Technical innovation, renewable energy consumption, and CO2 emissions in the USA: a cross-quantile approach.

This study investigates whether technological innovation and the consumption of renewable energy tend to reduce the emissions of CO2 in the USA by analyzing datasets from January 2010 to May 2022. The main contribution to this study is that we applied a cross-quantile approach, which possesses several strengths compared to other methods used for directional predictability. The empirical results of this research can be concluded as three points: (1) both the consumption of renewable energy and technological innovation significantly and negatively impacted the emissions of CO2 in the short run (i.e., 1 month) across high quantiles, which gradually diminished over time (i.e., 3 months, 12 months, and 24 months), implying that technological innovation and the consumption of renewable energy possess a short-lived effect on CO2 emissions, respectively; (2) this relationship remains significant for causal links spanning 1 and 3 months and 1 and 2 years when the consumption of renewable energy and technological innovation are treated as control variables respectively; (3) a recursive cross-quantilogram was constructed to support further our findings, which showed that the consumption of renewable energy and technological innovation tend to negatively impact the emissions of CO2 across all quantiles. These results imply that an increase in the consumption of renewable energy and technological innovation can curb CO2 emissions in the USA; these effects tend to be more lasting when technological innovation and the consumption of renewable energy are combined. Therefore, future policies focused on curbing the emissions of CO2 should pay attention to the combined effect, which is the promotion of technological innovation and the exploitation of renewable energy sources in the USA.

Hedgehog signaling contributes to bone cancer pain by regulating sensory neuron excitability in rats.

Treating bone cancer pain continues to be a clinical challenge and underlying mechanisms of bone cancer pain remain elusive. Here, we reported that sonic hedgehog signaling plays a critical role in the development of bone cancer pain. Tibia bone cavity tumor cell implantation produces bone cancer-related mechanical allodynia, thermal hyperalgesia, and spontaneous and movement-evoked pain behaviors. Production and persistence of these pain behaviors are well correlated with tumor cell implantation-induced up-regulation and activation of sonic hedgehog signaling in primary sensory neurons and spinal cord. Spinal administration of sonic hedgehog signaling inhibitor cyclopamine prevents and reverses the induction and persistence of bone cancer pain without affecting normal pain sensitivity. Inhibiting sonic hedgehog signaling activation with cyclopamine, in vivo or in vitro, greatly suppresses tumor cell implantation-induced increase of intracellular Ca2+ and hyperexcitability of the sensory neurons and also the activation of GluN2B receptor and the subsequent Ca2+-dependent signals CaMKII and CREB in dorsal root ganglion and the spinal cord. These findings show a critical mechanism underlying the pathogenesis of bone cancer pain and suggest that targeting sonic hedgehog signaling may be an effective approach for treating bone cancer pain.

IL-18 Contributes to Bone Cancer Pain by Regulating Glia Cells and Neuron Interaction.

Glial cell hyperactivity has been proposed to be responsible for chronic pain, however, the mechanisms remain unclear. Interleukin (IL)-18, released from glial cells, has been reported to be involved in neuropathic pain. In this study, we investigated the role of IL-18 in bone cancer pain. Bone cancer pain was mimicked by injecting Walker-256 mammary gland carcinoma cells into the intramedullary space of the tibia in rats. Expression and location of IL-18 and the IL-18 receptor were tested. To investigate the contribution of IL-18 signaling to bone cancer pain, IL-18 binding protein and recombinant IL-18 were used. To investigate the mechanisms of glial cells effects, MK801, N-methyl-D-aspartate (NMDA) receptor inhibitor, and Src kinase-specific inhibitor PP1 were used. Tumor cell implantation (TCI) treatment increased expression of IL-18 and IL-18 receptor in spinal cord. The time course of IL-18 upregulation was correlated with TCI-induced pain behaviors. Blocking the IL-18 signaling pathway prevented and reversed bone cancer-related pain behaviors. Meanwhile, blocking IL-18 signaling also suppressed TCI-induced glial cell hyperactivity, as well as activation of GluN2B and subsequent Ca2+-dependent signaling. Spinal administration of recombinant IL-18 in naive rat induced significant mechanical allodynia, as well as GluN2B activation. However, intrathecal injection of MK801 failed to suppress recombinant IL-18-induced GluN2B phosphorylation, whereas Src kinase inhibitor PP1 significantly inhibited IL-18-induced GluN2B activation. IL-18-mediated glial-glia and glial-neuron interaction may facilitate bone cancer pain. Blocking IL-18 signaling may effectively prevent and/or suppress bone cancer pain. PERSPECTIVE: IL-18 signaling may be a new target for cancer pain therapy.

Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation.

OBJECTIVE: The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI). METHODS: Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg) were administrated intragastrically at early phase of postoperation (before pain appearance) and later phase of postoperation (after pain appearance), respectively. The concentrations of TNF-α, IL-1ß, and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment. RESULTS: TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI-induced activation of microglial cells and the increased levels of TNF-α and IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI-induced astrocytes activation and IL-1ß increase. CONCLUSION: This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase.

cGMP and cGMP-dependent protein kinase I pathway in dorsal root ganglia contributes to bone cancer pain in rats.

STUDY DESIGN: A prospective, randomized experimental research. OBJECTIVE: To demonstrate the role of cGMP (cyclic guanosine monophosphate)-cGKI (cGMP-dependent protein kinase I) pathway in dorsal root ganglia (DRG) in bone cancer pain. SUMMARY OF BACKGROUND DATA: Treating bone cancer pain continues to possess a major clinical challenge because the specific cellular and molecular mechanisms underlying bone cancer pain remain elusive. cGMP and cGMP-dependent protein kinases pathway in DRG plays important role in nerve injury-induced hyperexcitability of DRG neurons, as well as neuropathic pain, however, whether this pathway participates in bone cancer pain is unknown. METHODS: The rat model of bone cancer pain was produced by intramedullary injection of rat breast cancer cells (Walker 256) into right tibia. Thermal hyperalgesia and mechanical allodynia were measured before and after administration of inhibitor of cGMP-cGKs pathway (Rp-8-pCPT-cGMPS). Immunofluorescence and reverse transcription-polymerase chain reaction were used to reflect expression of cGKI in DRG neurons, whereas the concentration of cGMP in DRG was tested using enzyme-linked immunosorbent assay method. Whole-cell patch clamp was used to record the hyperexcitability of small neurons in DRG with or without cGKs inhibitor after tumor cell implantation (TCI). RESULTS: TCI treatment significantly increased the concentration of cGMP in DRG and activity of cGKs in DRG and the spinal cord. TCI treatment also induced upregulation of cGKI messenger ribonucleic acid and protein in DRG, as well as enhanced hyperexcitability in DRG neurons. Spinal administration of Rp-8-pCPT-cGMPS, cGMP-cGKs inhibitor, significantly suppressed TCI-induced activation of cGMP-cGKI signaling, and hyperexcitability of DRG neurons. Meanwhile, in vivo intrathecal delivery of the Rp-8-pCPT-cGMPS significantly prevented and suppressed TCI-induced hyperalgesia and allodynia. CONCLUSION: From these results, we confirm that TCI treatment activates cGMP-cGKI signaling pathway and continuing activation of this pathway in DRG is required for hyperalgesia and/or hyperalgesia and allodynia after TCI treatment. LEVEL OF EVIDENCE: N/A.

Autophagy in pulmonary macrophages mediates lung inflammatory injury via NLRP3 inflammasome activation during mechanical ventilation.

The inflammatory response is a primary mechanism in the pathogenesis of ventilator-induced lung injury. Autophagy is an essential, homeostatic process by which cells break down their own components. We explored the role of autophagy in the mechanisms of mechanical ventilation-induced lung inflammatory injury. Mice were subjected to low (7 ml/kg) or high (28 ml/kg) tidal volume ventilation for 2 h. Bone marrow-derived macrophages transfected with a scrambled or autophagy-related protein 5 small interfering RNA were administered to alveolar macrophage-depleted mice via a jugular venous cannula 30 min before the start of the ventilation protocol. In some experiments, mice were ventilated in the absence and presence of autophagy inhibitors 3-methyladenine (15 mg/kg ip) or trichostatin A (1 mg/kg ip). Mechanical ventilation with a high tidal volume caused rapid (within minutes) activation of autophagy in the lung. Conventional transmission electron microscopic examination of lung sections showed that mechanical ventilation-induced autophagy activation mainly occurred in lung macrophages. Autophagy activation in the lungs during mechanical ventilation was dramatically attenuated in alveolar macrophage-depleted mice. Selective silencing of autophagy-related protein 5 in lung macrophages abolished mechanical ventilation-induced nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation and lung inflammatory injury. Pharmacological inhibition of autophagy also significantly attenuated the inflammatory responses caused by lung hyperinflation. The activation of autophagy in macrophages mediates early lung inflammation during mechanical ventilation via NLRP3 inflammasome signaling. Inhibition of autophagy activation in lung macrophages may therefore provide a novel and promising strategy for the prevention and treatment of ventilator-induced lung injury.

Effects of selective phosphodiesterases-4 inhibitors on learning and memory: a review of recent research.

Phosphodiesterase-4 (PDE-4) regulates the intracellular level of cyclic adenosine monophosphate. Recent studies demonstrated that PDE-4 inhibitors can counteract deficits in long-term memory caused by aging or increased expression of mutant forms of human amyloid precursor proteins, and can influence the process of memory function and cognitive enhancement. Therapeutics, such as ketamine, a drug used in clinical anesthesia, can also cause memory deficits as adverse effects. Targeting PDE-4 with selective inhibitors may offer a novel therapeutic strategy to prevent, slow the progress, and, eventually, treat memory deficits.

Discussion on the education reform of anesthesiology / 中华医学教育探索杂志

Currently,the environment for establishing anesthesiologic undergraduate education no longer exists,and the side-effects of its narrow professional content are more and more apparent,so canceling undergraduate education of anesthesiology is becoming imperative.The education of anesthesia must be reformed.However,the direction of reform is not clear.Anesthesia long-term system education and Anesthesia and preoperative medical education are two optical reform directions with its own advantages and disadvantages.Comparing these two directions,the Anesthesia and preoperative medical education seems to be the better one.

Caveolin-1 Tyr14 phosphorylation induces interaction with TLR4 in endothelial cells and mediates MyD88-dependent signaling and sepsis-induced lung inflammation.

Activation of TLR4 by the endotoxin LPS is a critical event in the pathogenesis of Gram-negative sepsis. Caveolin-1, the signaling protein associated with caveolae, is implicated in regulating the lung inflammatory response to LPS; however, the mechanism is not understood. In this study, we investigated the role of caveolin-1 in regulating TLR4 signaling in endothelial cells. We observed that LPS interaction with CD14 in endothelial cells induced Src-dependent caveolin-1 phosphorylation at Tyr(14). Using a TLR4-MD2-CD14-transfected HEK-293 cell line and caveolin-1-deficient (cav-1(-/-)) mouse lung microvascular endothelial cells, we demonstrated that caveolin-1 phosphorylation at Tyr(14) following LPS exposure induced caveolin-1 and TLR4 interaction and, thereby, TLR4 activation of MyD88, leading to NF-κB activation and generation of proinflammatory cytokines. Exogenous expression of phosphorylation-deficient Y14F caveolin-1 mutant in cav-1(-/-) mouse pulmonary vasculature rendered the mice resistant to LPS compared with reintroduction of wild-type caveolin-1. Thus, caveolin-1 Y14 phosphorylation was required for the interaction with TLR4 and activation of TLR4-MyD88 signaling and sepsis-induced lung inflammation. Inhibiting caveolin-1 Tyr(14) phosphorylation and resultant inactivation of TLR4 signaling in pulmonary vascular endothelial cells represent a novel strategy for preventing sepsis-induced lung inflammation and injury.

Sevoflurane postconditioning ameliorates oxygen-glucose deprivation-reperfusion injury in the rat hippocampus.

INTRODUCTION: Sevoflurane is well known to exert a neuroprotective effect through anesthetic preconditioning. However, its effects on postconditioning, a neuroprotective phenomenon following an insult, have not been well studied. AIMS: In this study, we examined the ability of sevoflurane to induce postconditioning in rat hippocampal slices, in vitro. RESULTS: 2%, 4%, and 6% sevoflurane reduced neurophysiologic and morphologic neuronal injury following oxygen-glucose deprivation (OGD) and reperfusion. The quantity of damaged neurons was significantly reduced on immunofluorescence staining; excitatory amino acids (Asp, Glu) increased and inhibitory amino acids (GABA) decreased significantly. The effect was concentration-dependent. CONCLUSION: Postconditioning with sevoflurane reduces neuronal damage after OGD-reperfusion injury in the CA1 area of rat hippocampus, in vitro.

Effects of infusion of different fluids during controlled hypotension on gastric intramucosal pH and postoperative gastroenterological function.

The present study was aimed to investigate the effects of infusion of different fluids combined with controlled hypotension on gastric intramucosal pH (pHi) and postoperative gastrointestinal function in patients undergoing hepatocarcinoma surgery. Forty-five patients (ASA II) scheduled for surgical resection of hepatocarcinoma undergoing controlled hypotension were randomly assigned to three groups and received infusion of 20 mL/kg Ringer's solution (R group), 6% HAES(H group) or 6% Voluven group (W group). Intragastric PgCO2, pHi, hematocrit and hemoglobin were measured. The significant decrease of pHi and increase of PgCO2 were produced at 1 and 2 h after controlled hypotension in the R group (P < 0.05 or P < 0.01). The time of bowel movement after operation was shorter in the W group than the R group. Meanwhile, we also did not find obvious difference in blood gas indexes among the three groups. The infusion of HAES and Voluven during controlled hypotension could improve gastrointestinal perfusion and accelerate the recovery of postoperative gastrointestinal function.

Intracerebroventricular or intrathecal injection of glycine produces analgesia in thermal nociception and chemical nociception via glycine receptors.

The present study was designed to investigate the role of glycine receptors in analgesia induced by injection of glycine in vivo. Glycine was injected intracerebroventricularly or intrathecally and strychnine, a glycine receptor antagonist, was injected intracerebroventricularly or intrathecally before glycine injection. The effects on the pain threshold index in hot-plate test and the writhing times in acetic acid-induced writhing test were observed. The locomotor activity and motor performance (rotarod test) were also observed. The dosages of glycine and strychnine we choose had no effect on locomotor activity or motor performance in conscious mice. Glycine increased the pain threshold index in hot-plate test and decreased the writhing times of the mice. Strychnine antagonized the effects induced by glycine above. These results demonstrated that intracerebroventricular or intrathecal injection of glycine can produce analgesia in thermal nociception and chemical nociception in vivo, which is mediated by glycine receptors.

p38MAPK inhibition attenuates LPS-induced acute lung injury involvement of NF-kappaB pathway.

The pathogenesis of acute lung injury/acute respiratory distress syndrome (ARDS) is complex and involves multiple signal transduction processes. It is believed that p38MAPK (mitogen-activated protein kinase) is one of the most kinases in inflammatory signaling. At present study, we demonstrated the role of p38MAPK in lipopolysaccharide (LPS)-induced acute lung injury with pharmacologic p38MAPK inhibition by SB203580. SB203580, p38MAPK specific inhibitor, was injected (10 mg/kg, i.v.) 30 min before LPS administration (5 mg/kg, i.v.). The hematoxylin-eosin staining of lung tissues showed that p38MAPK inhibition significantly attenuated the pulmonary inflammatory responses induced by LPS. Moreover, SB203580 can also inhibit the inflammatory cytokine release, and reduce the mortality rate of LPS-induced acute lung injury. Further, western blot analysis that showed SB203580 administration can inhibit the activation of NF-kappaB, which was associated with the inhibition of IkappaBalpha degradation in cytoplasm. These data suggest that p38MAPK signaling may be involved in the activation of NF-kappaB, and activation of p38MAPK signaling may be one of the mechanisms of acute lung injury.

Lidocaine attenuates lipopolysaccharide-induced acute lung injury through inhibiting NF-kappaB activation.

BACKGROUND AND OBJECTIVES: Lidocaine has been reported to attenuate the inflammatory response in addition to its anesthetic activity, but the mechanisms are poorly understood. The objective of this study is to determine if lidocaine prior to endotoxemia diminishes pulmonary dysfunction by blocking the NF-kappaB activation. METHODS: Rats were assigned to: (1) control (0.9% sodium chloride); (2) lipopolysaccharides (LPS); (3) LPS + lidocaine 1 mg/kg; (4) LPS + lidocaine 2 mg/kg, and (5) LPS + lidocaine 4 mg/kg. The LPS and LPS + lidocaine 4 mg/kg groups were subjected to 1-, 3-, 6- and 12-hour time points. To investigate the activation of NF-kappaB, the expression of NF-kappaB in the nuclear and I kappaB alpha in the cytosol extracts were analyzed by Western blot. The concentration of TNF-alpha and IL-6 in serum was detected by ELISA. The pathologic changes of the lung were observed using HE staining. RESULTS: After i.p. injection of LPS, the expression of NF-kappaB in the nuclear extracts was significantly increased and I kappaB alpha in the cytosol extracts was markedly decreased. The concentration of TNF-alpha and IL-6 in serum was increased. Pathological examination showed that the normal structure of the lung was destroyed badly. However, lidocaine reversed the above results. CONCLUSION: Lidocaine attenuates LPS-induced lung injury via mechanisms involving inhibiting NF-kappaB activation and cytokine release, which implies that lidocaine may be a potential anti-inflammatory agent in endotoxemia.