Preference of carbon absorption determines the competitive ability of algae along atmospheric CO2 concentration.

Although many studies have focused on the effects of elevated atmospheric CO2 on algal growth, few of them have demonstrated how CO2 interacts with carbon absorption capacity to determine the algal competition at the population level. We conducted a pairwise competition experiment of Phormidium sp., Scenedesmus quadricauda, Chlorella vulgaris and Synedra ulna. The results showed that when the CO2 concentration increased from 400 to 760 ppm, the competitiveness of S. quadricauda increased, the competitiveness of Phormidium sp. and C. vulgaris decreased, and the competitiveness of S. ulna was always the lowest. We constructed a model to explore whether interspecific differences in affinity and flux rate for CO2 and HCO3 - could explain changes in competitiveness between algae species along the gradient of atmospheric CO2 concentration. Affinity and flux rates are the capture capacity and transport capacity of substrate respectively, and are inversely proportional to each other. The simulation results showed that, when the atmospheric CO2 concentration was low, species with high affinity for both CO2 and HCO3 - (HCHH) had the highest competitiveness, followed by the species with high affinity for CO2 and low affinity for HCO3 - (HCLH), the species with low affinity for CO2 and high affinity for HCO3 - (LCHH) and the species with low affinity for both CO2 and HCO3 - (LCLH); when the CO2 concentration was high, the species were ranked according to the competitive ability: LCHH > LCLH > HCHH > HCLH. Thus, low resource concentration is beneficial to the growth and reproduction of algae with high affinity. With the increase in atmospheric CO2 concentration, the competitive advantage changed from HCHH species to LCHH species. These results indicate the important species types contributing to water bloom under the background of increasing global atmospheric CO2, highlighting the importance of carbon absorption characteristics in understanding, predicting and regulating population dynamics and community composition of algae.

Optogenetic Neuronal Stimulation Promotes Functional Recovery After Spinal Cord Injury.

Although spinal cord injury (SCI) is the main cause of disability worldwide, there is still no definite and effective treatment method for this condition. Our previous clinical trials confirmed that the increased excitability of the motor cortex was related to the functional prognosis of patients with SCI. However, it remains unclear which cell types in the motor cortex lead to the later functional recovery. Herein, we applied optogenetic technology to selectively activate glutamate neurons in the primary motor cortex and explore whether activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI in rats and the preliminary neural mechanisms involved. Our results showed that the activation of glutamate neurons in the motor cortex could significantly improve the motor function scores in rats, effectively shorten the incubation period of motor evoked potentials and increase motor potentials' amplitude. In addition, hematoxylin-eosin staining and nerve fiber staining at the injured site showed that accurate activation of the primary motor cortex could effectively promote tissue recovery and neurofilament growth (GAP-43, NF) at the injured site of the spinal cord, while the content of some growth-related proteins (BDNF, NGF) at the injured site increased. These results suggested that selective activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI and may be of great significance for understanding the neural cell mechanism underlying functional recovery induced by motor cortex stimulation.

Effect of transcranial direct-current stimulation on cognitive function in stroke patients: A systematic review and meta-analysis.

OBJECTIVE: Transcranial direct-current stimulation (tDCS) is a noninvasive approach that can alter brain excitability. Several studies have shown the effectiveness of tDCS in improving language and movement function in stroke patients. However, the effect of tDCS on cognitive function after stroke remains uncertain. METHODS: We searched Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the China National Knowledge Infrastructure, the China Science and Technology Journal Database, and the Wanfang Data Knowledge Service Platform from inception to April 2, 2019. Two reviewers independently screened the studies, extracted the data, and evaluated the quality of the included studies using the Cochrane Collaboration Risk of Bias Tool. All statistical analyses were performed in RevMan 5.3, and the mean difference (MD) or standard mean difference (SMD) were used as the pooled statistics. RESULTS: Fifteen studies involving 820 participants were included. When compared with passive tDCS, anodal tDCS was associated with improved general cognitive performance as examined by the Minimum Mental State Examination or Montreal Cognitive Assessment (SMD = 1.31, 95% CI 0.91-1.71, P < 0.00001), attention performance (SMD = 0.66, 95% CI 0.11-1.20, P = 0.02). There was no significant difference in memory performance (SMD = 0.41, 95% CI -0.67-1.50, P = 0.46). CONCLUSIONS: tDCS is likely to be effective for patients with cognitive impairment after stroke. The evidence for different effects based on population characteristics and stimulation methods was limited, but a real effect cannot be ruled out. More high-quality research in this field is required to determine the potential benefits of tDCS in the treatment of cognitive deficits after stroke and to establish the optimal treatment program.

Reevaluating the ability of cerebellum in associative motor learning.

It has been well established that the cerebellum and its associated circuitry constitute the essential neuronal system for both delay and trace classical eyeblink conditioning (DEC and TEC). However, whether the cerebellum is sufficient to independently modulate the DEC, and TEC with a shorter trace interval remained controversial. Here, we used direct optogenetic stimulation of mossy fibers in the middle cerebellar peduncle (MCP) as a conditioned stimulus (CS) replacement for the peripheral CS (eg, a tone CS or a light CS) paired with a periorbital shock unconditioned stimulus (US) to examine the ability of the cerebellum to learn the DEC and the TEC with various trace intervals. Moreover, neural inputs to the pontine nucleus (PN) were pharmacological blocked to limit the associative motor learning inside the cerebellum. We show that all rats quickly acquired the DEC, indicating that direct optogenetic stimulation of mossy fibers in the left MCP is a very effective and sufficient CS to establish DEC and to limit the motor learning process inside the cerebellum. However, only five out of seven rats acquired the TEC with a 150-ms trace interval, three out of nine rats acquired the TEC with a 350-ms trace interval, and none of the rats acquired the TEC with a 500-ms trace interval. Moreover, pharmacological blocking glutamatergic and GABAergic inputs to the PN from the extra-cerebellar and cerebellar regions has no significant effect on the DEC and TEC learning with the optogenetic CS. These results indicate that the cerebellum has the ability to independently support both the simple DEC, and the TEC with a trace interval of 150 or 350 ms, but not the TEC with a trace interval of 500 ms. The present results are of great importance in our understanding of the mechanisms and ability of the cerebellum in associative motor learning and memory.

In vivo evaluation of microglia activation by intracranial iron overload in central pain after spinal cord injury.

BACKGROUND: Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent microglia activate in the remodeling of the brain after SCI. METHODS: An SCI-induced CP model was established in Sprague-Dawley rats that were randomly assigned to SCI, sham operation, deferoxamine (DFX), minocycline, and nitric oxide synthase inhibitor treatment groups. At 12 weeks, pain behavior and thermal pain threshold were evaluated in each group, and iron transferrin receptor (TfR)1 and ferritin (Fn) mRNA, as well as iron-regulatory protein (IRP)1, FN, lactoferrin, and nuclear factor (NF)-κB protein levels in the rat brains were measured. Microglia proliferation and differentiation and IRP1 expression were evaluated by immunohistochemistry. RESULTS: Autophagy was observed in rats after SCI, accompanied by reduced latency of thermal pain, increased iron content and IRP1 and NF-κB levels in the hindlimb sensory area, hippocampus, and thalamus, and decreased Fn levels in the hindlimb sensory area. TfR1 mRNA expression was upregulated in activated microglia. Treatment with an iron-chelating agent, or inhibitors of nitric oxide synthase or microglia suppressed microglia proliferation. CONCLUSIONS: SCI may induce intracranial iron overload, which activates microglia via NF-κB signaling. Microglia secrete inflammatory factors that induce neuronal damage and lead to CP. Treatment with an iron-chelating agent or NF-κB or microglia inhibitors can relieve CP resulting from SCI.

Effect of oxidative stress induced by intracranial iron overload on central pain after spinal cord injury.

BACKGROUND: Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent oxidative stress in the remodeling of the brain after SCI. METHODS: We established a rat model of central pain after SCI. Rats were divided randomly into four groups: SCI, sham operation, SCI plus deferoxamine (DFX) intervention, and SCI plus nitric oxide synthase (NOS) inhibitor treatment. Pain behavior was observed and thermal pain threshold was measured regularly, and brain levels of iron, transferrin receptor 1 (TfR1), ferritin (Fn), and lactoferrin (Lf), were detected in the different groups 12 weeks after establishment of the model. RESULTS: Rats demonstrated self-biting behavior after SCI. Furthermore, the latent period of thermal pain was reduced and iron levels in the hind limb sensory area, hippocampus, and thalamus increased after SCI. Iron-regulatory protein (IRP) 1 levels increased in the hind limb sensory area, while Fn levels decreased. TfR1 mRNA levels were also increased and oxidative stress was activated. Oxidative stress could be inhibited by ferric iron chelators and NOS inhibitors. CONCLUSIONS: SCI may cause intracranial iron overload through the NOS-iron-responsive element/IRP pathway, resulting in central pain mediated by the oxidative stress response. Iron chelators and oxidative stress inhibitors can effectively relieve SCI-associated central pain.

Resting-state functional connectivity abnormalities in patients with obsessive-compulsive disorder and their healthy first-degree relatives.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common, heritable neuropsychiatric disorder, hypothetically underpinned by dysfunction of brain cortical-striatal-thalamic-cortical (CSTC) circuits; however, the extent of brain functional abnormalities in individuals with OCD is unclear, and the genetic basis of this disorder is poorly understood. We determined the whole brain functional connectivity patterns in patients with OCD and their healthy first-degree relatives. METHODS: We used resting-state fMRI to measure functional connectivity strength in patients with OCD, their healthy first-degree relatives and healthy controls. Whole brain functional networks were constructed by measuring the temporal correlations of all brain voxel pairs and further analyzed using a graph theory approach. RESULTS: We enrolled 39 patients with OCD, 20 healthy first-degree relatives and 39 healthy controls in our study. Compared with healthy controls, patients with OCD showed increased functional connectivity primarily within the CSTC circuits and decreased functional connectivity in the occipital cortex, temporal cortex and cerebellum. Moreover, patients with OCD and their first-degree relatives exhibited overlapping increased functional connectivity strength in the bilateral caudate nucleus, left orbitofrontal cortex (OFC) and left middle temporal gyrus. LIMITATIONS: Potential confounding factors, such as medication use, heterogeneity in symptom clusters and comorbid disorders, may have impacted our findings. CONCLUSION: Our preliminary results suggest that patients with OCD have abnormal resting-state functional connectivity that is not limited to CSTC circuits and involves abnormalities in additional large-scale brain systems, especially the limbic system. Moreover, resting-state functional connectivity strength abnormalities in the left OFC, bilateral caudate nucleus and left middle temporal gyrus may be neuroimaging endophenotypes for OCD.

Nicotinamide pretreatment protects cardiomyocytes against hypoxia-induced cell death by improving mitochondrial stress.

BACKGROUND/AIMS: Nicotinamide plays a protective role in hypoxia-induced cardiomyocyte dysfunction. However, the underlying molecular mechanisms remain poorly understood. The purpose of this study was to investigate these and the effect of nicotinamide pretreatment on hypoxic cardiomyocytes. METHODS: Cultured rat cardiomyocytes were pretreated with nicotinamide, subjected to hypoxia for 6 h, and then cell necrosis and apoptosis were examined. The effects of nicotinamide pretreatment on hypoxia-induced reactive oxygen species (ROS) formation, antioxidant enzyme expression, nicotinamide adenine dinucleotide (NAD(+)) and nicotinamide adenine dinucleotide phosphate (NADP(+)) levels, adenosine triphosphate (ATP) production and mitochondrial membrane potential were tested to elucidate the underlying mechanisms. RESULTS: Based on the findings that nicotinamide treatment decreased protein expression of receptor-interacting protein (RIP; a marker for cell necrosis) and cleaved caspase-3 (CC3; a marker for cell apoptosis) in normoxic cardiomyocytes, we found that it dramatically reduced hypoxia-induced necrosis and apoptosis in cardiomyocytes. The underlying mechanisms of these effects are associated with the fact that it increased protein expression of superoxide dismutase and catalase, increased intracellular levels of NAD(+) and ATP concentration, decreased mitochondrial ROS generation and prevented the loss of mitochondrial membrane potential. CONCLUSION: All of these results indicate that nicotinamide pretreatment protects cardiomyocytes by improving mitochondrial stress. Our study provides a new clue for the utilization of nicotinamide in therapies for ischemic heart disease.

[Correlation analysis between the expression of aquaporin 4 and magnetic resonance imaging of brain tissue in severely scalded rabbit with brain edema during early stage].

OBJECTIVE: To observe expression pattern of aquaporin 4 (AQP4) in brain tissue of severely scalded rabbit during early stage of brain edema and its relationship with signal changes in magnetic resonance imaging (MRI), and to explore the feature of water transmembrane transportation in brain edema at early stage after severe scald. METHODS: Thirty-five healthy New Zealand white rabbits were divided into control group (C, n = 5) and scald group (S, n = 30) according to the random number table. Rabbits in S group were inflicted with 50% TBSA full-thickness scald with brain edema (confirmed by histopathologic examination). At post scald hour (PSH) 1, 2, 3, 4, 5, and 6, signal change in cerebral MRI, as well as dynamic change in apparent diffusion coefficient (ADC) were examined in rabbits of S group. Specimens were harvested from frontal cortex, parietal cortex, temporal lobe cortex, basal ganglia, and cerebellum in rabbits of S group for determination of protein and gene expressions of AQP4 with immunohistochemical method and RT-PCR. Above-mentioned indexes were also determined in C group. Data were processed with one-way analysis of variance and linear correlation analysis (between protein expression of AQP4 and ADC value). RESULTS: There was no significant change in image signal of MRI at each time point in S group as compared with that in C group, including T1WI, T2WI, and DWI. Compared with those in C group, ADC in S group at PSH 4, 5, and 6 were significantly decreased (with F values from 0.492 to 2.271, P values all below 0.05). The expression of AQP4 protein in each part of brain tissue in S group was obviously increased at PSH 2, 3, 4, 5, and 6 as compared with those in C group (from 0.164 ± 0.022 to 0.247 ± 0.018), and it peaked at PSH 3 or 4 (from 0.237 ± 0.042 to 0.306 ± 0.026), with F values from 2.420 to 11.439, P values all below 0.05. The expressions of AQP4 protein were similar in brain tissue of all regions, and they were negatively correlated with corresponding ADC values (with r values from -0.489 to -0.337, P < 0.05 or P < 0.01). Compared with that in C group, the expression of AQP4 mRNA in each part of brain tissue in S group was obviously increased at each time point, and it reached the peak at PSH 2 (with F values from 39.992 to 238.584, P values all below 0.05). The expressions of AQP4 mRNA were similar in all brain tissue regions. CONCLUSIONS: Brain edema within 6 hours after severe scald was mainly characterized by cytotoxicity, in which AQP4 may play an important role. ADC value may have important reference value for non-invasive and convenient assessment of development of brain edema.