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Background: Traumatic brain injury (TBI) is a leading cause of high mortality and disability worldwide. Overactivation of astrocytes and overexpression of inflammatory responses in the injured brain are characteristic pathological features of TBI. Rosiglitazone (ROS) is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist known for its anti-inflammatory activity. However, the relationship between the inflammatory response involved in ROS treatment and astrocyte A1 polarization remains unclear. Objective: This study aimed to investigate whether ROS treatment improves dysfunction and astrocyte A1 polarization induced after TBI and to elucidate the underlying mechanisms of these functions. Methods: SD rats were randomly divided into sham operation group, TBI group, TBI+ROS group, and TBI+ PPAR-γ antagonist group (GW9662 + TBI). The rat TBI injury model was prepared by the CCI method; brain water content test and wire grip test scores suggested the prognosis; FJB staining showed the changes of ROS on the morphology and number of neurons in the peripheral area of cortical injury; ELISA, immunofluorescence staining, and western blotting analysis revealed the effects of ROS on inflammatory response and astrocyte activation with the degree of A1 polarization after TBI. Results: Brain water content, inflammatory factor expression, and astrocyte activation in the TBI group were higher than those in the sham-operated group (P < 0.05); compared with the TBI group, the expression of the above indexes in the ROS group was significantly lower (P < 0.05). Compared with the TBI group, PPAR-γ content was significantly higher and C3 content was considerably lower in the ROS group (P < 0.05); compared with the TBI group, PPAR-γ content was significantly lower and C3 content was substantially higher in the inhibitor group (P < 0.05). Conclusion: ROS can exert neuroprotective effects by inhibiting astrocyte A1 polarization through the PPAR-γ pathway based on the reduction of inflammatory factors and astrocyte activation in the brain after TBI.

Aneurysmal subarachnoid hemorrhage (aSAH) accounts for only 5 % of all stroke cases, but carries a heavy burden of morbidity and mortality. Activity regulated cytoskeleton associated protein (Arc) is an immediate early gene (IEG)-coded postsynaptic protein that is involved in synaptic plasticity. Increasing evidence and our previous studies have shown that Arc might be involved in the pathological mechanism of various neurological diseases, such as traumatic brain injury (TBI). In this study, we investigated the level of Arc in cerebrospinal fluids (CSF) of aSAH patients and its potential role in brain damage following experimental SAH model. We found that the levels of Arc in aSAH patients’ CSF positively correlated with Hunt-Hess (H&H) grades. Knockdown of endogenous Arc expression by small interfere RNA (siRNA) significantly increased brain edema and oxidative stress following SAH. The results of immunostaining in brain sections showed that knockdown of Arc enhanced activation of microglia and astrocytes. In congruent, generation of inflammatory cytokines following SAH was increased by Si-Arc transfection. The results of western blot analysis showed that knockdown of Arc inhibited the expression of Sirt1 and Nrf2, which was accompanied by decreased enzymatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px). In addition, activation of sirtuin 1 (Sirt1) via agonist SRT2104 markedly decreased the brain damage and neuroinflammation induced by Arc knockdown. In conclusion, knockdown of endogenous Arc could aggravate brain damage and neuroinflammation following experimental SAH, and Arc levels in aSAH patients’ CSF might be a potential indicator of brain damage and prognosis.

Study Region: The Ganges-Brahmaputra-Meghna (GBM) delta in Bangladesh Study Focus: The flow distribution in a deltaic channel network is complicated by tidal wave propagation. We use a 2DH numerical model to investigate the variability of the tide-modulated seasonal, subtidal, intratidal and residual divided discharges. New Hydrological Insights: Simulations show that the divided subtidal discharges and correlated subtidal water levels display remarkable fortnightly fluctuations in dry months, whereas they are heavily distorted by the rapid rising & falling limbs of main stream flood waves in wet months. A subtidal water circulation that net water is transported from the tributaries to the main stream maintains at lower upstream discharges but is reversed by larger upstream discharges. With a series of increasing upstream riverine discharges routing downstream, the subtidal inflows experience a phase shift in the fortnightly cycles, in which the inflow peaks gradually move from spring tide to neap tide; moreover, the residual inflows demonstrate a non-monotonic variability, i.e. enlargements to the river-only case occur at two particular upstream discharges, compared to the reduced residual inflows at the majority of upstream discharges. These characteristic processes are explained by the mean amplitudes and phase relationships of tidal species (D1,D2,D4,D1/14) and the increasing dominance of river discharge over tidal wave. Our findings deepen the understandings of the complex nonlinear river-tide interactions in a deltaic channel network.

The mitochondrial permeability transition pore is a nonspecific transmembrane channel. Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling, calcium overload, and axonal degeneration. Cyclophilin D is an important component of the mitochondrial permeability transition pore. Whether cyclophilin D participates in mitochondrial impairment and axonal injury after intracerebral hemorrhage is not clear. In this study, we established mouse models of intracerebral hemorrhage in vivo by injection of autologous blood and oxyhemoglobin into the striatum in Thy1-YFP mice, in which pyramidal neurons and axons express yellow fluorescent protein. We also simulated intracerebral hemorrhage in vitro in PC12 cells using oxyhemoglobin. We found that axonal degeneration in the early stage of intracerebral hemorrhage depended on mitochondrial swelling induced by cyclophilin D activation and mitochondrial permeability transition pore opening. We further investigated the mechanism underlying the role of cyclophilin D in mouse models and PC12 cell models of intracerebral hemorrhage. We found that both cyclosporin A inhibition and short hairpin RNA interference of cyclophilin D reduced mitochondrial permeability transition pore opening and mitochondrial injury. In addition, inhibition of cyclophilin D and mitochondrial permeability transition pore opening protected corticospinal tract integrity and alleviated motor dysfunction caused by intracerebral hemorrhage. Our findings suggest that cyclophilin D is used as a key mediator of axonal degeneration after intracerebral hemorrhage; inhibition of cyclophilin D expression can protect mitochondrial structure and function and further alleviate corticospinal tract injury and motor dysfunction after intracerebral hemorrhage. Our findings provide a therapeutic target for preventing axonal degeneration of white matter injury and subsequent functional impairment in central nervous diseases.

Abstract Dysfunction of ionotropic glutamate receptors (iGluRs) is a key molecular mechanism of excitotoxic neuronal injury following traumatic brain injury (TBI). Edonerpic maleate is a low molecular-weight compound that was screened as a candidate neuroprotective agent. In this study, we investigated its effects on TBI and GluRs signaling. Traumatic neuronal injury (TNI) induced by scratch followed by glutamate treatment was performed to mimic TBI in vitro. Edonerpic maleate at 1 and 10 μM exerted protective activity when it was added within 2 h following injury. The protective activities were also confirmed by the reduction of lipid peroxidation and oxidative stress. In addition, edonerpic maleate inhibited the expression of surface NR2B, total GluR1, and surface GluR1, and mitigated the intracellular Ca2+ responses following injury in vitro. Western blot analysis showed that edonerpic maleate reduced the cleavage of collapsing response mediator protein 2 (CRMP2), but increased the expression of postsynaptic protein Arc. By using gene overexpression and silencing technologies, CRMP2 was overexpressed and Arc was knockdown in cortical neurons. The results showed that the effect of edonerpic maleate on NMDA receptor expression was mediated by CRMP2, whereas the edonerpic maleate-induced AMPA receptor regulation was dependent on Arc activation. In in vivo TBI model, 30 mg/kg edonerpic maleate alleviated the TBI-induced brain edema, neuronal loss, and microglial activation, with no effect on locomotor function at 24 h. However, edonerpic maleate improves long-term neurological function after TBI. Furthermore, edonerpic maleate inhibited CRMP2 cleavage but increased Arc activation in vivo. In summary, our results identify edonerpic maleate as a clinically potent small compound with which to attenuate TBI-related brain damage through regulating GluRs signaling.

Traumatic brain injury (TBI) is a serious disease that threatens life and health of people. It poses a great economic burden on the healthcare system. Thus, seeking effective therapy to cure a patient with TBI is a matter of great urgency. Microglia are macrophages in the central nervous system (CNS) and play an important role in neuroinflammation. When TBI occurs, the human body environment changes dramatically and microglia polarize to one of two different phenotypes: M1 and M2. M1 microglia play a role in promoting the development of inflammation, while M2 microglia play a role in inhibiting inflammation. How to regulate the polarization direction of microglia is of great significance for the treatment of patients with TBI. The polarization of microglia involves many cellular signal transduction pathways, such as the TLR-4/NF-κB, JAK/STAT, HMGB1, MAPK, and PPAR-γ pathways. These provide a theoretical basis for us to seek therapeutic drugs for the patient with TBI. There are several drugs that target these pathways, including fingolimod, minocycline, Tak-242 and erythropoietin (EPO), and CSF-1. In this study, we will review signaling pathways involved in microglial polarization and medications that influence this process.

Abstract. Background. Previous studies have demonstrated that various circular RNAs are involved in the malignant proliferation of cancers, such as liver cancer, lung cancer, breast cancer, and others. The potential role of circular RNAs in glioblastoma, however, is still uncertain. In this study, we aimed to study the potential role of hsa_circ_01844 in glioblastoma. Methods. Using reverse transcription-polymerase chain reaction (RT-PCR) method, hsa_circ_01844 expression was measured in five glioblastoma samples and five normal brain samples. To evaluate the potential function of hsa_circ_01844 in glioblastoma, hsa_circ_01844 was overexpressed in glioblastoma cell lines (U251 and U87 cells). Using these two cell lines, in vitro experiments including the flow cytometry assay, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, Transwell assay, and cell apoptosis assay were performed to investigate the role of hsa_circ_01844 in glioblastoma. Student t test and one-way analysis of variance were used for statistical analysis. Results. The expression of circular RNA hsa_circ_01844 was lower in glioblastoma tissues when compared with the normal brain tissues by RT-PCR method (0.034 ± 0.036 vs. 1.630 ± 0.891, P

Traumatic brain injury (TBI) is still a major public health problem worldwide, and the research of neuroprotective drugs has encountered great difficulties. Whole body vibration (WBV) is a safe and powerful rehabilitative intervention in various clinical settings, but its effect on neurological diseases is not well documented. In this study, we investigated the effects of WBV pretreatment on brain damage following experimental TBI mimicked by controlled cortical impact (CCI) in mice. C57BL/6 J male mice were expose to WBV at 30 Hz twice per day for 20 days and injured by CCI. WBV had no effect on animal body weight, but significantly reduced the TBI-induced brain edema in the cortex. The results of immunostaining showed that the activation of microglia and astrocytes induced by TBI in brain sections was attenuated by WBV. In consistent, WBV markedly inhibited the expression of pro-inflammatory cytokines, while increased the levels of anti-inflammatory cytokine interleukin 10 (IL-10). In addition, WBV pretreatment alleviated neuronal apoptosis in the cortex and suppressed the cleavage of the apoptotic executive molecule caspase-1. The neurological dysfunction following TBI was determined by open field test and Morris Water Maze (MWM) assay. The results showed that motor activity, learning and memory ability were preserved by WBV compared to TBI-injured mice. In summary, our present data identified WBV as a clinically potent strategy with which to attenuate TBI-related brain damage through regulating neuroinflammation.

Atorvastatin has been shown to reduce early brain edema and neuronal death after subarachnoid hemorrhage, but its mechanism is not clear. In this study, rat models of subarachnoid hemorrhage were established by autologous blood injection in the cisterna magna. Rat models were intragastrically administered 20 mg/kg atorvastatin 24 hours before subarachnoid hemorrhage, 12 and 36 hours after subarachnoid hemorrhage. Compared with the controls, atorvastatin treatment demonstrated that at 72 hours after subarachnoid hemorrhage, neurological function had clearly improved; brain edema was remarkably relieved; cell apoptosis was markedly reduced in the cerebral cortex of rats; the number of autophagy-related protein Beclin-1-positive cells and the expression levels of Beclin-1 and LC3 were increased compared with subarachnoid hemorrhage only. The ultrastructural damage of neurons in the temporal lobe was also noticeably alleviated. The similarities between the effects of atorvastatin and rapamycin were seen in all the measured outcomes of subarachnoid hemorrhage. However, these were contrary to the results of 3-methyladenine injection, which inhibits the signaling pathway of autophagy. These findings indicate that atorvastatin plays an early neuroprotective role in subarachnoid hemorrhage by activating autophagy. The experimental protocol was approved by the Animal Ethics Committee of Anhui Medical University, China (904 Hospital of Joint Logistic Support Force of PLA; approval No. YXLL-2017-09) on February 22, 2017.

Long non-coding RNAs (lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101st Hospital of the People’s Liberation Army, China (specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue. Volcano plot filtering identified 99 lncRNAs and 63 mRNAs differentially expressed in frontotemporal tissue of the two groups (P < 0.05, fold change > 1.2). Microarray analysis showed that 43 lncRNAs were up-regulated and 56 lncRNAs were down-regulated. Meanwhile, 59 mRNAs were up-regulated and 4 mRNAs were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed 27 signaling pathways associated with target genes and, in particular, legionellosis and influenza A signaling pathways. Subsequently, a lncRNA-gene network was generated, which showed an absolute correlation coefficient value > 0.99 for 12 lncRNA-mRNA pairs. Finally, quantitative real-time polymerase chain reaction confirmed different expression of the five most up-regulated mRNAs within the two groups, which was consistent with the microarray results. In summary, our results show that expression profiles of mRNAs and lncRNAs are significantly different between human traumatic brain injury tissue and surrounding tissue, providing novel insight regarding lncRNAs’ involvement in human traumatic brain injury. All participants provided informed consent. This research was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-TCC-13004002) and the protocol version number is 1.0.

Downdrift shoreline recession associated with the construction of a shore-crossing hard structure represents one of coastal erosional hotspots that must be addressed for an integrated, sustainable coastal zone management. To prevent siltation within the navigation channel, two rubber-mounted jetties were installed at the Sheyang River mouth on the open mesotidal muddy coast in Jiangsu province, China, in October 2013. The north jetty is 7.9 km long, while the south jetty is 7.8 km long. The net longshore sediment transport is from the north to the south due to flood-tide dominance. As disclosed by high-resolution satellite images, a 36-km-long downdrift shoreline stretch had experienced remarkable retreats at alongshore varying rates by March 2019. The eroding shoreline planform does not resemble a classic “S” shape, a crescentic shape, or a parabolic shape but an irregularly indented curved shape. Transect topographic survey also reveals an almost immediate response of the downdrift coast from the original accretionary scenery to an erosional regime, with the erosion front translocating downcoast at a much faster speed than a normal speed of 1–1.5 km/yr. Using FVCOM and SWAN, 2DH process-based numerical simulations are performed to simulate the flow, the sediment transport, and the yearly-magnitude accretion/erosion distribution in the jetty-affected area by a representative tidal force and an annual-magnitude wave force. The results demonstrate that the reciprocal tidal flow is predominantly responsible for the muddy sediment accretions at downdrift intertidal and surf zones shallower than a 4.0-m isobath, whereas big wind waves play a decisive role in triggering and developing the downdrift erosional process. The predicted spatial extent of the downdrift erosional segment matches closely the actual eroding front. The loss of the net annual longshore sediment transport volume, i.e., 3.08 million m3 due to the blockage by the twin jetties is recovered from a much larger spatial extent than the 36-km-long retreating shoreline stretch. With regard to the Bruun model, the one-line model, the headland-bay model, and the 2DH numerical model, the potential maximum recession length and the planform shape of the downdrift erosional shoreline arc are further elaborated to gain new insights into the spatial and temporal impact of a hard structure on the adjacent shoreline and flat (beach).

Sirtuin1 (Sirt1) and Sirtuin3 (Sirt3) are two well-characterized members of the silent information regulator 2 (Sir2) family of proteins. Both Sirt1 and Sirt3 have been shown to play vital roles in resistance to cellular stress, but the interaction between these two sirtuins has not been fully determined. In this study, we investigated the role of Sirt1-Sirt3 axis in blood-brain barrier (BBB) permeability after ischemia in vitro. Human brain microvascular endothelial cells and astrocytes were co-cultured to model the BBB in vitro and oxygen and glucose deprivation (OGD) was performed to mimic ischemia. The results of transepithelial electrical resistance (TEER) showed that suppression of Sirt1 via siRNA or salermide significantly decreased BBB permeability, whereas Sirt3 knockdown increased BBB permeability. In addition, Sirt1 was shown to regulate Sirt3 expression after OGD through inhibiting the AMPK-PGC1 pathway. Application of the AMPK inhibitor compound C partially prevented the effects of Sirt1-Sirt3 axis on BBB permeability after OGD. The results of flow cytometry and cytochrome c release demonstrated that Sirt1 and Sirt3 exert opposite effects on OGD-induced apoptosis. Furthermore, suppression of Sirt1 was shown to attenuate mitochondrial reactive oxygen species (ROS) generation, which contribute to the Sirt1-Sirt3 axis-induced regulation of BBB permeability and cell damage. In summary, these findings demonstrate that the Sirt1-Sirt3 axis might act as an important modulator in BBB physiology, and could be a therapeutic target for ischemic stroke via regulating mitochondrial ROS generation. Keywords: Stroke, Blood-brain barrier, Sirt1, Sirt3, Mitochondrial ROS

Neuroinflammation plays important roles in neuronal cell death and functional deficits after TBI. Small conductance Ca2+-activated K+ channels (SK) have been shown to be potential therapeutic targets for treatment of neurological disorders, such as stroke and Parkinson’s disease (PD). The aim of the present study was to investigate the role of SK channels in an animal model of TBI induced by controlled cortical impact (CCI). The SK channels activator NS309 at a concentration of 2 mg/kg was administered by intraperitoneal injection, and no obviously organ-related toxicity of NS309 was found in Sprague-Dawley (SD) rats. Treatment with NS309 significantly reduced brain edema after TBI, but had no effect on contusion volume. This protection can be observed even when the administration was delayed by 4 h after injury. NS309 attenuated the TBI-induced deficits in neurological function, which was accompanied by the reduced neuronal apoptosis. The results of immunohistochemistry showed that NS309 decreased the number of neutrophils, lymphocytes, and microglia cells, with no effect on astrocytes. In addition, NS309 markedly decreased the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and chemokines (MCP-1, MIP-2, and RANTES), but increased the levels of anti-inflammatory cytokines (IL-4, IL-10, and TGF-β1) after TBI. The results of RT-PCR and western blot showed that NS309 increased TSG-6 expression and inhibited NF-κB activation. Furthermore, knockdown of TSG-6 using in vivo transfection with TSG-6 specific shRNA partially reversed the protective and anti-inflammatory effects of NS309 against TBI. In summary, our results indicate that the SK channel activator NS309 could modulate inflammation-associated immune cells and cytokines via regulating the TSG-6/NF-κB pathway after TBI. The present study offers a new sight into the mechanisms responsible for SK channels activation with implications for the treatment of TBI.

Spinal cord ischemia-reperfusion injury (SCI/R) is a rare but devastating disorder with a poor prognosis. Small conductance calcium-activated K+ (SK/KCa) channels are a family of voltage-independent potassium channels that are shown to participate in the pathological process of several neurological disorders. The aim of this study was to investigate the role of SK/KCa channels in experimental SCI/R in rabbits. The expression of SK/KCa1 protein significantly decreased in both cytoplasm and mitochondria in spinal cord tissues after SCI/R. Treatment with 2 mg/kg NS309, a pharmacological activator for SK/KCa channel, attenuated SCI/R-induced neuronal loss, spinal cord edema and neurological dysfunction. These effects were still observed when the administration was delayed by 6 h after SCI/R initiation. NS309 decreased the levels of oxidative products and promoted activities of antioxidant enzymes in both serum and spinal cord tissues. The results of ELISA assay showed that NS309 markedly decreased levels of pro-inflammatory cytokines while increased anti-inflammatory cytokines levels after SCI/R. In addition, treatment with NS309 was shown to preserve mitochondrial respiratory complexes activities and enhance mitochondrial biogenesis. The results of western blot analysis showed that NS309 differentially regulated the expression of mitochondrial dynamic proteins. In summary, our results demonstrated that the SK/KCa channel activator NS309 protects against SCI/R via anti-oxidative activity and inhibition of mitochondrial dysfunction, indicating a therapeutic potential of NS309 for SCI/R.

Oxidative stress is a well-established event in the pathology of several neurobiological diseases. Sirt3 is a nicotinamide adenine nucleotide (NAD+)-dependent protein deacetylase that regulates mitochondrial function and metabolism in response to caloric restriction and stress. This study aims to investigate the role of Sirt3 in H2O2 induced oxidative neuronal injury in primary cultured rat cortical neurons. We found that H2O2 treatment significantly increased the expression of Sirt3 in a time-dependent manner at both mRNA and protein levels. Knockdown of Sirt3 with a specific small interfering RNA (siRNA) exacerbated H2O2-induced neuronal injury, whereas overexpression of Sirt3 by lentivirus transfection inhibited H2O2-induced neuronal damage reduced the generation of reactive oxygen species (ROS), and increased the activities of endogenous antioxidant enzymes. In addition, the intra-mitochondrial Ca2+ overload, but not cytosolic Ca2+ increase after H2O2 treatment, was strongly attenuated after Sirt3 overexpression. Overexpression of Sirt3 also increased the content of mitochondrial DNA (mtDNA) and the expression of mitochondrial biogenesis related transcription factors. All these results suggest that Sirt3 acts as a prosurvival factor playing an essential role to protect cortical neurons under H2O2 induced oxidative stress, possibly through regulating mitochondrial Ca2+ homeostasis and mitochondrial biogenesis.

Therapy using acellular spinal cord (ASC) scaffolds seeded with bone marrow stromal cells (BMSCs) has previously been shown to restore function of the damaged spinal cord and improve functional recovery in a rat model of acute hemisected spinal cord injury (SCI). The aim of the present study was to determine whether BMSCs and ASC scaffolds promote the functional recovery of the damaged spinal cord in a rat SCI model through regulation of apoptosis and immune responses. Whether this strategy regulates secondary inflammation, which is characterized by the infiltration of immune cells and inflammatory mediators to the lesion site, in SCI repair was investigated. Basso, Beattie, and Bresnahan scores revealed that treatment with BMSCs seeded into an ASC scaffold led to a significant improvement in motor function recovery compared with treatment with an ASC scaffold alone or untreated controls at 2 and 8 weeks after surgery (P<0.05). Two weeks after transplantation, the BMSCs seeded into an ASC scaffold significantly decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, as compared with the ASC scaffold only and control groups. These results suggested that the use of BMSCs decreased the apoptosis of neural cells and thereby limited tissue damage at the lesion site. Notably, the use of BMSCs with an ASC scaffold also decreased the recruitment of macrophages (microglia; P<0.05) and T lymphocytes (P<0.05) around the SCI site, as indicated by immunofluorescent markers. By contrast, there was no inhibition of the inflammatory response in the control and ASC scaffold only groups. BMSCs regulated inflammatory cell recruitment to promote functional recovery. However, there was no significant difference in IgM-positive expression among the three groups (P>0.05). The results of this study demonstrated that BMSCs seeded into ASC scaffolds for repair of spinal cord hemisection defects promoted functional recovery through the early regulation of inflammatory cell recruitment with inhibition of apoptosis and secondary inflammation. [ABSTRACT FROM AUTHOR]

Oxidative stress is a well-established event in the pathology of several neurobiological diseases. Sirt3 is a nicotinamide adenine nucleotide (NAD+)-dependent protein deacetylase that regulates mitochondrial function and metabolism in response to caloric restriction and stress. This study aims to investigate the role of Sirt3 in H2O2 induced oxidative neuronal injury in primary cultured rat cortical neurons. We found that H2O2 treatment significantly increased the expression of Sirt3 in a time-dependent manner at both mRNA and protein levels. Knockdown of Sirt3 with a specific small interfering RNA (siRNA) exacerbated H2O2-induced neuronal injury, whereas overexpression of Sirt3 by lentivirus transfection inhibited H2O2-induced neuronal damage reduced the generation of reactive oxygen species (ROS), and increased the activities of endogenous antioxidant enzymes. In addition, the intra-mitochondrial Ca2+ overload, but not cytosolic Ca2+ increase after H2O2 treatment, was strongly attenuated after Sirt3 overexpression. Overexpression of Sirt3 also increased the content of mitochondrial DNA (mtDNA) and the expression of mitochondrial biogenesis related transcription factors. All these results suggest that Sirt3 acts as a prosurvival factor playing an essential role to protect cortical neurons under H2O2 induced oxidative stress, possibly through regulating mitochondrial Ca2+ homeostasis and mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

In terms of the coupled mode theory, formulas of the transfer function and the output power gain are presented for an Er3+/Yb3+ co-doped parallel-cascaded double microring resonator. Around the pump wavelength of 0.98 μm and the central signal wavelength of 1.55 μm, analysis is performed for the dependence of the output power gain on the pump power, signal power, dopant concentration, amplitude coupling ratio, and ring spacing. The results show that the output power gain of this device is much larger than that of the Er3+/Yb3+ co-doped waveguide amplifier with identical waveguide lengths. In the case of the amplitude coupling ratio κ = 0.064, ring spacing L2 = 10π R, pump power Pp0 = 8 mW, signal power Ps0 = 37.2 μW, Er3+ ion concentration NEr = 1 × 26 m-3, and Yb3+ ion concentration NYb = 3 × 27 m-3, the device can produce higher signal power gain from 11.9 dB even up to 70 dB. [ABSTRACT FROM AUTHOR]

Novel formulas for analyzing the gain characteristics of the phosphate glass erbium-ytterbium (Er3+-Yb3+) co-doped waveguide amplifier (EYCDWA) are derived from the rate equations and the light propagation equations under the uniform dopant and steady-state conditions. In the derivation of these formulas, we have neglected the amplified spontaneous emission (ASE) and have introduced the initial energy transfer efficiency. By using these formulas, the effects of the pump power, signal power, dopant concentration and waveguide length on the gain characteristics of the EYCDWA are analyzed, the comparison is performed between the EYCDWA and the singly erbium-doped waveguide amplifier (EDWA), and some useful results are obtained. [ABSTRACT FROM AUTHOR]