Astrocyte-to-neuron reprogramming and crosstalk in the treatment of Parkinson's disease.

Parkinson's disease (PD) is currently the fastest growing disabling neurological disorder worldwide, with motor and non-motor symptoms being its main clinical manifestations. The primary pathological features include a reduction in the number of dopaminergic neurons in the substantia nigra and decrease in dopamine levels in the nigrostriatal pathway. Existing treatments only alleviate clinical symptoms and do not stop disease progression; slowing down the loss of dopaminergic neurons and stimulating their regeneration are emerging therapies. Preclinical studies have demonstrated that transplantation of dopamine cells generated from human embryonic or induced pluripotent stem cells can restore the loss of dopamine. However, the application of cell transplantation is limited owing to ethical controversies and the restricted source of cells. Until recently, the reprogramming of astrocytes to replenish lost dopaminergic neurons has provided a promising alternative therapy for PD. In addition, repair of mitochondrial perturbations, clearance of damaged mitochondria in astrocytes, and control of astrocyte inflammation may be extensively neuroprotective and beneficial against chronic neuroinflammation in PD. Therefore, this review primarily focuses on the progress and remaining issues in astrocyte reprogramming using transcription factors (TFs) and miRNAs, as well as exploring possible new targets for treating PD by repairing astrocytic mitochondria and reducing astrocytic inflammation.

Complementary belowground strategies underlie species coexistence in an early successional forest.

Unravelling belowground strategies is critical for understanding species coexistence and successional dynamics; yet, our knowledge of nutrient acquisition strategies of forest species at different successional stages remains limited. We measured morphological (diameter, specific root length, and root tissue density), architectural (branching ratio), physiological (ammonium, nitrate, and glycine uptake rates) root traits, and mycorrhizal colonisation rates of eight coexisting woody species in an early successional plantation forest in subtropical China. By incorporating physiological uptake efficiency, we revealed a bi-dimensional root economics space comprising of an 'amount-efficiency' dimension represented by morphological and physiological traits, and a 'self-symbiosis' dimension dominated by architectural and mycorrhizal traits. The early pioneer species relied on root-fungal symbiosis, developing densely branched roots with high mycorrhizal colonisation rates for foraging mobile soil nitrate. The late pioneer species invested in roots themselves and allocated effort towards improving uptake efficiency of less-mobile ammonium. Within the root economics space, the covariation of axes with soil phosphorus availability also distinguished the strategy preference of the two successional groups. These results demonstrate the importance of incorporating physiological uptake efficiency into root economics space, and reveal a trade-off between expanding soil physical space exploration and improving physiological uptake efficiency for successional species coexistence in forests.

The circadian clock protein Rev-erbα provides neuroprotection and attenuates neuroinflammation against Parkinson's disease via the microglial NLRP3 inflammasome.

BACKGROUND: Circadian disturbance is a common nonmotor complaint in Parkinson's disease (PD). The molecular basis underlying circadian rhythm in PD is poorly understood. Neuroinflammation has been identified as a key contributor to PD pathology. In this study, we explored the potential link between the core clock molecule Rev-erbα and the microglia-mediated NLR family pyrin domain-containing 3 (NLRP3) inflammasome in PD pathogenesis. METHODS: We first examined the diurnal Rev-erbα rhythms and diurnal changes in microglia-mediated inflammatory cytokines expression in the SN of MPTP-induced PD mice. Further, we used BV2 cell to investigate the impacts of Rev-erbα on NLRP3 inflammasome and microglial polarization induced by 1-methyl-4-phenylpyridinium (MPP+) and αsyn pre-formed fibril. The role of Rev-erbα in regulating microglial activation via NF-κB and NLRP3 inflammasome pathway was then explored. Effects of SR9009 against NLRP3 inflammasome activation, microgliosis and nigrostriatal dopaminergic degeneration in the SN and striatum of MPTP-induced PD mice were studied in detail. RESULTS: BV2 cell-based experiments revealed the role of Rev-erbα in regulating microglial activation and polarization through the NF-κB and NLRP3 inflammasome pathways. Circadian oscillation of the core clock gene Rev-erbα in the substantia nigra (SN) disappeared in MPTP-induced PD mice, as well as diurnal changes in microglial morphology. The expression of inflammatory cytokines in SN of the MPTP-induced mice were significantly elevated. Furthermore, dopaminergic neurons loss in the nigrostriatal system were partially reversed by SR9009, a selective Rev-erbα agonist. In addition, SR9009 effectively reduced the MPTP-induced glial activation, microglial polarization and NLRP3 inflammasome activation in the nigrostriatal system. CONCLUSIONS: These observations suggest that the circadian clock protein Rev-erbα plays an essential role in attenuating neuroinflammation in PD pathology, and provides a potential therapeutic target for PD treatment.

Mycorrhizal symbiosis pathway and edaphic fertility frame root economics space among tree species.

The root economics space (RES) is multidimensional and largely shaped by belowground biotic and abiotic influences. However, how root-fungal symbioses and edaphic fertility drive this complexity remains unclear. Here, we measured absorptive root traits of 112 tree species in temperate and subtropical forests of China, including traits linked to functional differences between arbuscular mycorrhizal (AM) and ectomycorrhizal (ECM) hosts. Our data, from known mycorrhizal tree species, revealed a 'fungal-symbiosis' dimension distinguishing AM from ECM species. This divergence likely resulted from the contrasting mycorrhizal evolutionary development of AM vs ECM associations. Increased root tissue cortical space facilitates AM symbiosis, whereas increased root branching favours ECM symbiosis. Irrespective of mycorrhizal type, a 'root-lifespan' dimension reflecting aspects of root construction cost and defence was controlled by variation in specific root length and root tissue density, which was fully independent of root nitrogen content. Within this function-based RES, we observed a substantial covariation of axes with soil phosphorus and nitrate levels, highlighting the role played by these two axes in nutrient acquisition and conservation. Overall, our findings demonstrate the importance of evolved mycorrhizal symbiosis pathway and edaphic fertility in framing the RES, and provide theoretical and mechanistic insights into the complexity of root economics.

Reactive microglia enhance the transmission of exosomal α-synuclein via toll-like receptor 2.

Increasing evidence suggests that microglial activation is strongly linked to the initiation and progression of Parkinson's disease. Cell-to-cell propagation of α-synuclein pathology is a highlighted feature of Parkinson's disease, and the focus of such research has been primarily on neurons. However, recent studies as well as the data contained herein suggest that microglia, the primary phagocytes in the brain, play a direct role in the spread of α-synuclein pathology. Recent data revealed that plasma exosomes derived from Parkinson's disease patients (PD-EXO) carry pathological α-synuclein and target microglia preferentially. Hence, PD-EXO are likely a key tool for investigating the role of microglia in α-synuclein transmission. We showed that intrastriatal injection of PD-EXO resulted in the propagation of exosomal α-synuclein from microglia to neurons following microglia activation. Toll-like receptor 2 (TLR2) in microglia was activated by exosomal α-synuclein and acted as a crucial mediator of PD-EXO-induced microglial activation. Additionally, partial microglia depletion resulted in a significant decrease of exogenous α-synuclein in the substantia nigra. Furthermore, exosomal α-synuclein internalization was initiated by binding to TLR2 of microglia. Excessive α-synuclein phagocytosis may induce the inflammatory responses of microglia and provide the seed for microglia-to-neuron transmission. Consistently, TLR2 silencing in microglia mitigated α-synuclein pathology in vivo. Overall, the present data support the idea that the interaction of exosomal α-synuclein and microglial TLR2 contribute to excessive α-synuclein phagocytosis and microglial activation, which lead to the further propagation and spread of α-synuclein pathology, thereby highlighting the pivotal roles of reactive microglia in α-synuclein transmission.

An Anomaly Detection Algorithm Based on Ensemble Learning for 5G Environment.

With the advent of the digital information age, new data services such as virtual reality, industrial Internet, and cloud computing have proliferated in recent years. As a result, it increases operator demand for 5G bearer networks by providing features such as high transmission capacity, ultra-long transmission distance, network slicing, and intelligent management and control. Software-defined networking, as a new network architecture, intends to increase network flexibility and agility and can better satisfy the demands of 5G networks for network slicing. Nevertheless, software-defined networking still faces the challenge of network intrusion. We propose an abnormal traffic detection method based on the stacking method and self-attention mechanism, which makes up for the shortcoming of the inability to track long-term dependencies between data samples in ensemble learning. Our method utilizes a self-attention mechanism and a convolutional network to automatically learn long-term associations between traffic samples and provide them to downstream tasks in sample embedding. In addition, we design a novel stacking ensemble method, which computes the sample embedding and the predicted values of the heterogeneous base learner through the fusion module to obtain the final outlier results. This paper conducts experiments on abnormal traffic datasets in the software-defined network environment, calculates precision, recall and F1-score, and compares and analyzes them with other algorithms. The experimental results show that the method designed in this paper achieves 0.9972, 0.9996, and 0.9984 in multiple indicators of precision, recall, and F1-score, respectively, which are better than the comparison methods.

Mycorrhizal and environmental controls over root trait-decomposition linkage of woody trees.

Traits are critical in predicting decomposition that fuels carbon and nutrient cycling in ecosystems. However, our understanding of root trait-decomposition linkage, and especially its dependence on mycorrhizal type and environmental context, remains limited. We explored the control of morphological and chemical (carbon- and nutrient-related) traits over decomposition of absorptive roots in 30 tree species associated with either arbuscular mycorrhizal (AM) or ectomycorrhizal (ECM) fungi in temperate and subtropical forests in China. Carbon-related traits (acid-unhydrolysable residue (AUR) and cellulose concentrations) had predominant control of root decomposition in AM species while nutrient-related traits (magnesium concentration) predominately controlled that in ECM species. Thicker absorptive roots decomposed faster in AM species as a result of their lower AUR concentrations, but more slowly in ECM angiosperm species potentially as a result of their higher magnesium concentrations. Root decomposition was linked to root nutrient economy in both forests while root diameter-decomposition coordination emerged only in the subtropical forest where root diameter and decomposition presented similar cross-species variations. Our findings suggest that root trait-decomposition linkages differ strongly with mycorrhizal type and environment, and that root diameter can predict decomposition but in opposing directions and with contrasting mechanisms for AM and ECM species.

Below-ground determinants and ecological implications of shrub species' degree of isohydry in subtropical pine plantations.

The degree of plant iso/anisohydry is a popular framework for characterising species-specific drought responses. However, we know little about associations between below-ground and above-ground hydraulic traits as well as the broader ecological implications of this framework. For 24 understory shrub species in seasonally dry subtropical coniferous plantations, we investigated contributions of the degree of isohydry to species' resource economy strategies, abundance, and importance value, and quantified the hydraulic conductance (Kh ) of above-ground and below-ground organs, magnitude of deep water acquisition (WAdeep ), shallow absorptive root traits (diameter, specific root length, tissue density), and resource-use efficiencies (Amax , maximum photosynthesis rate; PNUE, photosynthetic nitrogen-use efficiency). The extreme isohydric understory species had lower wood density (a proxy for higher growth rates) because their higher WAdeep and whole-plant Kh allowed higher Amax and PNUE, and thus did not necessarily show lower abundance and importance values. Although species' Kh was coordinated with their water foraging capacity in shallow soil, the more acquisitive deep roots were more crucial than shallow roots in shaping species' extreme isohydric behaviour. Our results provide new insights into the mechanisms through which below-ground hydraulic traits, especially those of deep roots, determine species' degree of isohydry and economic strategies.

Linking reliance on deep soil water to resource economy strategies and abundance among coexisting understorey shrub species in subtropical pine plantations.

Strategies for deep soil water acquisition (WAdeep ) are critical to a species' adaptation to drought. However, it is unknown how WAdeep determines the abundance and resource economy strategies of understorey shrub species. With data from 13 understorey shrub species in subtropical coniferous plantations, we investigated associations between the magnitude of WAdeep , the seasonal plasticity of WAdeep , midday leaf water potential (Ψmd ), species abundance and resource economic traits across organs. Higher capacity for WAdeep was associated with higher intrinsic water use efficiency, but was not necessary for maintaining higher Ψmd in the dry season nor was it an ubiquitous trait possessed by the most common shrub species. Species with higher seasonal plasticity of WAdeep had lower wood density, indicating that fast species had higher plasticity in deep soil resource acquisition. However, the magnitude and plasticity of WAdeep were not related to shallow fine root economy traits, suggesting independent dimensions of soil resource acquisition between deep and shallow soil. Our results provide new insights into the mechanisms through which the magnitude and plasticity of WAdeep interact with shallow soil and aboveground resource acquisition traits to integrate the whole-plant economic spectrum and, thus, community assembly processes.

Reduced VMAT2 expression exacerbates the hyposmia in the MPTP model of Parkinson's disease.

Hyposmia occurs during the prodromal phase of Parkinson's disease (PD), while the underlying mechanisms remain unclear. Discussed are altered dopamine content and impairment of neurogenesis of olfactory bulbs (OB), which has been suggested to be linked to olfactory dysfunction. Given that mouse with reduced vesicular monoamine transporter 2 (VMAT2) expression is now deemed as a relatively new PD animal model simulating motor and nonmotor symptoms, it may provide a new insight into investigating the mechanisms of hyposmia in the context of PD. In this study, we examined the effect of subacute administration of MPTP on mice with a reduced expression of VMAT2, focusing on the histopathological and biochemical alterations, specifically, TH expression level, dopamine content as well as neurogenesis in OB. Interestingly, mice with a reduced VMAT2 expression displayed more obvious olfactory impairment in response to MPTP administration accompanied by markedly decreased dopaminergic interneurons in OB. Furthermore, neurogenesis in OB was also further impaired after MPTP due to reduced VMAT2 expression. We therefore demonstrated that reduced expression of VMAT2 contributed to the impairment of hyposmia, pathologically, the degeneration of extranigral systems and reduced neurogenesis might be the underlying mechanisms.

Unaltered phenology but increased production of ectomycorrhizal roots of Pinus elliottii under 4 years of nitrogen addition.

Timing (phenology) and amount (production) are two integral facets of root growth, and their shifts have profound influences on below-ground resource acquisition. However, the environmental control and the effects of nitrogen (N) deposition on the production and phenology of ectomycorrhizal (ECM) roots remain unclear. Using a 4 yr minirhizotron experiment, we explored the control of the production and three phenophases (initiation, peak, and cessation of growth) of ECM roots in two soil layers and investigated their dynamic responses to N addition in a seasonally dry subtropical Pinus elliottii forest. We found a stronger control of water availability on the production and a stronger control of temperature on the phenology of ECM roots under ambient conditions. Temperature was correlated positively with initiation and negatively with cessation, especially in the shallow layer. N addition did not affect the phenology of ECM roots but increased their production by modifying N and phosphorus (P) stoichiometry in the soil and foliage. Our findings suggest a greater sensitivity of production than phenology of ECM roots to N addition. The increased production of ECM roots under N addition could be driven by N-induced P limitation or some combination of below-ground resources (P, N, water).

Nitrogen deposition increases root production and turnover but slows root decomposition in Pinus elliottii plantations.

Fine roots of woody plants comprise multiple root orders, which can be functionally partitioned into two pools: absorptive fine roots (AFRs, orders 1, 2) and transport fine roots (TFRs, orders 3-5). However, the function-based fine-root dynamics and especially their responses to increased nitrogen (N) availability remain unclear. We explored dynamic responses of both AFRs and TFRs of Pinus elliottii to N addition in subtropical China based on a 4-yr minirhizotron experiment and a two-stage - early (0.5 yr) vs late (4 yr) - decomposition experiment. N addition increased the production, mortality, and turnover of AFRs but not TFRs. High rates of N persistently inhibited AFR decomposition but affected TFR decomposition differentially at the early (no effect) and late (negative effect) stages. The increased production of AFRs was driven by N-induced decrease in foliar and soil phosphorus (P) concentrations. The decreased decomposition of AFRs might be due to the increased acid-unhydrolyzable residues in decomposing roots. AFRs are the resource-acquiring module, the increased carbon allocation to AFRs may represent a P-acquiring strategy when N no longer limits growth of P. elliottii. Our results suggest that AFRs and TFRs respond differently to N deposition, both in terms of production, mortality, and turnover and in terms of decomposition.

Multi-focus image fusion algorithm based on Laplacian pyramids.

In this paper, we propose a method named region mosaicking on Laplacian pyramids (RMLP) to fuse multi-focus images that are captured by microscope. First, we apply the sum-modified Laplacian to measure the focus of multi-focus images. Then the density-based region growing algorithm is utilized to segment the focused region mask of each image. Finally, the mask is decomposed into a mask pyramid to supervise region mosaicking on a Laplacian pyramid. The region level pyramid keeps more original information than the pixel level. The experiment results show that RMLP has the best performance in quantitative comparison with other methods. In addition, RMLP is insensitive to noise and can reduce the color distortion of the fused images on two datasets.

The perivascular phenotype and behaviors of dedifferentiated cells derived from human mature adipocytes.

Derived from mature adipocytes, dedifferentiated fat (DFAT) cells represent a special group of multipotent cells. However, their phenotype and cellular nature remain unclear. Our study found that human DFAT cells adopted perivascular characteristics and behaviors. Flow cytometry and immunofluorescent staining revealed that human DFAT cells positively expressed markers highly related to perivascular cell lineages, such as CD140b, NG2 and desmin, but were negative for common endothelial markers, including CD31, CD34, and CD309. Furthermore, DFAT cells displayed vascular network formation ability in Matrigel, and they noticeably promoted and stabilized the vessel structures formed by human umbilical vascular endothelial cells (HUVECs) in vitro. These results provide novel evidence on the pericyte nature of human DFAT cells, further supporting the recent model for the perivascular origin of adult stem cells, in which tissue-specific progenitor cells in mesenchymal tissues associate with blood vessels, exhibiting perivascular characteristics and functions.

Effects of moderate static magnetic fields on the voltage-gated sodium and calcium channel currents in trigeminal ganglion neurons.

AIM: To study the effects of static magnetic fields (SMF) on the electrophysiological properties of voltage-gated sodium and calcium channels on trigeminal ganglion (TRG) neurons. METHODS: Acutely dissociated TRG neurons of neonatal SD rats were exposed to 125-mT and 12.5-mT SMF in exposure devices and whole-cell patch-clamp recordings were carried out to observe the changes of voltage-gated sodium channels (VGSC) and calcium channels (VGCC) currents, while laser scanning confocal microscopy was used to detect intracellular free Ca(2+) concentration in TRG neurons, respectively. RESULTS: (1) No obvious change of current-voltage (I-V) relationship and the peak current densities of VGSC and VGCC currents were found when TRG neurons were exposed to 125-mT and 12.5-mT SMF. However, the activation threshold, inactivation threshold and velocity of the channel currents above were significantly altered by 125-mT and 12.5-mT SMF. (2) The fluctuation of intracellular free Ca(2+) concentration within TRG neurons were slowed by 125-mT and 12.5-mT SMF. When SMF was removed, the Ca(2+) concentration level showed partial recovery in the TRG neurons previously exposed by 125-mT SMF, while there was a full recovery found in 12.5-mT-SMF-exposed neurons. CONCLUSIONS: Moderate-intensity SMF could affect the electrophysiological characteristics of VGCS and VGCC by altering their activation and inactivation threshold and velocity. The fluctuations of intracellular free Ca(2+) caused by SMF exposure were not permanent in TRG neurons.

The phenotype and tissue-specific nature of multipotent cells derived from human mature adipocytes.

Dedifferentiated fat (DFAT) cells derived from mature adipocytes have been considered to be a homogeneous group of multipotent cells, which present to be an alternative source of adult stem cells for regenerative medicine. However, many aspects of the cellular nature about DFAT cells remained unclarified. This study aimed to elucidate the basic characteristics of DFAT cells underlying their functions and differentiation potentials. By modified ceiling culture technique, DFAT cells were converted from human mature adipocytes from the human buccal fat pads. Flow cytometry analysis revealed that those derived cells were a homogeneous population of CD13(+) CD29(+) CD105(+) CD44(+) CD31(-) CD34(-) CD309(-) α-SMA(-) cells. DFAT cells in this study demonstrated tissue-specific differentiation properties with strong adipogenic but much weaker osteogenic capacity. Neither did they express endothelial markers under angiogenic induction.

Polyelectrolyte-stabilized graphene oxide liquid crystals against salt, pH, and serum.

Stabilization of colloids is of great significance in nanoscience for their fundamental research and practical applications. Electrostatic repulsion-stabilized anisotropic colloids, such as graphene oxide (GO), can form stable liquid crystals (LCs). However, the electrostatic field would be screened by ions. To stabilize colloidal LCs against electrolyte is an unsolved challenge. Here, an effective strategy is proposed to stabilize GO LCs under harsh conditions by association of polyelectrolytes onto GO sheets. Using sodium poly(styrene sulfonate) (PSS) and poly[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (PMEDSAH), a kind of polyzwitterion, GO LCs were well-maintained in the presence of NaCl (from 0 M to saturated), extreme pH (from 1 to 13), and serum. Moreover, PSS- or PMEDSAH-coated chemically reduced GO (rGO) also showed stability against electrolyte.

Relationships between root exudation and root morphological and architectural traits vary with growing season.

Plants allocate a substantial amount of C belowground for root exudates and for the construction and adjustment of root morphological and architectural traits. What relationships exist between root exudates and other root traits and these relationships change with growing season, however, remain unclear. We quantified the root exudation rate and root morphological traits, including total root length (RL), total root surface area (RS), root diameter (RD), specific root length (SRL), specific root area (SRA) and root tissue density (RTD), and architectural traits, such as branching intensity (BI), and investigated their associations during the rapidly growing season (April and August) and the slowly growing season (December) of three common native tree species, Liquidambar formosana, Michelia maudiae and Schima superba, in subtropical China. We found that the linkages of RD, SRL, SRA, RTD and BI did not change with the growing season, reflecting their highly conservative relationships. The root exudation rate varied significantly with growing season (P < 0.05) and produced various associations with other root traits at different growing seasons. During the rapidly growing season (i.e., April), the exudation rate was the highest and was positively correlated with RL. The exudation rate was the lowest during the slowly growing season (i.e., December) and was negatively associated with RL, RS and RTD. Our findings demonstrate the seasonality of the linkages of root exudation rate with other root traits, which highlights the highly plastic and complex associations of belowground root traits. These findings help to deepen our understanding of plant nutrient acquisition strategies.

A trait-based root acquisition-defence-decomposition framework in angiosperm tree species.

To adapt to the complex belowground environment, plants make trade-offs between root resource acquisition and defence ability. This includes forming partnerships with different types of root associating microorganisms, such as arbuscular mycorrhizal and ectomycorrhizal fungi. These trade-offs, by mediating root chemistry, exert legacy effects on nutrient release during decomposition, which may, in turn, affect the ability of new roots to re-acquire resources, thereby generating a feedback loop. However, the linkages at the basis of this potential feedback loop remain largely unquantified. Here, we propose a trait-based root 'acquisition-defence-decomposition' conceptual framework and test the strength of relevant linkages across 90 angiosperm tree species. We show that, at the plant species level, the root-fungal symbiosis gradient within the root economics space, root chemical defence (condensed tannins), and root decomposition rate are closely linked, providing support to this framework. Beyond the dichotomy between arbuscular mycorrhizal-dominated versus ectomycorrhizal-dominated systems, we suggest a continuous shift in feedback loops, from 'high arbuscular mycorrhizal symbiosis-low defence-fast decomposition-inorganic nutrition' by evolutionarily ancient taxa to 'high ectomycorrhizal symbiosis-high defence-slow decomposition-organic nutrition' by more modern taxa. This 'acquisition-defence-decomposition' framework provides a foundation for testable hypotheses on multidimensional linkages between species' belowground strategies and ecosystem nutrient cycling in an evolutionary context.