high energy consumption and tedious steps. Here, this work proposes a green recycling method to directly regenerate the degraded LFP electrode via an in situ electrochemical process with a functionalized prelithiation separator. Compared with the existing recycling strategies for LFP batteries, the proposed method takes full advantage of the degraded cathode scraps without destroying the original structure, greatly reducing the cost of the remanufacture of the cathode electrodes simply via a prelithiation technique.
Degraded LiFePO4 (D‐LFP) electrodes are directly reassembled into a new battery with a functionalized prelithiation separator and fresh graphite anode. Extra Li+ ions provided by the sacrificial lithium‐containing layer compensate the Li+ loss in the D‐LFP during the initial electrochemical process and thus the capacity of the regenerated battery is largely restored.
Chemical modification of electrode materials by heteroatom dopants is crucial for improving storage performance in rechargeable batteries. Electron configurations of different dopants significantly ...influence the chemical interactions inbetween and the chemical bonding with the host material, yet the underlying mechanism remains unclear. We revealed competitive doping chemistry of Group IIIA elements (boron and aluminum) taking nickel‐rich cathode materials as a model. A notable difference between the atomic radii of B and Al accounts for different spatial configurations of the hybridized orbital in bonding with lattice oxygen. Density functional theory calculations reveal, Al is preferentially bonded to oxygen and vice versa, and shows a much lower diffusion barrier than BIII. In the case of Al‐preoccupation, the bulk diffusion of BIII is hindered. In this way, a B‐rich surface and Al‐rich bulk is formed, which helps to synergistically stabilize the structural evolution and surface chemistry of the cathode.
A model study has been performed on Group IIIA element (boron and aluminum) co‐doped high‐nickel layered oxide cathode materials to understand competitive doping chemistry. A notable difference between the atomic radii of B and Al accounts for different spatial configurations of the hybridized orbital in bonding with lattice oxygen, resulting in the formation of a B‐rich surface and an Al‐rich bulk.
The interfacial stability is highly responsible for the longevity and safety of sodium ion batteries (SIBs). However, the continuous solid‐electrolyte interphase(SEI) growth would deteriorate its ...stability. Essentially, the SEI growth is associated with the electron leakage behavior, yet few efforts have tried to suppress the SEI growth, from the perspective of mitigating electron leakage. Herein, we built two kinds of SEI layers with distinct growth behaviors, via the additive strategy. The SEI physicochemical features (morphology and componential information) and SEI electronic properties (LUMO level, band gap, electron work function) were investigated elaborately. Experimental and calculational analyses showed that, the SEI layer with suppressed growth delivers both the low electron driving force and the high electron insulation ability. Thus, the electron leakage is mitigated, which restrains the continuous SEI growth, and favors the interface stability with enhanced electrochemical performance.
We have given insights into the electron leakage behavior that underlies the distinct SEI growth, by investigating the specific SEI component type/distribution in detail. The uniform SEI layer with favorable component and distribution is found to have both low electron driving force and high electron insulation. Therefore, the electron leakage causing SEI growth is largely restrained.
This paper aims to explore structural and social-economic determinants of China's transport CO2 emissions (TCEs) from 2004 to 2016, by using logarithmic mean Divisa index (LMDI). Compared with ...existing studies, two new factors, i.e., spatial pattern and age structure, that should have impacts on TCEs, are considered in this study. Results show that during 2004–2016: (1) transportation demand and urbanization were dominant in TCEs growth, while energy intensity and industrial structure were the key factors of CO2 emissions reduction. (2) The effects exerted by age structure and CO2 emission factor change were relatively mild. The former one has a stable promoting effect, while the latter one inhibits TCEs growth. Additionally, the influence of spatial pattern on the growth of CO2 emissions from transportation was limited. (3) Energy structure and energy intensity played more important roles in reducing emissions of the transport sector in the eastern region. The effects of population size on the eastern region were much greater than those of the central and western regions, presenting the phenomenon of “eastern agglomeration”. (4) In Tianjin, energy intensity and energy structure did not perform well for TCEs.
•This paper analyzed the nine drivers of China's transport CO2 emissions from 2004 to 2016.•Urbanization and transportation demand were the main drivers of CO2 emissions.•Energy intensity and industrial stnucture were the key emissions reduction factors.•The effects of age structure had a stable promoting effect.•Energy structural and energy intensity did not perform well for TCEs in all provinces.
Role of MicroRNAs in Parkinson's Disease Goh, Suh Yee; Chao, Yin Xia; Dheen, Shaikali Thameem ...
International journal of molecular sciences,
11/2019, Volume:
20, Issue:
22
Journal Article
Peer reviewed
Open access
Parkinson's disease (PD) is a disabling neurodegenerative disease that manifests with resting tremor, bradykinesia, rigidity and postural instability. Since the discovery of microRNAs (miRNAs) in ...1993, miRNAs have been shown to be important biological molecules involved in diverse processes to maintain normal cellular functions. Over the past decade, many studies have reported dysregulation of miRNA expressions in PD. Here, we identified 15 miRNAs from 34 reported screening studies that demonstrated dysregulation in the brain and/or neuronal models, cerebrospinal fluid (CSF) and blood. Specific miRNAs-of-interest that have been implicated in PD pathogenesis include miR-30, miR-29, let-7, miR-485 and miR-26. However, there are several challenges and limitations in drawing definitive conclusions due to the small sample size in clinical studies, varied laboratory techniques and methodologies and their incomplete penetrance of the blood-brain barrier. Developing an optimal delivery system and unravelling druggable targets of miRNAs in both experimental and human models and clinical validation of the results may pave way for novel therapeutics in PD.
There was no evidence of brain COVID-19 infection (from spinal tap) nor were the MRI brain scans abnormal, although positron emission tomography (PET) scan and dopamine transporter (DaT) scan did ...reveal asymmetric findings in all 3 cases. 2 in their report did not specifically state if a thorough neurological examination has excluded signs of parkinsonism at the time of admission for COVID-19 infection. Since viral parkinsonism is far less common than PD 5, it is possible that these reported patients may already have preexisting PD but the symptoms/signs were unmasked by the acute viral infection. ...there was no neuroimaging evidence of inflammation or structural damage in basal ganglia or olfactory tract, nor evidence of COVID-19 infection in the cerebral spinal fluid (CSF). Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
Alloying combined with plastic deformation processing is widely used to improve mechanical properties of pure Zn. As-cast Zn and its alloys are brittle. Beside plastic deformation processing, no ...effective method has yet been found to eliminate the brittleness and even endow room temperature super-ductility. Second phase, induced by alloying, not only largely determines the ability of plastic deformation, but also influences strength, corrosion rate and cytotoxicity. Controlling second phase is important for designing biodegradable Zn alloys. In this review, knowledge related to second phases in biodegradable Zn alloys has been analyzed and summarized, including characteristics of binary phase diagrams, volume fraction of second phase in function of atomic percentage of an alloying element, and so on. Controversies about second phases in Zn–Li, Zn–Cu and Zn–Fe systems have been settled down, which benefits future studies. The effects of alloying elements and second phases on microstructure, strength, ductility, corrosion rate and cytotoxicity have been neatly summarized. Mg, Mn, Li, Cu and Ag are recommended as the major alloying elements, owing to their prominent beneficial effects on at least one of the above properties. In future, synergistic effects of these elements should be more thoroughly investigated. For other nutritional elements, such as Fe and Ca, refining second phase is a matter of vital concern.
Display omitted
•Features of 23 nontoxic alloying elements of forming second phases are analyzed.•Controversy in Zn–Li, Zn–Cu and Zn–Fe alloy systems has been clarified.•Refining second phases is important for biodegradable Zn alloys.
China’s transportation industry, with its typical characteristics of “high energy consumption and high emissions”, is a key point for China’s CO2 emission reduction. An investigation of the driving ...factors of China’s transport energy-related CO2 emissions has great importance for clarifying the “gains” and “losses” as well as the future focuses of CO2 emissions emission reduction in this sector. Existing studies on the driving factors of transport CO2 emissions in China fail to incorporate effects of technology and efficiency into decomposition analysis framework. Based on the provincial panel data of China’s transportation industry for the period of 2004–2016, this paper uses a comprehensive decomposition framework, which combines the logarithmic mean Divisia index method (LMDI) and production-theoretical decomposition analysis (PDA), to decompose China’s transport CO2 emissions into nine components: emission factor effect, energy structure effect, scale effect, regional structure effect, energy-saving technology effect, production technology effect, energy efficiency effect, production efficiency effect, and potential energy intensity effect. The main results indicate that: (1) during the sample period, China’s transport industry witnessed 498.998 million tons (Mt) CO2 emissions growth. Scale effect was the largest contributor, followed by production technology, energy-saving technology, and energy structure; (2) the improvement of energy efficiency and production efficiency, the decline of electricity’s emission factor, and regional structure adjustment played active roles in the CO2 emission reduction of transportation industry; (3) the performance of various driving factors varies greatly in different provinces. Local governments should establish and implement policies tailored to their characteristics.
•A production-theoretical approach was used for China’s transport CO2 emissions.•It can decompose CO2 emissions from technology and efficiency perspectives.•Results show that during 2004–2016, China’s transport CO2 emissions increased by 498.998 Mt.•Output effect was the largest contributor to this remarkable increase of transport CO2 emissions.•Technology and efficiency factors cumulatively reduced 242.1 Mt transport CO2 emissions.