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The anatomical structure of the mammalian cerebral cortex is the essential foundation for its complex neural activity. This structure is developed by proliferation, differentiation, and migration of neural progenitor cells (NPCs), the fate of which is spatially and temporally regulated by the proper gene. This study was used in utero electroporation and found that the well-known oncogene c-Myc mainly promoted NPCs' proliferation and their transformation into intermediate precursor cells. Furthermore, the obtained results also showed that c-Myc blocked the differentiation of NPCs to postmitotic neurons, and the expression of telomere reverse transcriptase was controlled by c-Myc in the neocortex. These findings indicated c-Myc as a key regulator of the fate of NPCs during the development of the cerebral cortex.

Although several genes have been identified to promote axon regeneration in the CNS, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using female mouse sensory axon and optic nerve regeneration as model systems, we reveal an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provide evidence that TERT and p53 act downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells is sufficient to promote sensory axon and optic never regeneration, respectively. The study reveals a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration.SIGNIFICANCE STATEMENTDespite significant progress during the past decade, our understanding of the molecular mechanisms by which mammalian CNS axon regeneration is regulated is still fragmented. By using sensory axon and optic nerve regeneration as model systems, the study revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. The results also delineated a c-Myc-TERT-p53 pathway in controlling axon growth. Last, our results demonstrated that p53 alone was sufficient to promote sensory axon and optic nerve regenerationin vivo. Collectively, the study not only revealed a new mechanisms underlying mammalian axon regeneration, but also expanded the pool of potential targets that can be manipulated to enhance CNS axon regeneration.

While axon regeneration is a key determinant of functional recovery of the nervous system after injury, it is often poor in the mature nervous system. Influx of extracellular calcium (Ca2+ ) is one of the first phenomena that occur following axonal injury, and calcium/calmodulin-dependent protein kinase II (CaMKII), a target substrate for calcium ions, regulates the status of cytoskeletal proteins such as F-actin. Herein, we found that peripheral axotomy activates CaMKII in dorsal root ganglion (DRG) sensory neurons, and inhibition of CaMKII impairs axon outgrowth in both the peripheral and central nervous systems (PNS and CNS, respectively). Most importantly, we also found that the activation of CaMKII promotes PNS and CNS axon growth, and regulatory effects of CaMKII on axon growth occur via affecting the length of the F-actin. Thus, we believe our findings provide clear evidence that CaMKII is a critical modulator of mammalian axon regeneration.

The inflammatory response is a critical regulator for the regeneration of axon following nervous system injury. Nuclear factor-kappa B (NF-κB) is characteristically known for its ubiquitous role in the inflammatory response. However, its functional role in adult mammalian axon growth remains elusive. Here, we found that the NF-κB signaling pathway is activated in adult sensory neurons through peripheral axotomy. Furthermore, inhibition of NF-κB in peripheral sensory neurons attenuated their axon growth in vitro and in vivo. Our results also showed that NF-κB modulated axon growth by repressing the phosphorylation of STAT3. Furthermore, activation of STAT3 significantly promoted adult optic nerve regeneration. Taken together, the findings of our study indicated that NF-κB/STAT3 cascade is a critical regulator of intrinsic axon growth capability in the adult nervous system.

The matrix remodeling associated 7 (MXRA7) gene had been ill-studied and its biology remained to be discovered. Inspired by our previous findings and public datasets concerning MXRA7, we hypothesized that the MXRA7 gene might be involved in bone marrow mesenchymal stem cells (BMSCs) functions related to bone formation, which was checked by utilizing in vivo or in vitro methodologies. Micro-computed tomography of MXRA7-deficient mice demonstrated retarded osteogenesis, which was reflected by shorter femurs, lower bone mass in both trabecular and cortical bones compared with wild-type (WT) mice. Histology confirmed the osteopenia-like feature including thinner growth plates in MXRA7-deficient femurs. Immunofluorescence revealed less osteoblasts in MXRA7-deficient femurs. Polymerase chain reaction or western blot analysis showed that when WT BMSCs were induced to differentiate toward osteoblasts or adipocytes in culture, MXRA7 messenger RNA or protein levels were significantly increased alongside osteoblasts induction, but decreased upon adipocytes induction. Cultured MXRA7-deficient BMSCs showed decreased osteogenesis upon osteogenic differentiation induction as reflected by decreased calcium deposition or lower expression of genes responsible for osteogenesis. When recombinant MXRA7 proteins were supplemented in a culture of MXRA7-deficient BMSCs, osteogenesis or gene expression was fully restored. Upon osteoblast induction, the level of active β-catenin or phospho-extracellular signal-regulated kinase in MXRA7-deficient BMSCs was decreased compared with that in WT BMSCs, and these impairments could be rescued by recombinant MXRA7 proteins. In adipogenesis induction settings, the potency of MXRA7-deficient BMSCs to differentiate into adipocytes was increased over the WT ones. In conclusion, this study demonstrated that MXRA7 influences bone formation via regulating the balance between osteogenesis and adipogenesis in BMSCs.

Beneficial actions of EGb 761 against ischemia/reperfusion (I/R) injury in lung, brain and renal ischemia have been described. However, the relationship between EGb 761 and signal molecules in myocardial ischemia reperfusion has not been well elucidated. In this study, we investigated the effects and mechanism of EGb 761 preconditioning on anti-myocardial I/R injuries in vivo. Meanwhile, their potential anti-oxidative stress and anti-inflammation effect were assessed. Hemodynamic parameters were monitored as left ventricular systolic pressure, LV end-diastolic pressure and maximal rate of increase and decrease of left ventricular pressure (dP/dtmax). The oxidative stress indicators and inflammatory factors were also evaluated. Western blot method was used for analysis of toll-like receptor 4 (TLR4), p-TLR4, nuclear factor-κB (NF-κB), p-NF-κB p65, Bax and Bcl-2 protein expressions. EGb 761 significantly improved cardiac function, decreased levels of creatine kinase, aspartate aminotransferase and lactate dehydrogenase. EGb 761 also restrained the oxidative stress related to myocardial ischemia injury as evidenced by decreased malondialdehyde, superoxide dismutase, catalase, glutathione-peroxidase, glutathione reductase activity. Meanwhile, the inflammatory cascade was inhibited as evidenced by decreased cytokines such as tumor necrosis factor-α, interleukin-6 and interleukin-1β. Our results still showed that EGb 761 pretreatment significantly decrease the level of cleaved Bax, and increase the level of Bcl-2 in rats subjected to I/R injury. Simultaneously, the expressions of myocardial TLR4 and NF-κB were significantly decreased. It can be concluded that EGb 761 pretreatment was protected against myocardium I/R injury by decreasing oxidative stress, repressing inflammatory cascade in vivo and inhibiting TLR4/NF-κB pathway.

A sensitive, rapid, precise and specific analytical method of hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (HILIC-UHPLC–QTRAP®/MS2) combined with a high-efficiency and easy sample preparation technology of ultrasound-assisted ionic liquid dispersive liquid–liquid microextraction (UA-IL-DLLME) was developed to investigate neurotransmitters (NTs) in mild cognitive impairment, mild dementia and moderate dementia patients’ urine samples. Firstly, the UA-IL-DLLME parameters were optimized using Plackett–Burman screening and rotatable central composite design, and the main optimal conditions were obtained: ultrasound power of 307 W, ultrasound time of 4.3 min and agitation time of 4.8 min. Secondly, HILIC-UHPLC–QTRAP®/MS2 method was developed to simultaneously determine 15 underivatized NTs in urine samples. The analysis results of clinical samples showed that some NTs such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamic acid (Glu) presented significant differences in different dementia stages. Finally, multivariate analysis based on the combination of principal component analysis and supervised counter propagation artificial neural network was developed for comprehensive analysis of the obtained clinical data sets. As a result, GABA and Glu were simultaneously presented meaningful contribution for classification of samples, and might be considered as potential differential compounds to the urine samples from cluster patients with different dementia stages. In summary, the presented strategy of preparation, analysis and statistics might be used to investigate NTs in different clinical biological fluids.

SummaryAlthough several genes have been identified to promote axon regeneration in the central nervous system, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using sensory axon and optic nerve regeneration as model systems, we revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provided strong evidence that TERT and p53 acted downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells (RGCs) was sufficient to promote sensory axon and optic never regeneration, respectively. The study revealed a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration.

While axon regeneration is a key determinant of functional recovery of the nervous system after injury, it is often poor in the mature nervous system. Influx of extracellular calcium (Ca2+) is one of the first phenomena that occur following axonal injury, and calcium/calmodulin-dependent protein kinase (CaMKII), a target protein for calcium ions, regulates the status of cytoskeletal proteins such as F-actin. Herein, we found that peripheral axotomy activates CaMKII in dorsal root ganglion (DRG) sensory neurons, and inhibition of CaMKII impairs axon growth in both the peripheral and central nervous systems (PNS and CNS, respectively). Most importantly, we also found that activation of CaMKII promotes PNS and CNS axon growth, and regulatory effects of CaMKII on axon growth occur via affecting the length of the F-actin. Thus, we believe our findings provide clear evidence that CaMKII is a critical modulator of mammalian axon regeneration.

In this work, the solid–liquid phase equilibrium data for ternary system of adipic acid + glutaric acid + ethanol were measured using an isothermal saturation method at the three temperatures of 283.15, 303.15, and 313.15 K under 101.3 kPa. Three isothermal phase diagrams were built according to the measured solubility data. There were two pure solids formed in the ternary system at a given temperature, which corresponded to pure adipic acid and pure glutaric acid, and were confirmed by Schreinemaker's method of wet residue. The crystallization region of glutaric acid was smaller than that of adipic acid at each temperature. Two thermodynamic models, NRTL and Wilson were employed to correlate and calculate the mutual solubility data for the ternary adipic acid + glutaric acid + ethanol system. Results indicated that calculated results with NRTL model agreed well than those with Wilson model. Furthermore, the densities of the equilibrium liquid phase were obtained and correlated with an empirical equation.

Sm3+-doped β-dicalcium silicate (β-Ca2SiO4: Sm3+) was resoundingly prepared by the traditional high-temperature solid-state reaction method. The crystal structure, morphology and composition of β-Ca2SiO4: Sm3+ before and after mineralization was characterized by X-ray diffractometer (XRD), fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), respectively. The luminescence properties of β-Ca2SiO4: Sm3+ before and after mineralization were investigated by luminescence spectroscopy. The results show that Sm3+ ion has the effect of stabilizing β-Ca2SiO4 and β-Ca2SiO4: Sm3+ has good biological activity and can be converted to hydroxyapatite (HA) in simulated body fluid. Meanwhile, with the prolongation of mineralization time, the luminescence intensity of Sm3+ ion decreased gradually, and the CIE chromaticity coordinates moved from orange region to yellow green region. This suggests that the evolution of luminescence properties can be used as an obvious qualitative feature to monitor the mineralization process of β-Ca2SiO4: Sm3+.

Background Steroids such as glucocorticoid have been widely used for their excellent anti-inflammatory, anti-immune, and anti-shock properties. However, the long-term use in high doses has been found to cause necrosis of femoral head and other serious adverse reactions. Thus, it is of great importance to safely use these medications on patients without inducing bone necrosis. Methods In this preclinical study, we examined the effects of erythropoietin (EPO) to attenuate the induction of steroid-induced femoral bone necrosis using rats to build up the in-vivo models. Rats were randomly divided into three groups: negative control group (group A), disease group (group B), and EPO group (group C). 20 mg/kg methylprednisolone was administrated into group B and group C for 6 weeks with two intramuscular injections per week per rat. Group C was further given daily intraperitoneal injections of rHuEPO during this period. Group A received only injection of saline at the same schedule. 12 weeks after the initial drug administration, the rats’ femoral tissues were harvested for HE staining, immunohistochemistry studies for PECAM-1(also CD31) expression and Western Blotting for VEGF expression. Results Histology studies showed that compared with the disease group, EPO group had significant improvement and bone morphology being much closer to the negative control group. Immunohistochemical studies revealed that EPO group had statistically much more expression of PECAM-1 than the other groups did. Western Blot demonstrated that the EPO group had significantly higher VEGF expression than the disease group. Conclusion Results suggested that simultaneous injection of EPO could partially prevent steroid-induced ANFH.

In this paper, we summarized the existing three-dimensional virtual human body model representation method with real-time and realistic requirements as a starting point, and proposed several virtual human motion rendering method to realize virtual human real-time drawing.

A Gram-negative, strictly aerobic, yellow-pigmented and rod-shaped bacterium, designated strain NSL10(T), was isolated from the waste surface soil of a chemical factory in Hongan, China. Strain NSL10(T) was found to grow optimally at pH 7.0, 30 °C and in the absence of NaCl in modified LB medium. Cells were found to be positive for catalase and oxidase. The G+C content of the total DNA was determined to be 66.8 mol%. The 16S rRNA gene sequence of strain NSL10(T) showed the highest similarity to that of Devosia albogilva IPL15(T) (96.80 %), followed by Devosia geojensis BD-c194(T) (96.46 %) and Devosia chinhatensis IPL18(T) (96.27 %). The major cellular fatty acids of strain NSL10(T) were identified as C18:1 ω7c/C18:1 ω6c (48.2 %) and C16:0 (17.7 %). The major polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids and an unidentified compound. Minor amounts of unidentified glycolipids and unidentified polar lipids were also detected. These chemotaxonomic data supported the affiliation of strain NSL10(T) to the genus Devosia. In conclusion, on the basis of biochemical, physiological characteristics and molecular properties, strain NSL10(T) represents a novel species within the genus Devosia, for which the name Devosia honganensis sp. nov., is proposed. The type strain is NSL10(T) (=KCTC 42281(T) = ACCC 19737(T)).

RF Hyperthermia has received much attention due to its noninvasive nature in cancer treatment. Precise measurement of the electric field in RF hyperthermia system is of critical importance in the control of heating effect and treatment. In this paper, a comparative measurement method of the electric field intensity of a 13.56MHz RF heating system is presented. A calibrated dipole antenna was utilized to measure the electric field of the applicator. In comparison with the results measured by the capacitance partial voltage technique, it is found that the two methods are in good agreement with each other with an accuracy of 92%.

This paper doing research on the technology of multiple virtual human’s rendering. With the problem of too much triangular patches needed to be rendering ,make improvement on the technology of instancing based on GPU and combinate the method of LOD, put forward the algorithm of large-scale animated virtual human rendering based on instancing. This algorithm reduces the communicating overhead between CPU and GPU, raises the efficiency of large-scale animated virtual human rendering.

Objective: To systematically investigate the main active components, targets, target-related diseases and action mechanism of Yiyi Fuzi Baijiang powder (YFBP) of Zhang Zhongjing, a Chinese physician of Eastern Han Dynasty of China (3 century A.D.) using the method of network pharmacology. Methods: The active components of YFBP were identified from several databases (TCMSP, TCM Database@Taiwan and TCMID). The potential active compounds were screened based on oral bioavailability and drug-like index in the TCMSP database. DrugBank, TCMSP, and TCMID database searches were performed to predict target-related diseases. Biological functions and KEGG pathway outcomes of all potential targets were analyzed using the DAVID database. Results: A total of 24 active compounds of YFBP, 133 related targets, and 305 potential related diseases were obtained. These results showed that YFBP may treat inflammation, pain, and cancer. The functional enrichment analysis indicated that YFBP probably exerts its therapeutic effects by regulating neuroactive ligand-receptor interactions, the TNF signaling pathway, and the PI3K-Akt signaling pathway. Conclusion: This study provides preliminary confirmation that YFBP has the great potentials to treat inflammation, pain, and tumors, which supports Zhang Zhongjing’s original intention to treat intestinal carbuncle with ancient prescription YFBP, but also provides a scientific basis for its treatment in the malignant tumors.

Objective: To compare the clinical application in the percutaneous vertebroplasty under the guidance of one or two C-arm fluoroscopes. Methods: One hundred forty three elderly patients with Osteoporotic vertebral compression fractures (OVCFs) underwent percutaneous vertebroplasty under the guidance of one or two C-arm fluoroscopes. The number of pulsed imagings, the time of operation and the incidence of cement leakage were recorded. Results: The average number of pulsed imagings was 16.00±1.58 vs 13.07±2.00 per patient under the guidance of one vs two C-arm fluoroscopes. The average time of operation was 48.42±5.00 minutes vs 39.70±7.42 minutes per patient under the guidance of one vs two C-arm fluoroscopes. The incidence of cement leakage was 20% vs 15.7% of the patients under the guidance of one vs two C-arm fluoroscopes. The differences in the number of pulsed imagings and the time of operation were statistically significant. The difference in incidence of cement leakage was not statistically significant. Conclusion: The two-fluoroscopic technique reduce the labor cost, the radiation, the time of operation and the operation risk.

In aggregated Computer Generated Force System, firepower allocation is one of the most important tasks in intelligent decision. In this paper, three kinds of classical firepower allocation model are analyzed, and a new method is present, which uses structure of Multi-Agent System, to solve the firepower allocation problem of aggregated CGF entity, through distilling firepower allocation rules of firepower unit in firepower application process. This method not only reflects the internal command relationship between commanding entity and firepower cells in firepower unit but also realize dynamic firepower allocation relying on change of battlefield situation. Because of its good expansibility and convenience for computer realization, method on firepower allocation of CGF has a well research and application perspective.

The current support of the armored equipment is traditional extensive mode. There are many problems, such as excessive maintenance, late maintenance and high ratio of expenses to battle effectiveness. Aiming at these problems, the significance of Precise Support research on armored equipment is analyzed. Precise Support is the certain trend for equipment support under it-based conditions, which means to succeed in gaining possession of maximal efficiency with minimum cost and high effectiveness with low risk. The factors restricting Precise Support for armored equipment is made up of information collection, malfunction prediction, decision forming, support resources using. The future research directions about Precise Support for armored equipment of the key factors are pointed out, and framework of Precise Support for armored equipment are clarified. It is pointed out that C4ISR based on advanced sensors is the key part to Research on Precise Support for Armored Equipment.