Free-space dissemination of time and frequency with 10-19 instability over 113 km.

Networks of optical clocks find applications in precise navigation1,2, in efforts to redefine the fundamental unit of the 'second'3-6 and in gravitational tests7. As the frequency instability for state-of-the-art optical clocks has reached the 10-19 level8,9, the vision of a global-scale optical network that achieves comparable performances requires the dissemination of time and frequency over a long-distance free-space link with a similar instability of 10-19. However, previous attempts at free-space dissemination of time and frequency at high precision did not extend beyond dozens of kilometres10,11. Here we report time-frequency dissemination with an offset of 6.3 × 10-20 ± 3.4 × 10-19 and an instability of less than 4 × 10-19 at 10,000 s through a free-space link of 113 km. Key technologies essential to this achievement include the deployment of high-power frequency combs, high-stability and high-efficiency optical transceiver systems and efficient linear optical sampling. We observe that the stability we have reached is retained for channel losses up to 89 dB. The technique we report can not only be directly used in ground-based applications, but could also lay the groundwork for future satellite time-frequency dissemination.

Military Brain Science - How to influence future wars.

Military Brain Science is a cutting-edge innovative science that uses potential military application as the guidance. It was preliminarily divided into 9 aspects by authors: understanding the brain, protecting the brain, monitoring the brain, injuring the brain, interfering with the brain, repairing the brain, enhancing the brain, simulating the brain and arming the brain. In this review, we attempt to propose the concept, content and meaning of the Military Brain Science, with the hope to provide some enlightenment and understanding of the research area.

Definition and application of precision medicine.

"No abstract".

Blast-induced traumatic brain injury: a new trend of blast injury research.

Blast injury has become the major life- and function-threatening injuries in recent warfares. There is increased research interest in the mental disorders caused by blast-induced traumatic brain injury (bTBI), which has been proved as one of the "signature wounds" in modern battlefield. We reviewed the recent progresses in bTBI-related researches and concluded that the new era of blast injury research has shifted from the traditional physical impairments to cognitive dysfunctional/mental disorders that are proved to be more related to the outcome of combat casualty care.

PKCγ receptor mediates visceral nociception and hyperalgesia following exposure to PTSD-like stress in the spinal cord of rats.

BACKGROUND: Clinical studies indicate that patients with post-traumatic stress disorder (PTSD) frequently share comorbidity with numerous chronic pain conditions. However, the sustained effects of PTSD-like stress over time on visceral nociception and hyperalgesia have been rarely studied, and the underlying mechanisms of stress-induced modulation of visceral hyperalgesia remain elusive. The purpose of this study was to investigate the characterization of visceral nociception and hyperalgesia over time in rats exposed to PTSD-like stress, and to explore the potential role of protein kinase C gamma (PKCγ) in mediating visceral hyperalgesia following exposure to PTSD-like stress. RESULTS: On day 1, the rats exposed to single-prolonged stress (SPS, an established animal model for PTSD) exhibited an analgesic response and its visceromotor response (VMR) to graded colorectal distention (CRD) at 40 and 60 mmHg was reduced compared with the control group (all P < 0.05). On day 6, the VMR returned to the baseline value. However, as early as 7 days after SPS, VMR dramatically increased compared with its baseline value and that in the controls (all P < 0.001) and this increase persisted for 28 days, with the peak on day 9. Abdominal withdrawal reflex (AWR) scores were higher in SPS rats than in controls on days 7, 9, 14, 21 and 28 (all P < 0.001). Intrathecal administration of GF109203X (an inhibitor of PKC gamma), attenuated the SPS-induced increase in both VMR and AWR scores on days 7, 14, 21 and 28 (all P < 0.05). PKCγ protein expression determined by immunofluorescence was reduced in the spinal cord within 3 days after the exposure to SPS (P < 0.01), which returned to normal levels between days 4 and 6, and significantly increased from day 7, and this increase was maintained on days 14, 21, and 28 (all P < 0.001), with the peak on day 9. In addition, Western blotting showed a consistent trend in the changes of PKCγ protein expression. CONCLUSIONS: The modified SPS alters visceral sensitivity to CRD, and contributes to the maintenance of visceral hyperalgesia, which is associated with enhanced PKCγ expression in the spinal cord. Functional blockade of the PKCγ receptors attenuates SPS-induced visceral hyperalgesia. Thus, the present study identifies a specific molecular mechanism for visceral hyperalgesia which may pave the way for novel therapeutic strategies for PTSD-like conditions.

Adipose-derived stem cells induced dendritic cells undergo tolerance and inhibit Th1 polarization.

Adipose tissue-derived stem cells (ADSC) have been shown to possess stem cell properties such as transdifferentiation, self-renewal and therapeutic potential. However, the property of ADSC to accommodate immune system is still unknown. In this study, ADSC were cocultured with allogenetic dendritic cells (DC), and then treated DC were mixed with allogenetic CD4+ T cells. The results demonstrated that ADSC could downregulate costimulatory molecules, including CD80, CD83, CD86, and cytokine secretion such as interleukin (IL)-12 and tumor necrosis factor (TNF)-α, while upregulate indoleamine-2,3-dioxygenase (IDO) of allogenetic DC. In addition, treated DC could inhibit CD4+ T cell activation and naïve T cells toward Th1 polarization. The results suggest that ADSC could negatively modulate immunity and induce immune tolerance, which provide a promising strategy in transplantation or autoimmune disease.

Major stress hormones suppress the response of macrophages through down-regulation of TLR2 and TLR4.

BACKGROUND: Severe trauma often leads to diminished cytokines especially from macrophages to Toll-like receptor (TLR) agonists. However, the molecular mechanisms remain to be elucidated. As surgical trauma could also induce neuroendocrine hormones to modulate the immune system, we investigated the effects of major hormones, including endogenous glucocorticoid (corticosterone (CORT)), epinephrine (E), and norepinephrine (NE) on the expression and response of TLR2 and TLR4 in macrophages. MATERIALS AND METHODS: Rat macrophages were pretreated by each hormone (1000 ng/mL of CORT, E, and NE) for 24 h, then restimulated with Pam3CSK4 or lipopolysaccharide (LPS) for further 24 h, and supernatant tumor necrosis factor-alpha (TNF-α) was measured. Additionally, macrophages were incubated with different concentrations of hormones (0-10,000 ng/mL) for 48 h or with 1000 ng/mL of hormones for 0-48 h, the expressions of TLR2 and TLR4 and intracellular molecules (MyD88, IRAK1, and TRAF6) in macrophages were analyzed by real-time quantitative polymerase chain reaction (PCR) and RT-PCR, respectively. RESULTS: Pam3CSK4-stimulated TNF-α production was significantly reduced from macrophages pretreated with CORT, and both Pam3CSK4- and LPS-stimulated TNF-α were suppressed with E. Moreover, CORT down-regulated only TLR2 expression in both time- and dose-dependent manner, but both TLR2 and TLR4 mRNA expressions were down-regulated in time- and dose-dependent manner after exposure to E. However, the transcript expression of MyD88, IRAK1, and TRAF6 remained unchanged after exposure to each hormone. CONCLUSIONS: These results suggested that the down-regulation of TLR2 and TLR4 expressions by CORT and E is involved in the hyporesponsiveness of macrophages.

Researches on regenerative medicine-current state and prospect.

Since 1980s, the rapid development of tissue engineering and stem cell research has pushed regenerative medicine to a new fastigium, and regenerative medicine has become a noticeable research field in the international biology and medicine. In China, about 100 million patients need repair and regeneration treatment every year, while the number is much larger in the world. Regenerative medicine could provide effective salvation for these patients. Both Chinese Academy of Sciences and Chinese Academy of Engineering have made roadmaps of 2010-2050 and 2011-2030 for regenerative medicine. The final goal of the two roadmaps is to make China go up to leading position in most research aspects of regenerative medicine. In accord with this strategy, the government and some enterprises have invested 3-5 billion RMB (0.5-0.8 billion USD) for the research on regenerative medicine. In order to push the translation of regenerative medicine forward-from bench to bedside, a strategic alliance has been established, and it includes 27 top-level research institutes, medical institutes, colleges, universities and enterprises in the field of stem cell and regeneration medicine. Recently the journal, Science, has published a special issue-Regenerative Medicine in China, consisting of 35 papers dealing with stem cell and regeneration, tissue engineering and regeneration, trauma and regeneration and bases for tissue repair and regenerative medicine. It is predicated that a greater breakthrough in theory and practice of regenerative medicine will be achieved in the near future (20 to 30 years).

Influence of degenerative changes of intervertebral disc on its material properties and pathology.

OBJECTIVE: To investigate the material properties of normal and degenerated intervertebral discs (IVDs) and examine the effect of degenerative changes on IVD pathology. METHODS: A computer-based online search was undertaken to identify English articles about material properties of IVDs published from January 1950 to 2011 in PubMed database. The retrieved keywords included material properties, intervertebral disc and degeneration. Based on the principles of reliability, advancement and efficiency, the obtained data were primarily examined, and the original source was retrieved to read the full-text. Repetitive articles were excluded. The data of material properties of normal and degenerated IVDs were summarized and analyzed by meta-analysis. RESULTS: The data of Young's modulus, Poisson's ratio, shear modulus, hydraulic permeability and intradiscal pressure of normal and degenerated IVDs were obtained. Compared with normal IVDs, the Young's modulus and shear modulus of annulus fibrosus and nucleus pulposus were higher in degenerated IVDs, the Poisson's ratio was lower while the hydraulic permeability and intradiscal pressure were higher. Besides, the degeneration-related alterations in IVDs had an influence both on itself and other spinal structures, leading to diseases such as bulging disc, discogenic pain and spinal stenosis. Meanwhile, the heavy mechanical loading and injury indicated important pathways to IVD degeneration. CONCLUSIONS: To a certain extent, the degenerative changes of IVD influence its material properties. And the degeneration-related alterations of composition can cause structural failure of IVDs, leading to injuries and diseases.

Cervical spinal canal narrowing and cervical neurological injuries.

Cervical spinal canal narrowing can lead to injury of the spinal cord and neurological symptoms including neck pain, headache, weakness and parasthesisas. According to previous and recent clinical researches, we investigated the geometric parameters of normal cervical spinal canal including the sagittal and transverse diameters as well as Torg ratio. The mean sagittal diameter of cervical spinal canal at C(1) to C(7) ranges from 15.33 mm to 20.46 mm, the mean transverse diameter at the same levels ranges from 24.45 mm to 27.00 mm and the mean value of Torg ratio is 0.96. With respect to narrow cervical spinal canal, the following charaterstics are found: firstly, extension of the cervical spine results in statistically significant stenosis as compared with the flexed or neutral positions; secondly, females sustain cervical spinal canal narrowing more easily than males; finally, the consistent narrowest cervical canal level is at C(4) for all ethnicity, but there is a slight variation in the sagittal diameter of cervical spinal stenosis (less than or equal to 14 mm in Whites, less than or equal to 12 mm in Japanese, less than or equal to 13.7 mm in Chinese). Narrow sagittal cervical canal diameter brings about an increased risk of neurological injuries in traumatic, degenerative and inflammatory conditions and is related with extension of cervical spine, gender, as well as ethnicity. It is hoped that this review will be helpful in diagnosing spinal cord and neurological injuries with the geometric parameters of cervical spine in the future.

Analysis of 86 fatal motorcycle frontal crashes in Chongqing, China.

OBJECTIVE: To analyze the injuries of motorcyclists involved in fatal motorcycle frontal crashes. METHODS: A survey group involving multi-discipline experts was built to randomly collect data on fatal motorcycle frontal collision accidents that occurred in Chongqing during 2006-2010. The sampled information included medical or autopsy reports, blood alcohol concentration (BAC) level, helmet use, accident witness, field sketch as well as field photos. The motorcyclist injuries were scored according to the Abbreviated Injury Scale (AIS) 2005. The involved riders with a BAC level larger than or equal to 20 mg/ml were attributed to alcohol use. Data were processed statistically with nonparametric test via software SPSS 11.0. RESULTS: A total of 86 fatal motorcycle frontal crashes were sampled and further analyzed. The age of motorcyclists enrolled in this investigation showed nominal distribution and the middle-aged (30-39 years) occupied the highest percentage of fatalities. There were only 14 motorcyclists (16.3%) wearing helmets at the moment of collision. And 12.8% of these motorcyclist crashes were attributable to alcohol use. Impact injury was the main fatal cause, accounting for 72% of motorcyclist deaths, followed by tumbling injury (26%) and run-over (2%). Respectively 84%, 22% and 19% of motorcyclists who sustained head, chest and abdominal trauma died. Extremity injury was the most frequently observed injury type. CONCLUSIONS: This investigation is helpful to build accident prevention programs and develop protection devices which may effectively mitigate injuries and prevent deaths following motorcycle frontal collision accidents. Further investigations on motorcycle collision accidents are still needed.

Effects of hypothalamus destruction on the level of plasma corticosterone after blast injury and its relation to interleukin-6 in rats.

Hypothalamus-pituitary-adrenal (HPA) axis is involved in the modulation of the innate immune response. The purpose of this study was to evaluate the dynamic relationship between plasma corticosterone and interleukin-6 in the hypothalamus-destroyed rats after blast injury. A total of 105 Sprague-Dawley rats were divided randomly into normal control (normal), sham operated (sham), blast injury plus sham operated (blast injury) and blast injury plus hypothalamus destruction groups. Symmetric electrolytic bilateral destruction of the hypothalamus was performed for the deeply anesthetic rats under sterile conditions. Seven days after the destruction of the hypothalamus, the animals were succumbed to moderate blast injury using a BST-I bioimpact machine. Plasma corticosterone and IL-6 levels were determined by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. After blast injury, the corticosterone level in the hypothalamus-destroyed rats was significantly lower than that in the rats without destruction of hypothalamus at 3h (P<0.01) or from 5 to 8h (P<0.05). Reduction of corticosterone may be intrinsically correlated with the severe tissue injury and increased mortality (4/15 vs. 0/15, P<0.05). Circulating IL-6 level was markedly elevated in response to blast injury and hypothalamus destruction further increased IL-6 secretion (P<0.05). We concluded that elevation of pro-inflammatory IL-6 secretion might compensate the impaired HPA axis function after the trauma occurred in the hypothalamus-destroyed rats. These results also suggested that release of hypothalamus hormones is necessary to maintain certain magnitude of innate immunity after trauma.

X-ray observation on how axial compression stimulates tibial fracture healing.

OBJECTIVE: To validate the hypothesis that there exists an optimal axial compression stress range to enhance tibial fracture healing. METHODS: Rabbits with a surgically induced V-shaped tibial fracture were separated into 2 main groups: the control group (C Group, n equal to 6) without application of any axial compression stress stimulation postoperatively and the stimulation group (S Group, n equal to 90). The S Group was further divided into 20 subgroups (S11 to S54) in terms of 5 axial compression stress stimulation levels (112.8 kPa, 289.8 kPa, 396.5 kPa, 472.7 kPa, and 602.3 kPa) and 4 experimental endpoints (1, 3, 5 and 8 weeks after operation). A custom made circular external fixator was used to provide the axial compression stress of the fracture sites. Based on X-ray observation, a fracture healing scoring system was created to evaluate the fracture healing process. RESULTS: At 8 weeks after operation, there existed a "arch shape" relationship between healing score and axial compression stress stimulation level of fracture site. The optimal axial compression stress stimulation ranged from 289.8 kPa to 472.7 kPa, accompanying the best fracture healing, i.e. the fracture line became indistinct or almost disappeared, and a lot of callus jointed the two fracture ends. Meanwhile, at 5 weeks after operation, corresponding to the relatively low healing scores, there was a fracture healing performance similar to that at 8 weeks. Besides, at 1 or 3 weeks after operation, for all the axial compression stress levels (0-602.3 kPa), no obvious healing effect was found. CONCLUSIONS: It is implied from the stated X-ray observation results in this study that the potential optimal axial compression stress stimulation and optimal fracture healing time are available. The axial compression stress level of 289.8-472.7 kPa and fracture healing time of more than 8 weeks jointly comprise the optimal axial compression stress stimulation conditions to enhance tibial fracture healing.

Establishment of the model of motorcyclist ejection injury.

OBJECTIVE: To establish the device and model of motorcyclist ejection injury. METHODS: Based on our laboratory devices, a motorcyclist ejection injury simulation system was developed. A total of 18 pigs were approved by the local animal experimentation and ethics committee to serve as the motorcyclist substitutes. In this ejection motion, the animal rode freely at the motor driver seat and was straightly accelerated by means of our custom motorcyclist ejection injury simulation system. When it was speeded up to the preset velocity (v equal to 30, 40 or 50 km/h) at the preset position, the animal was ejected forward. Pathological and dynamic analyses were conducted, accompanied with the high-speed photograph, acceleration/velocity signal test, gross observation and light microscope examination as well as the abbreviated injury score-injury severity score (AIS-ISS) scale. RESULTS: The high-speed photograph indicated that during the ejection procedure the motorcycle was first arrested and decelerated suddenly, and then the motorcycle driver was ejected forward, accompanied with the rotation motion in the air. Finally, the head, shoulder and thorax of the ejected animal impacted directly on the hard ground. Varying degrees of injury focusing on the liver, heart, lung and spleen were found. There existed a significant positive correlation between ISS and the ejection velocity of the motorcycle drivers (ISS equal to 16.7+/-2.9 for 30 km/h, 25.0+/-0.0 for 40 km/h and 37.3+/-1.0 for 50 km/h). The detailed injury characteristics were as follows: for the mildly injured animals, there were interlobar gaps or leaf gaps and lobar surface blood coagulation blocks in the liver, and mild lung hemorrhage; for the severely injured animals, there were liver comminuted laceration, moderate lung hemorrhage and heart injury. Animals suffering from the most severe injuries died half an hour later. CONCLUSION: The new injury model stated in this paper has a high stability and good repeatability, and is likely to be helpful to deeply investigate the injury mechanisms and protection countermeasures of motorcyclist ejection injury.

Incidence, casualties and risk characteristics of civilian explosion blast injury in China: 2000-2017 data from the state Administration of Work Safety.

BACKGROUND: Civilian explosion blast injury is more frequent in developing countries, including China. However, the incidence, casualties, and characteristics of such incidents in China are unknown. METHODS: This is a retrospective analysis of the State Administration of Work Safety database. Incidents during a period from January 1, 2000 to April 30, 2017 were included in the analysis. The explosions were classified based on the number of deaths into extraordinarily major, major, serious and ordinary type. Descriptive statistics was used to analyze the incidence and characteristics of the explosions. Correlation analysis was performed to examine the potential correlations among various variables. RESULTS: Data base search identified a total of 2098 explosions from 2000 to 2017, with 29,579 casualties: 15,788 deaths (53.4%), 12,637 injured (42.7%) and 1154 missing (3.9%). Majority of the explosions were serious type (65.4%). The number of deaths (39.5%) was also highest with the serious type (P = 0.006). The highest incidence was observed in the fourth quarter of the year (October to December), and at 9:00-11:00 am and 4:00-6:00 pm of the day. The explosions were most frequent in coal-producing provinces (Guizhou and Shanxi Province). Coal mine gas explosions resulted majority of the deaths (9620, 60.9%). The number of explosion accidents closely correlated with economic output (regional economy and national GDP growth rate) (r = - 0.372, P = 0.040; r = 0.629, P = 0.028). CONCLUSIONS: The incidence and civilian casualties due to explosions remain unacceptabe in developing China. Measures that mitigate the risk factors are of urgently required.