Screening of genes interacting with high myopia and neuropsychiatric disorders.

Clinical studies have demonstrated an association between high myopia (HM) and neuropsychiatric disorders; however, the underlying mechanism of the association is not clear. We used whole exome sequencing (WES) in combination with the Genetic Variants Classification Criteria and Guidelines published by the American College of Medical Genetics (ACMG) and bioinformatics analysis to clarify the interrelationship between candidate genes. Causative genes for ocular diseases (45.38%) followed by neuropsychiatric disorders (22.69%) accounted for the highest proportion of genes that exhibited high pathogenicity in HM patients were found. Four pathogenic gene mutations were identified according to ACMG guidelines: c.164_165insACAGCA and c.C1760T in POLG, c.G1291A in COL5A1, and c.G10242T in ZNF469. Three causative genes for neuropsychiatric diseases, PTPRN2, PCDH15 and CDH23, were found to fall at the HM locus. The above results suggest that these genes may interact in high myopia and neuropsychiatric diseases.

Xuebijing attenuates decompression-induced lung injuries.

INTRODUCTION: The lung is among the primary organs involved in decompression sickness (DCS). Xuebijing (XBJ), a traditional Chinese medicine, has been widely used in the treatment of various acute lung diseases. This study aimed to explore potential benefit of XBJ on lung injuries induced by DCS in a rabbit model. METHODS: Twenty-four male New Zealand white rabbits underwent a simulated air dive to 50 meters' sea water for 60 min with 2.5 min decompression, and received an intravenous injection of XBJ (5 ml·kg-1) or an equal volume of saline immediately following decompression. DCS signs were monitored for 24 h, and blood was sampled before simulated diving and at 6 h and 12 h following decompression for determination of inflammatory indices. Lung tissues were sampled after euthanasia for histology analysis and lung water content, as well as tumour necrosis factor-α level. Another six rabbits were used as control. RESULTS: XBJ significantly ameliorated lung injuries (lung wet/dry ratio and total protein content in bronchoalveolar lavage fluid), and notably inhibited systemic (serum level of interleukin-1ß) and local (tumour necrosis factor-α in bronchoalveolar lavage fluid) inflammation responses. CONCLUSIONS: The results strongly suggest the benefits of XBJ on ameliorating DCS lung injuries, which is possibly via inhibiting systemic and local inflammation. XBJ may be a potential candidate for the treatment of decompression-induced lung injuries.

Ulinastatin: A Potential Alternative to Glucocorticoid in the Treatment of Severe Decompression Sickness.

Inflammatory reaction is the crux in various clinical critical diseases including decompression sickness (DCS). Ulinastatin (UTI), a potent anti-inflammatory agent, has been used clinically, including as a substitution for steroids. This study aimed to explore the potential effects of UTI upon DCS in a rabbit model. Eighty-eight rabbits were subjected to simulated diving to 6 atmospheres absolute (ATA) for 60 min with 2.5-minute decompression. Three doses of UTI (15/7.5/3.75 × 105 U/kg) or saline were intravenously administered immediately following decompression. Circulating bubbles were monitored for 3 h following decompression and DCS signs were evaluated for 24 h. Blood was sampled 8 times during 72 h after decompression for inflammatory, endothelial, oxidative and routine blood indices. Lung tissues were also sampled for evaluating endothelial function. Another six rabbits were used as Normal controls. In the high dose UTI group the mortality, general morbidity and incidence of severe DCS was decreased from 31.25 to 9.38% (P = 0.030), 84.38 to 62.50% (P = 0.048) and 46.88 to 21.88% (P = 0.035), respectively. The high dose of UTI significantly postponed the occurrence of DCS (P = 0.030) and prolonged survival time (P = 0.009) compared with the Saline group, and significantly ameliorated inflammation responses, endothelial injuries and oxidative damage. The results strongly suggest the benefit of UTI on DCS, especially for severe cases. Large doses are needed to achieve significant effects. UTI may be a potential ideal pharmacological candidate for the treatment of severe DCS.

Author Correction: Molecular marker assisted breeding and genome composition analysis of Zhengmai 7698, an elite winter wheat cultivar.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Corrigendum: Benefits of Escin for Decompression Sickness in Bama Pigs by Endothelial-Targeting Protection.

[This corrects the article DOI: 10.3389/fphys.2019.00605.].

Benefits of Escin for Decompression Sickness in Bama Pigs by Endothelial-Targeting Protection.

Endothelial dysfunction has been considered as pivotal in the pathogenesis of decompression sickness (DCS) and contributes substantively to subsequent inflammatory responses. Escin is well known for its endothelial protection and anti-inflammatory properties, and its protection against DCS has been proved in a rat model. This study aimed to further investigate the protection of escin against DCS in swine. Sixteen swine were subjected to a two-stage experiment with an interval of 7 days. In each stage, 7 days before a simulated air dive, the swine were treated with escin or saline. The first group received a successive administration of escin for 7 days prior to the first dive and saline for 7 days prior to the second; the second group was treated with saline and then escin. After decompression, signs of DCS and circulating bubbles were monitored, and blood was sampled for platelet count and determination of inflammatory and endothelial related indices. The death rate of DCS was markedly decreased in swine treated with escin compared with that in animals treated with saline, though not statistically significant due to the limited number of animals. Escin had no effect on bubble load but significantly ameliorated platelet reduction and endothelial dysfunction, as well as oxidative and inflammatory responses. The results further suggest the beneficial effects of escin on DCS by its endothelia-protective properties, and escin has the potential to be a candidate drug for DCS prevention and treatment.

[Distribution Characteristics of Mercury in Reed Leaves from the Jiapigou Gold Mine in the Songhua River Upstream].

At the Jiapigou gold mine of the Songhua River upstream, reed leaves (Phragmites australis), soil, and water samples were collected from June (summer) and September (autumn) 2016 for the determination of mercury. Moreover, the mercury concentrations in the air were determined synchronously. Furthermore, the level of mercury pollution in the reed leaves was determined by a single factor pollution index method, and the relationships among mercury concentrations in the reed leaves and environmental factors were analyzed to research the distribution characteristics, influencing factors, and correlations around the gold mining area. The results show that, in terms of spatial distribution, the mercury concentrations in reed leaves, soil, and water gradually decay with the distance from the gold mining area, and the spatial distribution of the mercury concentrations in the air was not obvious. Regarding a temporal distribution, the mercury concentrations in the reed leaves in summer were lower than those in autumn in the heavy pollution areas, while the distribution in the light pollution areas was the opposite, as the mercury concentrations of air and soil in summer were higher than those in autumn. The influence of environmental factors on the mercury concentrations in the reed leaves was soil > air > water. In addition, after stopping gold mining and processing using mercury, the mercury source in the area was the soil.

Molecular marker assisted breeding and genome composition analysis of Zhengmai 7698, an elite winter wheat cultivar.

Zhengmai 7698 is an elite winter wheat variety widely cultivated in the Southern regions of the Yellow-Huai River Valley of China. Here, we report the molecular markers used for breeding Zhengmai 7698 and the genome composition of this cultivar revealed using genome-wide SNPs. A total of 26 DNA markers derived from the genes controlling gluten protein quality, grain hardness, flour color, disease resistance, or pre-harvesting sprouting resistance were used during breeding. Consequently, Zhengmai 7698 had strong gluten, high grain hardness index, white flour color, and high levels of resistance to powdery mildew, stripe rust infections, and pre-harvesting sprouting. Using genome complexity reduction, 28,996 high-quality SNPs distributed on 21 wheat chromosomes were identified among Zhengmai 7698 and its three parental lines (4B269, Zhengmai 9405 and Zhoumai 16). Zhengmai 7698 shared 12,776, 14,411 and 16,085 SNPs with 4B269, Zhengmai 9405 and Zhoumai 16, respectively. Thus, the contributions of 4B269, Zhengmai 9405 and Zhoumai 16 to the genome of Zhengmai 7698 were comparable. Interestingly, Zhengmai 7698 had 307 unique SNPs that are absent in all three parents. We suggest that molecular markers facilitate selection of a wheat cultivar with multiple elite traits. Analysis of genome composition with SNPs may provide useful clues for further dissecting the genetic basis of improved wheat performance.

Benefits of hyperbaric oxygen pretreatment for decompression sickness in Bama pigs.

Decompression sickness (DCS) occurs when ambient pressure is severely reduced during diving and aviation. Hyperbaric oxygen (HBO) pretreatment has been shown to exert beneficial effects on DCS in rats via heat-shock proteins (HSPs). We hypothesized that HBO pretreatment will also reduce DCS via HSPs in swine models. In the first part of our investigation, six swine were subjected to a session of HBO treatment. HSP32, 60, 70 and 90 were detected, before and at 6, 12, 18, 24 and 30 h following exposure in lymphocytes. In the second part of our investigation, another 10 swine were randomly assigned into two groups (five per group). All swine were subjected to two simulated air dives in a hyperbaric chamber with an interval of 7 days. Eighteen hours before each dive, the swine were pretreated with HBO or air: the first group received air pretreatment prior to the first dive and HBO pretreatment prior to the second; the second group were pretreated with HBO first and then air. Bubble loads, skin lesions, inflammation and endothelial markers were detected after each dive. In lymphocytes, all HSPs increased significantly (P<0.05), with the greatest expression appearing at 18 h for HSP32 and 70. HBO pretreatment significantly reduced all the determined changes compared with air pretreatment. The results demonstrate that a single exposure to HBO 18 h prior to diving effectively protects against DCS in the swine model, possibly via induction of HSPs.

Polarization of macrophages in the blood after decompression in mice.

The veins are a major site of bubble formation after decompression and the lung is a target organ of bubbles. Bubble-induced inflammation has been implicated in the pathogenesis of decompression sickness (DCS). Macrophages play a central role in the inflammation, and macrophage polarization is closely related to the pathogenesis of some lung diseases. This study aimed to investigate the blood macrophage polarization in mice after decompression. BALB/c mice were exposed to hyperbaric air for 60 minutes, and rapid decompression was performed to induce DCS. Slow decompression and hyperoxia (150 kPa, 60 minutes) served as control groups, and hyperbaric oxygen (HBO; 250 kPa, 60 minutes) was employed for DCS treatment. Macrophage phenotype was determined by flow cytometry, and cytokines related to macrophage polarization were measured by enzyme-linked immunosorbent assay. Our results showed rapid decompression significantly induced the shift to M1 phenotype, which was not observed in slow decompression group, HBO and hyperoxia groups. These changes were consistent with the change in blood tumor necrosis factor α level. Moreover, any treatment could significantly increase the M2 macrophages, but blood interleukin-10 remained unchanged after different treatments. In addition, the blood and lung levels of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 increased significantly after rapid decompression, but reduced markedly after HBO treatment. Taken together, rapid decompression is able to induce the shift to M1 phenotype in blood macrophages, which may then migrate into the lung involving decompression-induced lung injury.

Effects of adenosine metabolism in astrocytes on central nervous system oxygen toxicity.

Hyperbaric oxygen (HBO) is widely used in military operations, especially underwater missions. However, prolonged and continuous inhalation of HBO can cause central nervous system oxygen toxicity (CNS-OT), which greatly limits HBO's application. The regulation of astrocytes to the metabolism of adenosine is involved in epilepsy. In our study, we aimed to observe the effects of HBO exposure on the metabolism of adenosine in the brain. Furthermore, we aimed to confirm the possible mechanism underlying adenosine's mediation of the CNS-OT. Firstly, anesthetized rats exposed to 5 atm absolute HBO for 80 min. The concentrations of extracellular adenosine, ATP, ADP, and AMP were detected. Secondly, free-moving rats were exposed to HBO at the same pressure for 20 min, and the activities of 5'-nucleotidase and ADK in brain tissues were measured. For the mechanism studies, we observed the effects of a series of different doses of drugs related to adenosine metabolism on the latency of CNS-OT. Results showed HBO exposure could increase adenosine content by inhibiting ADK activity and improving 5'-nucleotidase activity. And adenosine metabolism during HBO exposure may be a protective response against HBO-induced CNS-OT. Moreover, the improvement of adenosine concentration, activation of adenosine A1R, or suppression of ADK and adenosine A2AR, which are involved in the prevention of HBO-induced CNS-OT. This is the first study to demonstrate HBO exposure regulated adenosine metabolism in the brain. Adenosine metabolism and adenosine receptors are related to HBO-induced CNS-OT development. These results will provide new potential targets for the termination or the attenuation of CNS-OT.

Glutamate metabolism of astrocytes during hyperbaric oxygen exposure and its effects on central nervous system oxygen toxicity.

Hyperbaric oxygen (HBO) has been used widely in many underwater missions and clinical work. However, exposure to extremely high oxygen pressure may cause central nervous system oxygen toxicity (CNS-OT). The regulation of astrocyte glutamate metabolism is closely related to epilepsy. This study aimed to observe the effects of HBO exposure on glutamate metabolism in astrocytes and confirm the role of glutamate metabolism in CNS-OT. Anesthetized rats were exposed to 5 atmosphere absolute HBO for 80 min and microdialysis samples of brain interstitial fluid were continuously collected. Extracellular glutamate and glutamine concentrations were also detected. Freely moving rats were exposed to HBO of the same pressure for 20 min and glutamine synthetase (GS) activity in brain tissues was measured. Finally, we observed the effects of different doses of drugs related to glutamate metabolism on the latency of CNS-OT. Results showed that HBO exposure significantly increased glutamate content, whereas glutamine content was significantly reduced. Moreover, HBO exposure significantly reduced GS activity. Glutamate transporter-1 (GLT-1) selective antagonist ceftriaxone prolonged CNS-OT latency, whereas GLT-1 selective inhibitor dihydrokainate shortened CNS-OT latency. In summary, HBO exposure improved glutamate concentration and reduced glutamine concentration by inhibition of GS activity. GLT-1 activation also participated in the prevention of HBO-induced CNS-OT. Our research will provide a potential new target to terminate or attenuate CNS-OT.

SC5b-9-induced pulmonary microvascular endothelial hyperpermeability participates in ventilator-induced lung injury.

Mechanical ventilation with large tidal volumes can increase lung alveolar permeability and initiate inflammatory responses, termed ventilator-induced lung injury (VILI). VILI is characterized by an influx of inflammatory cells, increased pulmonary permeability, and endothelial and epithelial cell death. But the underlying molecular mechanisms that regulate VILI remain unclear. The purpose of this study was to investigate the mechanisms that regulate pulmonary endothelial barrier in an animal model of VILI. These data suggest that SC5b-9, as the production of the complement activation, causes increase in rat pulmonary microvascular permeability by inducing activation of RhoA and subsequent phosphorylation of myosin light chain and contraction of endothelial cells, resulting in gap formation. In general, the complement-mediated increase in pulmonary microvascular permeability may participate in VILI.

[Effects of vegetation on river flow: a review].

Vegetation is a component of the natural river. To understand the interaction between vegetation and water flow is of scientific and practical significance for the protection of wildlife habitats, the control of water body eutrophication, the ecological restoration of rivers and lakes, and the management of riverways. This paper reviewed the researches about the interaction between vegetation and water flow in riverways, summarized the research progress in the effects of the vegetation on the resistance coefficient and water flow structure, and introduced the applications of numerical simulation in this research field. Based on the previous studies, the effects of river section shape, plant individual form, and vegetation distribution pattern on the flow regime of water flow in vegetation section were analyzed. For further study, the importance of deeply understanding the hydraulics mechanisms of the interaction between vegetation and water flow in terms of the diversity of river morphology, the vegetation variation at different spatiotemporal scales, the water flow distribution in vegetation section, and the three dimensional turbulent simulation was expatiated.

Heat-shock protein 70 is involved in hyperbaric oxygen preconditioning on decompression sickness in rats.

Decompression sickness (DCS) is a major concern in diving and space walk. Hyperbaric oxygen (HBO) preconditioning has been proved to enhance tolerance to DCS via nitric oxide. Heat-shock protein (HSP) 70 was also found to have protective effects against DCS. We hypothesized that the beneficial effects of HBO preconditioning on DCS was related to levels of elevated HSP70. HSPs (70, 27 and 90) expressed in tissues of spinal cord and lung in rats was detected at different time points following HBO exposure by Western blot. HSP27 and HSP90 showed a slight but not significant increase after HBO. HSP70 increased and reached highest at 18 h following exposure before decreasing. Then rats were exposed to HBO and subjected to simulated air dive and rapid decompression to induce DCS 18 h after HBO. The severity of DCS, along with levels of HSP70 expression, as well as the extent of oxidative and apoptotic parameters in the lung and spinal cord were compared among different groups of rats pretreated with HBO, HBO plus NG-nitro-l-arginine-methyl ester (l-NAME), HBO plus quercetin or normobaric air. HBO preconditioning significantly reduced the morbidity of DCS (from 66.7% to 36.7%), reduced levels of oxidation (malondialdehyde, 8-hydroxyguanine and hydrogen peroxide) and apoptosis (caspase-3 and -9 activities and the number of apoptotic cells). l-NAME or quercetin eliminated most of the beneficial effects of HBO on DCS, and counteracted the stimulation of HSP70 by HBO. Bubbles in pulmonary artery were detected using ultrasound imaging to observe the possible effect of HBO preconditioning on DCS bubble formation. The amounts of bubbles in rats pretreated with HBO or air showed no difference. These results suggest that HSP70 was involved in the beneficial effects of HBO on DCS in rats, suspected be by the antioxidation and antiapoptosis effects.

Combined effects of intravenous perfluorocarbon emulsion and oxygen breathing on decompression-induced spinal cord injury in rats.

The spinal cord is one of the most commonly affected sites in decompression sickness (DCS). Alternative methods have long been sought to protect against DCS spinal cord dysfunction, especially when hyperbaric treatment is unavailable. Use of perfluorocarbon (PFC) emulsion with or without oxygen breathing has shown survival benefits in DCS animal models. The effectiveness of intravenous PFC emulsion with oxygen breathing on spinal cord function was studied. Somatosensory-evoked potentials (SSEPs) and histologic examination were chosen to serve as measures. After fast decompression (203 kPa/minute) from 709 kPa (for 60 minutes), male Sprague-Dawley rats randomly received: 1) air and saline; 2) oxygen (O2) and saline; 3) O2 and PFC emulsion. The incidence and average number of abnormal SSEP waves in survival animals that received O2 and PFC emulsion were significantly reduced (P < 0.05). Foci of demyelination, necrosis and round non-staining defects in white matter regions of the spinal cord could be found in severe DCS rats. We concluded that administration of PFC emulsion combined with oxygen breathing was beneficial for DCS spinal conductive dysfunction in rats.

Protective effect of hydrogen-rich saline on decompression sickness in rats.

INTRODUCTION: Hydrogen (H2) has been reported to be effective in the treatment of oxidative injury, which plays an important role in the process of decompression sickness (DCS). This study was designed to test whether H2-rich saline (saline saturated with molecular hydrogen) protected rats against DCS. METHODS: Models of DCS were induced in male Sprague-Dawley rats weighing 300-310 g. H2-rich (0.86 mmol x L(-1)) saline was administered intraperitoneally (10 ml x kg(-1)) at 24 h, 12 h, immediately before compression, and right after fast decompression. RESULTS: H2-rich saline significantly decreased the incidence of DCS from 67.57 to 35.14% and partially counteracted the increases in the total concentration of protein in the bronchoalveolar lavage from 0.33 +/- 0.05 to 0.14 +/- 0.01 mg x ml(-1) (mean +/- SD; P < 0.05), myeloperoxidase activity from 0.86 +/- 0.16 to 0.44 +/- 0.13 U/g, levels of malondialdehyde (MDA) from 0.80 +/- 0.10 to 0.48 +/- 0.05 nmol x mg(-1), 8-hydroxydeoxyguanosine from 253.7 +/- 9.3 to 191.2 +/- 4.8 pg x mg(-1) in the lungs, and MDA level from 1.77 +/- 0.20 to 0.87 +/- 0.23 nmol x mg(-1) in the spinal cord in rat DCS models. The histopathology results also showed that H2-rich saline ameliorated DCS injuries. DISCUSSION: It is concluded that H2-rich saline may have a protective effect against DCS, possibly due to its antioxidant action.

Hyperbaric oxygen preconditioning reduces the incidence of decompression sickness in rats via nitric oxide.

Divers are at risk of decompression sickness (DCS) when the ambient pressure decrease exceeds a critical threshold. Hyperbaric oxygen (HBO2) preconditioning has been used to prevent various injuries, but the protective effect on DCS has not been well explored. To investigate the prophylactic effect of HBO2 on DCS, rats were pretreated with HBO2 (250 kPa-60 minutes) (all the pressures described here are absolute pressure) for 18 hours before a simulated air dive (700 kPa-100 minutes) with fast decompression to the surface at the rate of 200 kPa/min (n=33). During the following 30 minutes, the rats walked in a 3 m/minute rotating cage and were monitored for signs of DCS. The control rats were pretreated with normobaric air (n=30), normoxic hyperbaric nitrox (250 kPa, 8.4% O2) (n=13), or N(G)-nitro-L-arginine methyl ester (L-NAME) 30 minutes before HBO2 exposure (n=13). Nitric oxide (NO) levels were recorded immediately and 18 hours after HBO2 exposure in the brain and spinal cord. The incidence of DCS in rats pretreated with HBO2 was 30.3%, which was significantly lower than those treated with normobaric air (63.3%) (p<0.05) or hyperbaric nitrox (61.5%) (p<0.05). The onset time of DCS of the rats pretreated with HBO2 was significantly delayed compared with those treated with air (p<0.05). L-NAME nullified the HBO2 preconditioning effect. HBO2 increased NO level in the rat brain and spinal cord right after exposure; this effect was inhibited by L-NAME. Taken together, HBO2 preconditioning reduced the incidence of DCS in rats, and NO was involved in the prophylactic effect.

Mechanism of ischemic tolerance induced by hyperbaric oxygen preconditioning involves upregulation of hypoxia-inducible factor-1alpha and erythropoietin in rats.

We studied the effect of hyperbaric oxygen (HBO) preconditioning on the molecular mechanisms of neuroprotection in a rat focal cerebral ischemic model. Seventy-two male Sprague-Dawley rats were pretreated with HBO (100% O(2), 2 atmospheres absolute, 1 h once every other day for 5 sessions) or with room air. In experiment 1, HBO-preconditioned rats and matched room air controls were subjected to focal cerebral ischemia or sham surgery. Postinjury motor parameters and infarction volumes of HBO-preconditioned rats were compared with those of controls. In experiment 2, HBO-preconditioned rats and matched room air controls were killed at different time points. Brain levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and its downstream target gene erythropoietin (EPO) analyzed by Western blotting and RT-PCR as well as HIF-1alpha DNA-binding and transcriptional activities were determined in the ipsilateral hemisphere. HBO induced a marked increase in the protein expressions of HIF-1alpha and EPO and the activity of HIF-1alpha, as well as the expression of EPO mRNA. HBO preconditioning dramatically improved the neurobehavioral outcome at all time points (3.0 +/- 2.1 vs. 5.6 +/- 1.5 at 4 h, 5.0 +/- 1.8 vs. 8.8 +/- 1.4 at 8 h, 6.4 +/- 1.8 vs. 9.7 +/- 1.3 at 24 h; P < 0.01, respectively) and reduced infarction volumes (20.7 +/- 4.5 vs. 12.5 +/- 3.6%, 2,3,5-Triphenyltetrazolium chloride staining) after cerebral ischemia. This observation indicates that the neuroprotection induced by HBO preconditioning may be mediated by an upregulation of HIF-1alpha and its target gene EPO.