Structure Design and Heat Transfer Performance Analysis of a Novel Composite Phase Change Active Cooling Channel Wall for Hypersonic Aircraft.

Efficient and stable heat dissipation structure is crucial for improving the convective heat transfer performance of thermal protection systems (TPSs) for hypersonic aircraft. However, the heat dissipation wall of the current TPS is limited by a single material and structure, inefficiently dissipating the large amount of accumulated heat generated during the high-speed maneuvering flight of hypersonic aircraft. Here, a convection cooling channel structure of TPS is proposed, which is an innovative multi-level structure inspired by the natural honeycomb. An active cooling channel (PCM-HC) is designed by using a variable-density topology optimization method and filled with phase change material (PCM). Numerical simulations are used to investigate the thermal performance of the PCM-HC wall, focusing on the influence of PCM properties, structural geometric parameters, and PCM types on heat transfer characteristics. The results demonstrate that the honeycomb-like convection cooling channel wall, combined with PCM latent heat of phase change, exhibits superior heat dissipation capability. With a heat flux input of 50 kW/m2, the maximum temperature on the inner wall of PCM-HC is reduced by 12 K to 20 K. Different PCMs have opposing effects on heat transfer performance due to their distinct thermophysical properties. This work can provide a theoretical basis for the design of high-efficiency cooling channel, improving the heat dissipation performance in the TPS of hypersonic aircraft.

Effect of fence tray matching care on excess adhesive and bracket placement accuracy for orthodontic bonding: an in vitro study.

OBJECTIVE: This study aimed to evaluate the effect of fence tray matching care (FTMC) in bracket bonding by measuring excess adhesive, as well as linear and angular deviations, and by comparing it with the half-wrapped tray (HWT). MATERIALS AND METHODS: An intraoral scanner was used to acquire data on the maxillary dental arch of a patient with periodontitis.Furthermore, 20 maxillary dental arch models were 3D printed. Using 3Shape, PlastyCAD software, and 3D printing technology, 10 FTMC (method I) and HWT (method II) were obtained. By preoperative preparation, intraoperative coordination, and postoperative measurement, the brackets were transferred from the trays to the 3D-printed maxillary dental arch models. Additionally, the bracket's excess adhesive as well as linear and angular deviations were measured, and the differences between the two methods were analyzed. RESULTS: Excess adhesive was observed in both methods, with FTMC showing less adhesive (P< 0.001), with a statistical difference. Furthermore, HWT's vertical, tip and torque, which was significantly greater than FTMC (P< 0.05), with no statistical difference among other respects. The study data of incisors, canines, and premolars, showed that the premolars had more adhesive residue and were more likely to have linear and angular deviations. CONCLUSIONS: The FTMC had higher bracket bonding effect in comparison to HWT, and the adhesive residue, linear and angular deviations are smaller. The fence tray offers an intuitive view of the precise bonding of the bracket, and can remove excess adhesive to prevent white spot lesions via care, providing a different bonding method for clinical applications.

B-cell specific Moloney murine leukemia virus insertion site 1 contributes to invasion, metastasis, and poor prognosis in salivary adenoid cystic carcinoma.

Background/purpose: Upregulation of B-cell specific Moloney murine leukemia virus insertion site 1 (BMI-1) has been involved in the invasion, metastasis, and poor prognosis of many cancers. The aim of this study was to evaluate the levels and clinical significance of BMI-1 in saliva of patients with salivary adenoid cystic carcinoma (SACC), and to analyze biological function and mechanism of BMI-1 in the invasion and metastasis of SACC. Materials and methods: The levels of BMI-1 in saliva and tumor tissues of SACC patients were determined. The correlation of salivary BMI-1 levels with clinicopathological parameters and clinical outcomes in patients with SACC was analyzed. Additionally, the effects of BMI-1 on wound-healing, transwell invasion, and epithelial-mesenchymal transition (EMT)-related protein expression in vitro as well as on tumorigenicity and experimental lung metastasis in vivo were investigated through exogenous overexpression and silencing of BMI-1 in SACC cells. Results: BMI-1 levels increased in saliva and tumor tissues in SACC patients with invasion or metastasis. High salivary BMI-1 levels were correlated with poor TNM stage, poor overall survival, and disease-free survival. Exogenous expression of BMI-1 in SACC-83 promoted its migration and invasion, while silencing BMI-1 in SACC-LM inhibited its migration and invasion in vitro and suppressed tumorigenesis and lung metastasis in vivo. Furthermore, BMI-1 regulated the expression of EMT-related proteins in SACC. Conclusion: Our study shows that BMI-1 can serve as a valuable biomarker to identify tumor invasion and metastasis in SACC, predict its prognosis, and act as a promising therapeutic target for SACC.

Study on the application of quality control circle activity in postoperative nursing of elderly dental implants.

BACKGROUND: To explore the application effect of "quality control circle" activity in postoperative nursing of elderly dental implants. METHODS: From January 2022 to December 2022, a total of 60 elderly patients were selected and divided into an experimental group and a control group, with 30 cases in each group using the random number table method. The elderly patients with dental implants received postoperative care under the supervision of a quality control circle. The control group was treated with conventional nursing methods. The success rate, postoperative complications, and satisfaction of the 2 groups were compared. RESULTS: By comparing the postoperative care effect of the 2 groups of patients, the satisfaction of the experimental group and the control group was 93.3% and 73.3%, respectively, showing the satisfaction of the experimental group was higher than the control group (P < .05). The planting success rate of the experimental and control groups were 96.7% and 66.7%, respectively, with the experimental group outperforming the control group (P < .05). The proportion of complications in the experimental was found to be fewer (6.7%) than in the control group (33.3%) (P < .05). CONCLUSION: Quality control circle activities can effectively improve the success rate of dental implants, reduce the occurrence of postoperative complications, improve patient satisfaction, and help medical staff in providing better treatment for patients.

CD1d-dependent neuroinflammation impairs tissue repair and functional recovery following a spinal cord injury.

Tissue damage resulting from a spinal cord injury (SCI) is primarily driven by a robust neuroimmune/neuroinflammatory response. This intricate process is mainly governed by a multitude of cytokines and cell surface proteins in the central nervous system (CNS). However, the critical components of the neuroimmune/neuroinflammatory response during SCI are still not well-defined. In this study, we investigated the impact of CD1d, an MHC class I-like molecule mostly known for presenting lipid antigens to natural killer T (NKT) cells and regulating immune/inflammatory responses, on neuroimmune/neuroinflammatory responses induced by SCI. We observed an increased expression of CD1d on various cell types within the spinal cord, including microglia/macrophages, oligodendrocytes (ODCs), and endothelial cells (DCs), but not on neurons or astrocytes post-SCI. In comparison to wildtype (WT) mice, a T10 contusive SCI in CD1d knockout (CD1dKO or Cd1d -/- ) mice resulted in markedly reduced proinflammatory cytokine release, microglia/macrophage activation and proliferation. Following SCI, the levels of inflammatory cytokines and activation/proliferation of microglia/macrophages were dramatically reduced, while anti-inflammatory cytokines such as IL-4 and growth factors like VEGF were substantially increased in the spinal cord tissues of CD1dKO mice when compared to WT mice. In the post-acute phase of SCI (day 7 post-SCI), CD1dKO mice had a significantly higher frequency of tissue-repairing macrophages, but not other types of immune cells, in the injured spinal cord tissues compared to WT mice. Moreover, CD1d-deficiency protected spinal cord neuronal cells and tissue, promoting functional recovery after a SCI. However, the neuroinflammation in WT mouse spinal cords was independent of the canonical CD1d/NKT cell axis. Finally, treatment of injured mice with a CD1d-specific monoclonal antibody significantly enhanced neuroprotection and improved functional recovery. Therefore, CD1d promotes the proinflammatory response following a SCI and represents a potential therapeutic target for spinal cord repair. Significance Statement: The cell surface molecule, CD1d, is known to be recognized by cells of the immune system. To our knowledge, this is the first observation that the CD1d molecule significantly contributes to neuroinflammation following a spinal cord injury (SCI) in a manner independent of the CD1d/NKT cell axis. This is important, because this work reveals CD1d as a potential therapeutic target following an acute SCI for which there are currently no effective treatments.

A Review of Energy Supply for Biomachine Hybrid Robots.

Biomachine hybrid robots have been proposed for important scenarios, such as wilderness rescue, ecological monitoring, and hazardous area surveying. The energy supply unit used to power the control backpack carried by these robots determines their future development and practical application. Current energy supply devices for control backpacks are mainly chemical batteries. To achieve self-powered devices, researchers have developed solar energy, bioenergy, biothermal energy, and biovibration energy harvesters. This review provides an overview of research in the development of chemical batteries and self-powered devices for biomachine hybrid robots. Various batteries for different biocarriers and the entry points for the design of self-powered devices are outlined in detail. Finally, an overview of the future challenges and possible directions for the development of energy supply devices used to biomachine hybrid robots is provided.

Controllable adhesive mechanisms via the internal fibers in soft footpads of honeybees.

The dynamic adhesive systems in nature have served as inspirations for the development of intelligent adhesive surfaces. However, the mechanisms underlying the rapid controllable contact adhesion observed in biological systems have never been adequately explained. Here, the control principle for the unfolding adhesive footpads (alterable contact area) of honeybees is investigated. The footpads can passively unfold, even without neuro-muscular reflexes, in response to specific dragging activity (generating shear force) toward their bodies. This passive unfolding is attributed to the structural features of the soft footpads, which cooperate closely with shear force. Then, the hierarchical structures supported by numerous branching fibers were observed and analyzed. Experimental and theoretical findings demonstrated that shear force can decrease fibril angles with respect to the shear direction, which consequently induces the rotation of the interim contact area of the footpads and achieves their passive unfolding. Furthermore, the decrease in fibril angles can lead to an increase in the liquid pressure within the footpads, and subsequently enhance their unfolding. This study presents a novel approach for passively controlling the contact areas in adhesive systems, which can be applied to develop various bioinspired switchable adhesive surfaces.

Accuracy of Microimplant Placement Using a 3D Guide Plate for Orthodontic Anchorage.

This study aimed to design a three-dimensional (3D) guide plate using computer-aided design and a 3D printing system for precise implantation of microimplants for orthodontic treatment and investigate the accuracy and feasibility of a 3D guide plate in clinical practice. A total of 30 microimplants were placed in 15 patients in the Department of Stomatology, Affiliated Hospital of Jiangnan University. Before surgery, DICOM data from cone-beam computed tomography (CBCT) scans and STereoLithography data from the 3D model scan were imported to 3Shape Dental System. Data fitting and matching were performed, and 3D guide plates were designed primarily focusing on the thickness of guide plates, amount of concave compensation, and dimensions of the ring. Assist implantation method was used to place the microimplants, and postoperative CBCT images were used to evaluate the position and implantation angle. The feasibility of placing microimplants and precise implantation guided by the 3D guide plate. CBCT data before and after the placement of microimplants were compared. Regarding the secure positioning of microimplants based on CBCT data, 26 implants were categorized as Grade i, four as Grade ii, and none as Grade iii. No loosening of microimplants 1 and 3 months after surgery was reported. The implantation of microimplants is more accurate under the guidance of a 3D guide plate. This technology can achieve accurate implant positioning, thus ensuring safety, stability, and improved success rates after implantation.

Restoring mitochondrial cardiolipin homeostasis reduces cell death and promotes recovery after spinal cord injury.

Alterations in phospholipids have long been associated with spinal cord injury (SCI). However, their specific roles and signaling cascades in mediating cell death and tissue repair remain unclear. Here we investigated whether alterations of cardiolipin (CL), a family of mitochondrion-specific phospholipids, play a crucial role in mitochondrial dysfunction and neuronal death following SCI. Lipidomic analysis was used to determine the profile of CL alteration in the adult rat spinal cord following a moderate contusive SCI at the 10th thoracic (T10) level. Cellular, molecular, and genetic assessments were performed to determine whether CL alterations mediate mitochondrial dysfunction and neuronal death after SCI, and, if so, whether reversing CL alteration leads to neuroprotection after SCI. Using lipidomic analysis, we uncovered CL alterations at an early stage of SCI. Over 50 distinct CL species were identified, of which 50% showed significantly decreased abundance after SCI. The decreased CL species contained mainly polyunsaturated fatty acids that are highly susceptible to peroxidation. In parallel, 4-HNE, a lipid peroxidation marker, significantly increased after SCI. We found that mitochondrial oxidative stress not only induced CL oxidation, but also resulted in CL loss by activating cPLA2 to hydrolyze CL. CL alterations induced mitochondrial dysfunction and neuronal death. Remarkably, pharmacologic inhibition of CL alterations with XJB-5-131, a novel mitochondria-targeted electron and reactive oxygen species scavenger, reduced cell death, tissue damage and ameliorated motor deficits after SCI in adult rats. These findings suggest that CL alteration could be a novel mechanism that mediates injury-induced neuronal death, and a potential therapeutic target for ameliorating secondary SCI.

Transhemispheric cortex remodeling promotes forelimb recovery after spinal cord injury.

Understanding the reorganization of neural circuits spared after spinal cord injury in the motor cortex and spinal cord would provide insights for developing therapeutics. Using optogenetic mapping, we demonstrated a transhemispheric recruitment of neural circuits in the contralateral cortical M1/M2 area to improve the impaired forelimb function after a cervical 5 right-sided hemisection in mice, a model mimicking the human Brown-Séquard syndrome. This cortical reorganization can be elicited by a selective cortical optogenetic neuromodulation paradigm. Areas of whisker, jaw, and neck, together with the rostral forelimb area, on the motor cortex ipsilateral to the lesion were engaged to control the ipsilesional forelimb in both stimulation and nonstimulation groups 8 weeks following injury. However, significant functional benefits were only seen in the stimulation group. Using anterograde tracing, we further revealed a robust sprouting of the intact corticospinal tract in the spinal cord of those animals receiving optogenetic stimulation. The intraspinal corticospinal axonal sprouting correlated with the forelimb functional recovery. Thus, specific neuromodulation of the cortical neural circuits induced massive neural reorganization both in the motor cortex and spinal cord, constructing an alternative motor pathway in restoring impaired forelimb function.

A biopolymer hydrogel electrostatically reinforced by amino-functionalized bioactive glass for accelerated bone regeneration.

Composite hydrogels incorporating natural polymers and bioactive glass (BG) are promising materials for bone regeneration. However, their applications are compromised by the poor interfacial compatibility between organic and inorganic phases. In this study, we developed an electrostatically reinforced hydrogel (CAG) with improved interfacial compatibility by introducing amino-functionalized 45S5 BG to the alginate/gellan gum (AG) matrix. BAG composed of AG and unmodified BG (10 to 100 µm in size) was prepared as a control. Compared with BAG, CAG had a more uniform porous structure with a pore size of 200 µm and optimal compressive strength of 66 kPa. Furthermore, CAG promoted the M2 phenotype transition of macrophages and up-regulated the osteogenic gene expression of stem cells. The new bone formation in vivo was also accelerated due to the enhanced biomineralization of CAG. Overall, this work suggests CAG with improved interfacial compatibility is an ideal material for bone regeneration application.

Analysis of Carbapenemase-Resistant Genotypes of Highly Virulent Klebsiella pneumoniae and Clinical Infection Characteristics of Different MLST Types.

Carbapenemase-resistant Klebsiella pneumoniae (CR-KP) has become one of the nosocomial infections that seriously threaten the lives of patients, greatly increasing the burden on patients. In order to explore the resistance mechanism of clinically isolated CR-KP to carbapenems and perform multilocus sequence typing (MLST), to study the clinical characteristics of patients with different ST types of infection, we collected 74 CR-KP strains clinically isolated from the main 6 hospitals in Zhejiang province from January 2018 to July 2020. The sensitivity of the tested strains to 23 antibacterial drugs was determined by the microbroth dilution method, and PCR was applied. Gene amplification technology and DNA sequencing methods were used to detect the carbapenemase gene of the tested strains. Through the MLST of the tested strains, the clonal correlation and molecular epidemiological characteristics of the tested strains were explored, and the characteristics of CR-KP resistance, resistance mechanisms, and clinical characteristics of bacterial infections under different MLST types were analyzed at the same time. The results showed that 74 carbapenem-resistant Klebsiella pneumoniae strains showed high resistance to 21 commonly used antibacterial drugs, and all carbapenemase phenotypic screening tests were positive. MLST typing showed that 74 CR-KP strains had 17 ST typings, and ST11 was the dominant type (54.05%). The study also found that these ST11 strains are more likely to be resistant to carbapenem antibiotics. Most of them produce KPC carbapenemase, and a few are IMP, VIM, and NDM. Univariate analysis suggested that the proportion of patients in the ST11 group receiving treatment in ICU, the use rate of mechanical ventilation, and the proportion of drainage tube indwelling were higher than those in the non-ST11 group, and the survival rate of the ST11 group was lower than that of the non-ST11 group. Clinical data suggested that the same hospital was dominated by the same clonal epidemic in the same period. In view of the analysis of clinical data suggesting that patients who have received ICU treatment, mechanical ventilation, and drainage tube indwelling are prone to the risk of CR-KP strain (especially ST11) infection and low survival rate, such patients should arouse extensive clinical attention.

Melatonin prevents peri­implantitis via suppression of TLR4/NF-κB.

Peri­implantitis, which is characterized by peri­implant mucositis and alveolar bone resorption, significantly shortens the service life of dental implants. Melatonin is well-known for its anti-inflammatory and osteoprotective activities. Nevertheless, the effects and mechanisms of melatonin to prevent peri­implantitis remain unknown. In this study, the lipopolysaccharide-induced peri­implantitis model was established after the titanium implants were osseointegrated, and the rats received daily administrations of melatonin. The gingival fibroblasts and osteoclasts/osteoblasts were also co-cultured to simulate the inflammatory environment in vitro. We found that prophylactic administration of melatonin decreased proinflammatory cytokine levels and osteoclast numbers, attenuated alveolar bone resorption, and reduced the incidence of peri­implantitis in vivo. Furthermore, melatonin suppressed osteoclastic formation and function in the inflammatory co-culture environment, while melatonin promoted osteoblastic differentiation and function in the in vitro model. Mechanistically, melatonin reduced TLR4 protein levels, and inhibited activation of NF-κB to downregulate the levels of TNF, IL-1ß, and IL-6. These data showed that melatonin was a potent agent to prevent peri­implantitis through inhibiting TLR4/NF-κB signaling. Our findings provide a novel strategy to prevent peri­implantitis, and expand the applications of melatonin. STATEMENT OF SIGNIFICANCE: Dental implants have become the first choice for restoring partial and full edentulism, but its service life is seriously affected by peri­implantitis. Exploration of novel and effective approaches to prevent peri­implantitis is an important and urgent need. In the present study, we have reported for the first time that prophylactic administration of melatonin delayed the occurrence and reduced the incidence of peri­implantitis by decreasing proinflammatory cytokine levels, inhibiting osteoclastogenesis, and promoting osteogenesis. The study is expected to have an important significance on the prevention of peri­implantitis.

Circ_0008542 in osteoblast exosomes promotes osteoclast-induced bone resorption through m6A methylation.

With an increasing aging society, China is the world's fastest growing markets for oral implants. Compared with traditional oral implants, immediate implants cause marginal bone resorption and increase the failure rate of osseointegration, but the mechanism is still unknown. Therefore, it is important to further study mechanisms of tension stimulus on osteoblasts and osteoclasts at the early stage of osseointegration to promote rapid osseointegration around oral implants. The results showed that exosomes containing circ_0008542 from MC3T3-E1 cells with prolonged tensile stimulation promoted osteoclast differentiation and bone resorption. Circ_0008542 upregulated Tnfrsf11a (RANK) gene expression by acting as a miR-185-5p sponge. Meanwhile, the circ_0008542 1916-1992 bp segment exhibited increased m6A methylation levels. Inhibiting the RNA methyltransferase METTL3 or overexpressing the RNA demethylase ALKBH5 reversed osteoclast differentiation and bone resorption induced by circ_0008542. Injection of circ_0008542 + ALKBH5 into the tail vein of mice reversed the same effects in vivo. Site-directed mutagenesis study demonstrated that 1956 bp on circ_0008542 is the m6A functional site with the abovementioned biological functions. In conclusion, the RNA methylase METTL3 acts on the m6A functional site of 1956 bp in circ_0008542, promoting competitive binding of miRNA-185-5p by circ_0008542, and leading to an increase in the target gene RANK and the initiation of osteoclast bone absorption. In contrast, the RNA demethylase ALKBH5 inhibits the binding of circ_0008542 with miRNA-185-5p to correct the bone resorption process. The potential value of this study provides methods to enhance the resistance of immediate implants through use of exosomes releasing ALKBH5.

Disrupting nNOS-PSD95 Interaction Improves Neurological and Cognitive Recoveries after Traumatic Brain Injury.

Excessive activation of N-methyl-D-aspartate receptors (NMDARs) and the resulting neuronal nitric oxide synthase (nNOS) activation plays a crucial role in the pathogenesis of traumatic brain injury (TBI). However, directly inhibiting NMDARs or nNOS produces adverse side effects because they play key physiological roles in the normal brain. Since interaction of nNOS-PSD95 is a key step in NMDAR-mediated excitotoxicity, we investigated whether disrupting nNOS-PSD95 interaction with ZL006, an inhibitor of nNOS-PSD95 interaction, attenuates NMDAR-mediated excitotoxicity. In cortical neuronal cultures, ZL006 treatment significantly reduced glutamate-induced neuronal death. In a mouse model of controlled cortical impact (CCI), administration of ZL006 (10 mg/kg, i.p.) at 30 min postinjury significantly inhibited nNOS-PSD95 interaction, reduced TUNEL- and phospho-p38-positive neurons in the motor cortex. ZL006 treatment also significantly reduced CCI-induced cortical expression of apoptotic markers active caspase-3, PARP-1, ratio of Bcl-2/Bax, and phosphorylated p38 MAPK (p-p38). Functionally, ZL006 treatment significantly improved neuroscores and sensorimotor performance, reduced somatosensory and motor deficits, reversed CCI-induced memory deficits, and attenuated cognitive impairment. Histologically, ZL006 treatment significantly reduced the brain lesion volume. These findings collectively suggest that blocking nNOS-PSD95 interaction represents an attractive strategy for ameliorating consequences of TBI and that its action is mediated via inhibiting neuronal apoptosis and p38 MAPK signaling.

Sulforaphane prevents PC12 cells from oxidative damage via the Nrf2 pathway.

The aim of this study was to investigate the protective effect of sulforaphane (SFN) on 1­methyl­4­phenyl pyridine ion (MPP+)­induced cytotoxicity and to investigate its possible mechanisms. METHODS: PC12 cell toxicity induced by MPP+ served as a cell model of Parkinson's diseases. The cell culture + experiments were divided into four groups based on the different treatments, namely, vehicle control, SFN, MPP+ and SFN pretreatment plus MPP+. Cell viability and apoptosis were examined by MTT assay and flow cytometry, respectively. Expressions of nuclear factor erythroid 2­related factor 2 (Nrf2), heme oxygenase 1 (HO­1) and nicotinamide quinone oxidoreductase 1 (NQO1) were detected using western blotting. RESULTS: MPP+ reduced the survival rate of PC12 cells in a dose­ and time­dependent manner. After 24­h treatment with 500 µmol/l MPP+, the survival rate of PC12 cells decreased to 58.2±0.03% of that in the control groups. Under the same conditions MPP+ resulted in significant apoptosis of PC12 cells (apoptosis rate: 30.4±0.6%). However, SFN pretreatment significantly attenuated the cell damage induced by MPP+. Furthermore, it was demonstrated that SFN reversed the reduction of Nrf2, HO­1 and NQO1 expression induced by MPP+. CONCLUSION: SFN may protect PC12 cells from MPP+­induced damage via activating the Nrf2­ARE (antioxidant responsive element) pathway.

Bisperoxovanadium Mediates Neuronal Protection through Inhibition of PTEN and Activation of PI3K/AKT-mTOR Signaling after Traumatic Spinal Injuries.

Although mechanisms involved in progression of cell death in spinal cord injury (SCI) have been studied extensively, few are clear targets for translation to clinical application. One of the best-understood mechanisms of cell survival in SCI is phosphatidylinositol-3-kinase (PI3K)/Akt and associated downstream signaling. Clear therapeutic efficacy of a phosphatase and tensin homologue (PTEN) inhibitor called bisperoxovanadium (bpV) has been shown in SCI, traumatic brain injury, stroke, and other neurological disease models in both neuroprotection and functional recovery. The present study aimed to elucidate mechanistic influences of bpV activity in neuronal survival in in vitro and in vivo models of SCI. Treatment with 100 nM bpV(pic) reduced cell death in a primary spinal neuron injury model (p < 0.05) in vitro, and upregulated both Akt and ribosomal protein S6 (pS6) activity (p < 0.05) compared with non-treated injured neurons. Pre-treatment of spinal neurons with a PI3K inhibitor, LY294002 or mammalian target of rapamycin (mTOR) inhibitor, rapamycin blocked bpV activation of Akt and ribosomal protein S6 activity, respectively. Treatment with bpV increased extracellular signal-related kinase (Erk) activity after scratch injury in vitro, and rapamycin reduced influence by bpV on Erk phosphorylation. After a cervical hemicontusive SCI, Akt phosphorylation decreased in total tissue via Western blot analysis (p < 0.01) as well as in penumbral ventral horn motor neurons throughout the first week post-injury (p < 0.05). Conversely, PTEN activity appeared to increase over this period. As observed in vitro, bpV also increased Erk activity post-SCI (p < 0.05). Our results suggest that PI3K/Akt signaling is the likely primary mechanism of bpV action in mediating neuroprotection in injured spinal neurons.

A Laser-Guided Spinal Cord Displacement Injury in Adult Mice.

Mouse models are unique for studying molecular mechanisms of neurotrauma because of the availability of various genetic modified mouse lines. For spinal cord injury (SCI) research, producing an accurate injury is essential, but it is challenging because of the small size of the mouse cord and the inconsistency of injury production. The Louisville Injury System Apparatus (LISA) impactor has been shown to produce precise contusive SCI in adult rats. Here, we examined whether the LISA impactor could be used to create accurate and graded contusive SCIs in mice. Adult C57BL/6 mice received a T10 laminectomy followed by 0.2, 0.5, and 0.8 mm displacement injuries, guided by a laser, from the dorsal surface of the spinal cord using the LISA impactor. Basso Mouse Scale (BMS), grid-walking, TreadScan, and Hargreaves analyses were performed for up to 6 weeks post-injury. All mice were euthanized at the 7th week, and the spinal cords were collected for histological analysis. Our results showed that the LISA impactor produced accurate and consistent contusive SCIs corresponding to mild, moderate, and severe injuries to the cord. The degree of injury severities could be readily determined by the BMS locomotor, grid-walking, and TreadScan gait assessments. The cutaneous hyperalgesia threshold was also significantly increased as the injury severity increased. The terminal lesion area and the spared white matter of the injury epicenter were strongly correlated with the injury severities. We conclude that the LISA device, guided by a laser, can produce reliable graded contusive SCIs in mice, resulting in severity-dependent behavioral and histopathological deficits.

Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery.

Retrogradely-transported neurotrophin signaling plays an important role in regulating neural circuit specificity. Here we investigated whether targeted delivery of neurotrophin-3 (NT-3) to lumbar motoneurons (MNs) caudal to a thoracic (T10) contusive spinal cord injury (SCI) could modulate dendritic patterning and synapse formation of the lumbar MNs. In vitro, Adeno-associated virus serotype two overexpressing NT-3 (AAV-NT-3) induced NT-3 expression and neurite outgrowth in cultured spinal cord neurons. In vivo, targeted delivery of AAV-NT-3 into transiently demyelinated adult mouse sciatic nerves led to the retrograde transportation of NT-3 to the lumbar MNs, significantly attenuating SCI-induced lumbar MN dendritic atrophy. NT-3 enhanced sprouting and synaptic formation of descending serotonergic, dopaminergic, and propriospinal axons on lumbar MNs, parallel to improved behavioral recovery. Thus, retrogradely transported NT-3 stimulated remodeling of lumbar neural circuitry and synaptic connectivity remote to a thoracic SCI, supporting a role for retrograde transport of NT-3 as a potential therapeutic strategy for SCI.

Transglutaminase 3 contributes to malignant transformation of oral leukoplakia to cancer.

Oral leukoplakia (OL) is the most common premalignancy in the oral cavity. The objective of this study was to investigate the biological role of transglutaminase 3 (TGM3) in malignant transformation of OL and its clinical value for predicting oral squamous cell carcinoma (OSCC) risk in patients with OL. Immunohistochemistry was used to measure TGM3 expression in OL samples from 98 patients. Patient clinicopathological and follow-up data were analyzed. The TGM3 biological role in OL cells was investigated in gain-of-function and loss-of-function assays, and the TGM3 downregulated mechanism in OLs was characterized. TGM3 mRNA and protein expressions were frequently downregulated in OL cells and samples. DNA hypermethylation was a mechanism of TGM3 downregulation. TGM3 overexpression and silencing affected the proliferation, colony formation, and apoptosis of OL cells through apoptosis-related protein dysregulations. Lower TGM3 levels were strongly associated with the grade of epithelial dysplasia and OSCC development. Multivariate analyses showed that TGM3 was the independent predictor for malignant transformation of OL. Collectively, these data indicated that TGM3 played an important role in OL malignant transformation and may serve as a predictor to identify OL with OSCC development.