Higher-Order Split Operator Schemes for Solving Tetratomic Reactions Using the Time-Dependent Wave Packet Method.

In this work, using the time-dependent quantum wave packet method, quite a few typical higher-order split operators (HOSOs) were for the first time applied to calculate the tetratomic reactive scattering processes in the hyperspherical coordinate. It was found that the HOSOs were hardly efficient for a tetratomic reaction calculation, unlike those for a triatomic reactive scattering calculation. We proposed an efficient HOSO with a force gradient (denoted as 2G1 in the main text) for efficiently and accurately calculating a tetratomic reaction using the quantum wave packet method. Several typical tetratomic reactions, such as H2 + OH, HF + OH, and H2 + OH+, are calculated for demonstrating the effectiveness of the proposed 2G1 in terms of (product state-resolved) reaction probability and inelastic probability, by comparing with the performance of the previously reported various HOSOs. We suggest that the 2G1 propagator could be applied to efficiently calculate a general tetratomic reaction.

Reactant-Product Decoupling Technique Using the Intermediate Coordinate Method.

Although the reactant-product decoupling (RPD) technique was proposed over two decades ago, it remains an efficient approach for calculating product state-resolved information on some simple direct reactions using the quantum wave packet method. In the past, usually the RPD technique employed the collocation method to transform the wave function between reactant and product arrangements, which requires quite large computational efforts. In this work, the intermediate coordinate (IC) method is employed to realize the RPD technique. Numerical examples demonstrate that this new IC RPD (IRPD) technique has superior computational efficiency compared with the original method employing the collocation method. Especially, the new IRPD technique significantly saves disk space and computer memory. To illustrate the features of our new method, the total reaction probabilities of the H + H2, H + Br2, and F + H2 reactions with J = 0 and the differential cross sections of the H + H2 and F + H2 reactions at a series of collision energy are calculated and presented. With this efficient and effective new RPD technique, the Li + HF reaction, which involves sharp resonances with long-range wave functions in the van der Waals wells in both the reactant and product arrangements, is also calculated with several J at the product state-resolved level to reveal the ability of the RPD technique for describing resonance wave functions. With these numerical examples, it is found that, for the reaction with resonances, the RPD approach should be applied carefully. Otherwise, it is very possible that the resonances could disappear with the application of the RPD technique.

The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence.

Anaesthetics may modify colorectal cancer cell biology which potentially affects long-term survival. This study aims to compare propofol and sevoflurane regarding with the direct anaesthetic effects on cancer malignancy and the indirect effects on host immunity in a cancer xenograft mode of mice. Cultured colon cancer cell (Caco-2) was injected subcutaneously to nude mice (day 1). Mice were exposed to either 1.5% sevoflurane for 1.5 h or propofol (20 µg g-1; ip injection) with or without 4 µg g-1 lipopolysaccharide (LPS; ip) from days 15 to 17, compared with those without anaesthetic exposure as controls. The clinical endpoints including tumour volumes over 70 mm3 were closely monitored up to day 28. Tumour samples from the other cohorts were collected on day 18 for PCR array, qRT-PCR, western blotting and immunofluorescent assessment. Propofol treatment reduced tumour size (mean ± SD; 23.0 ± 6.2mm3) when compared to sevoflurane (36.0 ± 0.3mm3) (p = 0.008) or control (23.6 ± 4.7mm3). Propofol decreased hypoxia inducible factor 1α (HIF1α), interleukin 1ß (IL1ß), and hepatocyte growth factor (HGF) gene expressions and increased tissue inhibitor of metalloproteinases 2 (TIMP-2) gene and protein expression in comparison to sevoflurane in the tumour tissue. LPS suppressed tumour growth in any conditions whilst increased TIMP-2 and anti-cancer neutrophil marker expressions and decreased macrophage marker expressions compared to those in the LPS-untreated groups. Our data indicated that sevoflurane increased cancer development when compared with propofol in vivo under non-surgical condition. Anaesthetics tested in this study did not alter the effects of LPS as an immune modulator in changing immunocyte phenotype and suppressing cancer development.

Circular RNAs in organ injury: recent development.

Circular ribonucleic acids (circRNAs) are a class of long non-coding RNA that were once regarded as non-functional transcription byproducts. However, recent studies suggested that circRNAs may exhibit important regulatory roles in many critical biological pathways and disease pathologies. These studies have identified significantly differential expression profiles of circRNAs upon changes in physiological and pathological conditions of eukaryotic cells. Importantly, a substantial number of studies have suggested that circRNAs may play critical roles in organ injuries. This review aims to provide a summary of recent studies on circRNAs in organ injuries with respect to (1) changes in circRNAs expression patterns, (2) main mechanism axi(e)s, (3) therapeutic implications and (4) future study prospective. With the increasing attention to this research area and the advancement in high-throughput nucleic acid sequencing techniques, our knowledge of circRNAs may bring fruitful outcomes from basic and clinical research.

Long Chain Non Coding RNA Targeting miR Signal Axis Regulates the Mechanism of Apoptosis and Invasion and Migration of Glioma U251 Cells.

The occurrence of glioma is gradually promoted by various factors, and it has gone through multiple stages of development, involving abnormal expression of multiple genes. One of the important reasons for the development of gliomas is the interaction of genetic factors and the environment. Non-coding transcripts can also form this high-level structure, and the formation of binding sites for interactions between lncRNA and proteins, DNA, and other RNA molecules may be related to their structural diversity. Due to the importance of glioma-related research and the potential effectiveness of lncRNA, this paper focuses on the mechanism of long-chain non-coding RNA targeting the Mir signal axis to regulate apoptosis, invasion and migration of glioma U251 cells. In this paper, human glioma cell line U251 was used as experimental material for simulation analysis. The results showed that after miR simulation, the pass rate of U251 stem cells through the filter was 17.3%, which was significantly less than 85.4% of group C; compared with 77.6% of the negative control group, the cell penetration rate of the miR inhibitor group was significantly improved. 92.5%. The miR expression level can affect the invasion ability of U251 stem cells, and can negatively regulate the expression of fzd4 to inhibit the invasion and metastasis of glioma U251 cells.

Pretreatment with valproic acid alleviates pulmonary fibrosis through epithelial-mesenchymal transition inhibition in vitro and in vivo.

Epithelial-mesenchymal transition (EMT) plays a crucial role in the development of pulmonary fibrosis. This study aims to investigate the effects of valproic acid (VPA) on EMT in vitro and in vivo. In vitro, EMT was induced by the administration of transforming growth factor-ß1 (TGF-ß1) in a human alveolar epithelial cell line (A549). The dose effects of VPA (0.1-3 mM) on EMT were subsequently evaluated at different timepoints. VPA (1 mM) was applied prior to the administration of TGF-ß1 and the expression of E-cadherin, vimentin, p-Smad2/3 and p-Akt was assessed. In addition, the effects of a TGF-ß type I receptor inhibitor (A8301) and PI3K-Akt inhibitor (LY294002) on EMT were evaluated. In vivo, the effects of VPA on bleomycin-induced lung fibrosis were evaluated by assessing variables such as survival rate, body weight and histopathological changes, whilst the expression of E-cadherin and vimentin in lung tissue was also evaluated. A8301 and LY294002 were used to ascertain the cellular signaling pathways involved in this model. The administration of VPA prior to TGF-ß1 in A549 cells prevented EMT in both a time- and concentration-dependent manner. Pretreatment with VPA downregulated the expression of both p-Smad2/3 and p-Akt. A8301 administration increased the expression of E-cadherin and reduced the expression of vimentin. LY294002 inhibited Akt phosphorylation induced by TGF-ß1 but failed to prevent EMT. Pretreatment with VPA both increased the survival rate and prevented the loss of body weight in mice with pulmonary fibrosis. Interestingly, both VPA and A8301 prevented EMT and facilitated an improvement in lung structure. Overall, pretreatment with VPA attenuated the development of pulmonary fibrosis by inhibiting EMT in mice, which was associated with Smad2/3 deactivation but without Akt cellular signal involvement.

Significant Improvement of Catalytic Performance for Chlorinated Volatile Organic Compound Oxidation over RuOx Supported on Acid-Etched Co3O4.

Ru catalysts have attracted increasing attention in catalytic oxidation of chlorinated volatile organic compounds (CVOCs). However, the development of Ru catalysts with high activity and thermal stability for CVOC oxidation still poses significant challenges due to their restrictive relationship. Herein, a strategy for constructing surface defects on Co3O4 support by acid etching was utilized to strengthen the interaction between active RuOx species and the Co3O4 support. Consequently, both the dispersity and thermal stability of RuOx species were significantly improved, achieving both high activity and stability of Ru catalysts for CVOC oxidation. The optimized Ru catalyst on the HF-etched Co3O4 support (Ru/Co3O4-F) achieved complete oxidation of vinyl chloride at 260 °C under 30 000 mL·g-1·h-1, which was lower than 300 °C for the Ru catalyst on the original Co3O4 (Ru/Co3O4). More importantly, the Ru species on the Ru/Co3O4-F catalyst were hardly lost after calcination at 500-700 °C and even reacting at 650 °C for 120 h. On this basis, the polychlorinated byproducts over the Ru/Co3O4-F catalyst were almost completely effaced by phosphate modification on the catalyst surface. These findings show that the method combining acid etching of the support and phosphate modification provides a strategy for the advancement of catalyst design for CVOC oxidation.

Interaction-Asymptotic Region Decomposition Method for an Insertion Reaction: Application to the S(1D) + H2 Reaction.

With adjusting principal axes hyperspherical (APH) coordinate in the interaction region, and the Jacobi coordinates in the asymptotic regions, an efficient multidomain interaction-asymptotic region decomposition (IARD) method has been developed to solve the "coordinate problem" in a product-state-resolved reactive scattering calculation using the quantum wave packet method. Although the APH coordinate treats with all three channels equally, and is efficient for describing the interaction region for some direct reactions, it is inefficient for describing the insertion-type reaction due to the singularity problem, such as the S(1D) + H2 reaction. To deal with this issue, in this work, the channel-dependent Delves hyperspherical (DH) coordinate is proposed to describe the interaction region using the IARD method. The proposed DH-IARD method was applied to calculate the product-state-resolved reaction probabilities of the H + HD reaction, and the differential and integral cross sections of the typical insertion reaction S(1D) + H2. It is found that the new DH-IARD method is much more efficient than the previous APH-IARD method for dealing with insertion reactions. The partial wave resonance structures were observed in the integral cross section. It is found that at a low collision energy, the position of the initial wave packet has to be put far away. Otherwise, the partial wave resonance structures could not be correctly reproduced due to the reef well arising with a large total angular momentum J.

Interaction-Asymptotic Region Decomposition Method for a Triatomic Reactive Scattering with Symmetry Adoption.

For solving the "coordinate problem" in a product state-resolved calculation with the quantum wave packet method, an interaction-asymptotic region decomposition (IARD) method has been proposed for a general triatomic reactive scattering process. In the IARD method, the three asymptotic regions are represented by the corresponding Jacobi coordinates, but the hyperspherical coordinate is applied for representing the interaction region. For a triatomic reaction A + B2 with symmetry, explicit inclusion of all three channels in the calculations is unnecessary. Thus, numerical methods for exploring the symmetry of the A + B2 reaction need to be developed. Due to the symmetry of reactant B2, spherical harmonics with only even or odd number are required for representing the angular degree of freedom in the reactant channel and only one product channel needs to be considered. For representing the interaction region, the symmetry in the hyperspherical coordinate could also be explored to reduce the computational effort. The advantages of the IARD method with symmetry adoption were illustrated by calculating the product state-resolved reaction probabilities of the 16O + 36O2, 18O + 32O2, F + H2, and D+ + H2 reactions in the ultracold collision region. The numerical results calculated using the famous ABC code and the reactant coordinate-based method were provided for comparison.

Effects of circadian rhythm on Narcotrend index and target-controlled infusion concentration of propofol anesthesia.

BACKGROUND: The effects of circadian rhythms on drug metabolism and efficacy are being increasingly recognized. However, the extent to which they affect general anesthesia remains unclear. This study aims to investigate the effects of circadian rhythms on anesthetic depth and the concentrations of propofol target-controlled infusion (TCI). METHODS: Sixty patients undergoing laparoscopic surgeries were sequentially assigned to four groups. Group ND (n = 15): Propofol TCI with Narcotrend monitor during the day (8:00-18:00), Group NN (n = 15): Propofol TCI with Narcotrend monitor during the night (22:00-5:00), Group CLTD (n = 15): Propofol closed-loop TCI guided by bispectral index (BIS) during the day (8:00-18:00), Group CLTN (n = 15): Propofol closed-loop TCI guided by BIS during the night (22:00-5:00). The Narcotrend index, mean arterial pressure (MAP) and heart rate (HR) were compared between group ND and NN at 7 time points, from 5 min before induction to the end of operation. The propofol TCI concentrations, MAP and HR were compared between group CLTD and CLTN at 7 time points, from 5 min after induction to the end of operation. RESULTS: The Narcotrend index, MAP, and HR in group NN were lower than those in group ND from the beginning of mechanical ventilation to the end of operation (p < 0.05). The propofol TCI concentrations in group CLTN were lower than those in group CLTD from the beginning of operation to the end of operation (p < 0.05). CONCLUSION: Circadian rhythms have a significant effect on the depth of anesthesia and drug infusion concentrations during propofol TCI. When using general anesthesia during night surgery, the propofol infusion concentration should be appropriately reduced compared to surgery during the day. TRIAL REGISTRATION: The present study was registered on the ClinicalTrials.gov website ( NCT02440269 ) and approved by the Medical Ethics Committee of Southwest Hospital of Third Military Medical University (ethics lot number: 2016 Research No. 93). All patients provided informed written consent to participate in the study.

Apoptosis and necroptosis occur in the different brain regions of hippocampus in a rat model of hypoxia asphyxia.

AIM OF THE STUDY: Hypoxic-ischemic encephalopathy (HIE) is a major cause of newborn brain injury. Apoptosis and necroptosis are two forms of cell death which may occur in HIE but reported data are yet limited. This study investigates the expression of receptor interacting protein kinase (RIPK) 1 and 3, and caspase3, the key modulators of necroptosis and apoptosis, respectively, in a model of HIE to determine whether both forms of cell death occur in the corresponding brain regions. MATERIALS AND METHODS: Postneonatal day 7 Sprague-Dawley rats were subjected to right carotid artery ligation followed by hypoxia or subjected to skin incision under surgical anesthesia without ligation and hypoxia. Neuroglioma (H4) cell was cultured and subjected to 24 h hypoxic insults. Necrostatin-1, a RIPK1 inhibitor, was administered in both in vivo and in vitro settings before insult. RESULTS: After hypoxic-ischemic insults, both RIPK1 and RIPK3 expression were significantly increased in the region of hippocampal dentate gyrus in the injurious hemisphere. However, cleaved caspase3 was significantly increased in the hippocampal cornu ammonis 1 region in the injurious hemisphere. After hypoxic insults, RIPK1 and RIPK3 expression was also found in H4 cells. In addition, it was identified that the increased RIPK1 and RIPK3 can be inhibited by necrostatin-1 in both in vivo and in vitro. CONCLUSIONS: These data indicated that apoptosis and necroptosis occur in different brain regions of hippocampus in a model of HIE which may suggest that strategies to prevent each form of neuronal death is valuable to be developed.

Inhalational Anesthetics Inhibit Neuroglioma Cell Proliferation and Migration via miR-138, -210 and -335.

Inhalational anesthetics was previously reported to suppress glioma cell malignancy but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNAs upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.

Sevoflurane and Desflurane Exposure Enhanced Cell Proliferation and Migration in Ovarian Cancer Cells via miR-210 and miR-138 Downregulation.

Inhalational anaesthetics were previously reported to promote ovarian cancer malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the role of sevoflurane- or desflurane-induced microRNA (miRNA) changes on ovarian cancer cell behaviour. The cultured SKOV3 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. Expression of miR-138, -210 and -335 was determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and Cell Counting Kit-8 (CCK8) assay with or without mimic miR-138/-210 transfections. The miRNA downstream effector, hypoxia inducible factor-1α (HIF-1α), was also analysed with immunofluorescent staining. Sevoflurane or desflurane exposure to cancer cells enhanced their proliferation and migration. miR-138 expression was suppressed by both sevoflurane and desflurane, while miR-210 expression was suppressed only by sevoflurane. miR-335 expression was not changed by either sevoflurane or desflurane exposure. The administration of mimic miR-138 or -210 reduced the promoting effects of sevoflurane and desflurane on cancer cell proliferation and migration, in line with the HIF-1α expression changes. These data indicated that inhalational agents sevoflurane and desflurane enhanced ovarian cancer cell malignancy via miRNA deactivation and HIF-1α. The translational value of this work needs further study.

Xenon blunts NF-κB/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice.

Xenon, an inert anesthetic gas, is increasingly recognized to possess desirable properties including cytoprotective and anti-inflammatory effects. Here we evaluated the effects of xenon on the progression of lupus nephritis (LN) in a mouse model. A two hour exposure of either 70% xenon or 70% nitrogen balanced with oxygen was administered daily for five weeks to female NZB/W F1 mice that had been induced to develop accelerated and severe LN. Xenon treatment improved kidney function and renal histology, and decreased the renal expression of neutrophil chemoattractants, thereby attenuating glomerular neutrophil infiltration. The effects of xenon were mediated primarily by deceasing serum levels of anti-double stranded DNA autoantibody, inhibiting reactive oxygen species production, NF-κB/NLRP3 inflammasome activation, ICAM-1 expression, glomerular deposition of IgG and C3 and apoptosis, in the kidney; and enhancing renal hypoxia inducible factor 1-α expression. Proteomic analysis revealed that the treatment with xenon downregulated renal NLRP3 inflammasome-mediated cellular signaling. Similarly, xenon was effective in improving renal pathology and function in a spontaneous LN model in female NZB/W F1 mice. Thus, xenon may have a therapeutic role in treating LN but further studies are warranted to determine applicability to patients.

Sevoflurane Enhances Proliferation, Metastatic Potential of Cervical Cancer Cells via the Histone Deacetylase 6 Modulation In Vitro.

BACKGROUND: Sevoflurane is commonly used for cervical cancer surgery, but its effect on cervical cancer cell biology remains unclear. This mechanistic study explores how sevoflurane affects the proliferation and metastatic potential of immortalized cervical cancer cell lines. METHODS: Cultured cervical cancer Caski and HeLa lines were exposed to 1, 2, or 3% sevoflurane for 2 or 4 h. Cell proliferation was determined through the Kit-8 assay and Ki-67 immunofluorescent staining. Cell migration and invasion were evaluated with the Transwell assay. Immunofluorescent staining and Western blot analysis were used to identify sevoflurane-induced morphological and biochemical changes. RESULTS: Sevoflurane exposure for either 2 or 4 h significantly increased HeLa cell proliferation in a time- and concentration-dependent manner to be 106 ± 2.7% and 107 ± 1.4% relative to the controls (n = 10; P = 0.036; P = 0.022) at 24 h after exposure and to be 106 ± 2.2% and 106 ± 1.7% relative to the controls (n = 10; P = 0.031; P = 0.023) at the highest concentration of 3% sevoflurane studied, respectively, but not Caski cells. Sevoflurane promoted invasion ability (1.63 ± 0.14 and 1.92 ± 0.12 relative to the controls) and increased cell size (1.69 ± 0.21 and 1.76 ± 0.13 relative to the controls) of Caski and HeLa cells (n = 6; all P < 0.001), respectively. Sevoflurane increased histone deacetylase 6 expression in both cells, and histone deacetylase 6 knockdown abolished the prometastatic effects of sevoflurane. Sevoflurane also induced deacetylation of α-tubulin in a histone deacetylase 6-dependent manner. The protein kinase B (AKT) or extracellular regulated protein kinase (ERK1/2) phosphorylation inhibition attenuated sevoflurane-induced histone deacetylase 6 expression. CONCLUSIONS: Sevoflurane enhanced proliferation, migration, and invasion of immortalized cervical cancer cells, which was likely associated with increasing histone deacetylase 6 expression caused by phosphatidylinositide 3-kinase/AKT- and ERK1/2-signaling pathway activation.

Non-adiabatic dynamics studies of the K(4p2P) + H2(X1Σ) reaction based on new diabatic potential energy surfaces.

Global diabatic potential energy surfaces (PESs) of the KH2 system corresponding to the ground (12A') and first excited (22A') states were constructed for the first time. In ab initio calculations, the MRCI-F12 method with AVTZ and def2-QZVP basis sets was adopted and 17 865 ab initio energy points were calculated. The mixing angle, which is used to obtain the diabatic energies, was calculated by the molecular properties of the transition dipole moment. The diabatic PESs were fitted individually by the permutation invariant polynomial neural network method and the topographical features of the diabatic PESs are discussed in detail. The non-adiabatic dynamics studies of the K(4p2P) + H2(v0 = 0, 1, j0 = 0) reaction were carried out using the APH method based on the new diabatic PESs. The collision reaction processes K(4p2P) + H2(v0 = 0, 1, j0 = 0) → H + KH and the quenching processes K(4p2P) + H2(v0 = 0, 1, j0 = 0) → K(4s2S) + H2 were studied at the state-to-state level of theory. For the reaction process, the dynamics results indicated that the vibrational excitation of H2 was significantly more effective at promoting the reaction than the translational energy. In addition, the differential cross-sections were forward-biased scattering, which indicated that the direct abstraction mechanism plays a dominant role in the reaction. For the quenching process, the vibrational excitation of H2 molecules could improve the quenching efficiency obviously.

Dexmedetomidine-Mediated Prevention of Renal Ischemia-Reperfusion Injury Depends in Part on Cholinergic Anti-Inflammatory Mechanisms.

BACKGROUND: Organ ischemia-reperfusion injury often induces local and systemic inflammatory responses, which in turn worsen organ injury. These inflammatory responses can be regulated by the central nervous system, particularly by the vagal nerve and nicotinic acetylcholine receptors, which are the key components of cholinergic anti-inflammatory pathway. Activation of the cholinergic anti-inflammatory pathway can suppress excessive inflammatory responses and be a potential strategy for prevention of ischemia-reperfusion injury of organs including the kidney. METHODS: Vagal nerve activity, plasma acetylcholine, catecholamine and inflammatory mediators, renal tissue injury, and cell death were measured in mice with bilateral renal ischemia/reperfusion with or without treatment with dexmedetomidine (Dex), an α2-adrenergic receptor agonist. RESULTS: Dex significantly increased the discharge frequency of the cervical vagal nerve by up to 142 Hz (mean) (P < .001), and preserved kidney gross morphology and structure and attenuated cell apoptosis after ischemia-reperfusion. Furthermore, Dex also significantly increased acetylcholine release to 135.8 pmol/L (median) when compared to that (84.7 pmol/L) in the sham group (P < .001) and reduced the levels of several inflammatory mediators induced by renal ischemia/reperfusion. All the effects were abolished by vagotomy, splenectomy, or combinative administration of atipamezole, an α2-adrenergic receptor antagonist. CONCLUSIONS: Our findings suggest that Dex provides renoprotection, at least in part, through anti-inflammatory effects of the parasympathetic nervous system activation in addition to its direct actions on α2-adrenergic receptors.

Inhibition of tyrosine kinases protects against lipopolysaccharide-induced acute lung injury by preventing nuclear export of Nrf2.

Acute Lung Injury is a common severe pathological condition that is usually caused by lipopolysaccharide (LPS) infection from bacteria. Enhanced activity of nuclear factor erythroid 2-related factor 2 (Nrf2) could attenuate LPS induced lung injury, However, it still remains unknown whether the enhanced activity of Nrf2 via suppression of Nrf2 nucleus export attenuates the LPS induced lung injury. The aim of this study is to investigate the effects of inhibitors of Fyn on the LPS-induced acute lung injury and to explore its underlying molecular mechanisms. Nrf2 localization in the cells was observed by using confocal microscopy and its transcriptional activation was measured by Electrophoretic Mobility Shift Assay and controlled genes expression levels. The lung injury severity was examined by histopathological scoring and oxidative stress level. In this study, we showed that PP2, LMB, and Nrf2 Y568A abrogated Nrf2 nuclear export and thus enhance the Nrf2 transcriptional activity. PP2 attenuated lung injury and the reduction of cells viability induced by LPS. The current study demonstrated, for the first time, that increase of expression of Nrf2 controlled protective genes via suppression of Nrf2 nucleus export could attenuate lung injury.

Osteopontin mediates necroptosis in lung injury after transplantation of ischaemic renal allografts in rats.

BACKGROUND: Respiratory complications after surgery are associated with morbidity and mortality. Acute lung injury can result from the systemic inflammatory response after acute kidney injury. The mechanisms behind this remote injury are not fully understood. In this study, a renal transplantation model was used to investigate remote lung injury and the underlying molecular mechanisms, especially the role of osteopontin (OPN). METHODS: In vitro, human lung epithelial cell line (A549) and monocyte/macrophage cell line (U937) were challenged with tumour necrosis factor-alpha (TNF-α) in combination with OPN. In vivo, the Fischer rat renal grafts were extracted and stored in 4°C University of Wisconsin preserving solution for up to 16 h, and transplanted into Lewis rat recipients. Lungs were harvested on Day 1 after grafting for further analysis. RESULTS: Renal engraftment was associated with pathological changes and an increase in TNF-α and interleukin-1 beta in the lung of the recipient. OPN, endoplasmic reticulum (ER) stress, and necroptosis were increased in both the recipient lung and A549 cells challenged with TNF-α. Exogenous OPN exacerbated lung injury and necroptosis. Suppression of OPN through siRNA reduced remote lung injury by mitigation of ER stress, necroptosis, and the inflammatory response. CONCLUSIONS: Renal allograft transplant triggers recipient remote lung injury, which is, in part, mediated by OPN signalling. This study may provide a molecular basis for strategies to be developed to treat such perioperative complications.

An interaction-asymptotic region decomposition method for general state-to-state reactive scatterings.

A single set of coordinates, which is optimal for both asymptotic product and reactant, is difficult to find in a state-to-state reactive scattering calculation using the quantum wave packet method. An interaction-asymptotic region decomposition (IARD) method was proposed in this work to solve this "coordinate problem." In the method, the interaction region and asymptotic regions are applied with the local optimal coordinate system, i.e., hyperspherical and corresponding Jacobi coordinates. The IARD method is capable of efficiently and accurately accomplishing a calculation with a grid box for the Jacobi coordinate R extending several hundred bohrs for both reactant and product arrangements. We demonstrate the effectiveness of the IARD method with the reaction of H + HD, which is the simplest direct reaction, and F + HD, which is a typical reaction involving resonances with products of extremely slow translational energy and requires extremely long absorbing potential in all channels.