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Iron-dependent lipid peroxidation causes ferroptosis. This study was aimed at verifying that irisin postconditioning can inhibit ferroptosis and minimize lung ischemia/reperfusion (I/R) damage via activating the Nrf2/HO-1 signal axis. We constructed a murine model of I/R lung damage. At the onset of reperfusion, irisin, ferroptosis inhibitor ferrostatin-1, and ferroptosis inducer Fe-citrate were all administered. We discovered that irisin could reduce lung I/R injury, consistent with ferrostatin-1’s action. Furthermore, irisin suppressed ferroptosis in lung I/R damage, as evidenced by lower ROS, MDA, and Fe2+, as well as alterations in critical protein expression (GPX4 and ACSL4). However, Fe-citrate abolished the protective effects of irisin. Transcriptome research found that irisin increased the mRNA levels of Nrf2 and HO-1. Thus, we used siRNA to investigate the role of the Nrf2/HO-1 axis in irisin-mediated protection against hypoxia/reoxygenation (H/R) damage in MLE-12 cells. Irisin consistently reduced ferroptosis and improved mitochondrial dysfunction caused by H/R. Irisin’s cytoprotective function was eliminated when Nrf2 was silenced. As a result, irisin postconditioning may protect against lung I/R damage by suppressing ferroptosis via the Nrf2/HO-1 signaling axis.

Age-related cognitive impairment is associated with diminished autophagy and progressively increased neuroinflammation. Histone acetylation has been shown to be a key process in sevoflurane-induced neurobehavioral abnormalities. Here, we investigated whether histone acetylation regulates the interaction between autophagy and the NLRP3 inflammasome in models of sevoflurane-induced cognitive impairment and explored the underlying molecular mechanisms. Aged C57BL/6 J mice and cultured primary hippocampal neurons were exposed to 3% sevoflurane for 2 h. Hippocampal tissue samples and hippocampal neurons were harvested. The processes of histone acetylation and autophagy and the activation of the NLRP3 inflammasome were observed using western blotting, immunofluorescence staining, and transmission electron microscopy. Suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylases, increased histone H3 and H4 acetylation in both the mouse hippocampus and primary neurons. Concomitantly, sevoflurane upregulated components of the NLRP3 inflammasome (NLRP3, cleaved caspase-1, and IL-1β) by promoting autophagic degradation in the aging brain. Cognitive deficits and inadequate autophagy induced by sevoflurane were reversed and NLRP3 inflammasome activation was inhibited by SAHA. Treatment with 3-MA, an autophagy inhibitor, eliminated the neuroprotective effects of SAHA on improving cognition in mice, activating autophagy and downregulating the NLRP3 inflammasome. Based on these results, histone acetylation activates autophagy plays an important role in inhibiting the activation of the NLRP3 inflammasome to protect the host from excessive neuroinflammation and sevoflurane-induced cognitive dysfunction in the aging brain.

Here, we show that aqueous dispersions of inorganic nanoparticles bearing negative surface charges would trigger the chiral assembly of organic radical cations solubilized in organic solvent at the liquid-liquid interface, which consequently produces stable droplets covered by a layer of inorganic/organic chiral nanocomposites. We demonstrate that chirality transfer across the liquid-liquid interface from the chiral organic monomers to the nanoparticle assemblies is realized. Surprisingly, opposite handedness between molecular assemblies and nanoparticle assemblies is determined from both CD and CPL measurements. Moreover, the functionalities of these "chiral" droplets could be further engineered through either a simple mixing or a droplet merging strategy, which enables to produce fluorescent emissive-tunable, magnetic, as well as magnetofluorescent dual-functional droplets.

Binding of fluorescent molecules to the porous matrix through noncovalent interactions will synergistically expand their application spectrum. In this regard, we report an integrative self-assembly of molecule 1 with benzothiadizole and 9,9-dihexyl fluorene units, and covalent organic frameworks (COFs) via an emulsion-modulated polymerization process, within which molecules of 1 are able to interact with the scaffolds of COFs through CH-π interactions. Thus the π-π interactions between the fluorescent molecules are largely suppressed, giving rise to their remarkable monomer-like optical properties. Of particular interest is that, given by the specific interaction between COFs and a nerve agent simulant diethyl chlorophosphite (DCP), these assembled composites show the ability of ultrasensitive detection of DCP with a detection limit of ~40 ppb. Moreover, the present integrative assembly strategy can be extended to encapsulate multiple fluorescent molecules, enabling the assemblies with white light emission. Our results highlight opportunities for the development of highly emissive porous materials by molecular self-assembly of fluorophores and molecular units of COFs.

Background and objectives: Preoperative use of flurbiprofen axetil (FA) is extensively adopted to modulate the effects of analgesia. However, the relationship between FA and sedation agents remains unclear. In this study, we aimed to investigate the effects of different doses of FA on the median Effective Concentration (EC50) of propofol. Methods: Ninety-six patients (ASA I or II, aged 18–65 years) were randomly assigned into one of four groups in a 1:1:1:1 ratio. Group A (control group) received 10 mL of Intralipid, and groups B, C and D received 0.5 mg.kg−1, 0.75 mg.kg−1 and 1 mg.kg−1 of FA, respectively, 10 minutes before induction. The depth of anesthesia was measured by the Bispectral Index (BIS). The “up-and-down” method was used to calculate the EC50 of propofol. During the equilibration period, if BIS ≤ 50 (or BIS > 50), the next patient would receive a 0.5 μg.mL−1-lower (or -higher) propofol Target-Controlled Infusion (TCI) concentration. The hemodynamic data were recorded at baseline, 10 minutes after FA administration, after induction, after intubation and 15 minutes after intubation. Results: The EC50 of propofol was lower in Group C (2.32 μg.mL−1, 95% Confidence Interval [95% CI] 1.85–2.75) and D (2.39 μg.mL−1, 95% CI 1.91–2.67) than in Group A (2.96 μg.mL−1, 95% CI 2.55–3.33) (p = 0.023, p = 0.048, respectively). There were no significant differences in the EC50 between Group B (2.53 μg.mL−1, 95% CI 2.33–2.71) and Group A (p > 0.05). There were no significant differences in Heart Rate (HR) among groups A, B and C. The HR was significantly lower in Group D than in Group A after intubation (66 ± 6 vs. 80 ± 10 bpm, p 50, o próximo paciente tinha a infusão de propofol ajustada para uma concentração alvo-controlada 0,5 μg.mL−1 inferior ou superior, respectivamente. Os dados hemodinâmicos foram registrados no início do estudo, 10 minutos após a administração de FA, após a indução, após a intubação e 15 minutos após a intubação. Resultados: A CE50 do propofol foi menor no Grupo C (2,32 μg.mL−1, Intervalo de Confiança de 95% [95% IC] 1,85–2,75) e D (2,39 μg.mL−1, 95% IC 1,91–2,67) do que no Grupo A (2,96 μg.mL−1; 95% IC 2,55–3,33) (p = 0,023, p = 0,048, respectivamente). Não houve diferenças significantes na CE50 entre o Grupo B (2,53 μg.mL−1, 95% IC 2,33–2,71) e o Grupo A (p > 0,05). Não houve diferenças significantes na Frequência Cardíaca (FC) entre os grupos A, B e C. A FC foi significantemente menor no grupo D do que no grupo A após a intubação (66 ± 6 vs. 80 ± 10 bpm, p

Resumo Justificativa e objetivos A administracao pre‐operatoria de Flurbiprofeno Axetil (FA) e amplamente usada para a modulacao da analgesia. No entanto, a relacao entre FA e farmacos sedativos permanece obscura. Neste estudo, nosso objetivo foi investigar os efeitos de diferentes doses de FA na Concentracao Efetiva mediana (CE50) do propofol. Metodos Noventa e seis pacientes (ASA I ou II, com idades de 18–65 anos) foram alocados aleatoriamente em quatro grupos na proporcao de 1:1:1:1. Dez minutos antes da inducao, o Grupo A (grupo controle) recebeu 10 mL de Intralipid, enquanto os grupos B, C e D receberam FA na dose de 0,5 mg.kg‐1; 0,75 mg.kg‐1 e 1 mg.kg‐1, respectivamente. A profundidade da anestesia foi medida pelo Indice Bispectral (BIS). O metodo up‐and‐down foi usado para calcular a CE50 do propofol. Durante o periodo de equilibrio, se o valor do BIS fosse ≤ 50 ou BIS > 50, o proximo paciente tinha a infusao de propofol ajustada para uma concentracao alvo‐controlada 0,5 μg.mL‐1 inferior ou superior, respectivamente. Os dados hemodinâmicos foram registrados no inicio do estudo, 10 minutos apos a administracao de FA, apos a inducao, apos a intubacao e 15 minutos apos a intubacao. Resultados A CE50 do propofol foi menor no Grupo C (2,32 μg.mL‐1, Intervalo de Confianca de 95% [95% IC] 1,85–2,75) e D (2,39 μg.mL‐1, 95% IC 1,91–2,67) do que no Grupo A (2,96 μg.mL‐1; 95% IC 2,55–3,33) (p = 0,023, p = 0,048, respectivamente). Nao houve diferencas significantes na CE50 entre o Grupo B (2,53 μg.mL‐1, 95% IC 2,33–2,71) e o Grupo A (p > 0,05). Nao houve diferencas significantes na Frequencia Cardiaca (FC) entre os grupos A, B e C. A FC foi significantemente menor no grupo D do que no grupo A apos a intubacao (66 ± 6 vs. 80 ± 10 bpm, p Conclusao FA em altas doses (0,75 mg.kg‐1 ou 1 mg.kg‐1) reduz a CE50 do propofol, e 1 mg.kg‐1 de FA reduz a FC durante niveis adequados de anestesia em pacientes nao estimulados. Embora esse resultado deva ser investigado na presenca de estimulacao cirurgica, sugerimos que a pre‐administracao de FA pode reduzir a necessidade de propofol durante anestesia cuja profundidade seja monitorada pelo BIS.

Background This study aimed to investigate the role of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in protection by peritoneal resuscitation (PR) using pyruvate-peritoneal dialysis solution (PY-PDS) against intestinal injury from hemorrhagic shock (HS) in rats. Materials and Methods Sixty-four rats were assigned to eight groups: group SHAM; group intravenous resuscitation (VR); groups NS, LA, and PY in which the rats were subjected to HS and PR with normal saline (NS), lactate-peritoneal dialysis solution (LA-PDS), and PY-PDS, respectively, combined with VR; and groups DMSO, RPM, and AG490 in which the rats were subjected to HS and VR with pretreatment of dimethyl sulfoxide (DMSO), rapamycin (RPM), and tyrphostin B42 (AG490). Results At 2 h after HS and resuscitation, the levels of diamine oxidase, 15-F2t-isoprostane, thromboxane B2, and endothelin-1, in the blood and the intestinal mucosal apoptotic index and caspase-3 were lower in groups PY, RPM, and AG490 than in groups VR, NS, LA, and DMSO. Group PY showed lower levels of malondialdehyde and myeloperoxidase and a higher level of superoxide dismutase than groups VR, NS, and LA. Phosphorylated JAK2 and phosphorylated STAT3 levels were lower in groups PY, RPM, AG490, and LA than in groups VR, NS, and DMSO. Conclusions The protection mechanism of PR with PY-PDS combined with VR was related to the inhibition of the JAK/STAT signaling pathway during HS and resuscitation. The process might include suppression of oxidative stress, reduction of neutrophil infiltration, regulation of microcirculation, and inhibition of apoptosis.

To investigate the effects of direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution (Pyr-PDS) of different concentrations combined with intravenous resuscitation on acid–base imbalance and intestinal ischemia reperfusion injury in rats with hemorrhagic shock. Sixty rats were randomly assigned to group SHAM, group intravenous resuscitation, and four direct peritoneal resuscitation groups combined with intravenous resuscitation: group NS, LA, PY1, and PY2, that is, normal saline, lactate-PDS (Lac-PDS), lower concentration Pyr-PDS (Pyr-PDS1), and higher concentration Pyr-PDS (Pyr-PDS2), respectively. Two hours after hemorrhagic shock and resuscitation, the pH, oxygen partial pressure, carbon dioxide partial pressure (PCO2), base excess, and bicarbonate ion concentration (HCO3−) of the arterial blood were measured. The intestinal mucosal damage index and intercellular adhesion molecule 1 (ICAM-1), tumor necrosis factor-α, interleukin-6, zonula occludens-1, claudin-1, and occludin levels in intestinal issues were detected. Two hours after resuscitation, group PY2 had higher mean arterial pressure, pH, oxygen partial pressure, and base excess and lower PCO2of arterial blood than group PY1 ( P < 0.05). Tumor necrosis factor-α and interleukin-6 levels in group PY2 were significantly lower than those in group PY1 ( P < 0.05). Zonula occludens-1, claudin-1, and occludin expression levels were significantly higher in group PY2 than in group PY1 ( P < 0.05). Direct peritoneal resuscitation with Pyr-PDS2 combined with intravenous resuscitation enhanced the hemodynamics, improved the acid–base balance, and alleviated intestinal ischemia reperfusion injury from hemorrhagic shock and resuscitation in rats. The mechanisms might include correction of acidosis, inhibition of inflammatory response, enhancement of systemic immune status, regulation of intestinal epithelial permeability, and maintenance of intestinal mucosal barrier function.Impact statementHemorrhagic shock is a life-threatening condition after trauma or during surgery. Acid–base imbalance and intestinal ischemia reperfusion injury are two significant causes in the pathogenetic process and multiple organ dysfunction. As a result, it is urgent and necessary to find an effective method of resuscitation in order to reverse the acid–base imbalance and protect organ function. This current study confirmed the protection against hypoxic acidosis and intestinal ischemia reperfusion injury by peritoneal resuscitation with pyruvate combined with intravenous resuscitation in rats with hemorrhagic shock. And the peritoneal dialysis solution with pyruvate of high concentration plays a crucial role in the process. It provided a new idea and possible direction of fluid resuscitation for alleviating organ injuries, protecting organ functions, and improving clinical prognosis after hemorrhagic shock and resuscitation.

Toll-like receptor 4 (TLR4) is a crucial receptor in neuroinflammation and apoptotic neuronal death, and increasing evidences indicated that β2-microglobulin (B2M) is thought to be a major contributor to age-related cognitive decline. In present study, we designed to investigate the effects of TLR4 on B2M-induced age-related cognitive decline. Wild-type (WT) C57BL/6, TLR4 knockout (TLR4 -KO) mice and hippocampal neurons from the two type mice were respectively divided into two groups: (1) Veh group; (2) B2M-treated group. The behavioral responses of mice were measured using Morris Water Maze. Hippocampal neurogenesis and neuronal damage, inflammatory response, apoptosis, synaptic proteins and neurotrophic factors, and TLR4/MyD88/NF-κB signaling pathway proteins were examined using molecular biological or histopathological methods. The results showed that WT mice received B2M in the DG exhibited age-related cognitive declines, increased TLR4 mRNA expression and high levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and apoptotic neuronal death in the hippocampus, which were partially attenuated in TLR4-KO mice. Moreover, in absence of TLR4, B2M treatment improved hippocampus neurogenesis and increased synaptic related proteins. Our cell experiments further demonstrated that deletion of TLR4 could significantly increase synaptic related protein, decrease neuroinflammatory fators, inhibited apoptotic neuronal death, and regulated MyD88/NF-κB signal pathway after B2M treatment. In summary, our results support the TLR4 contributes to B2M-induced age-related cognitive decline due to neuroinflammation and apoptosis through TLR4/MyD88/NF-κB signaling pathway via a modulation of hippocampal neurogenesis and synaptic function. This may provide an important neuroprotective mechanism for improving age-related cognitive decline.

Postoperative delirium (POD) is a common complication following surgery and anesthesia (Surgery/Anesthesia). Mitochondrial dysfunction, which is demonstrated by energy deficits and excessively activated oxidative stress, has been reported to contribute to POD. The dynamic balance between mitochondrial fusion and fission processes is critical in regulating mitochondrial function. However, the impact of Surgery/Anesthesia on mitochondrial fusion/fission dynamics remains unclear. Here, we evaluate the effects of laparotomy under 1.4% isoflurane anesthesia for 2 hours on mitochondrial fission/fusion dynamics in the brain of aged mice. Mice in Surgery/Anesthesia group showed unbalanced fission/fusion dynamics, with decreased DISC1 expression and increased expression of Drp1 and Mfn2 in the mitochondrial fraction, leading to excessive mitochondrial fission and disturbed mitochondrial morphogenesis in the hippocampus and prefrontal cortex. In addition, surgical mice presented mitochondrial dysfunction, demonstrated by abnormally activated oxidative stress (increased ROS level, decreased SOD level) and energy deficits (decreased levels of ATP and MMP). Surgery/Anesthesia also decreased the expression of neuronal/synaptic plasticity-related proteins such as PSD-95 and BDNF. Furthermore, Surgery/Anesthesia induced delirium-like behavior in aged mice. In conclusion, Surgery/Anesthesia disturbed mitochondrial fission/fusion dynamics and then impaired mitochondrial function in the brain of aged mice; these effects may be involved in the underlying mechanism of POD.

Younian Xu,1 Yangyang Ge,1 Miaomiao Zhou,2 Zongze Zhang2 1Anesthesiology Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Anesthesiology Department, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Miaomiao ZhouAnesthesiology Department, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, People’s Republic of ChinaTel/Fax +86 027-67812903Email 879475227@qq.comBackground: Large ischemic stroke provokes an inflammatory response, promoting the release of norepinephrine (NE) by intensifying the sympathetic nervous system. This augmented sympathetic outflow was deemed to act on β 2-adrenergic receptors (β 2-ARs) expressed by immune cells, rendering organisms to post-stroke infections, like pneumonia. To clarify this issue, we introduced selective β 2-ARs agonist clenbuterol (CLEN) to stroke mice to investigate how β 2-adrenergic signaling augmentation after stroke affects immune response and post-stroke outcomes, including central and peripheral.Methods: We developed a middle cerebral artery occlusion (MCAO) stroke model in mice to induce large ischemic stroke and administered CLEN 24 h after the onset of MCAO stroke. First, we assessed infarct volume and NE levels in plasma and spleen 3ds later. Next, the immune state was identified by analyzing the spleen index, immune cell populations, and immune cytokines. Finally, peripheral outcomes were assessed by measuring signs of pneumonia, such as pathology, bacterial burden, and lung cytokines.Results: We report that CLEN treatment 24 h after MCAO stroke causes an enlarged infarct volume and a decrease in NE levels at 3ds after stroke. Consistent with a reduction of total T cells, T helper cells, and increase of cytotoxic T cells, the immune milieu after CLEN treatment presents an anti-inflammatory landscape, showing raised expression of anti-inflammatory cytokines: IL-4, IL-10, and TGF-β 1, and decreased expression of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IFN-γ, with a dramatically reduced percentage of Gr-1+ neutrophils and B cells but an increased percentage of NK cells. In our study, CLEN treatment results in no higher risk of pneumonia but relieves bacterial burden, inhibits or limits pneumonia, and diminishes TNF-α expression in lung tissues after MCAO.Conclusion: We identified increased β 2-adrenergic signaling after MCAO stroke, inhibits or limits post-stroke pneumonia but enlarges stroke volume in MCAO mice. Thus, careful consideration must be taken to improve post-stroke outcomes by manipulation over β 2-adrenergic receptors.Keywords: ischemic stroke, β 2-adrenergic receptor, infarct, pneumonia, immunity, sympathetic

Preoperative sleep loss can amplify post-operative mechanical hyperalgesia. However, the underlying mechanisms are still largely unknown. In the current study, rats were randomly allocated to a control group and an acute sleep deprivation (ASD) group which experienced 6 h ASD before surgery. Then the variations in cerebral function and activity were investigated with multi-modal techniques, such as nuclear magnetic resonance, functional magnetic resonance imaging, c-Fos immunofluorescence, and electrophysiology. The results indicated that ASD induced hyperalgesia, and the metabolic kinetics were remarkably decreased in the striatum and midbrain. The functional connectivity (FC) between the nucleus accumbens (NAc, a subregion of the ventral striatum) and the ventrolateral periaqueductal gray (vLPAG) was significantly reduced, and the c-Fos expression in the NAc and the vLPAG was suppressed. Furthermore, the electrophysiological recordings demonstrated that both the neuronal activity in the NAc and the vLPAG, and the coherence of the NAc-vLPAG were suppressed in both resting and task states. This study showed that neuronal activity in the NAc and the vLPAG were weakened and the FC between the NAc and the vLPAG was also suppressed in rats with ASD-induced hyperalgesia. This study highlights the importance of preoperative sleep management for surgical patients.

Sevoflurane, which is widely used in paediatric anaesthesia, induces neural apoptosis in the developing brain and cognitive impairment in young mammals. Glucose hypometabolism is the key pathophysiological modulator of cognitive dysfunction. However, the effects and mechanism of sevoflurane on cerebral glucose metabolism after its use as an anaesthetic and its complete elimination are still unknown. We therefore investigated the influence of sevoflurane on neuronal glucose transporter isoform 3 (GLUT3) expression, glucose metabolism and apoptosis in vivo and in vitro and on neurocognitive function in young mice 24 h after the third exposure to sevoflurane. Postnatal day 14 (P14) mice and neural cells were exposed to 3% sevoflurane 2 h daily for three days. We found that sevoflurane anaesthesia decreased GLUT3 gene and protein expression in the hippocampus and temporal lobe, consistent with a decrease in glucose metabolism in the hippocampus and temporal lobe observed by [18F] fluorodeoxyglucose positron emission tomography (18F-FDG PET). Moreover, sevoflurane anaesthesia increased the number of TUNEL-positive cells and the levels of Bax, cleaved caspase 3 and cleaved PARP and reduced Bcl-2 levels in the hippocampus and temporal lobe. Young mice exposed to sevoflurane multiple times also showed learning and memory impairment. In addition, sevoflurane inhibited GLUT3 expression in primary hippocampal neurons and PC12 cells. GLUT3 overexpression in cultured neurons ameliorated the sevoflurane-induced decrease in glucose utilization and increase in the apoptosis rate. These data indicate that GLUT3 deficiency may contribute to sevoflurane-induced learning and memory deficits in young mice.

Nanoscale curvature-dependent interactions are of paramount importance in biological systems. Here, we report that nanoscale curvature plays an important role in regulating the chirality of self-assembled nanocomposites from chiral organic molecules and achiral nanoparticles. Specifically, we show that the supramolecular chirality of the nanocomposites markedly depends on the nanoparticle curvature, where small-sized nanoparticles of high curvature and large-sized nanoparticles of low curvature lead to nanocomposites with opposite chirality. Quantitative kinetic experiments and molecular dynamics simulations reveal that nanoparticle curvature plays a key role in promoting the pre-nucleation oligomerization of chiral molecules, which consequently regulates the supramolecular chirality of the nanocomposites. We anticipate that this study will aid in rational design of an artificial cooperative system giving rise to emergent assembling phenomena that can be surprisingly rich and often cannot be understood by studying the conventional noncooperative systems.

Chronic pain during adolescence can lead to mental health disorders in adulthood, but the underlying mechanism is still unclear. Furthermore, the homeostasis of cerebral glucose metabolism and neurotransmitter metabolic kinetics are closely associated with cognitive development and pain progression. The present study investigated changes in cognitive function and glucose metabolism in adult rats, which had experienced chronic pain during their adolescence. Here, spared nerve injury (SNI) surgery was conducted in 4-week-old male rats. Mechanical nociceptive reflex thresholds were analyzed, and SNI chronic pain (SNI-CP) animals were screened. Based on animal behavioral tests (open field, three-chambered social, novel object recognition and the Y maze), the SNI-CP animals showed learning and memory impairment and anxiety-like behaviors, compared to SNI no chronic pain (SNI-NCP) animals. The cerebral glucose metabolism in the prefrontal cortex and hippocampus of adult SNI-CP animals was decreased with positron emission tomography/computed tomography. GABA2 and Glu4 levels in the metabolic kinetics study were significantly decreased in the hippocampus, frontal cortex, and temporal cortex, and the expression of GLUT3 and GLUT4 was also significantly downregulated in the prefrontal cortex and hippocampus of adult rats in the SNI-CP group. These findings suggest that the rats which suffered chronic pain during adolescence have lower cerebral glucose metabolism in the cortex and hippocampus, which could be related to cognitive function during the development of the central nervous system.

Background The blood samples of jugular vein and radial artery were obtained from healthy adults by induced oxygen desaturation test under pulse oximetry conditions on each platform. The oxygen saturation of the two blood samples was analyzed and measured by a Co-oximeter. Thus, the oxygen saturation value of jugular vein (SjvO2) and radial artery (SaO2) were obtained. According to the clinical empirical formula Sa/vO2 = 0.7×S jvO2 + 0.3×SaO2, the oxygen saturation value of brain tissue for invasive blood gas analysis was calculated. To calculate the difference between brain oxygen saturation (rSO2) measured by brain oxygen saturation monitor (hereinafter referred to as brain oxygen analyzer) and brain oxygen saturation (Sa/vO2) measured by invasive blood gas analysis, analyze the consistency of brain oxygen saturation measured by brain oxygen saturation analyzer and blood gas analyzer, and calculate the accuracy of brain oxygen saturation monitoring. The blood samples of jugular vein and radial artery were obtained from healthy adults by induced oxygen desaturation test under pulse oximetry conditions on each platform. The oxygen saturation of the two blood samples was analyzed and measured by a Co-oximeter. Thus, the oxygen saturation value of jugular vein (SjvO2) and radial artery (SaO2) were obtained. According to the clinical empirical formula Sa/vO2 = 0.7×S jvO2 + 0.3×SaO2, the oxygen saturation value of brain tissue for invasive blood gas analysis was calculated. To calculate the difference between brain oxygen saturation (rSO2) measured by brain oxygen saturation monitor (hereinafter referred to as brain oxygen analyzer) and brain oxygen saturation (Sa/vO2) measured by invasive blood gas analysis, analyze the consistency of brain oxygen saturation measured by brain oxygen saturation analyzer and blood gas analyzer, and calculate the accuracy of brain oxygen saturation monitoring. MethodsIn healthy adult volunteers, the induced desaturation test, in which blood gas analysis measures the subjects' internal jugular vein and carotid artery blood samples at each pulse oximetry platform range. Clinical trials were conducted to verify the expected effectiveness and safety of the brain oxygen saturation monitor. Ten subjects were selected into the study according to strict inclusion criteria and exclusion criteria. Subjects should monitor their electrocardiogram, pulse, blood pressure, SPO2 and other vital signs, perform retrograde puncture catheterization of internal jugular vein and radial artery catheterization, ensure the safety of subjects during the period, and record the values of blood samples before and after collection. The oxygen was lowered according to the set platform(according to Figure2), and physiological parameters were monitored during the process. There were 9 platforms in total, and each platform lasted about 5 minutes. The oxygen saturation value of jugular vein (SJVO2) and the oxygen saturation value of carotid artery (SaO2) were obtained, and the tissue oxygen saturation value of sa1vO2 was calculated according to the clinical empirical formula SA1VO2 = 0.7xSJVO2 + 0.3xSaO2. During the blood collection process, the blood oxygen saturation (RSO2) of the subjects' brain was continuously monitored by tissue oximeter noninvastively. The consistency of non-invasive monitoring value RSO2 and invasive measurement value sa1vO2 was compared, and scientific statistical analysis was carried out to confirm whether the accuracy of tissue oxygen meter meets clinical requirements. ResultsAbsolute accuracy evaluation: Further linear regression analysis was performed on the non-invasive monitoring value of the test instrument and the blood gas analysis detection value. The fitting linear equation was rSO2=4.89+0.93×Sa/vO2, where the slope was 0.93, close to 1. The regression line was close to the 45° diagonal trend. The correlation coefficient between rSO2 and Sa/vO2 was 0.95, indicating that there was a good correlation between the non-invasive monitoring value and the invasive blood gas analysis value. Trend accuracy evaluation: It can be seen that the average difference between the trend change value of the test instrument monitoring value and the blood gas analysis value is very small (Bs=Means(△rSO2-△Sa/vO2)=-0.32%), indicating that the trend change of the test instrument monitoring value and the blood gas analysis value is basically consistent in statistical significance. The 95% consistency interval of the difference of trend change between the two devices is narrow ([BS-1.96SD, Bs+1.96SD]=[-6.13%, 5.5%]), indicating that the difference of trend change between the two devices has small variation. The above analysis shows that there is a good consistency between the non-invasive monitoring value of the test equipment and the invasive test results of the blood gas analysis equipment. The linear regression analysis was made on the changes of the test instrument monitoring value and blood gas analysis detection value. The fitting linear equation was △rSO2=-0.98+0.93△Sa/vO2, and the slope was 0.93, which was close to 1. The regression line was close to the 45° diagonal trend. The correlation coefficient of trend changes of the two equipment is 0.95, indicating that the change trend of the test equipment and blood gas analyzer has a good correlation. Analyze the trend changes value, due to the variation of every subjects is relative to the first platform first blood gas analysis values as the base to calculate, so the data points less than 10 absolute value analysis, the test equipment and the trend of blood gas analysis change the average deviation is 0.32%, the standard deviation is 2.97%, RMS very different trend is 2.97%, The clinical evaluation standard of trend Arms≤5% was met. ConclusionThere is good correlation and consistency between the test instrument monitoring value and the absolute value of blood gas analyzer.Trial Registration: The study has been retrospectively registered in Chinese Clinical Trial Registration with the registration number ChiCTR2100052321, date of registration 24/10/2021.

Irisin, which can be released in the hippocampus after physical exercise, is demonstrated to have beneficial effects on neurovascular diseases. This study investigated the impact of exercise linked-irisin on mortality and cognition in a mice model of cerebral ischemia and further explored its underlying mechanism. The cerebrospinal concentrations of irisin and klotho from ischemic stroke patients were measured with an enzyme-linked immunosorbent assay (ELISA). The cognitive function of mice was evaluated by a series of behavioural experiments. The expressions of klotho, MnSOD, and FOXO3a in the hippocampus of mice were detected by Western blot. Superoxide production in the brain tissue of mice was evaluated with the dihydroethidium (DHE) dying. The results demonstrated that stroke patients showed a positive correlation between their CSF irisin concentration and klotho concentration. In addition, when mice subjected to cerebral ischemia, their cognitive function was impaired, the protein expressions of klotho, MnSOD, and FOXO3a downregulated, and the production of reactive oxygen species (ROS) increased compared with the sham group. After pretreatment with exogenous irisin, improved cognitive impairment, upregulated protein expressions of klotho, MnSOD, and FOXO3a, and reduced ROS generation were observed in mice with MCAO. However, the neuroprotective effects of irisin compromised with the evidence of severe cognitive impairment, decreased protein expressions of MnSOD and FOXO3a, and increased ROS production in klotho knockout mice. Thus, our results indicated that exercise-linked irisin could prevent mortality and improve cognitive impairment after cerebral ischemia by regulating klotho expression.

P2X7 receptor is a crucial receptor related to neuronal activation, neurosensitization, and pain transmission, and increasing evidences indicated that glial cells is thought to be a major contributor to the chronic neuropathic pain after nerve injury. In present study, we designed to investigate whether the P2X7R in glial plays a role in chronic neuropathic pain. We divided adult male Sprague Dawley rats were respectively into four groups:(1) vehicle group (Veh), (2) CCI (C group), (3) P2X7 inhibitor group (P group), (4) CCI+ P2X7R inhibition (CP group). Behavior test, real-time polymerase chain reaction, western blot, immunofluorescence staining, and transmission electron microscope were used to analyze the scientific hypothesis. The results of the experiment is that(i) P2X7R of microglia was downregulated by A-70003 after CCI. (ii) Downregulation of P2X7R on microglia is coincident with remission of NP after CCI. (iii) P2X7R of microglia participates in NP via regulating autophagy and apoptosis. In summary, our results support P2X7R inhibition can counteract the CCI-induced NP due to microglia activation via a modulation of autophagy and apoptosis in mPFC and spinal cord. This may provide an importantly neuroprotective mechanism for the improved NP and also help devising new therapeutic to improve chronic pain in patients.

Background Postoperative cognitive dysfunction (POCD) is a common complication after surgery and its occurrence is associated with increased morbidity and mortality. However, the pathophysiology of this complication remains largely unknown. Efforts to identify causes of POCD have focused on the hippocampal neuroinflammation. Recently, accumulated evidence indicates that NeurimmiRs, a subset of microRNAs (miRNAs), which modulate both neuronal and immune processes, play an important role in neuroinflammation. However, the impact of NeurimmiRs on POCD has not been investigated. We hypothesized that NeurimmiRs is involved in surgery-induced cognitive impairment in adult mice via mediating hippocampal neuroinflammation. Methods MicroRNA(miR)-181b-5p was found to be downregulated in the hippocampi of mice with POCD using microRNA array, which was also verified in vivo in the mouse model of POCD by Quantitative real-time polymerase chain reaction (qPCR). Subsequently, the expression of miR-181b-5p was measured in lipopolysaccharide (LPS) stimulated BV-2 microglial cells and hippocampal tissues of the mice with POCD. Then, loss of function and overexpression studies were performed by transfection with miR-181b-5p mimic/ inhibitor in cultured BV-2 cell lines and intrahippocampal injection of miR-181b-5p agomir before Surgery/Anesthesia, to identify the role of miR-181b-5p in neuroinflammation and cognitive impairments. QPCR, western blot and ELISA were used to determine the expression of proinflammatory mediators. Immunofluorescence staining was applied to evaluate the activation of microglia. Furthermore, we used bioinformatics analysis and dual-luciferase assay to predict and verify the potential target of miR-181b-5p. Results The results indicated that miR-181b-5p mimic could repress the mRNA and protein expression of proinflammatory mediators, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and monocyte chemoattractant protein (MCP)-1 in LPS-stimulated BV-2 microglial cells, while the miR-181b-5p inhibitor induced upregulation of the above-mentioned proinflammatory factors. Further bioinformatics analysis showed that miR-181b-5p was predicted to potentially target the 3′-untranslated region (UTR) of TNF-α, and binding sites of miR-181b-5p in the 3′-UTR of TNF-α were identified by dual-luciferase assay. Importantly, injecting miR-181b-5p agomir into the hippocampus of mice before surgery, ameliorated the hippocampus-dependent memory, and was accompanied by downregulation of proinflammatory factors expression and reduced microglial activation in the hippocampus of POCD mice. Conclusions Collectively, these findings suggest that miR-181b-5p attenuates early POCD by suppressing hippocampal neuroinflammation in mice. They also highlight the importance of studying miRNAs in the context of POCD and identify miR-181b-5p as a novel potential therapeutic target for improving POCD.

Postoperative cognitive dysfunction (POCD) is a common postoperative complication that is associated with increased morbidity and mortality. However, the neuropathogenesis of this complication remains largely unknown. Neuroinflammation, in particular hippocampal inflammation, contributes to POCD. Recently, increasing evidence has supported the involvement of microRNAs (miRNAs) in the regulation of neuroinflammation in human neurological disorders. In the present study, we investigated the role of miR-146a, a key regulator of the innate immune response, in surgery-induced hippocampal inflammation and cognitive impairment. The expression of miR-146a was measured in BV-2 microglial cells stimulated with lipopolysaccharide (LPS) and hippocampal tissues of mice with POCD. Loss of function and overexpression studies were performed via transfection with miR-146a mimic/inhibitor in cultured BV-2 cell lines and intrahippocampal injection of miR-146a agomir/antagomir before surgery/anesthesia to identify the role of miR-146a in neuroinflammation and cognitive impairment. QPCR, Western blot and ELISA were used to determine the expression levels of downstream adaptor proteins and proinflammatory cytokines. Immunofluorescence staining was applied to evaluate the activation of microglia. Increased expression of miR-146a was observed in BV-2 microglial cells stimulated with LPS and hippocampal tissues of mice with POCD. Modulation of miR-146a expression via transfection of microglia with miR-146a mimic or inhibitor regulated the mRNA and protein expression levels of downstream targets of miR-146a (IRAK1 and TRAF6) as well as the release of proinflammatory cytokines (TNF-α, IL-1β and IL-6). In addition, overexpression of miR-146a attenuated hippocampus-dependent learning and memory impairment in mice with POCD, which was accompanied by decreased expression of the IRAK1/TRAF6/nuclear factor (NF)-κB pathway and downregulation of microglial activation in the hippocampus. Conversely, knockdown of miR-146a expression may exacerbate hippocampus-dependent learning and memory deficiency and hippocampal inflammation in mice with POCD. Collectively, our findings demonstrate the important role of miR-146a in the neuropathogenesis of POCD and suggest that miR-146a may be a potential therapeutic target for POCD.

Postoperative delirium (POD) is a common post-operative complication in elderly patients that is associated with increased morbidity and mortality. However, the neuropathogenesis of this complication remains unknown. The blood-cerebrospinal fluid barrier (BCB) and brain-blood barrier (BBB) are composed of tight junctions between cells that form physical barriers, and BBB damage plays an important role in the neuropathogenesis of POD. Nevertheless, the role of BCB in POD remains to be elucidated. Herein, we investigated the effect of adenosine A

Background Cannabinoid receptor 2 (CB2), whose activities are upregulated during sepsis, may be related to the regulation of inflammatory programmed cell death called pyroptosis. The aim of this study is to investigate the role of CB2 activation in attenuation of inflammation through inhibiting pyroptosis in cecal ligation puncture (CLP)-induced sepsis and lipopolysaccharide (LPS) + ATP-stimulated macrophages. Methods C57BL/6 mice were subjected to CLP procedure and treated with CB2 agonist HU308 and CB2 antagonist AM630. Lung tissues were collected for analyses of lung W/D ratio, inflammatory factors levels, and pyroptosis-related protein expression. Murine bone-marrow-derived macrophages (BMDM) were treated with LPS and ATP to construct a septic model in vitro in the presence of HU308 and AM630 for assessment of cell injury, cytokine levels and pyroptosis-related protein expression accordingly. To verify the relationship between CB2 receptors and pyroptosis in the process of inflammatory response, BMDM were transduced with CB2 receptors knockdown lentiviral vectors in the presence of HU308 and AM630 for assessment of pyroptosis-related protein expression. Results CB2 activation ameliorated the release of inflammatory mediators. The results showed that CLP-induced pyroptosis was elevated, and CB2 agonist HU308 treatment inhibited the pyroptosis activity through a decrease of the protein levels of NLRP3 as well as caspase-1 and GSDMD activation. Similar results were obtained in BMDM after LPS and ATP treatment. Treatment with CB2 knockdown lentiviral particles prevented the HU308-induced decreases in cell pyroptosis, demonstrating that endogenous CB2 receptors are required for the cannabinoid-induced cell protection. Conclusions CB2 receptors activation plays a protective role in sepsis through inhibition of pyroptosis. The effect of CB2 receptors against pyroptosis depends on the existence of endogenous CB2 receptors.

Energy metabolism and neurotransmission are necessary for sustaining normal life activities. Hence, neurological or psychiatric disorders are always associated with changes in neurotransmitters and energy metabolic states in the brain. Most studies have only focused on the most important neurotransmitters, particularly GABA and Glu, however, other metabolites such as NAA and aspartate which are also very important for cerebral function are rarely investigated. In this study, most of the metabolic kinetics information of different brain regions was investigated in awake rats using the [

The European sunflower moth, Homoesoma nebulellum (Denis et Schiffermüller), emerged as a major new pest in Bayannur, China, in 2006. Insecticidal control with a single application is problematic because timing is critical, and multiple applications increase production and environmental costs. Management of H. nebulellum by planting date adjustment can be effective, but the optimal time window for late planting is unknown. Natural levels of H. nebulellum infestation were compared among sunflowers planted on five dates from April 25 to June 5 in two years, and the relationship between timing of adult abundance and flowering assessed. Delaying planting of sunflower from the traditional planting period of April 25 –May 5 to May 15 –June 5 significantly decreased damage by H. nebulellum. Seed infestation rate was 30–40 times higher, and number of larvae/head 75–100 times higher in the earliest two plantings than in the latest two. Within two years of implementing delayed planting in Bayannur city, infestation area decreased from 72% in 2006 to 1.5% in 2008, and production losses decreased from 4.5 ton/ha in 2006 to 0.36 ton/ha in 2008, a 97% decrease compared to 2006. Moreover, the infestation area caused by H. nebulellum was continuously controlled below 5.3% of the planting area since 2008. We found the overlap between the first two days of flowering and peak adult presence was the key factor influencing level of damage caused by H. nebulellum. Because the number of eggs laid in the first two days of flowering accounted for 68% of the total, and sunflower seed infestation rate was positively correlated with the number of trapped adults weighted by proportion of daily oviposition. Oviposition of the majority of eggs in the first two days of flowering suggests an evolutionary mechanism whereby females choose host plants most conducive to larval development, consistent with the preference-performance hypothesis.