Icariin mitigates anxiety-like behaviors induced by hemorrhagic shock and resuscitation via inhibiting of astrocytic activation.

BACKGROUND: Abnormal activation of astrocytes in the amygdala contributes to anxiety after hemorrhagic shock and resuscitation (HSR). Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-associated epigenetic reprogramming of astrocytic activation is crucial to anxiety. A bioactive monomer derived from Epimedium icariin (ICA) has been reported to modulate NF-κB signaling and astrocytic activation. PURPOSE: The present study aimed to investigate the effects of ICA on post-HSR anxiety disorders and its potential mechanism of action. METHODS: We first induced HSR in mice through a bleeding and re-transfusion model and selectively inhibited and activated astrocytes in the amygdala using chemogenetics. Then, ICA (40 mg/kg) was administered by oral gavage once daily for 21 days. Behavioral, electrophysiological, and pathological changes were assessed after HSR using the light-dark transition test, elevated plus maze, recording of local field potential (LFP), and immunofluorescence assays. RESULTS: Exposure to HSR reduced the duration of the light chamber and attenuated open-arm entries. Moreover, HSR exposure increased the theta oscillation power in the amygdala and upregulated NF-κB p65, H3K27ac, and H3K4me3 expression. Contrarily, chemogenetic inhibition of astrocytes significantly reversed these changes. Chemogenetic inhibition in astrocytes was simulated by ICA, but chemogenetic activation of astrocytes blocked the neuroprotective effects of ICA. CONCLUSION: ICA mitigated anxiety-like behaviors induced by HSR in mice via inhibiting astrocytic activation, which is possibly associated with NF-κB-induced epigenetic reprogramming.

Hemorrhagic Shock and Resuscitation Causes Excessive Dopaminergic Signaling in the mPFC and Cognitive Dysfunction.

Peri-operative hemorrhagic shock and resuscitation (HSR), a severe traumatic stress, is closely associated with post-operative anxiety, depression, and cognitive dysfunction, subsequently causing a serious burden on families and society. Following the co-release of corticotropin-releasing factor and catecholamine, traumatic stress activates dopaminergic neurons, increasing the addictive behavior and neurocognitive impairment risks. This study investigates the association between cognitive dysfunction and dopaminergic neurons in the mPFC under HSR conditions. This study established an HSR model by bleeding and re-transfusion in the mice. After HSR exposure, a dopamine D1 receptor antagonist, SKF-83566, was administered intraperitoneally for three consecutive days. Novel object recognition (NOR), conditioned fearing (FC), and conditioned place preference (CPP) were used to assess cognitive changes 16 days after HSR exposure. Local field potential (LFP) in the mPFC was also investigated during the novel object exploration. Compared with the mice exposed to sham, there was a significant decrease in the object recognition index, a reduction in context- and tone-related freezing time, an increase in CPP values, a downregulation of ß-power but upregulation of γ-power in the mPFC in the mice exposed to HSR. Moreover, the mice exposed to HSR showed significantly upregulated TH-positive cell number, cleaved caspase-1- and TH-positive cells, and interleukin (IL)-1ß/18 expression in the mPFC compared with sham; SKF-83566 could partially reverse these alternations. The HSR caused excessive dopaminergic signaling and cognitive dysfunction in the mPFC, a condition that might be ameliorated using a dopamine D1 receptor inhibitor.

Spautin-1 administration mitigates mild TBI-induced cognitive and memory dysfunction in mice via activation of caspase-3.

BACKGROUND: Cognitive and memory dysfunction, a common sequela of traumatic brain injury (TBI), places a heavy social and economic burden on individuals, families, communities, and countries. Although the potent anti-tumor effects of spautin-1, a novel autophagy inhibitor, have been documented in malignant melanoma, little is known regarding its efficacy on alleviation of cognitive and memory dysfunction. Here, we describe the effect of spautin-1 administration on cognitive and memory impairment post-TBI, and reveal its underlying mechanism of action. METHODS: We first induced mild TBI in mice through Feeney's weight-drop model, then immediately administered spautin-1 (10 mmol/µl, 2 µl) into the left lateral ventricle. Behavioral and pathological changes were assessed at 24 h, 7 and 30 days after TBI by analyzing neurological severity scores (NSS), novel objective recognition (NOR), Morris water maze (MWM) test, recording of local field potential (LFP), as well as western blot, and immunofluorescence assays. RESULTS: Mild TBI not only reduced recognition index and times crossing platform, but also aggravated neuronal injury, including reduced MAP2, GAD2, VGlut2, and CHAT intensity. It also elevated activated microglia and CD86-occupied areas in TMEM119-positive cells, but suppressed θ, ß, and γ oscillation power in the hippocampal CA1. However, spautin-1 administration significantly reversed these changes, whereas AC-DEVD-CHO an inhibitor of caspase-3 partially blocked the neuroprotective effects of spautin-1. CONCLUSION: Spautin-1 administration mitigates mild TBI-induced cognitive and memory dysfunction in mice, potentially through activation of caspase-3.

Subanesthetic dose of S-ketamine improved cognitive dysfunction via the inhibition of hippocampal astrocytosis in a mouse model of post-stroke chronic stress.

Post-stroke chronic stress (PSCS) is generally associated with the poorer recovery and more pronounced cognitive dysfunction. Recent evidence has implied that S-ketamine can reduce suicidal ideation in treatment-resistant depression. In this current study, we aimed to investigate whether the administration of S-ketamine ameliorated cognitive deficits under PSCS conditions, which was established by a model combining middle cerebral artery occlusion (MCAO) and chronic restraint stress. Our data suggested that mice exposed to PSCS exhibited depression-like behavior and cognitive impairment, which coincided with astrocytosis as indicated by increased GFAP-positive cells and impairment of long-time potentiation (LTP) in the hippocampal CA1. Subanesthetic doses (10 mg/kg) of S-ketamine have significantly mitigated depression-like behaviors, cognitive deficits and LTP impairment, reduced astrocytosis, excessive GABA, and inflammatory factors, including NLRP3 and IL-18 in astrocytes in the CA1. Besides, neuroprotective effects induced by S-ketamine administration were found in vitro but could be partially reversed by an agonist of the NLRP3 nigericin. Our current data also suggests that the subanesthetic doses of S-ketamine improved cognitive dysfunction via the inhibition of hippocampal astrocytosis in a mouse model of PSCS.

Hyperparallel transistor, router and dynamic random access memory with unity fidelities.

We theoretically implement some hyperparallel optical elements, including quantum single photon transistor, router, and dynamic random access memory (DRAM). The inevitable side leakage and the imperfect birefringence of the quantum dot (QD)-cavity mediates are taken into account, and unity fidelities of our optical elements can be achieved. The hyperparallel constructions are based on polarization and spatial degrees of freedom (DOFs) of the photon to increase the parallel efficiency, improve the capacity of channel, save the quantum resources, reduce the operation time, and decrease the environment noises. Moreover, the practical schemes are robust against the side leakage and the coupling strength limitation in the microcavities.

A heralded and error-rejecting three-photon hyper-parallel quantum gate through cavity-assisted interactions.

Hyper-parallel quantum computation is a promising and fruitful area of research with its high capacity and low loss rate characters. In this paper, we propose a heralded, compact, scalable, and deterministic error-rejecting scheme for implementing three-photon hyper-parallel Toffoli gate simultaneously acting on polarization and spatial degrees of freedom. It is a practical and unity gate without strong coupling strength limitations, since the undesired performances caused by the side leakage and the limited coupling strength are detected by the single-photon detectors. The success of our proposal can be heralded by the detectors, and the efficiency can be further improved by repeating the operation processes when the detectors are clicked. The evaluation of gate performance with experimental parameters shows that it is feasible with current experimental technology.

Dynamic model for controller design of condensate throttling systems.

Improving the load adjustment rate of coal-fired power plants in China is very important because of grid load fluctuations and the construction of new large-scale power plants connected to the country's power grid. In this paper, a new application of condensate throttling system for rapid load adjustment is proposed on the basis of the characteristics of turbine-stored energy. To ensure effective and safe operation of the condensate throttling system, a non-linear control model is derived through reasonable simplifications of fundamental physical laws, and the model parameters are identified using experimental data from a 660 MW supercritical coal-fired power plant. The model outputs are compared with actual measured data for different unit loads. Results show that the established model's responses strongly correlate with the actual unit's responses and can be used for controller design.

[Effect of phosphor on accumulation and chemical forms of cadmium, and physiological characterization in different varieties of Capsicum annuum L].

Pot experiments were carried out to investigate the influence of different Phosphor (P) levels (0, 0.3% and 0.5%) on the plant growth, activities of antioxidant enzymes, accumulation and chemical forms of cadmium (Cd) in Capsicum annuum L. when exposed to Cd (10 mg x kg(-1)). The results showed that dry weights of leaf, fruit, roots and total dry weights of plant, and concentration and accumulation of Cd significantly differed between two varieties of Capsicum annuum L. Dry weights of fruit and total plant of Chaotianjiao increased by P (0.3% and 0.5%), while that of Yanjiao425 was inhibited. Activities of catalase (CAT) were increased at first, and then reduced in the presence of P; Activities of superoxide dismutase (SOD) and peroxidase (POD) of Chaotianjiao increased with increasing levels of P, but activities of SOD and POD of Yanjiao425 decreased with increasing levels of P. Chemical forms of Cd in fruit of Capsicum annuum L. were in order of F(NaCl) > F(HAC) > F(E) > Fr > F(HC) > F(W). The total extractable Cd, ethanol-extractable Cd, hydrochloric acid-extractable Cd and residual Cd in fruit of Ynajiao425 obviously decreased in the presence of P compared to the control, while the total extractable Cd, water-extractable Cd, acetic acid-extractable Cd and residual Cd in fruit of Chaotianjiao increased. Cadmium accumulations of Capsicum annuum L. were in order of roots > stew > leaf > fruit. Cadmium accumulations in fruit and plant of Yanjiao425 were decreased by 47.7% and 58.5% , 5.5% and 13. 1% in the presence of 0.3% and 0.5% P when exposed to Cd, and Cd accumulations in fruit and plant of Chaotianjiao were decreased by 23.6% in the presence of 0.3% P.

[Effect of different zinc levels on accumulation and chemical forms of cadmium, and physiological characterization in Capsicum annuum L].

Pot experiments were carried out to investigate the influence of different zinc (Zn) levels (0, 100, 200, 400 and 600 micromol x L(-1)) on the plant growth,activities of antioxidant enzymes, contents of chlorophyll a and b, accumulation and chemical forms of cadmium (Cd) in Capsicum annuum L. when exposed to Cd (20 mg x kg(-1)). The results showed that dry weights of leaf, stem, fruit and root, and contents of chlorophyll a and b in Capsicum annuum L. were increased by Zn ( < or = 400 micromol x L(-1)), while inhibited by high Zn (600 micromol x L(-1)). Activities of superoxide dismutase (SOD) and catalase (CAT) were reduced by Zn ( < or =400 micromol x L(-1)), the lowest activities of SOD and CAT were recorded in 400 micromol x L(-1) Zn, but activities of SOD and CAT were increased when Zn >400 micromol x L(-1). Cadmium concentrations in stem, fruit and root of Capsicum annuum L. were decreased by 2.7%-5.4%, 7.5%-28.1% and 7.6%-21.8% in the presence of Zn when exposed to Cd. The total extractable Cd, NaCl- extractable Cd, water-extractable Cd and ethanol-extractable Cd in fruit were reduced by 7.7%-21.8%, 4.11%-23.6%, 54.5%-66.8% and 4.8%-86.7% in the presence of Zn,while acetic acid- extractable Cd and residual Cd were increased by 28.0%-68.0% and 12.6%-25.0%.

[Changes of Foxp3 and IL-10 and TGF-beta in aging of mice].

AIM: To compare the expression levels of Foxp3 mRNA in the spleen PBMC (peripheral blood mononuclear cell) in the progress of aging mice and analyse the relevance with serum IL-10 and TGF-beta. METHODS: Healthy male BALB/c mice were divided into 3 groups at random (8 mice each group): 2m group with 2 months mice (young), 6m group with 6 months mice (middle-aged) and 15m group with 15 months mice (aged). The phenotype of CD4(+);CD25(+);Foxp3(+); T cells derived from normal murine SPL were analyzed by FCM. Real-time fluorescence quantitative RT-PCR was used to determine the expression levels of Foxp3 mRNA in the spleen PBMC. ELISA was used to detect the concentration of IL-10 and TGF-beta. RESULTS: The subsets of CD4(+);CD25(+);Foxp3(+); T lymphocytes from murine splenocytes were significantly higher in 15m group than that in 2m group(P<0.01). The expression levels of Foxp3 mRNA in the spleen PBMC were significantly higher in 15m group than that in 2m group(P<0.01).The serum concentration of IL-10 and TGF-beta were significantly higher in 15m group than that in 2m group(P<0.01).There was no correlation between serum concentration of IL-10 and TGF-beta and Foxp3 mRNA expression levels in the spleen PBMC in 15m group. CONCLUSION: The level of the CD4(+);CD25(+);Foxp3(+); T cells and Foxp3 mRNA expression levels were up-regulated and IL-10 and TGF-beta contents were increased in the progress of aging mice. Foxp3 and IL-10 and TGF-beta may be play a part in the process of immunosenescence. Quantitative detection of Foxp3 mRNA by the method of SYBR Green I real-time fluorescence quantitative RT-PCR is stable and reliable.