Ramelteon protects against social defeat stress-associated abnormal behaviors.

Psychological stress affects the neuroendocrine regulation, which modulates mental status and behaviors. Melatonin, a hormone synthesized primarily by the pineal gland, regulates many brain functions, including circadian rhythms, pain, sleep, and mood. Selective pharmacological melatonin agonist ramelteon has been clinically used to treat mood and sleep disorders. Posttraumatic stress disorder (PTSD) is a psychiatric condition associated with severe trauma; it is generally triggered by traumatic events, which lead to severe anxiety and uncontrollable trauma recall. We recently reported that repeated social defeat stress (RSDS) may induce robust anxiety-like behaviors and social avoidance in mice. In the present study, we investigated whether melatonin receptor activation by melatonin and ramelteon regulates RSDS-induced behavioral changes. Melatonin treatment improved social avoidance and anxiety-like behaviors in RSDS mice. Moreover, treatment of the non-selective MT1/MT2 receptor agonist, ramelteon, markedly ameliorated RSDS-induced social avoidance and anxiety-like behaviors. Moreover, activating melatonin receptors also balanced the expression of monoamine oxidases, glucocorticoid receptors, and endogenous antioxidants in the hippocampus. Taken together, our findings indicate that the activation of both melatonin and ramelteon regulates RSDS-induced anxiety-like behaviors and PTSD symptoms. The current study also showed that the regulatory effects of neuroendocrine mechanisms and cognitive behaviors on melatonin receptor activation in repeated social defeat stress.

LPS priming-induced immune tolerance mitigates LPS-stimulated microglial activation and social avoidance behaviors in mice.

In this study, we investigated the regulatory mechanisms underlying the effects of LPS tolerance on the inflammatory homeostasis of immune cells. LPS priming-induced immune tolerance downregulated cyclooxygenase-2, and lowered the production of prostaglandin-E2 in microglial cells. In addition, LPS tolerance downregulated the expression of suppressor of cytokine signaling 3, and inducible nitric oxide synthase/nitric oxide; suppressed the LPS-mediated induction of tumor necrosis factor-α, interleukin (IL)-6, and IL-1; and reduced reactive oxygen species production in microglial cells. LPS stimulation increased the levels of the adaptive response-related proteins heme oxygenase-1 and superoxide dismutase 2, and the levels of heme oxygenase-1 (HO-1) enhanced after LPS priming. Systemic administration of low-dose LPS (0.5 mg/kg) to mice for 4 consecutive days attenuated high-dose LPS (5 mg/kg)-induced inflammatory response, microglial activation, and proinflammatory cytokine expression. Moreover, repeated exposure to low-dose LPS suppressed the recruitment of peripheral monocytes or macrophages to brain regions and downregulated the expression of proinflammatory cytokines. Notably, LPS-induced social avoidance behaviors in mice were mitigated by immune tolerance. In conclusion, immune tolerance may reduce proinflammatory cytokine expression and reactive oxygen species production. Our findings provide insights into the effects of endotoxin tolerance on innate immune cells and social behaviors.

Prediction method of longitudinal surface settlement caused by double shield tunnelling based on deep learning.

The deep learning method faces the challenges of small sample data and high dimensional shield operational parameters in predicting the longitudinal surface settlement caused by shield excavation. In this study, various optimization algorithms were compared, and the slime mould algorithm (SMA) was optimally chosen to optimize the hyperparameters of random forest (RF), and SMA-RF was used for dimensionality reduction and feature contribution analysis. A double-input deep neural network (D-DNN) framework was proposed for the prediction of surface settlement, which considers the influence of twin tunnels and effectively increases the high-fidelity data in the database. The results show that SMA performs best among various optimization algorithms; employing features that have a cumulative contribution value exceeding 90% as input can result in high prediction accuracy; there is significant uncertainty in the feature contribution analysis for small sample data; the reduced shield running parameters show a strong nonlinear relationship with surface settlement; compared with S-DNN, D-DNN takes into account the excavation of twin tunnels and expands the database capacity by more than 1.5 times, with an average increase of 27.85% in the R2 and an average decrease of 53.2% in the MAE.

Fabrication and characterization of ZnGa1.01Te2.13/g-C3N4 heterojunction with enhanced photocatalytic activity.

The extensive consumption of fossil fuels increases CO2 concentration in the atmosphere, resulting in serious global warming problems. Meanwhile, the problem of water contamination by organic substances is another significant global challenge. We have successfully synthesized ZnGa1.01Te2.13/g-C3N4 (ZGT/GCN) composites for the first time as effective photocatalysts for both pollutant degradation and CO2 reduction. ZGT/GCN composites were synthesized by a simple hydrothermal method. The prepared photocatalysts were characterized by XRD, SEM, TEM-EDS, DRS, BET, PL, and XPS. The ZGT/GCN heterojunction exhibited considerably enhanced photocatalytic activity in the degradation of crystal violet (CV) as well as in the photoreduction of CO2 when compared to pure ZGT and GCN semiconductors. The optimal rate constant for CV degradation was obtained with the ZGT-80%GCN composite (0.0442 h-1), which is higher than the constants obtained with individual ZGT and GCN by 7.75 and 1.63 times, respectively. Moreover, the CO2 reduction yields into CH4 by ZGT-80%GCN was 1.013 µmol/g in 72 h, which is 1.21 and 1.08 times larger than the yields obtained with ZGT and GCN. Scavenger and ESR tests were used to propose the photocatalytic mechanism of the ZGT/GCN composite as well as the active species in the CV degradation.

Coplanarity Constrained Ultrasound Probe Calibration Based on N-Wire Phantom.

OBJECTIVE: N-wire phantom-based ultrasound probe calibration has been used widely in many freehand tracked ultrasound imaging systems. The calibration matrix is obtained by registering the coplanar point cloud in ultrasound space and non-coplanar point cloud in tracking sensor space based on the least squares method. This method is sensitive to outliers and loses the coplanar information of the fiducial points. In this article, we describe a coplanarity-constrained calibration algorithm focusing on these issues. METHODS: We verified that the out-of-plane error along the oblique wire in the N-wire phantom followed a normal distribution and used it to remove the experimental outliers and fit the plane with the Levenberg-Marquardt algorithm. Then, we projected the points to the plane along the oblique wire. Coplanarity-constrained point cloud registration was used to calculate the transformation matrix. RESULTS: Compared with the other two commonly used methods, our method had the best calibration precision and achieved 25% and 36% improvement of the mean calibration accuracy than the closed-form solution and in-plane error method respectively at depth 16. Experiments at different depths revealed that our algorithm had better performance in our setup. CONCLUSION: Our proposed coplanarity-constrained calibration algorithm achieved significant improvement in both precision and accuracy compared with existing algorithms with the same N-wire phantom. It is expected that calibration accuracy will improve when the algorithm is applied to all other N-wire phantom-based calibration procedures.

Breaking the limitation of polarization multiplexing in optical metasurfaces with engineered noise.

Noise is usually undesired yet inevitable in science and engineering. However, by introducing the engineered noise to the precise solution of Jones matrix elements, we break the fundamental limit of polarization multiplexing capacity of metasurfaces that roots from the dimension constraints of the Jones matrix. We experimentally demonstrate up to 11 independent holographic images using a single metasurface illuminated by visible light with different polarizations. To the best of our knowledge, it is the highest capacity reported for polarization multiplexing. Combining the position multiplexing scheme, the metasurface can generate 36 distinct images, forming a holographic keyboard pattern. This discovery implies a new paradigm for high-capacity optical display, information encryption, and data storage.

Laboratory study of water infiltration and evaporation in biochar-amended landfill covers under extreme climate.

Biochar has been used as an environment-friendly enhancer to improve the soil hydraulic properties. Previous studies focused on the effect of biochar addition for irrigation in agricultural soils. However, the understanding of the influence of biochar addition on water infiltration in compacted soils as used in landfill covers is limited. This study investigated the effects of peanut shell biochar addition on soil water infiltration with consideration of soil microstructure variations. The performance of biochar-amended soil was also explored under extreme rainfall and drought conditions. In this experiment, peanut shell biochar with particles finer than 0.25 mm was amended into compacted silty sand. Index soil properties and microstructure were observed. One-dimension (1-D) column tests and corresponding numerical modelling were carried out to investigate the performance of this cover material under different climate scenarios. The results suggested that the application of biochar can increase soil porosity, but a significant number of large pores (i.e., larger than 20 µm) was minimized. With the application of biochar, the soil covers thus become more efficient in preventing infiltration and percolation. This is also crucial to minimize the need for a relatively large thickness of soil cover. With an increase in porosity, the biochar can improve the soil water retention. Under extreme drought, the application of biochar can reduce the very low pore-water pressure (PWP) in soils by more than 50%. From all of these, peanut shell biochar can potentially be an eco-friendly and more sustainable solution for soil covers, even under extreme climate conditions.

Multiple-polarization-sensitive photodetector based on a perovskite metasurface.

Most polarization-sensitive photodetectors detect either linearly polarized (LP) or circularly polarized (CP) light. Here, we experimentally demonstrate a multiple-polarization photodetector based on a hybrid organic-inorganic perovskite (HOIP) metasurface, which is sensitive to both LP and CP light simultaneously. The perovskite metasurface is composed of a HOIP antenna array on a single-crystal HOIP film. Owing to the antenna anisotropy, the absorption of linearly polarized light at the metasurface depends on the polarization angle; also, due to the mirror asymmetry of the antenna elements, the metasurface is also sensitive to different circular polarizations. Polarization-dependent photocurrent responses to both LP and CP light are detected. Our results highlight the potential of perovskite metasurfaces for integrated photoelectric applications.

Fenofibrate inhibits hypoxia-inducible factor-1 alpha and carbonic anhydrase expression through activation of AMP-activated protein kinase/HO-1/Sirt1 pathway in glioblastoma cells.

Cancer and its associated conditions have significant impacts on public health at many levels worldwide, and cancer is the leading cause of death among adults. Peroxisome proliferator-activated receptor α (PPARα)-specific agonists, fibrates, have been approved by the Food and Drug Administration for managing hyperlipidemia. PPARα-specific agonists exert anti-cancer effects in many human cancer types, including glioblastoma (GBM). Recently, we have reported that the hypoxic state in GBM stabilizes hypoxia-inducible factor-1 alpha (HIF-1α), thus contributing to tumor escape from immune surveillance by activating the expression of the pH-regulating protein carbonic anhydrase IX (CA9). In this study, we aimed to study the regulatory effects of the PPARα agonist fibrate on the regulation of HIF-1α expression and its downstream target protein in GBM. Our findings showed that fenofibrate is the high potency compound among the various fibrates that inhibit hypoxia-induced HIF-1α and CA9 expression in GBM. Moreover, fenofibrate-inhibited HIF-1α expression is mediated by HO-1 activation in GBM cells through the AMP-activated protein kinase (AMPK) pathway. In addition, fenofibrate-enhanced HO-1 upregulation activates SIRT1 and leads to subsequent accumulation of SIRT1 in the nucleus, which further promotes HIF-1α deacetylation and inhibits CA9 expression. Using a protein synthesis inhibitor, cycloheximide, we also observed that fenofibrate inhibited HIF-1α protein synthesis. In addition, the administration of the proteasome inhibitor MG132 showed that fenofibrate promoted HIF-1α protein degradation in GBM. Hence, our results indicate that fenofibrate is a useful anti-GBM agent that modulates hypoxia-induced HIF-1α expression through multiple cellular pathways.

Electroacupuncture improves repeated social defeat stress-elicited social avoidance and anxiety-like behaviors by reducing Lipocalin-2 in the hippocampus.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a trauma-related disorder that is associated with pro-inflammatory activation and neurobiological impairments in the brain and leads to a series of affective-like behaviors. Electroacupuncture (EA) has been proposed as a clinically useful therapy for several brain diseases. However, the potential role of EA treatment in PTSD and its molecular and cellular mechanisms has rarely been investigated. METHODS: We used an established preclinical social defeat stress mouse model to study whether EA treatment modulates PTSD-like symptoms and understand its underlying mechanisms. To this end, male C57BL/6 mice were subjected to repeated social defeat stress (RSDS) for 6 consecutive days to induce symptoms of PTSD and treated with EA at Baihui (GV 20) and Dazhui (GV 14) acupoints. RESULTS: The stimulation of EA, but not needle insertion at Baihui (GV 20) and Dazhui (GV 14) acupoints effectively improved PTSD-like behaviors such as, social avoidance and anxiety-like behaviors. However, EA stimulation at the bilateral Tianzong (SI11) acupoints did not affect the PTSD-like behaviors obtained by RSDS. EA stimulation also markedly inhibited astrocyte activation in both the dorsal and ventral hippocampi of RSDS-treated mice. Using next-generation sequencing analysis, our results showed that EA stimulation attenuated RSDS-enhanced lipocalin 2 expression in the hippocampus. Importantly, using double-staining immunofluorescence, we observed that the increased lipocalin 2 expression in astrocytes by RSDS was also reduced by EA stimulation. In addition, intracerebroventricular injection of mouse recombinant lipocalin 2 protein in the lateral ventricles provoked social avoidance, anxiety-like behaviors, and the activation of astrocytes in the hippocampus. Interestingly, the overexpression of lipocalin 2 in the brain also altered the expression of stress-related genes, including monoamine oxidase A, monoamine oxidase B, mineralocorticoid receptor, and glucocorticoid receptor in the hippocampus. CONCLUSIONS: This study suggests that the treatment of EA at Baihui (GV 20) and Dazhui (GV 14) acupoints improves RSDS-induced social avoidance, anxiety-like behaviors, astrocyte activation, and lipocalin 2 expression. Furthermore, our findings also indicate that lipocalin 2 expression in the brain may be an important biomarker for the development of PTSD-related symptoms.

Paliperidone Inhibits Glioblastoma Growth in Mouse Brain Tumor Model and Reduces PD-L1 Expression.

A previous study from our group reported that monocyte adhesion to glioblastoma (GBM) promoted tumor growth and invasion activity and increased tumor-associated macrophages (TAMs) proliferation and inflammatory mediator secretion as well. The present study showed that prescribed psychotropic medicine paliperidone reduced GBM growth and immune checkpoint protein programmed death ligand (PD-L)1 expression and increased survival in an intracranial xenograft mouse model. An analysis of the database of patients with glioma showed that the levels of PD-L1 and dopamine receptor D (DRD)2 were higher in the GBM group than in the low grade astrocytoma and non-tumor groups. In addition, GFP expressing GBM (GBM-GFP) cells co-cultured with monocytes-differentiated macrophage enhanced PD-L1 expression in GBM cells. The enhancement of PD-L1 in GBM was antagonized by paliperidone and risperidone as well as DRD2 selective inhibitor L741426. The expression of CD206 (M2 phenotype marker) was observed to be markedly increased in bone marrow-derived macrophages (BMDMs) co-cultured with GBM. Importantly, treatment with paliperidone effectively decreased CD206 and also dramatically increased CD80 (M1 phenotype marker) in BMDMs. We have previously established a PD-L1 GBM-GFP cell line that stably expresses PD-L1. Experiments showed that the expressions of CD206 was increased and CD80 was mildly decreased in the BMDMs co-cultured with PD-L1 GBM-GFP cells. On the other hands, knockdown of DRD2 expression in GBM cells dramatically decreased the expression of CD206 but markedly increased CD80 expressions in BMDMs. The present study suggests that DRD2 may be involved in regulating the PD-L1 expression in GBM and the microenvironment of GBM. Our results provide a valuable therapeutic strategy and indicate that treatments combining DRD2 antagonist paliperidone with standard immunotherapy may be beneficial for GBM treatment.

Flexible Phase Change Materials for Electrically-Tuned Active Absorbers.

Phase change materials (PCMs), such as GeSbTe (GST) alloys and vanadium dioxide (VO2 ), play an important role in dynamically tunable optical metadevices. However, the PCMs usually require high thermal annealing temperatures above 700 K, but most flexible metadevices can only work below 500 K owing to the thermal instability of polymer substrates. This contradiction limits the integration of PCMs into flexible metadevices. Here, a mica sheet is chosen as the chemosynthetic support for VO2 and a smooth and uniformly flexible phase change material (FPCM) is realized. Such FPCMs can withstand high temperatures while remaining mechanically flexible. As an example, a metal-FPCM-metal infrared meta-absorber with mechanical flexibility and electrical tunability is demonstrated. Based on the electrically-tuned phase transition of FPCMs, the infrared absorption of the metadevice is continuously tuned from 20% to 90% as the applied current changes, and it remains quite stable at bending states. The metadevice is bent up to 1500 times, while no visible deterioration is detected. For the first time, the FPCM metastructures are significantly added to the flexible material family, and the FPCM-based metadevices show various application prospects in electrically-tunable conformal metadevices, dynamic flexible photodetectors, and active wearable devices.

Regulatory effects of IL-1ß in the interaction of GBM and tumor-associated monocyte through VCAM-1 and ICAM-1.

Glioblastoma (GBM) is the most common and lethal brain tumor with high inflammation. GBM cells infiltrate microglia and macrophages and are surrounded by pro-inflammatory cytokines. Interleukin (IL)-1ß, which is abundantly expressed in the tumor microenvironment, is involved in tumor progression. Intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 mediate cell-cell interactions, and these cell adhesion molecules (CAMs) can be regulated by cytokines in immune cells or cancer cells in the inflammatory tumor microenvironment. In this study, we found that ICAM-1 and VCAM-1 expression was induced when GBM cells were treated with IL-1ß, and that adhesive interaction between monocytes and GBM cells increased accordingly. The levels of soluble CAMs (sICAM-1 and sVCAM-1) were also increased in the supernatants induced by IL-1ß. Furthermore, the conditioned media contained sICAM-1 and sVCAM-1, which further promoted IL-6 and CCL2 expression in differentiated macrophages. IL-1ß downregulated Src homology 1 domain-containing protein tyrosine phosphatase (SHP-1) in GBM. The expression of ICAM-1 and VCAM-1 was regulated by p38, AKT, and NF-κB signaling pathways, which were modulated by SHP-1 signaling. The present study suggests that IL-1ß-induced protein expression of ICAM-1 and VCAM-1 in GBM may modulate the adhesive interaction between GBM and monocytes. In addition, IL-1ß also induced the soluble form of ICAM-1 and VCAM-1 in GBM, which plays a key role in the regulation of tumor-associated monocyte/macrophage polarization.

Radiomics features of ascending and descending nasopharyngeal carcinoma. / ä¸Šè¡Œåž‹ä¸Žä¸‹è¡Œåž‹é¼»å’½ç™Œç›¸å ³å½±åƒç»„å­¦ç‰¹å¾.

OBJECTIVES: To evaluate the application value of CT-based radiomics features for the ascending and descending types of nasopharyngeal carcinoma (NPC). METHODS: A total of 217 NPC patients (48 ascending type and 169 descending type), who obtained CT images before radiotherapy in Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from February 2015 to October 2017, were analyzed retrospectively. All patients were randomly divided into a training set (n=153) and a test set (n=64). Gross tumor volume in the nasopharynx (GTVnx) was selected as regions of interest (ROI) and was analyzed by radiomics. A total of 1 300 radiomics features were extracted via IBEX. The least absolute shrinkage and selection operator (LASSO) logistic regression was performed to choose the significant features. Support vector machine (SVM) and random forest (RF) classifiers were built and verified. RESULTS: Six features were selected by the LASSO from 1 300 radiomics features. Compared with SVM classifier, RF classifier showed better classification performance. The area under curve (AUC) of the receiver operating characteristic (ROC) curve, accuracy, sensitivity, and specificity were 0.989, 0.941, 1.000, and 0.924, respectively for the training set; 0.994, 0.937, 1.000, and 0.924, respectively for the validation set. CONCLUSIONS: CT-based radiomics features possess great potential in differentiating ascending and descending NPC. It provides a certain basis for accurate medical treatment of NPC, and may affect the treatment strategy of NPC in the future.

Depth-resolved imaging of colon tumor using optical coherence tomography and fluorescence laminar optical tomography.

Early detection of neoplastic changes remains a critical challenge in clinical cancer diagnosis and treatment. Many cancers arise from epithelial layers such as those of the gastrointestinal (GI) tract. Current standard endoscopic technology is difficult to detect the subsurface lesions. In this research, we investigated the feasibility of a novel multi-modal optical imaging approach including high-resolution optical coherence tomography (OCT) and high-sensitivity fluorescence laminar optical tomography (FLOT) for structural and molecular imaging. The C57BL/6J-ApcMin/J mice were imaged using OCT and FLOT, and the correlated histopathological diagnosis was obtained. Quantitative structural (scattering coefficient) and molecular (relative enzyme activity) parameters were obtained from OCT and FLOT images for multi-parametric analysis. This multi-modal imaging method has demonstrated the feasibility for more accurate diagnosis with 88.23% (82.35%) for sensitivity (specificity) compared to either modality alone. This study suggested that combining OCT and FLOT is promising for subsurface cancer detection, diagnosis, and characterization.

Melittin inhibits tumor angiogenesis modulated by endothelial progenitor cells associated with the SDF-1α/CXCR4 signaling pathway in a UMR-106 osteosarcoma xenograft mouse model.

Endothelial progenitor cells (EPCs) are important in tumor angiogenesis. Stromal cell-derived factor-1α (SDF-1α) and its receptor C-X-C chemokine receptor type 4 (CXCR4) are key in stem cell homing. Melittin, a component of bee venom, exerts antitumor activity, however, the underlying mechanisms remain to be elucidated. The present study aimed to assess the effects of melittin on EPCs and angiogenesis in a mouse model of osteosarcoma. UMR­106 cells and EPCs were treated with various concentrations of melittin and cell viability was determined using the MTT assay. EPC adherence, migration and tube forming ability were assessed. Furthermore, SDF­1α, AKT and extracellular signal­regulated kinase (ERK)1/2 expression levels were detected by western blotting. Nude mice were inoculated with UMR­106 cells to establish an osteosarcoma mouse model. The tumors were injected with melittin, and its effects were assessed by immunohistochemistry and immunofluorescence. Melittin decreased the viability of UMR­106 cells and EPCs. In addition, it decreased EPC adhesion, migration and tube formation when compared with control and SDF­1α­treated cells. Melittin decreased the expression of phosphorylated (p)­AKT, p­ERK1/2, SDF­1α and CXCR4 in UMR­106 cells and EPCs when compared with the control. The proportions of cluster of differentiation (CD)34/CD133 double­positive cells were 16.4±10.4% in the control, and 7.0±4.4, 2.9±1.2 and 1.3±0.3% in tumors treated with 160, 320 and 640 µg/kg melittin per day, respectively (P<0.05). At 11 days, melittin reduced the tumor size when compared with that of the control (control, 4.8±1.3 cm3; melittin, 3.2±0.6, 2.6±0.5, and 2.0±0.2 cm3 for 160, 320 and 640 µg/kg, respectively; all P<0.05). Melittin decreased the microvessel density, and SDF­1α and CXCR4 protein expression levels in the tumors. Melittin may decrease the effect of osteosarcoma on EPC­mediated angiogenesis, possibly via inhibition of the SDF-1α/CXCR4 signaling pathway.

In Vivo Mesoscopic Voltage-Sensitive Dye Imaging of Brain Activation.

Functional mapping of brain activity is important in elucidating how neural networks operate in the living brain. The whisker sensory system of rodents is an excellent model to study peripherally evoked neural activity in the central nervous system. Each facial whisker is represented by discrete modules of neurons all along the pathway leading to the neocortex. These modules are called "barrels" in layer 4 of the primary somatosensory cortex. Their location (approximately 300-500 µm below cortical surface) allows for convenient imaging of whisker-evoked neural activity in vivo. Fluorescence laminar optical tomography (FLOT) provides depth-resolved fluorescence molecular information with an imaging depth of a few millimeters. Angled illumination and detection configurations can improve both resolution and penetration depth. We applied angled FLOT (aFLOT) to record 3D neural activities evoked in the whisker system of mice by deflection of a single whisker in vivo. A 100 µm capillary and a pair of microelectrodes were inserted to the mouse brain to test the capability of the imaging system. The results show that it is possible to obtain 3D functional maps of the sensory periphery in the brain. This approach can be broadly applicable to functional imaging of other brain structures.

Optical Coherence Tomographic Elastography Reveals Mesoscale Shear Strain Inhomogeneities in the Annulus Fibrosus.

STUDY DESIGN: Basic science study using in vitro tissue testing and imaging to characterize local strains in annulus fibrosus (AF) tissue. OBJECTIVE: To characterize mesoscale strain inhomogeneities between lamellar and inter-/translamellar (ITL) matrix compartments during tissue shear loading. SUMMARY OF BACKGROUND DATA: The intervertebral disc is characterized by significant heterogeneities in tissue structure and plays a critical role in load distribution and force transmission in the spine. In particular, the AF possesses a lamellar architecture interdigitated by a complex network of extracellular matrix components that form a distinct ITL compartment. Currently, there is not a firm understanding of how the lamellar and ITL matrix coordinately support tissue loading. METHODS: AF tissue samples were prepared from frozen porcine lumbar spines and mounted onto custom fixtures of a materials testing system that incorporates optical coherence tomography (OCT) imaging to perform tissue elastography. Tissues were subjected to 20 and 40% nominal shear strain, and OCT images were captured and segmented to identify regions of interest corresponding to lamellar and ITL compartments. Images were analyzed using an optical flow algorithm to quantify local shear strains within each compartment. RESULTS: Using histology and OCT, we first verified our ability to visualize and discriminate the ITL matrix from the lamellar matrix in porcine AF tissues. Local AF strains in the ITL compartment (22.0 ±â€Š13.8, 31.1 ±â€Š16.9 at 20% and 40% applied shear, respectively) were significantly higher than corresponding strains in the surrounding lamellar compartment (12.1 ±â€Š5.6, 15.3 ±â€Š5.2) for all tissue samples (P < 0.05). CONCLUSION: Results from this study demonstrate that the lamellar and ITL compartments of the AF distribute strain unevenly during tissue loading. Specifically, shear strain is significantly higher in the ITL matrix, suggesting that these regions may be more susceptible to tissue damage and more mechanobiologically active. LEVEL OF EVIDENCE: N/A.

Mesoscopic Fluorescence Molecular Tomography for Evaluating Engineered Tissues.

Optimization of regenerative medicine strategies includes the design of biomaterials, development of cell-seeding methods, and control of cell-biomaterial interactions within the engineered tissues. Among these steps, one paramount challenge is to non-destructively image the engineered tissues in their entirety to assess structure, function, and molecular expression. It is especially important to be able to enable cell phenotyping and monitor the distribution and migration of cells throughout the bulk scaffold. Advanced fluorescence microscopic techniques are commonly employed to perform such tasks; however, they are limited to superficial examination of tissue constructs. Therefore, the field of tissue engineering and regenerative medicine would greatly benefit from the development of molecular imaging techniques which are capable of non-destructive imaging of three-dimensional cellular distribution and maturation within a tissue-engineered scaffold beyond the limited depth of current microscopic techniques. In this review, we focus on an emerging depth-resolved optical mesoscopic imaging technique, termed laminar optical tomography (LOT) or mesoscopic fluorescence molecular tomography (MFMT), which enables longitudinal imaging of cellular distribution in thick tissue engineering constructs at depths of a few millimeters and with relatively high resolution. The physical principle, image formation, and instrumentation of LOT/MFMT systems are introduced. Representative applications in tissue engineering include imaging the distribution of human mesenchymal stem cells embedded in hydrogels, imaging of bio-printed tissues, and in vivo applications.

Study of the cortical representation of whisker frequency selectivity using voltage-sensitive dye optical imaging.

The facial whiskers of rodents act as a high-resolution tactile apparatus that allow the animal to detect the finest details of its environment. Previously it was shown that whisker-sensitive neurons in the somatosensory cortex show frequency selectivity to small amplitude stimuli, An intravital voltage-sensitive dye optical imaging (VSDi) method in combination with the different frequency whisker stimulation was used in order to visualize neural activity in the mice somatosensory cortex in response to the stimulation of a single whisker by different frequencies. Using the intravital voltage-sensitive dye optical imaging (VSDi) method in combination with the different frequency whisker stimulation we visualized neural activity in the mice somatosensory cortex in response to the stimulation of a single whisker by different frequencies. We found that whisker stimuli with different frequencies led to different optical signals in the barrel field. Our results provide evidence that different neurons of the barrel cortex have different frequency preferences. This supports prior research that whisker deflections cause responses in cortical neurons within the barrel field according to the frequency of the stimulation. Many studies of the whisker frequency selectivity were performed using unit recording but to map spatial organization, imaging methods are essential. In the work described in the present paper, we take a serious step toward detailed functional mapping of the somatosensory cortex using VSDi. To our knowledge, this is the first demonstration of whisker frequency sensitivity and selectivity of barrel cortex neurons with optical imaging methods.