Differential Alterations in Striatal Direct and Indirect Pathways Mediate Two Autism-like Behaviors in Valproate-Exposed Mice.

Autism is characterized by two key diagnostic criteria including social deficits and repetitive behaviors. Although recent studies implicated ventral striatum in social deficits and dorsal striatum in repetitive behaviors, here we revealed coexisting and opposite morphologic and functional alterations in the dorsostriatal direct and indirect pathways, and such alterations in these two pathways were found to be responsible, respectively, for the two abovementioned different autism-like behaviors exhibited by male mice prenatally exposed to valproate. The alteration in direct pathway was characterized by a potentiated state of basal activity, with impairment in transient responsiveness of D1-MSNs during social exploration. Concurrent alteration in indirect pathway was a depressed state of basal activity, with enhancement in transient responsiveness of D2-MSNs during repetitive behaviors. A causal relationship linking such differential alterations in these two pathways to the coexistence of these two autism-like behaviors was demonstrated by the cell type-specific correction of abnormal basal activity in the D1-MSNs and D2-MSNs of valproate-exposed mice. The findings support those differential alterations in two striatal pathways mediate the two coexisting autism-like behavioral abnormalities, respectively. This result will help in developing therapeutic options targeting these circuit alterations.SIGNIFICANCE STATEMENT Autism is characterized by two key diagnostic criteria including social deficits and repetitive behaviors. Although a number of recent studies have implicated ventral striatum in social deficits and dorsal striatum in repetitive behaviors, but social behaviors need to be processed by a series of actions, and repetitive behaviors, especially the high-order repetitive behaviors such as restrictive interests, have its scope to cognitive and emotional domains. The current study, for the first time, revealed that prenatal valproate exposure induced coexisting and differential alterations in the dorsomedial striatal direct and indirect pathways, and that these alterations mediate the two coexisting autism-like behavioral abnormalities, respectively. This result will help in developing therapeutic options targeting these circuit alterations to address the behavioral abnormalities.

Acute cannabinoids impair association learning via selectively enhancing synaptic transmission in striatonigral neurons.

BACKGROUND: Cannabinoids and their derivatives attract strong interest due to the tremendous potential of their psychoactive effects for treating psychiatric disorders and symptoms. However, their clinical application is restricted by various side-effects such as impaired coordination, anxiety, and learning and memory disability. Adverse impact on dorsal striatum-dependent learning is an important side-effect of cannabinoids. As one of the most important forms of learning mediated by the dorsal striatum, reinforcement learning is characterized by an initial association learning phase, followed by habit learning. While the effects of cannabinoids on habit learning have been well-studied, little is known about how cannabinoids influence the initial phase of reinforcement learning. RESULTS: We found that acute activation of cannabinoid receptor type 1 (CB1R) by the synthetic cannabinoid HU210 induced dose-dependent impairment of association learning, which could be alleviated by intra-dorsomedial striatum (DMS) injection of CB1R antagonist. Moreover, acute exposure to HU210 elicited enhanced synaptic transmission in striatonigral "direct" pathway medium spiny neurons (MSNs) but not indirect pathway neurons in DMS. Intriguingly, enhancement of synaptic transmission that is also observed after learning was abolished by HU210, indicating cannabinoid system might disrupt reinforcement learning by confounding synaptic plasticity normally required for learning. Remarkably, the impaired response-reinforcer learning was also induced by selectively enhancing the D1-MSN (MSN that selectively expresses the dopamine receptor type 1) activity by virally expressing excitatory hM3Dq DREADD (designer receptor exclusively activated by a designer drug), which could be rescued by specifically silencing the D1-MSN activity via hM4Di DREADD. CONCLUSION: Our findings demonstrate dose-dependent deleterious effects of cannabinoids on association learning by disrupting plasticity change required for learning associated with the striatal direct pathway, which furthers our understanding of the side-effects of cannabinoids and the underlying mechanisms.

3D reconstruction of line-structured light based on binocular vision calibration rotary axis.

High-precision 3D topography measurement is essential to ensure quality and performance of shaft parts. Generally, the main difficulty of measuring rotary objects on a turntable is the low accuracy of axis calibration. To solve this problem, this study introduces two methods for calibrating the rotation axis of the turntable and proposes a method for reconstructing the 3D shape of the object by converting the rotation axis parameters of the binocular vision. A calibration camera is used to shoot a 2D checkerboard calibration board against the rotating table, and the calibration process of a high-precision space rotation axis is developed and implemented. This laser vision measurement system consists of a calibration camera, a measurement camera, and a rotation system. This system can realize reconstruction of the 3D shape of the object in accordance with the rotation axis parameters in any position. The experiment on measuring standard parts verifies the effectiveness of the algorithm. It provides a new idea for the measurement of rotary object shapes.

An Experimental Study on the Mechanical Properties and Microstructure of the Cemented Paste Backfill Made by Coal-Based Solid Wastes and Nanocomposite Fibers under Dry-Wet Cycling.

The mechanical properties and microstructure of the cemented paste backfill (CPB) in dry-wet cycle environments are particularly critical in backfill mining. In this study, coal gangue, fly ash, cement, glass fiber, and nano-SiO2 were used to prepare CPB, and dry-wet cycle tests on CPB specimens with different curing ages were conducted. The compressive, tensile, and shear strength of CPB specimens with different curing ages under different dry-wet cycles were analyzed, and the microstructural damage of the specimens was observed by scanning electron microscopy (SEM). The results show that compared with the specimens without dry-wet cycles, the uniaxial compressive strength, tensile strength, and shear strength of the specimens with a curing age of 7 d after seven dry-wet cycles were the smallest, being reduced by 40.22%, 58.25%, and 66.8%, respectively. After seven dry-wet cycles, the compressive, tensile, and shear strength of the specimens with the curing age of 28 d decreased slightly. The SEM results show that with the increasing number of dry-wet cycles, the internal structure of the specimen becomes more and more loose and fragile, and the damage degree of the structural skeleton gradually increases, leading to the poor mechanical properties of CPB specimens. The number of cracks and pores on the specimen surface is relatively limited after a curing age of 28 d, while the occurrence of internal structural damage within the specimen remains insignificant. Therefore, the dry-wet cycle has an important influence on the both mechanical properties and microstructure of CPB. This study provides a reference for the treatment of coal-based solid waste and facilitates the understanding of the mechanical properties of backfill materials under dry-wet cycling conditions.

Experimental Study on Mechanical Properties of Coal-Based Solid Waste Nanocomposite Fiber Cementitious Backfill Material.

Previous studies have shown that coal-based solid waste can be utilized in combination with cement, silica fume, and other modified materials to create a cemented backfill material. However, traditional cemented backfill materials have poor mechanical properties, which may induce the emergence of mining pressure and trigger dynamic disaster under complex mining conditions. In this study, the nanocomposite fiber was used to modify the traditional cemented backfill materials and a new cemented backfill material was developed using coal-based solid waste, nanocomposite fiber and other materials. Specifically, coal gangue, fly ash, cement, and glass fibers were used as the basic materials, different mass fractions of nano-SiO2 were used to prepare cemented backfill materials, and the mechanical enhancement effect of the compressive strength, tensile strength, and shear strength of the modified materials was analyzed. The results show that when the nano-SiO2 dosage is 1%, the optimal compressive strength of the specimens at the curing age of 7 d can be obtained compared with cemented materials without nano-SiO2, and the compressive strength of the modified specimens raises by 84%; when the nano-SiO2 dosage is 1%, the optimal tensile strength and shear strengths of the modified specimens can be obtained at the curing age of 28 d, increasing by 82% and 142%. The results reveal that nanocomposite fibers can be used as additives to change the mechanical properties of cemented backfill materials made using coal-based solid waste. This study provides a reference for the disposal of coal-based solid waste and the enhancement of the mechanical properties of cemented backfill materials.

Evaluation of Efficiently Removing Secondary Effluent Organic Matters (EfOM) by Al-Based Coagulant for Wastewater Recycling: A Case Study with an Industrial-Scale Food-Processing Wastewater Treatment Plant.

The reuse of wastewater has been identified as an important initiative for the sustainable development of the environment; thus, the removal of secondary effluent organic matter (EfOM) to ensure the safety of reused wastewater is the key step and a subject of extensive research. In this study, Al2(SO4)3 and anionic polyacrylamide were selected as coagulant and flocculant, respectively, for the treatment of secondary effluent from a food-processing industry wastewater treatment plant to meet the standard regulatory specifications for water reuse. In this process, the removal efficiencies of chemical oxygen demand (COD), components with UV254, and specific ultraviolet absorbance (SUVA) were 44.61%, 25.13%, and 9.13%, respectively, with an associated reduction in chroma and turbidity. The fluorescence intensities (Fmax) of two humic-like components were reduced during coagulation, and microbial humic-like components of EfOM had a better removal efficiency because of a higher Log Km value of 4.12. Fourier transform infrared spectroscopy showed that Al2(SO4)3 could remove the protein fraction of the soluble microbial products (SMP) of EfOM by forming a loose SMP protein complex with enhanced hydrophobicity. Furthermore, flocculation reduced the aromaticity of secondary effluent. The cost of the proposed secondary effluent treatment was 0.034 CNY t-1 %COD-1. These results demonstrate that the process is efficient and economically viable for EfOM removal to realize food-processing wastewater reuse.

Analysis of Evolution, Expression and Genetic Transformation of TCP Transcription Factors in Blueberry Reveal That VcTCP18 Negatively Regulates the Release of Flower Bud Dormancy.

Plant-specific TEOSINTE BRANCHED 1, CYCLOIDEA, PROLIFERATING CELL FACTORS (TCP) transcription factors have versatile functions in plant growth, development and response to environmental stress. Despite blueberry's value as an important fruit crop, the TCP gene family has not been systematically studied in this plant. The current study identified blueberry TCP genes (VcTCPs) using genomic data from the tetraploid blueberry variety 'Draper'; a total of 62 genes were obtained. Using multiple sequence alignment, conserved motif, and gene structure analyses, family members were divided into two subfamilies, of which class II was further divided into two subclasses, CIN and TB1. Synteny analysis showed that genome-wide or segment-based replication played an important role in the expansion of the blueberry TCP gene family. The expression patterns of VcTCP genes during fruit development, flower bud dormancy release, hormone treatment, and tissue-specific expression were analyzed using RNA-seq and qRT-PCR. The results showed that the TB1 subclass members exhibited a certain level of expression in the shoot, leaf, and bud; these genes were not expressed during fruit development, but transcript levels decreased uniformly during the release of flower bud dormancy by low-temperature accumulation. The further transgenic experiments showed the overexpression of VcTCP18 in Arabidopsis significantly decreased the seed germination rate in contrast to the wild type. The bud dormancy phenomena as late-flowering, fewer rosettes and main branches were also observed in transgenic plants. Overall, this study provides the first insight into the evolution, expression, and function of VcTCP genes, including the discovery that VcTCP18 negatively regulated bud dormancy release in blueberry. The results will deepen our understanding of the function of TCPs in plant growth and development.

Involvement of Midbrain Dopamine Neuron Activity in Negative Reinforcement Learning in Mice.

The activity of the midbrain dopamine system reflects the valence of environmental events and modulates various brain structures to modify an organism's behavior. A series of recent studies reported that the direct and indirect pathways in the striatum are critical for instrumental learning, but the dynamic changes in dopamine neuron activity that occur during negative reinforcement learning are still largely unclear. In the present study, by using a negative reinforcement learning paradigm employing foot shocks as aversive stimuli, bidirectional changes in substantia nigra pars compacta (SNc) dopamine neuron activity in the learning and habituation phases were observed. The results showed that in the learning phase, before mice had mastered the skill of escaping foot shocks, the presence of foot shocks induced a transient reduction in the activity of SNc dopamine neurons; however, in the habituation phase, in which the learned skill was automated, it induced a transient increase. Microinjection of a dopamine D1 receptor (D1R) or D2 receptor (D2R) antagonist into the dorsomedial striatum (DMS) significantly impaired learning behavior, suggesting that the modulatory effects of dopamine on both the direct and indirect pathways are required. Moreover, during the learning phase, excitatory synaptic transmission to DMS D2R-expressing medium spiny neurons (D2-MSNs) was potentiated. However, upon completion of the learning and habituation phases, the synapses onto D1R-expressing medium spiny neurons (D1-MSNs) were potentiated, and those onto D2-MSNs were restored to normal levels. The bidirectional changes in both SNc dopamine neuron activity and DMS synaptic plasticity might be the critical neural correlates for negative reinforcement learning.

Local patterns of arbuscular mycorrhizal fungal diversity and community structure in a natural Toona ciliata var. pubescens forest in South Central China.

Toona ciliata var. pubescens (Toona in Meliaceae) (Tc) is listed as an endangered species, and there are natural regeneration obstacles due to its long-term excessive exploitation and utilization. Arbuscular mycorrhizal fungi (AMF) can produce beneficial effects for plant growth and natural regeneration. However, the characteristics of the AMF community in natural Tc forests are poorly understood. The Illumina PE250 high-throughput sequencing method was used to study the characteristics of the AMF community in the rhizosphere soil and roots associated with three dominant tree species (Tc; Padus buergeriana, Pb; and Maesa japonica, Mj) in a natural Tc forest in Guanshan National Natural Reserve, South Central China. The results found that Glomeraceae was the most abundant AMF family in the rhizosphere soil and roots. Moreover, the relative abundance of Archaeosporaceae in rhizosphere soil was significantly larger than that in the roots; in contrast, the relative abundance of Glomeraceae in rhizosphere soil was significantly lower than that in the roots (p < 0.05). Regarding different tree species, the relative abundances of Acaulosporaceae and Geosiphonaceae were larger in Mj and Tc than in Pb. AMF operational taxonomic units (OTUs) were 1.30-, 1.43-, and 1.71-fold higher in the Tc, Pb, and Mj rhizosphere soil, respectively, than in the corresponding roots. Nevertheless, higher AMF community richness was found in the roots compared to that in the rhizosphere soil based on the Chao index. This finding indicated that AMF of a relatively high aggregation degree were in roots, and more AMF groups with relatively low abundance occurred in the rhizosphere soil, which correspondingly lowered the calculated richness index of the AMF community. A redundancy analysis showed that different soil chemical properties impacted variations in the AMF community characteristics differently. This study has great significance for the interpretation of AMF diversity survey and the application design of AMF in vegetation restoration.

Progranulin promotes functional recovery and neurogenesis in the subventricular zone of adult mice after cerebral ischemia.

Progranulin (PGRN), a secreted glycosylated protein, has been reported to attenuate ischemia-induced cerebral injury through anti-inflammation, attenuation of blood-brain barrier disruption and neuroprotection. However, the effect of PGRN on neurogenesis in the subventricular zone (SVZ) after cerebral ischemia remains unclear. In this study, adult C57BL/6 mice were subjected to permanent middle cerebral artery occlusion (pMCAO), and different doses of recombinant mouse PGRN (r-PGRN, 0.3 ng, 1 ng, 5 ng) were intracerebroventricularly administered 30 min after pMCAO. Results showed that 1 ng r-PGRN markedly reduced infarct volume and rescued functional deficits 24 h after pMCAO. Meanwhile, 1 ng r-PGRN increased SVZ cell proliferation, as shown by a high number of bromodeoxyuridine-positive (BrdU+) cells and Ki-67+ cells in the ischemic ipsilateral SVZ 7 d after pMCAO. Additionally, PGRN increased the percentage of BrdU+/Doublecortin (DCX)+ cells in the ipsilateral SVZ 14 d after pMCAO and increased the percentage of new neurons (BrdU+/NeuN+ cells) in the peri-infarct striatum 28 d after pMCAO, suggesting that PGRN promotes neuronal differentiation. PGRN also upregulated phosphorylation of ERK1/2 and Akt in the ipsilateral SVZ 3 d after pMCAO. Our data indicate that PGRN treatment promotes acute functional recovery; most importantly, it also stimulates neurogenesis in the SVZ, which could be beneficial for long-term recovery after cerebral ischemia. The increase in neurogenesis could be associated with activation of the MAPK/ERK and PI3K/Akt pathways. These results suggest a potential new strategy utilizing PGRN in ischemic stroke therapy.

Maternal folic acid supplementation prevents autistic behaviors in a rat model induced by prenatal exposure to valproic acid.

Maternal vitamin supplementation has been demonstrated to reduce the risks of a number of neurodevelopmental diseases in children. Autism spectrum disorder (ASD) is a group of neurodevelopment defects with high prevalence but without satisfactory therapy. The present work detected the effects of pregnancy supplementation with folic acid (FA) at different doses on rat models of ASD induced by prenatal exposure to valproic acid (VPA), an anti-epileptic increasing the risk of ASD when administered during pregnancy. The results show that maternal FA supplementation at a high dose (4 mg kg-1) prevented the delay in growth and development, and the deficits in social communicative behaviors and repetitive behaviors, possibly by restoring the increased dendritic spine density and rectifying the over-expression of synaptic proteins associated with excitatory neurons and the lower expression with inhibitory ones. The results provided experimental evidence suggesting a possible role of maternal FA supplementation in preventing ASD.

A morphing-Based 3D point cloud reconstruction framework for medical image processing.

BACKGROUND AND OBJECTIVE: In the virtual surgery simulation system, the reconstruction of a highly precise soft tissue 3D model is an effective method to improve the user's visual telepresence. However, the traditional point cloud generation method based on subdivision and filling is unsatisfactory due to its low accuracy and slow speed. METHODS: To address this problem, we present a novel 3D point cloud reconstructing model based on Morphing. The 3D surface model of soft tissue (live) is obtained from a series of 2D CT images using Mimics. The 3D voxel model of soft tissue is reconstructed through a sequential change of the 3D surface model by utilizing Morphing. A nonlinear interpolation method is used to fit the irregular shape of the model and improve simulation accuracy. RESULTS: The point cloud model builds from discrete points, avoiding the problems of instability and computational complexity, which are inherent in both the surface and volume models for soft tissue. Compared with the volumetric subdividing and voxel filling method, the simulation results show that the 3D cloud model reconstructed based on Morphing is more fast, accurate and consistent with the real soft tissue. CONCLUSIONS: The simulating experiment of soft tissue deformation using 3D point cloud model which reconstructed using moprhing proved our method is effective and correct.

A Novel Haptic Interactive Approach to Simulation of Surgery Cutting Based on Mesh and Meshless Models.

In the present work, the majority of implemented virtual surgery simulation systems have been based on either a mesh or meshless strategy with regard to soft tissue modelling. To take full advantage of the mesh and meshless models, a novel coupled soft tissue cutting model is proposed. Specifically, the reconstructed virtual soft tissue consists of two essential components. One is associated with surface mesh that is convenient for surface rendering and the other with internal meshless point elements that is used to calculate the force feedback during cutting. To combine two components in a seamless way, virtual points are introduced. During the simulation of cutting, the Bezier curve is used to characterize smooth and vivid incision on the surface mesh. At the same time, the deformation of internal soft tissue caused by cutting operation can be treated as displacements of the internal point elements. Furthermore, we discussed and proved the stability and convergence of the proposed approach theoretically. The real biomechanical tests verified the validity of the introduced model. And the simulation experiments show that the proposed approach offers high computational efficiency and good visual effect, enabling cutting of soft tissue with high stability.

A New Deformation Model of Biological Tissue for Surgery Simulation.

A novel meshless deformation model of biological soft tissue, which is mainly based on the radial basis function point interpolation, is presented for interactive simulation applications such as virtual surgery simulators. Compared with conventional mesh models, the proposed model is particularly suitable for simulating large deformation, sucking and cutting tasks since there is no need to maintain grid information. Kelvin viscoelasticity, which represents relaxation, creep, and hysteresis of soft tissue, is integrated into the proposed model, making the simulation much more realistic than many existing meshless models. To verify the validity of the proposed model, a biomechanical test was performed on real-life biological tissue and the results show that the maximum relative error between the forces from the biomechanical test and those obtained from the model is less than 5.8%. The proposed model was also implemented on a neurosurgery simulator, which showed that the deformation of the brain tumor can be simulated in a high degree of accuracy with real-time performance. In particular, the error and distortion from the remeshing process inherited in conventional mesh models when deformation is large are avoided.