Dissecting the neurovascular unit in physiology and Alzheimer's disease: Functions, imaging tools and genetic mouse models.

The neurovascular unit (NVU) plays an essential role in regulating neurovascular coupling, which refers to the communication between neurons, glia, and vascular cells to control the supply of oxygen and nutrients in response to neural activity. Cellular elements of the NVU coordinate to establish an anatomical barrier to separate the central nervous system from the milieu of the periphery system, restricting the free movement of substances from the blood to the brain parenchyma and maintaining central nervous system homeostasis. In Alzheimer's disease, amyloid-ß deposition impairs the normal functions of NVU cellular elements, thus accelerating the disease progression. Here, we aim to describe the current knowledge of the NVU cellular elements, including endothelial cells, pericytes, astrocytes, and microglia, in regulating the blood-brain barrier integrity and functions in physiology as well as alterations encountered in Alzheimer's disease. Furthermore, the NVU functions as a whole, therefore specific labeling and targeting NVU components in vivo enable us to understand the mechanism mediating cellular communication. We review approaches including commonly used fluorescent dyes, genetic mouse models, and adeno-associated virus vectors for imaging and targeting NVU cellular elements in vivo.

Effect of dental malocclusion on cerebellar neuron activation via the dorsomedial part of the principal sensory trigeminal nucleus.

Occlusion has been proposed to play a role for body posture and balance, both of which are mediated mainly by the cerebellum. The dorsomedial part of the principal sensory trigeminal nucleus (Vpdm) has direct projection to the cerebellum. The experimental unilateral anterior crossbite (UAC) has an impact on the motor nuclei in the brain stem via trigeminal mesencephalic nucleus (Vme). The current aim was to explore whether UAC has an impact on Vpdm-cerebellum circuit. The inferior alveolar nerve was injected into cholera toxin B subunit (CTb), the cerebellum was injected into fluoro-gold (FG), and the Vpdm was injected into biotinylated dextran amine (BDA) to identify the activation of Vpdm-cerebellum circuit by UAC. Data indicated that there were more neuronal nuclei (NeuN)/CTb/FG triple-labelled neurons and NeuN/CTb/vesicular glutamate transporter 1(VGLUT1) triple-labelled neurons in the Vpdm, and more NeuN/BDA/ VGLUT1 triple-labelled neurons in the cerebellum of rats with UAC than in control rats. The VGLUT1 expression in the Vpdm and cerebellum in the UAC group was higher than that in control rats. These findings indicate an excitatory impact of UAC on the Vpdm-cerebellum pathway and support the role of occlusion for body posture and balance.

Dental malocclusion stimulates neuromuscular circuits associated with temporomandibular disorders.

Unilateral anterior crossbite (UAC) has been demonstrated to cause masseter hyperactivity via the periodontal trigeminal mesencephalic nucleus (Vme)-trigeminal motor nucleus circuit. Here, we studied activation of motor neurons of the facial nucleus (VII), hypoglossal nucleus (XII), nucleus ambiguus (Amb), and spinal nucleus of the accessory nerve (SNA) in rats with UAC via their similar connections with Vme. An anterograde tracer, biotinylated dextran amine (BDA), was injected into the Vme to identify the central axon terminals around the motor neurons of VII, XII, Amb, and SNA. The expression of vesicular glutamate transporter 1 (VGLUT1) in neurons of VII, XII, Amb, and SNA, and the expression of acetylcholinesterase (AChE) were measured in the stapedius, lingualis, palatopharyngeal, and sternocleidomastoid muscles. In BDA-treated rats, many BDA-labeled cell bodies in the Vme and terminals in VII, XII, Amb, and SNA were identified. Compared with control rats, rats with UAC showed higher expression of VGLUT1 in these nuclei, and statistically significantly higher expression of AChE in the stapedius, lingualis, and sternocleidomastoid muscles, but not in the palatopharyngeal muscle. These findings suggest that UAC activates orofacial, head, and cervical multimotor behaviors via connections between the Vme and the corresponding motor nuclei.

Parameter optimization of the spiral fertiliser discharger for mango orchards based on the discrete element method and genetic algorithm.

Introduction: In order to solve the problems of inaccurate fertilization, unstable fertilization and low fertiliserutilization rate in mango orchard. Methods: A small spiral fertiliser discharger was designed based on the agronomic characteristics of fertilization in mango orchard. The fertilizing performance test and parameter optimization of thespiral fertiliser discharger were carried out by combining bench and simulation test. Firstly, the main influencing factors of the fertilizing performance of the spiral fertiliser discharger were analyzed by theoretical calculation formula, and the range of its value was preliminarily determined. At the same time, the digital and discrete element models of the spiral fertiliser discharger were established. Then,the discrete element model of granular fertiliser was established on the basis of the physical and related mechanical simulation parameters of granular fertiliser obtained by experimental statistics.Taking the variable coefficient of fertilizing stability as the response value, the method of singlefactor simulation fertilizing test was used to explore the parameters that have a significant influence on the variable coefficient of fertilizing stability. The response surface method (RSM) was used tosimulate the fertilizing performance of three significant parameters. Based on the quadraticregression orthogonal rotation combination design test, a second-order regression mathematicalmodel between the variable coefficient of fertilizing stability and the significant parameters wasestablished. The variable coefficient of fertilizing stability was as small as possible. The geneticalgorithm (GA) was used to optimize the regression model. Finally, the verification test of thefluidity and applicability of different fertilisers was carried out. Results: The results of single factor test showed that the diameter of spiral blade, pitch and rotationalspeed of fertilizing shaft have significant influence on the variable coefficient of fertilizing stability.The optimal parameter combination of the spiral fertiliser discharger was obtained: 98.44 mm for thediameter of spiral blade, 54.8 mm for the pitch, and 24.43 r/min for the rotational speed of fertilizingshaft. The verification results showed that the average relative error of the test was small, and themass flow rate of different fertilisers and the variable coefficient of fertilizing stability could meetthe agronomic requirements of fertilization in mango orchards. The reliability of the discrete elementsimulation test results and research methods of the spiral fertiliser discharger was verified. Conclusion: The results and methods of this study can provide reference for the development of mangoorchard fertilization machinery and related fertilizing performance test.

Chemometrics in Tandem with Hyperspectral Imaging for Detecting Authentication of Raw and Cooked Mutton Rolls.

Authentication assurance of meat or meat products is critical in the meat industry. Various methods including DNA- or protein-based techniques are accurate for assessing meat authenticity, however, they are destructive, expensive, or laborious. This study explores the feasibility of chemometrics in tandem with hyperspectral imaging (HSI) for identifying raw and cooked mutton rolls substitution by pork and duck rolls. Raw or cooked samples (n = 180) of three meat species were prepared to collect hyperspectral images in range of 400-1000 nm. Spectra were extracted from representative regions of interest (ROIs), and spectral principal component analysis (PCA) revealed that PC1 and PC2 were effective for the identification. Different methods including standard normal variable (SNV), first and second derivatives, and normalization were individually employed for spectral preprocessing, and modeling methods of partial least squares-discriminant analysis (PLS-DA) and support vector machines (SVM) were also individually applied to develop classification models for both the raw and the cooked. Results showed that PLS-DA model developed by raw spectra presented the highest 100% correct classification rate (CCR) of success in all sets. After that, effective wavelengths selected by successive projections algorithm (SPA) built optimal simplified models which didn't influence the modeling results compared with full spectra regardless of the meat roll states. Therefore, SPA-PLS-DA models were subsequently used to visualize the raw and cooked meat rolls classification. As a consequence, the general meat species of both raw and cooked meat rolls were readily discernible in pixel-wise manner by generating classification maps. The results showed that HSI combined with chemometrics can be used to identify the authentication of raw and cooked mutton rolls substituted by pork and duck rolls accurately. This promising methodology provides a reference which can be extended to the classification or grading of other meat rolls.

Interaction and influence of a flow field and particleboard particles in an airflow forming machine with a coupled Euler-DPM model.

Particleboards are widely used in the artificial board market, which can be constructed from a variety of raw materials and require small amounts of energy to be produced. In the particleboard production process, forming machines play an important role as the key equipment for achieving continuous production. In recent years, airflow forming machines have received increasing attention in particleboard production lines because of their strong separation ability and low price. However, the internal flow field is complex and difficult to control, which affects the surface quality and strength of the particleboard. The most pressing technical difficulty is controlling the flow field characteristics of the airflow paver. At present, the research on this subject is conducted primarily through repeated experiments, which entail long research periods and high processing costs. To reduce human and financial costs, in this study, Computational Fluid Dynamics (CFD) is employed to investigate the flow field and the gas-solid two-phase flow field coupled with particle movement of an airflow forming machine. The accuracy of the calculation model is verified by comparing characteristic point velocities obtained from experimental analysis and a simulation. The simulation results show that in practical production, the frequency of a negative pressure fan should be greater than 27 Hz. It is necessary to set the shoulder properly, and the slab smoothness can be improved by moving the shoulder back on the premise of meeting the strength requirements of the box. The distance between the shoulders of the box body should be less than 2570 mm, and particles with uniform diameter should be added to the paving box to reduce the turbulence effect, improve the quality of particle forming and provide actual particleboard production with a solid theoretical foundation.

PKI-587 enhances radiosensitization of hepatocellular carcinoma by inhibiting the PI3K/AKT/mTOR pathways and DNA damage repair.

Radiation is an important therapeutic strategy for hepatocellular (HCC). In this study, we evaluated the role of the dual PI3K/mTOR inhibitor, PKI-587, on radiosensitization of HCC and its possible mechanism. MTT, colony formation, flow cytometry, and immunofluorescence were used to analyze the proliferation, cell cycle, formation of residual γ-H2AX foci, and apoptosis of HCC cells. A SK-Hep1 xenograft HCC model was used to assess the effects of PKI-587 in combination with ionizing radiation in vivo. The activation levels of PI3K/AKT/mTOR and DNA damage repair pathways and their downstream effector molecules were detected with Western blot. It was found that PKI-587 sensitized HCC cells to radiation by increasing DNA damage, enhancing G0/G1 cell-cycle arrest, and inducing apoptosis. In vivo, the combination of radiation with PKI-587 significantly inhibited tumor growth. These findings suggest the usefulness of PKI-587 on radiosensitization of HCC cells by inhibiting the PI3K/AKT/mTOR and DNA damage repair pathways. The combination of ionizing radiation and PKI-587 may be a strategy to improve the efficacy of treating HCC.

Excitatory Impact of Dental Occlusion on Dorsal Motor Nucleus of Vagus.

Neurons in the trigeminal mesencephalic nucleus (Vme) have axons that branch peripherally to innervate the orofacial region and project centrally to several motor nuclei in brainstem. The dorsal motor nucleus of vagus nerve (DMV) resides in the brainstem and takes a role in visceral motor function such as pancreatic exocrine secretion. The present study aimed to demonstrate the presence of Vme-DMV circuit, activation of which would elicit a trigeminal neuroendocrine response. A masticatory dysfunctional animal model termed unilateral anterior crossbite (UAC) model created by disturbing the dental occlusion was used. Cholera toxin B subunit (CTb) was injected into the inferior alveolar nerve of rats to help identify the central axon terminals of Vme neurons around the choline acetyltransferase (ChAT) positive motor neurons in the DMV. The level of vesicular glutamate transporter 1 (VGLUT1) expressed in DMV, the level of acetylcholinesterase (AChE) expressed in pancreas, the level of glucagon and insulin expression in islets and serum, and the blood glucose level were detected and compared between UAC and the age matched sham-operation control mice. Data indicated that compared with the controls, there were more CTb/VGLUT1 double labeled axon endings around the ChAT positive neurons in the DMV of UAC groups. Mice in UAC group expressed a higher VGLUT1 protein level in DMV, AChE protein level in pancreas, glucagon and insulin level in islet and serum, and higher postprandial blood glucose level, but lower fasting blood glucose level. All these were reversed at 15-weeks when UAC cessation was performed from 11-weeks (all, P < 0.05). Our findings demonstrated Vme-DMV circuit via which the aberrant occlusion elicited a trigeminal neuroendocrine response such as alteration in the postprandial blood glucose level. Dental occlusion is proposed as a potential therapeutic target for reversing the increased postprandial glucose level.

Rapid Identification and Visualization of Jowl Meat Adulteration in Pork Using Hyperspectral Imaging.

Minced pork jowl meat, also called the sticking-piece, is commonly used to be adulterated in minced pork, which influences the overall product quality and safety. In this study, hyperspectral imaging (HSI) methodology was proposed to identify and visualize this kind of meat adulteration. A total of 176 hyperspectral images were acquired from adulterated meat samples in the range of 0%-100% (w/w) at 10% increments using a visible and near-infrared (400-1000 nm) HSI system in reflectance mode. Mean spectra were extracted from the regions of interests (ROIs) and represented each sample accordingly. The performance comparison of established partial least square regression (PLSR) models showed that spectra pretreated by standard normal variate (SNV) performed best with Rp2 = 0.9549 and residual predictive deviation (RPD) = 4.54. Furthermore, functional wavelengths related to adulteration identification were individually selected using methods of principal component (PC) loadings, two-dimensional correlation spectroscopy (2D-COS), and regression coefficients (RC). After that, the multispectral RC-PLSR model exhibited the most satisfactory results in prediction set that Rp2 was 0.9063, RPD was 2.30, and the limit of detection (LOD) was 6.50%. Spatial distribution was visualized based on the preferred model, and adulteration levels were clearly discernible. Lastly, the visualization was further verified that prediction results well matched the known distribution in samples. Overall, HSI was tested to be a promising methodology for detecting and visualizing minced jowl meat in pork.

Malocclusion Generates Anxiety-Like Behavior Through a Putative Lateral Habenula-Mesencephalic Trigeminal Nucleus Pathway.

Malocclusion is an important risk factor for temporomandibular disorder (TMD), a series of disorders characterized by dysfunction in the orofacial region involving the temporomandibular joint (TMJ) and jaw muscles. We recently showed that experimental unilateral anterior crossbite (UAC) produced masseter hyperactivity through a circuit involving the periodontal proprioception, trigeminal mesencephalic nucleus (Vme), and trigeminal motor nucleus (Vmo). Anxiety is a common complication in patients with TMD. The lateral habenula (LHb) is involved in emotional modulation and has direct projections to the Vme. Therefore, the present research examined whether UAC facilitates excitatory input from the LHb to the Vme and, subsequently, anxiety-like behaviors in rats. The LHb activation was evaluated by the electrophysiological recording, assessment of vesicular glutamate transporter-2 (VGLUT2) mRNA expression, and measurement of anxiety-like behaviors. The effects of LHb activity on Vme were evaluated by electrophysiological recording from Vme neurons and local changes in VGLUT2 protein density. UAC produced anxiety in modeled rats and increased neuronal activity in the LHb. VGLUT2 mRNA expression was also increased in the LHb. Further, VGLUT2-positive boutons were observed in close apposite upon parvalbumin (PV)-labeled Vme neurons. VGLUT2 protein expression was also increased in the Vme. Significantly, injection of VGLUT2-targeted shRNA into the LHb reduced the expression of VGLUT2 protein in the Vme, attenuated UAC-associated anxiety-like behaviors, and attenuated electrophysiological changes in the Vme neurons. In conclusion, we show that UAC activates the LHb neurons as well as the periodontal proprioceptive pathway to provide excitatory input to the Vme and produce anxiety in rats. These findings provide a rationale for suppressing activity of the LHb to attenuate both the physical and psychological effects of TMD.