[Retracted] Intracisternal administration of an interleukin­6 receptor antagonist attenuates surgery­induced cognitive impairment by inhibition of neuroinflammatory responses in aged rats.

[This retracts the article DOI: 10.3892/etm.2014.2149.].

Hypercoagulable state in patients with schizophrenia: different effects of acute and chronic antipsychotic medications.

Background: Previous studies reported higher incidences of venous thromboembolism and cardiovascular disease in schizophrenia patients and higher indicators of thrombosis, thrombocyte activation, and platelet dysfunction. Objectives: To check if first-episode schizophrenia (FES) patients have a hypercoagulable state and determine whether acute and chronic antipsychotics have the same effect on blood coagulation or fibrinolysis-related biomarkers. Design: Case-control study. Methods: A total of 81 participants were grouped in FES, chronic schizophrenia (CS), and healthy controls (HCs). In addition to demographic data and clinical characteristics, immunological analyses were performed to measure plasma levels of D-dimer, plasminogen activator inhibitor-1 (PAI-1), soluble P selectin (sP-sel), tissue plasminogen activator (tPA), thrombotic precursor protein (TpP), and von Willebrand's disease factor (vWF). Results: Compared to HC group, FES patients showed higher PAI-1 (28.61 ng/ml versus 15.69 ng/ml), sP-sel (2.78 ng/ml versus 1.18 ng/ml), and TpP (15.61 µg/ml versus 5.59 µg/ml) along with a higher PAI-1/tPA (3.12 versus 2.00). Acute antipsychotic medication reduced higher PAI-1 (28.61 → 21.99), sP-sel (2.78 → 1.87), tPA (9.59 → 5.83), TpP (15.61 → 10.54), and vWF (383.18 → 291.08) in FES patients. However, plasma sP-sel and vWF in CS patients returned to the pre-treatment levels in FES patients, and PAI-1/tPA significantly decreased compared to FES patients. Conclusion: These results suggest a hypercoagulable state in FES patients and demonstrate contrast effects of acute and chronic antipsychotics on coagulation or fibrinolysis in schizophrenia patients.

Gas-Dependent Active Sites on Cu/ZnO Clusters for CH3OH Synthesis.

This study describes an instantaneously gas-induced dynamic transition of an industrial Cu/ZnO/Al2O3 catalyst. Cu/ZnO clusters become "alive" and lead to a promotion in reaction rate by almost one magnitude, in response to the variation of the reactant components. The promotional changes are functions of either CO2-to-CO or H2O-to-H2 ratio which determines the oxygen chemical potential thus drives Cu/ZnO clusters to undergo reconstruction and allows the maximum formation of Cu-Zn2+ sites for CH3OH synthesis.

Functional regulation of syntaxin-1: An underlying mechanism mediating exocytosis in neuroendocrine cells.

The fusion of the secretory vesicle with the plasma membrane requires the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein complexes formed by synaptobrevin, syntaxin-1, and SNAP-25. Within the pathway leading to exocytosis, the transitions between the "open" and "closed" conformations of syntaxin-1 function as a switch for the fusion of vesicles with the plasma membranes; rapid assembly and disassembly of syntaxin-1 clusters on the plasma membrane provide docking and fusion sites for secretory vesicles in neuroendocrine cells; and the fully zippered trans-SNARE complex, which requires the orderly, rapid and accurate binding of syntaxin-1 to other SNARE proteins, play key roles in triggering fusion. All of these reactions that affect exocytosis under physiological conditions are tightly regulated by multiple factors. Here, we review the current evidence for the involvement of syntaxin-1 in the mechanism of neuroendocrine cell exocytosis, discuss the roles of multiple factors such as proteins, lipids, protein kinases, drugs, and toxins in SNARE complex-mediated membrane fusion, and present an overview of syntaxin-1 mutation-associated diseases with a view to developing novel mechanistic therapeutic targets for the treatment of neuroendocrine disorders.

Initiating Continuous Renal Replacement Therapy in Patients With Transurethral Resection of Prostate Syndrome: A Case Report.

With advances and developments in hysteroscopy, cystoscopy, transurethral resection of bladder tumor, and arthroscopy, transurethral resection of prostate (TURP) syndrome has been increasingly reported. TURP syndrome is often accompanied by severe hyponatremia, fluid overload, and a plasma hypotonic state, resulting in heart failure and pulmonary and cerebral edema. Conventional treatment methods, such as intravenous infusion of hyperosmotic saline, can rapidly reverse the downward trend of serum sodium levels in efforts to prevent and treat cerebral edema. However, this may not be suitable for patients with cardiac and renal insufficiency and may induce central pontine myelinolysis due to the possibility of worsening volume load and difficulty in controlling the correction rate of serum sodium. The patient described in this report presented with severe hyponatremia (sodium<100 mmol/L) combined with intraoperative pulmonary edema; his cardiac function and oxygenation status deteriorated after an intravenous infusion of 3% hypertonic saline. He underwent continuous renal replacement therapy (CRRT) to prevent the progression of multiple-organ edema and cardiac insufficiency. CRRT has demonstrated efficacy in the treatment of chronic hyponatremia in patients with renal failure, and can slowly and continuously correct water-electrolyte imbalance, acid-base imbalance, and volume overload. TURP syndrome with severe hyponatremia and pulmonary edema was diagnosed; accordingly, the patient was treated with 3% hypertonic saline, furosemide, and CRRT, without the development of overt neurological sequelae.

Mechanism of dexmedetomidine preconditioning on spinal cord analgesia in rats with functional chronic visceral pain.

PURPOSE: To analyze the effect and mechanism of dexmedetomidine (DEX) analgesia pretreatment on functional chronic visceral pain in rats. METHODS: Rats were divided into six groups: W1, W2, W3, W4, W5, and W6. The behavioral changes and electrophysiological indexes of rats in each group before and after DEX treatment were detected. RESULTS: The levels of abdominal withdrawal reflex (AWR) in W5 and W6 groups were significantly lower than those in group W3, while the levels of thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were significantly higher than those in group W3 (p < 0.05). The electromyographic signals of W1, W5, and W6 groups showed little fluctuation, while those of groups W2, W3, and W4 showed obvious fluctuation. TLR4 mRNA expression, IRF3, P65, and phosphorylation levels in W4, W5, and W6 groups were significantly lower than those in group W2 (p < 0.05). CONCLUSIONS: Dexmedetomidine epidural anesthesia pretreatment could significantly inhibit visceral pain response in rats with functional chronic visceral pain, and its mechanism was related to the activation of TLR4 in spinal dorsal horn tissue of rats and the activation inhibition of IRF3 and P65 in the downstream key signals.

Effect of MnO2 Polymorphs' Structure on Low-Temperature Catalytic Oxidation: Crystalline Controlled Oxygen Vacancy Formation.

MnO2 polymorphs (α-, ß-, and ε-MnO2) were synthesized, and their chemical/physical properties for CO oxidation were systematically studied using multiple techniques. Density functional theory (DFT) calculations and temperature-programmed experiments reveal that ß-MnO2 shows low energies for oxygen vacancy generation and excellent redox properties, exhibiting significant CO oxidation activity (T90 = 75 °C) and stability even under a humid atmosphere. For the first time, we report that the specific reaction rate for ß-MnO2 (0.135 moleculeCO·nm-2·s-1 at 90 °C) is roughly approximately 4 and 17 times higher than that of ε-MnO2 and α-MnO2, respectively. The specific reaction rate order (ß-MnO2 > ε-MnO2 > α-MnO2) is not only in good agreement with reduction rates (CO-TPSR measurements) but also agrees with the DFT calculation. In combination with in situ spectra and intrinsic kinetic studies, the mechanisms of CO oxidation over various crystal structures of MnO2 were proposed as well. We believe the new insights from this study will largely inspire the design of such a kind of catalyst.

Dexmedetomidine alleviates the hypoxic-ischemic brain damage via miR-20a-5p/methionine adenosyltransferase 2B axis in rat pups.

OBJECTIVE: The neuroprotective effect of dexmedetomidine (DEX) has been demonstrated in hypoxic-ischemic brain damage (HIBD) animal models, the mechanism of which will be the foothold in this work. METHODS: After establishment of HIBD rat model, the rats were treated with DEX, miR-20a-5p agomir and adenoviral methionine adenosyltransferase 2B (MAT2B) overexpression vector, and then their brain tissues were harvested. The infarction volume and pathological changes of these brain tissues were measured using the triphenyl tetrazolium chloride (TTC), Nissl and hematoxylin-eosin (HE) stainings. The levels of miR-20a-5p, Bcl-2, Bax and MAT2B in these brain tissues were detected by Real-Time PCR (RT-PCR) and western blot. The binding sites of MAT2B and miR-20a-5p were predicted using the TargetScan and verified using the dual-luciferase reporter assay. The memory deficits and spatial learning of rat pups were assessed by Morris water maze test. RESULTS: MiR-20a-5p expression was upregulated, while MAT2B expression was downregulated in rats with HIBD. MAT2B was targeted by miR-20a-5p. DEX treatment improved the neurons and hippocampal tissue damage and decreased miR-20a-5p level in brain tissues of rats with HIBD. MiR-20a-5p overexpression overturned the protective effect of DEX on brain tissues and learning and memory abilities in rats with HIBD. Moreover, DEX promoted Bcl-2 level while inhibiting Bax level in HIBD rats' brain tissues. Besides, overexpressed MAT2B reversed the effect of overexpressed miR-20a-5p on the levels of MAT2B, Bcl-2 and Bax, brain tissue damage, as well as the learning and memory abilities in rats with HIBD. CONCLUSION: DEX alleviated HIBD via the miR-20a-5p/MAT2B axis in rats.

Mechanism of dexmedetomidine preconditioning on spinal cord analgesia in rats with functional chronic visceral pain

Purpose: To analyze the effect and mechanism of dexmedetomidine (DEX) analgesia pretreatment on functional chronic visceral pain in rats. Methods: Rats were divided into six groups: W1, W2, W3, W4, W5, and W6. The behavioral changes and electrophysiological indexes of rats in each group before and after DEX treatment were detected. Results: The levels of abdominal withdrawal reflex (AWR) in W5 and W6 groups were significantly lower than those in group W3, while the levels of thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were significantly higher than those in group W3 (p < 0.05). The electromyographic signals of W1, W5, and W6 groups showed little fluctuation, while those of groups W2, W3, and W4 showed obvious fluctuation. TLR4 mRNA expression, IRF3, P65, and phosphorylation levels in W4, W5, and W6 groups were significantly lower than those in group W2 (p < 0.05). Conclusions: Dexmedetomidine epidural anesthesia pretreatment could significantly inhibit visceral pain response in rats with functional chronic visceral pain, and its mechanism was related to the activation of TLR4 in spinal dorsal horn tissue of rats and the activation inhibition of IRF3 and P65 in the downstream key signals.

Dexmedetomidine Resists Intestinal Ischemia-Reperfusion Injury by Inhibiting TLR4/MyD88/NF-κB Signaling.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) is a common clinical problem that occurs during various clinical pathological processes. Dexmedetomidine (DEX), a widely used anesthetic adjuvant agent, can induce protection against intestinal I/R in vivo; however, the underlying mechanism is not fully understood. In the present study, we aimed to investigate the protective effects of DEX and examine whether its mechanism was associated with the TLR4/MyD88/NF-κB signaling pathway. METHODS: Sprague-Dawley rats were pretreated with DEX and then subjected to I/R-induced intestinal injury. In vivo, intestinal histopathological examination and scoring were performed, the levels of serum intestinal fatty acid-binding protein (I-FABP), intestinal tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and expression levels of TLR4, MyD88, and NF-κB in the intestine were determined. In in vitro experiments, the human colon carcinoma cell line (Caco-2) was incubated with DEX before deprivation/reoxygenation (OGD/R) treatment. The cell viability of Caco-2 cells, the levels of lactate dehydrogenase (LDH), TNF-α, and IL-1ß in the supernatant, as well as protein expression of TLR4, MyD88, and NF-κB in Caco-2 cells, were measured. Statistical analysis was performed using SPSS version 21.0. RESULTS: DEX preconditioning significantly reduced the intestinal pathological Chiu's score, serum I-FABP, intestinal TNF-α, IL-1ß levels, and the protein expression of TLR4, MyD88, and NF-κB in the rats with intestinal I/R injury. Similarly, in vitro, DEX pretreatment protected against OGD/R-induced Caco-2 cell damage and inhibited TLR4/MyD88/NF-κB signaling, as evidenced by increased cell viability, decreased LDH activity, reduced TNF-α and IL-1ß levels, as well as downregulated TLR4, MyD88, and NF-κB protein levels. CONCLUSIONS: Our findings suggested that DEX could reduce intestinal I/R injury in rats and OGD/R damage in Caco-2 cells, and this protection might be attributed to antiinflammatory effects and inhibition of the TLR4/MyD88/NF-κB signaling pathway.

Dorsal Root Ganglia Coactivator-associated Arginine Methyltransferase 1 Contributes to Peripheral Nerve Injury-induced Pain Hypersensitivities.

Neuropathic pain is associated with gene expression changes within the dorsal root ganglion (DRG) after peripheral nerve injury, which involves epigenetic mechanisms. Coactivator-associated arginine methyltransferase 1 (CARM1), an epigenetic activator, regulates gene transcriptional activity by protein posttranslational modifications. However, whether CARM1 plays an essential role in the development and maintenance of neuropathic pain is unknown. We report here that peripheral nerve injury induced the upregulation of the mRNA and protein expression of CARM1 in the injured DRG, and blocking its expression through small interfering RNA (siRNA) in the injured DRG attenuated the development and maintenance of neuropathic pain. Furthermore, pharmacological inhibition of CARM1 mitigated peripheral nerve injury-induced mechanical allodynia and thermal hyperalgesia. Given that CARM1 inhibition or knockdown attenuated the induction and maintenance of neuropathic pain after peripheral nerve injury, our findings suggest that CARM1 may serve as a promising therapeutic target for neuropathic pain treatment in clinical applications.

TRPA1 and substance P mediate stress induced duodenal lesions in water immersion restraint stress rat model.

BACKGROUND/AIMS: Transient receptor potential ankyrin 1 (TRPA1) and substance P (SP), both expression in sensory neurons, have important roles in stress-induced duodenal lesions. The possible contribution of TRPA1 and SP to stress-induced duodenal lesions was explored by using the water immersion restraint stress (WIRS) rat model. MATERIALS AND METHODS: Western blotting, Real-time polymerase chain reaction (RT-PCR), and immunohistochemistry assay were used to evaluate the changes of TRPA1and SP expression in the dorsal root ganglia (DRG, T8-11), the corresponding segment of the spinal cord (T8-11), and the duodenum in a duodenal lesions rat model. The SP concentrations of duodenal mucosa were investigated using an enzyme-linked immunosorbent assay (ELISA). Duodenal lesions were assessed according to histopathological changes. TRPA1 specific antagonist HC-030031 was intrathecally or intraperitoneally performed to suppress the expression of both TRPA1 and SP for evaluating the roles of TRPA1 and SP in duodenal lesions. RESULTS: In contrast to the control group, TRPA1 and substance P in the DRG (T8-11) and duodenum were up-regulated, and concentrations of SP in the duodenal mucosa were increased after WIRS (p<0.05), which are closely associated with duodenal lesions. SP concentrations in the duodenal mucosa were decreased and duodenal lesions were alleviated by pretreatment with TRPA1 antagonist HC-030031. We identified a protective role for HC-030031 in WIRS-induced duodenal lesions. Furthermore, we demonstrated that WIRS increased the concentrations of SP in the duodenal mucosa in a TRPA1-dependent manner. However, WIRS caused no significant changes of TRPA1 and SP in the spinal cord (T8-11) compared with the control group (p>0.05). CONCLUSION: Our study indicates that TRPA1 antagonist HC-030031 alleviates duodenal lesions. TRPA1 is activated and sensitized, therefore concomitant neuropeptide SP is released, which exerts a critical role in inducing and maintaining duodenal lesions following WIRS in rats. This provides evidence that neuroimmune interactions may control duodenal injury. TRPA1 may be a potential drug target to inhibit the development of duodenal lesions by stress-induced in patients.

The effect of dexmedetomidine on haemodynamics during intracranial procedures: a meta-analysis.

OBJECTIVES: Our aim of this study is to compare the effect of Dexmedetomidine versus placebo for patients with cerebral protection during intracranial procedures. METHODS: Rev.Man 5.1 and Stata 11.0 software is used for this study to make analysis, and use a fixed-effects model (the Mantel-Haenszel method) or a random-effects model (the DerSimonian and Laird method) to merge or aggregate the weighted mean difference (WMD) or risk ratio (RR) and its 95% confidence intervals (CI) of included studies. RESULTS: Nine studies involving 404 patients with cerebral protection during intracranial procedures (experimental group: 202; control group: 202) were performed in this study. Significant differences of MAP > 100 mmHg(RR = 0.45, 95%CI = 0.29 to 0.69, P < 0.05), MAP< 60 mmHg (RR = 0.66, 95%CI = 0.43 to 1.00, P = 0.05), MAP when extubation (WMD = -12.57, 95%CI = -16.31 to -8.83, P < 0.05) and heart rate when extubation (WMD = -22.79, 95%CI = -30.57 to -15.01, P < 0.05) were observed between the two groups. There are no significant differences were found in HR > 100 bpm (RR = 0.52, 95%CI = 0.22 to 1.19, P > 0.05) and HR< 50 bpm (RR = 0.86, 95%CI = 0.31 to 2.38, P > 0.05) between the two groups. CONCLUSIONS: Our results suggested that the efficacy of Dexmedetomidine for patients with cerebral protection during intracranial procedures is better than placebo treatment.

MBD1 Contributes to the Genesis of Acute Pain and Neuropathic Pain by Epigenetic Silencing of Oprm1 and Kcna2 Genes in Primary Sensory Neurons.

The transmission of normal sensory and/or acute noxious information requires intact expression of pain-associated genes within the pain pathways of nervous system. Expressional changes of these genes after peripheral nerve injury are also critical for neuropathic pain induction and maintenance. Methyl-CpG-binding domain protein 1 (MBD1), an epigenetic repressor, regulates gene transcriptional activity. We report here that MBD1 in the primary sensory neurons of DRG is critical for the genesis of acute pain and neuropathic pain as DRG MBD1-deficient mice exhibit the reduced responses to acute mechanical, heat, cold, and capsaicin stimuli and the blunted nerve injury-induced pain hypersensitivities. Furthermore, DRG overexpression of MBD1 leads to spontaneous pain and evoked pain hypersensitivities in the WT mice and restores acute pain sensitivities in the MBD1-deficient mice. Mechanistically, MDB1 represses Oprm1 and Kcna2 gene expression by recruiting DNA methyltransferase DNMT3a into these two gene promoters in the DRG neurons. DRG MBD1 is likely a key player under the conditions of acute pain and neuropathic pain.SIGNIFICANCE STATEMENT In the present study, we revealed that the mice with deficiency of methyl-CpG-binding domain protein 1 (MBD1), an epigenetic repressor, in the DRG displayed the reduced responses to acute noxious stimuli and the blunted neuropathic pain. We also showed that DRG overexpression of MBD1 produced the hypersensitivities to noxious stimuli in the WT mice and rescued acute pain sensitivities in the MBD1-deficient mice. We have also provided the evidence that MDB1 represses Oprm1 and Kcna2 gene expression by recruiting DNA methyltransferase DNMT3a into these two gene promoters in the DRG neurons. DRG MBD1 may participate in the genesis of acute pain and neuropathic pain likely through regulating DNMT3a-controlled Oprm1 and Kcna2 gene expression in the DRG neurons.

Dexmedetomidine Added to Sufentanil Patient-Controlled Intravenous Analgesia Relieves the Postoperative Pain after Cesarean Delivery: A Prospective Randomized Controlled Multicenter Study.

This study evaluated the efficacy and safety of dexmedetomidine in intravenous patient-controlled analgesia (PCA) after cesarean delivery. This multicenter study enrolled 208 subjects who were scheduled for selective cesarean delivery from 9 research centers. Patients received 0.5 ug/kg dexmedetomidine (study group) or normal saline (control group) after delivery and an intravenous PCA pump after surgery (100 µg sufentanil +300 µg dexmedetomidine for the study group, 100 µg sufentanil for the control group, background infusion: 1 ml/h, bolus dose: 2 ml and lock time: 8 min). The sufentanil consumption, pain scores, rescue analgesia, sedation scores, analgesic satisfaction, the incidence of postoperative nausea and vomiting (PONV) and the first passage of flatus were recorded within 24 h after surgery. The sufentanil consumption in the study group was significantly lower than that in the control group (p = 0.004). Compared with the control group, the study group had lower pain scores (p < 0.01), higher analgesic satisfaction degree [p < 0.001, odd ratio 4.28 and 95% CI (2.46, 7.46)], less requirement of rescue analgesia (p = 0.003), lower incidence of PONV (p = 0.005 and p < 0.001, respectively), and shorter time to first passage of flatus (p = 0.007). Dexmedetomidine added to sufentanil intravenous PCA significantly enhanced the analgesic effects, improved analgesic satisfaction, and had the potential benefits of reducing PONV and the recovery of intestinal functions after cesarean section.

Inhibition of mitochondrial permeability transition pore opening contributes to cannabinoid type 1 receptor agonist ACEA-induced neuroprotection.

Cannabinoid type 1 (CB1) receptor agonist arachidonyl-2-chloroethylamide (ACEA) induces neuroprotection against brain ischemia, and the mechanism, however, is still elusive. In this study, we used bilateral common carotid artery occlusion (BCCAO) in mice and oxygen-glucose deprivation (OGD) in primary cultured neurons to mimic brain ischemic injury, and hypothesized that cannabinoid CB1 receptor agonist ACEA protects ischemic neurons via inhibiting the opening of mitochondrial permeability transition pore (MPTP). In vivo, we found that BCCAO treatment reduced the neurological functions, increased the number of apoptotic neuronal cells and deteriorated the mitochondrial morphology in the ischemic brain tissue. And in vitro, we observed that OGD injury reduced cell viability, mitochondrial function and anti-oxidant SOD2 expression, increased lactate dehydrogenase (LDH), mitochondrial cytochrome C (Cyto C) and apoptosis-inducing factor (AIF) releases, elevated the cell apoptosis and mitochondrial superoxide level. And the CB1 receptor agonist ACEA significantly abolished the BCCAO and OGD-induced neuronal injury above. However, the MPTP opener atractyloside (Atr) markedly reversed the ACEA-induced neuroprotective effects, inhibited the mitochondrial Cyto C and AIF releases and relieved the mitochondrial swelling, but the MPTP inhibitor cyclosporin A (CsA) did not cause significant effects on the ACEA-induced neuroprotection above. These findings indicated that inhibition of MPTP opening may be involved in the cannabinoid CB1 receptor agonist ACEA-induced neuroprotection.

Transient Receptor Potential Ankyrin 1 and Substance P Mediate the Development of Gastric Mucosal Lesions in a Water Immersion Restraint Stress Rat Model.

BACKGROUND: Activation of substance P (SP) contributes to the development and maintenance of gastric lesions, but the mechanisms underlying the release of SP and SP-mediated damage to the gastric mucosa remain unknown. Transient receptor potential ankyrin 1 (TRPA1) is expressed in SP-positive neurons in the dorsal root ganglion (DRG) and stomach of rats. We hypothesized that water immersion restraint stress (WIRS) may activate and sensitize TRPA1 in DRG neurons, subsequently inducing the release of SP from DRG and stomach cells, causing the development of acute gastric mucosal lesions (AGML). METHODS: Changes in TRPA1 and SP expression in T8-11 DRG sensory neurons and the stomach in an AGML rat model were determined by reverse transcription polymerase chain reaction, western blotting and immunohistochemistry. The SP levels of serum and gastric mucosa were measured by using an enzyme-linked immunosorbent assay (ELISA). Gastric lesions were evaluated by histopathological changes. The TRPA1 antagonist HC-030031 and TRPA1 agonists allyl isothiocyanate were used to verify effect of TRPA1 and SP on AGML. RESULTS: SP and TRPA1 in the DRG and stomach were upregulated, and the serum and gastric mucosa levels of SP were increased after WIRS, which are closely associated with AGML. The release of SP was suppressed and AGML were alleviated following a selective TRPA1 antagonist HC-030031. TRPA1 agonists AITC increased release of SP and led to moderate gastric lesions. We confirmed that WIRS induced the release of SP in the DRG, stomach, serum and gastric mucosa, and in a TRPA1-dependent manner. CONCLUSIONS: Upregulated SP and TRPA1 in the DRG and stomach and increased serum and gastric mucosa SP levels may contribute to stress-induced AGML. TRPA1 is a potential drug target to reduce stress-induced AGML development in patients with acute critical illnesses. This study may contribute to the discovery of drugs for AGML treatment.

Direct and Selective Synthesis of Hydrogen Peroxide over Palladium-Tellurium Catalysts at Ambient Pressure.

Highly selective hydrogen peroxide (H2 O2 ) synthesis directly from H2 and O2 is a strongly desired reaction for green processes. Herein a highly efficient palladium-tellurium (Pd-Te/TiO2 ) catalyst with a selectivity of nearly 100 % toward H2 O2 under mild conditions (283 K, 0.1 MPa, and a semi-batch continuous flow reactor) is reported. The size of Pd particles was remarkably reduced from 2.1 nm to 1.4 nm with the addition of Te. The Te-modified Pd surface could significantly weaken the dissociative activation of O2 , leading to the non-dissociative hydrogenation of O2 . Density functional theory calculations illuminated the critical role of Te in the selective hydrogenation of O2 , in that the active sites composed of Pd and Te could significantly restrain side reactions. This work has made significant progress on the development of high-selectivity catalysts for the direct synthesis of H2 O2 at ambient pressure.

Targeting neuronal nitric oxide synthase by a cell penetrating peptide Tat-LK15/siRNA bioconjugate.

We developed a cell penetrating peptide (CPP) Tat-LK15, as a siRNA carrier to target nNOS. The feasibility, stability, efficiency and selectivity of this peptide-siRNA complex were evaluated in rat neuronal cells. We also compared the new method with conventional siRNA carrier Lipofectamine™. It was found that the CPP Tat-LK15 effectively and specifically delivered nNOS-siRNA into Rat retinal ganglia (RGC-5) cells and silenced the expression of nNOS. The CPP Tat-LK15 can conjugate with siRNA to form stable complex at a ratio of 2:1 (peptide/siRNA, w/w), which maintained stable in serum for as long as 4h. The CPP Tat-LK15 was low-toxicity to cells, as the apoptosis rate of treat cells was not increased significantly when the used peptide lower than 10µg/mL. Moreover, the cellular uptake of nNOS siRNA by Rat Neurons-dorsal spinal cord (RNdsc) cells was also significantly more than naked siRNA by RNdsc cells. The CPP Tat-LK15 was an efficient and stable, and non-cytotoxic siRNA delivery to neurons and effectively silenced the nNOS expression. The CPP Tat-LK15 mediated siRNA delivery was a potential tool to treat neuropathic diseases involving NO or nNOS neurotoxic cascades.

Consequences of Surface Oxophilicity of Ni, Ni-Co, and Co Clusters on Methane Activation.

This study describes a new C-H bond activation pathway during CH4-CO2 reactions on oxophilic Ni-Co and Co clusters, unlike those established previously on Ni clusters. The initial C-H bond activation remains as the sole kinetically relevant step on Ni-Co, Ni, and Co clusters, but their specific reaction paths vary. On Ni clusters, C-H bond activation occurs via an oxidative addition step that involves a three-center (H3C···*···H)⧧ transition state, during which a Ni-atom inserts into the C-H bond and donates its electron density into the C-H bond's antibonding orbital. Ni-Co clusters are more oxophilic than Ni; thus, their surfaces are covered with oxygen adatoms. An oxygen adatom and a vicinal Co-atom form a metal-oxygen site-pair that cleaves the C-H bond via a σ bond metathesis reaction, during which the Co inserts into the C-H bond while the oxygen abstracts the leaving H-atom in a concerted, four-center (H3C···*···H···O*)⧧ transition state. Similarly, Co clusters also catalyze the σ bond metathesis step, but much less effectively because of their higher oxophilicities, much stronger binding to oxygen, and less effective hydrogen abstraction than Ni-Co clusters. On Ni-Co and Co clusters, the pseudo-first-order rate coefficients are single-valued functions of the CO2-to-CO ratio (or H2O-to-H2 ratio), because this ratio prescribes the oxygen chemical potentials and the relative abundances of metal-oxygen site-pairs through the water-gas shift equilibrium. The direct involvement of reactive oxygen in the kinetically relevant step leads to more effective CH4 turnovers and complete elimination of coke deposition on Ni-Co bimetallic clusters.