Betulin Accelerated the Functional Recovery of Injured Muscle in a Mouse Model of Muscle Contusion.

Muscle contusion is an injury to muscle fibers and connective tissues. It commonly happens in impact events, and could result in pain, swelling, and limited range of motion. Diclofenac is one of commonly used nonsteroidal anti-inflammatory drugs to alleviate pain and inflammation after injury. However, it can potentially cause some side effects including gastrointestinal complications and allergy. Betulin is a lupine-type pentacyclic triterpenoid. It is showed to have valuable pharmacological effects, but the physiological effect of betulin on muscle contusion has not been reported. This study aimed to explore the therapeutic effects of betulin on muscle contusion that produced by the drop-mass method in mice. C57BL/6 mice were randomly assigned to control (no injury), only drop-mass injury (Injury), diclofenac treatment (Injury+diclofenac), and betulin treatment (Injury+betulin) groups. Injury was executed on the gastrocnemius of the right hind limb, and then phosphate-buffered saline (PBS), diclofenac, or betulin were oral gavage administrated respectively for 7 days. Results revealed that betulin significantly restored motor functions based on locomotor activity assessments, rota-rod test, and footprints analysis. Betulin also attenuated serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels after muscle injury. Neutrophil infiltration was alleviated and desmin levels were increased after betulin treatment. Our data demonstrated that betulin attenuated muscle damage, alleviated inflammatory response, improved muscle regeneration, and restored motor functions after muscle contusion. Altogether, betulin may be a potential compound to accelerate the repair of injured muscle.

Acute generation of reactive oxygen species that induced by doxycycline pretreatment results in rapid cell death in polyphyllin G-treated osteosarcoma cell lines.

Polyphyllin G, a pennogenyl saponin extracted from Paris polyphylla, has been shown to possess antitumor effects. In this study, we demonstrated that doxycycline, an antibiotic medicine, could significantly enhance the sensitivities of osteosarcoma cell lines to polyphyllin G. As the cells were pretreated with doxycycline at non-toxic concentrations and then co-exposed to polyphyllin G, this combination could induce a rapid cell death distinct from apoptosis. The non-apoptotic cell death was characterized by a loss of integrity of plasma membrane without externalization of phosphatidyl serine. Furthermore, this combined treatment resulted in suppression of cell viability and colony-forming ability, and increased the level of γ-H2A.X, a critical marker for DNA damage, in osteosarcoma cell lines. When examining the underlying mechanism, it was revealed combination of polyphyllin G and doxycycline triggered an enhanced generation of reactive oxygen species (ROS), and up-regulated mitochondrial oxidative stress within 0.5 h. Co-administration of the ROS inhibitor NAC reversed the suppressed cell viability and colony-forming ability, and abolished the increased level of γ-H2A.X in the cells with the combined treatment, indicating that the enhanced ROS was involved in the anti-proliferative effect of the combined treatment. Overall, the results demonstrated that doxycycline may function as chemosensitizers by inducing an acute and lethal ROS production to enhance cytotoxic of polyphyllin G in osteosarcoma cell lines, and the combined use of drugs may provide an alternative thinking for the development of new therapeutic agents.

TNFα-mediated necroptosis in brain endothelial cells as a potential mechanism of increased seizure susceptibility in mice following systemic inflammation.

BACKGROUND: Systemic inflammation is a potent contributor to increased seizure susceptibility. However, information regarding the effects of systemic inflammation on cerebral vascular integrity that influence neuron excitability is scarce. Necroptosis is closely associated with inflammation in various neurological diseases. In this study, necroptosis was hypothesized to be involved in the mechanism underlying sepsis-associated neuronal excitability in the cerebrovascular components (e.g., endothelia cells). METHODS: Lipopolysaccharide (LPS) was used to induce systemic inflammation. Kainic acid intraperitoneal injection was used to measure the susceptibility of the mice to seizure. The pharmacological inhibitors C87 and GSK872 were used to block the signaling of TNFα receptors and necroptosis. In order to determine the features of the sepsis-associated response in the cerebral vasculature and CNS, brain tissues of mice were obtained for assays of the necroptosis-related protein expression, and for immunofluorescence staining to identify morphological changes in the endothelia and glia. In addition, microdialysis assay was used to assess the changes in extracellular potassium and glutamate levels in the brain. RESULTS: Some noteworthy findings, such as increased seizure susceptibility and brain endothelial necroptosis, Kir4.1 dysfunction, and microglia activation were observed in mice following LPS injection. C87 treatment, a TNFα receptor inhibitor, showed considerable attenuation of increased kainic acid-induced seizure susceptibility, endothelial cell necroptosis, microglia activation and restoration of Kir4.1 protein expression in LPS-treated mice. Treatment with GSK872, a RIP3 inhibitor, such as C87, showed similar effects on these changes following LPS injection. CONCLUSIONS: The findings of this study showed that TNFα-mediated necroptosis induced cerebrovascular endothelial damage, neuroinflammation and astrocyte Kir4.1 dysregulation, which may coalesce to contribute to the increased seizure susceptibility in LPS-treated mice. Pharmacologic inhibition targeting this necroptosis pathway may provide a promising therapeutic approach to the reduction of sepsis-associated brain endothelia cell injury, astrocyte ion channel dysfunction, and subsequent neuronal excitability.

Ring-Opening Polymerization of ε-Caprolactone by Using Aluminum Complexes Bearing Aryl Thioether Phenolates: Labile Thioether Chelation.

In this study, aluminum complexes bearing ferrocene-based and arylthiomethylphenolate ligands were synthesized, and their catalytic activity for ε-caprolactone (CL) polymerization was investigated. The catalytic activity of the reduced form of Al complexes was higher than that of the oxidized form. The CL polymerization rate of the reduced form fcO2AlMe (75 min, conversion = 100%) was higher than that of the oxidized form fcoxO2AlMe (4320 min, conversion = 45%), and the CL polymerization rate of fc(OAlMe2)2 (40 min, conversion = 100%) was higher than that of fcox(OAlMe2)2 (60 min, conversion = 97%). Electron deficiency substituents on phenolate decreased the catalytic activity of Al complexes bearing arylthiomethylphenolate ligands. Density functional theory calculations revealed that thioether coordination stabilized the transition state (TS1) and that the oxidized form fcox(OAlMe2)2 exhibited weaker thioether coordination and higher activation energy in TS1 compared with those of the reduced form fcO2AlMe. In addition, our study determined that the thioether group is a suitable chelating group for Al catalysts in CL polymerization due to its labile nature.

Treatment-associated survival outcomes in real-world patients with de novo metastatic triple-negative breast cancer: Age as a significant treatment effect-modifier.

PURPOSE: Evidence for optimizing the first-line chemotherapy for patients with metastatic triple-negative breast cancer (mTNBC) is lacking. This study assessed the utilization patterns of chemotherapy and associated survival outcomes in de novo mTNBC patients. METHODS: Taiwan's cancer registry was utilized to extract study patients with newly-diagnosed breast cancer during 2011-2015 and confirmed metastatic triple-negative status. The patients' medical records (e.g., diseases, treatments) and death status were obtained from the National Health Insurance Research Database. Utilization of first-line chemotherapy regimens was analyzed and associated survival outcomes were assessed using Cox models. RESULTS: 93.60% of the mTNBC patients (n = 297) received chemotherapy, where combination regimens (75.54%) were more common than single-agent regimens (24.46%) in the first-line setting. A non-statistically lower all-cause death associated with combination versus single-agent chemotherapy (hazard ratio: 0.830 [0.589, 1.168]) was observed. Age was identified as a significant effect-modifier in treatment-associated survival outcomes (p = 0.008); younger patients (aged < 40 and 40-59 years) versus older patients (aged ≥ 60 years) had a lower all-cause mortality when receiving combination versus single-agent chemotherapy. A lower all-cause mortality associated with taxane- versus non-taxane-based therapy was revealed among those on single-agent chemotherapy (hazard ratio: 0.557 [0.311, 0.999]). CONCLUSION: Generally, single-agent and combination chemotherapies yielded comparable survival outcomes as the first-line treatment for de novo mTNBC. Younger patients may benefit more from combination regimens, in terms of better survival outcomes. Single-agent chemotherapy may be preferable as the first-line choice for elderly patients who are vulnerable to the toxicity of multiple chemotherapy agents.

Compression for Bayer CFA Images: Review and Performance Comparison.

Bayer color filter array (CFA) images are captured by a single-chip image sensor covered with a Bayer CFA pattern which has been widely used in modern digital cameras. In the past two decades, many compression methods have been proposed to compress Bayer CFA images. These compression methods can be roughly divided into the compression-first-based (CF-based) scheme and the demosaicing-first-based (DF-based) scheme. However, in the literature, no review article for the two compression schemes and their compression performance is reported. In this article, the related CF-based and DF-based compression works are reviewed first. Then, the testing Bayer CFA images created from the Kodak, IMAX, screen content images, videos, and classical image datasets are compressed on the Joint Photographic Experts Group-2000 (JPEG-2000) and the newly released Versatile Video Coding (VVC) platform VTM-16.2. In terms of the commonly used objective quality, perceptual quality metrics, the perceptual effect, and the quality-bitrate tradeoff metric, the compression performance comparison of the CF-based compression methods, in particular the reversible color transform-based compression methods and the DF-based compression methods, is reported and discussed.

Different Cell Responses to Hinokitiol Treatment Result in Senescence or Apoptosis in Human Osteosarcoma Cell Lines.

Hinokitiol is a tropolone-related compound isolated from the heartwood of cupressaceous plants. It is known to exhibit various biological functions including antibacterial, antifungal, and antioxidant activities. In the study, we investigated the antitumor activities of hinokitiol against human osteosarcoma cells. The results revealed that hinokitiol treatment inhibited cell viability of human osteosarcoma U-2 OS and MG-63 cells in the MTT assay. Further study revealed that hinokitiol exposure caused cell cycle arrest at the S phase and a DNA damage response with the induction of γ-H2AX foci in both osteosarcoma cell lines. In U-2 OS cells with wild-type tumor suppressor p53, we found that hinokitiol exposure induced p53 expression and cellular senescence, and knockdown of p53 suppressed the senescence. However, in MG-63 cells with mutated p53, a high percentage of cells underwent apoptosis with cleaved-PARP expression and Annexin V staining after hinokitiol treatment. In addition, up-regulated autophagy was observed both in hinokitiol-exposed U-2 OS and MG-63 cells. As the autophagy was suppressed through the autophagy inhibitor chloroquine, hinokitiol-induced senescence in U-2 OS cells was significantly enhanced accompanying more abundant p53 expression. In MG-63 cells, co-treatment of chloroquine increased hinokitiol-induced apoptosis and decreased cell viability of the treated cells. Our data revealed that hinokitiol treatment could result in different cell responses, senescence or apoptosis in osteosarcoma cell lines, and suppression of autophagy could promote these effects. We hypothesize that the analysis of p53 status and co-administration of autophagy inhibitors might provide more precise and efficacious therapies in hinokitiol-related trials for treating osteosarcoma.

Collaboration between Trinuclear Aluminum Complexes Bearing Bipyrazoles in the Ring-Opening Polymerization of ε-Caprolactone.

Trinuclear aluminum complexes bearing bipyrazoles were synthesized, and their catalytic activity for ε-caprolactone (CL) polymerization was investigated. DBu2Al3Me5 exhibited higher catalytic activity than did the dinuclear aluminum complex LBu2Al2Me4 (16 times as high for CL polymerization; [CL]:[DBu2Al3Me5]:[BnOH] = 100:0.5:5, [DBu2Al3Me5] = 10 mM, conversion 93% after 18 min at room temperature). Density functional theory calculations revealed a polymerization mechanism in which CL first approached the central Al atom and then moved to an external Al. The coordinated CL ring was opened because the repulsion of two tert-butyl groups on the ligands pushed an alkoxide initiator on an external Al to initiate CL. In these trinuclear Al catalysts, the central Al plays a role in monomer capture and then collaborates with the external Al to activate CL, accelerating polymerization.

A broad-range variable-temperature solid state NMR spectral and relaxation investigation of the water state in Nafion 117.

Understanding the water state in Nafion is not only crucial for operating a proton-exchange membrane (PEM)-based fuel cell, but also intimately related to the elucidation of the proton transport mechanism in a PEM. Although many studies have been published on this subject, some controversies and ambiguities remain unresolved. In this work, we design three different types of Nafion samples by substituting protons with lithium or sodium cations. We also pay special attention to the preparation of samples for carrying out broad-range variable temperature solid state NMR experiments so that no membrane dehydration occurs during the long experimental time at low temperatures. With these precautions and improvements, clear and largely straightforward information could be obtained to ensure minimal ambiguity and complexity in the interpretation of the experimental data. Our results show that about 40-60% of water remains unfrozen at -70 °C, depending on the type of the substituting cation. Both the 1H and 2H spectral and relaxation results indicate that water freezing starts from the center of the nanopores inside Nafion and increases gradually as the temperature decreases. The protons remain dissociated with sulfonate groups even at the lowest temperature we reached (-70 °C), whereas both lithium and sodium are associated with sulfonate groups at most temperatures below 0 °C. The experimental data also suggest that besides frozen and unfrozen water, there is broad distribution of water state and dynamics in Nafion as the temperature is lowered from above zero down to -70 °C. The effect of the size of the substituting cation significantly affects the properties of supercooled water by modifying the cation-water interaction and impeding the rotation of sulfonate groups. These novel results not only help us in establishing a better understanding of the water state in Nafion and its performance as a proton exchange mebrane, but also provide insights into water freezing, antifreeze and supercooling in other nanoscopic environments.

Multilevel calcium pyrophosphate dihydrate deposition in cervical ligamentum flavum: clinical characteristics and imaging features.

BACKGROUND: Involvement in cervical ligamentum flavum is a rare manifestation of the calcium pyrophosphate dihydrate deposition disease. Only few cases of this condition have been reported. We revealed eighteen cases of CPPD in cervical ligamentum flavum that diagnosed at a single medical center. In our case series, clinical characteristics and magnetic resonance imaging findings of patients are described. METHODS: We retrospectively reviewed the medical charts and imaging studies of the eighteen patients with pseudogout attack of the cervical ligamentum flavum. In addition, we discussed the differences between this disease and ossification of ligamentum flavum in image manifestations. RESULTS: There were fourteen men and four women aged between 59 and 87 years. Diabetes mellitus and hypertension were the most common comorbidities. Myelopathy and neck pain were presented in most patients. C4-5 and C5-6 were attacked most frequently, and multiple- rather than single-level involvement could be observed in our series. "Acute on chronic phenomenon" was a specific magnetic resonance image finding in patients whose symptom durations were between 2 to 5 months. Compared to ossification of ligamentum flavum, calcium pyrophosphate dihydrate crystal deposition had different image signs, including morphology, side of the involved ligament, no continuity with the lamina, acute on chronic phenomenon, and presence of retro-odontoid mass. CONCLUSIONS: Nodular calcifications in cervical ligamentum flavum raise highly suspicion for calcium pyrophosphate dihydrate deposition and must be diagnosed by histological examination and polarized light microscopy. This disease is different from ossification of ligamentum flavum, and it could be recognized by specific image features.

Butein induces cellular senescence through reactive oxygen species-mediated p53 activation in osteosarcoma U-2 OS cells.

Butein is a flavonoid isolated from various medicinal plants. It is known to have different biological activities including anti-inflammation, anti-adipogenesis, and anti-angiogenesis. In the study, we demonstrated the anti-proliferative effect of butein in human osteosarcoma U-2 OS cells. Our data showed that butein significantly suppressed the viability and colony formation ability of U-2 OS cells. Further experiments revealed butein exposure resulted in a cell cycle arrest at S and G2/M phase in U-2 OS cells. Importantly, we found that butein activated the tumor suppressor p53, and trigged a p53-dependent senescence in U-2 OS cells. Knockdown of p53 suppressed the senescence and rescued the viability in butein-treated U-2 OS cells. Furthermore, we observed that butein exposure significantly enhanced reactive oxygen species (ROS) levels in U-2 OS cells. Co-administration of the ROS inhibitor NAC largely abolished the up-regulated p53 protein level, and rescued the suppressed viability and colony formation ability in butein-exposed U-2 OS cells. Taken together, our data proposed the increased ROS by butein exposure activated p53, and the activated p53 was involved in the anti-proliferative effect of butein via inducing senescence in U-2 OS cells. This report suggests that butein is a promising candidate for cancer therapy against osteosarcoma.

Synergistic Catalysis by Brønsted Acid/Carbodicarbene Mimicking Frustrated Lewis Pair-Like Reactivity.

Carbodicarbene (CDC), unique carbenic entities bearing two lone pairs of electrons are well-known for their strong Lewis basicity. We demonstrate herein, upon introducing a weak Brønsted acid benzyl alcohol (BnOH) as a co-modulator, CDC is remolded into a Frustrated Lewis Pair (FLP)-like reactivity. DFT calculation and experimental evidence show BnOH loosely interacting with the binding pocket of CDC via H-bonding and π-π stacking. Four distinct reactions in nature were deployed to demonstrate the viability of proof-of-concept as synergistic FLP/Modulator (CDC/BnOH), demonstrating enhanced catalytic reactivity in cyclotrimerization of isocyanate, polymerization process for L-lactide (LA), methyl methacrylate (MMA) and dehydrosilylation of alcohols. Importantly, the catalytic reactivity of carbodicarbene is uniquely distinct from conventional NHC which relies on only single chemical feature of nucleophilicity. This finding also provides a new spin in diversifying FLP reactivity with co-modulator or co-catalyst.

NADPH oxidase 2 as a potential therapeutic target for protection against cognitive deficits following systemic inflammation in mice.

BACKGROUND: Research indicates that sepsis increases the risk of developing cognitive impairment. After systemic inflammation, a corresponding activation of microglia is rapidly induced in the brain, and multiple neurotoxic factors, including inflammatory mediators (e.g., cytokines) and reactive oxygen species (e.g., superoxide), are also released that contribute to neuronal injury. NADPH oxidase (NOX) enzymes play a vital role in microglial activation through the generation of superoxide anions. We hypothesized that NOX isoforms, particularly NOX2, could exhibit remarkable abilities in developing cognitive deficits induced by systemic inflammation. METHODS: Mice with deficits of NOX2 organizer p47phox (p47phox-/-) and wild-type (WT) mice treated with the NOX inhibitor diphenyleneiodonium (DPI) were used in this study. Intraperitoneal lipopolysaccharide (LPS) injection was used to induce systemic inflammation. Spatial learning and memory were compared among treatment groups using the radial arm maze task. Brain tissues were collected for evaluating the transcript levels of proinflammatory cytokines, whereas immunofluorescence staining and immunoblotting were conducted to determine the percentage of activated glia (microglia and astroglia) and damaged neurons and the expression of synaptic proteins and BDNF. RESULTS: Cognitive impairment induced by systemic inflammation was significantly attenuated in the p47phox-/- mice compared to that in the WT mice. The p47phox-/- mice exhibited reduced microglial and astroglial activation and neuronal damage and attenuated the induction of multiple proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and CCL2. Similar to that observed in the p47phox-/- mice, the administration of DPI significantly attenuated the cognitive impairment, reduced the glial activation and brain cytokine concentrations, and restored the expression of postsynaptic proteins (PSD-95) and BDNF in neurons and astrocytes, compared to those in the vehicle-treated controls within 10 days after LPS injection. CONCLUSIONS: This study clearly demonstrates that NOX2 contributes to glial activation with subsequent reduction in the expression of BDNF, synaptic dysfunction, and cognitive deficits after systemic inflammation in an LPS-injected mouse model. Our results provide evidence that NOX2 might be a promising pharmacological target that could be used to protect against synaptic dysregulation and cognitive impairment following systemic inflammation.

Betulin inhibits mTOR and induces autophagy to promote apoptosis in human osteosarcoma cell lines.

Betulin is a lupane type pentacyclic triterpenoid, and commonly found in the bark of birch trees. It displays various pharmacological properties, such as antibacterial, anti-inflammation, antitumor, and antiviral. In this report, we attempted to investigate the anti-proliferative and pro-apoptotic effects of betulin on osteosarcoma cell lines. Our results revealed that betulin significantly decreased cell viability and colony formation in osteosarcoma cell lines. Dose-dependent induction of Annexin V positive cells, activated caspase 8, activated caspase 9, activated caspase 3, and the cleavage of poly (ADP-ribose) polymerase were observed after the treatment with betulin, indicating betulin induces apoptosis in osteosarcoma cell lines. mTOR has been identified as a key modulator of autophagy in response to different stresses. In this study, we found that the treatment with betulin suppressed the activation of mTOR, and increased the level of LC 3-II, the autophagy marker, in osteosarcoma cell lines. Co-administration of the autophagy inhibitor chloroquine significantly rescued the cell viability and the clonogenic activity in betulin-treated osteosarcoma cell lines. Our data showed that betulin induced autophagy, and the up-regulated autophagy positively contributed to the apoptosis. Taken together, our findings suggested that betulin may serve as a promising anti-proliferative agent for treating osteosarcoma.

Licochalcone A Suppresses the Proliferation of Osteosarcoma Cells through Autophagy and ATM-Chk2 Activation.

Licochalcone A, a flavonoid extracted from licorice root, has been shown to exhibit broad anti-inflammatory, anti-bacterial, anticancer, and antioxidative bioactivity. In this study, we investigated the antitumor activity of Licochalcone A against human osteosarcoma cell lines. The data showed that Licochalcone A significantly suppressed cell viability in MTT assay and colony formation assay in osteosarcoma cell lines. Exposure to Licochalcone A blocked cell cycle progression at the G2/M transition and induced extrinsic apoptotic pathway in osteosarcoma cell lines. Furthermore, we found the Licochalcone A exposure resulted in rapid ATM and Chk2 activation, and high levels of nuclear foci of phosphorylated Chk2 at Thr 68 site in osteosarcoma cell lines. In addition, Licochalcone A exposure significantly induced autophagy in osteosarcoma cell lines. When Licochalcone A-induced autophagy was blocked by the autophagy inhibitor chloroquine, the expression of activated caspase-3 and Annexin V positive cells were reduced, and cell viability was rescued in Licochalcone A-treated osteosarcoma cell lines. These data indicate that the activation of ATM-Chk2 checkpoint pathway and autophagy may contribute to Licochalcone A-induced anti-proliferating effect in osteosarcoma cell lines. Our findings display the possibility that Licochalcone A may serve as a potential therapeutic agent against osteosarcoma.

Gender differences in inappropriate use of urinary catheters among hospitalized older patients.

This study investigated the incidence, rationales, and associated factors of inappropriate urinary catheter use among hospitalized older patients by gender. A longitudinal study of 321 patients with urinary catheter was conducted. Demographic factors, present health factors, urinary catheter factors, and indications of catheter use were collected. A total of 53.7% of urinary catheter-days were inappropriate. For both men and women, there was no significant difference in the incidence and common rationales of inappropriate use. Women, however, have another associated factor with inappropriate use. More tailored alternatives are needed for women to increase comfort to avoid inappropriate catheter use.

NADPH oxidases as potential pharmacological targets against increased seizure susceptibility after systemic inflammation.

BACKGROUND: Systemic inflammation associated with sepsis can induce neuronal hyperexcitability, leading to enhanced seizure predisposition and occurrence. Brain microglia are rapidly activated in response to systemic inflammation and, in this activated state, release multiple cytokines and signaling factors that amplify the inflammatory response and increase neuronal excitability. NADPH oxidase (NOX) enzymes promote microglial activation through the generation of reactive oxygen species (ROS), such as superoxide anion. We hypothesized that NOX isoforms, particularly NOX2, are potential targets for prevention of sepsis-associated seizures. METHODS: To reduce NADPH oxidase 2-derived ROS production, mice with deficits of NOX regulatory subunit/NOX2 organizer p47phox (p47phox-/-) or NOX2 major subunit gp91phox (gp91phox-/-) were used or the NOX2-selective inhibitor diphenyleneiodonium (DPI) was used to treat wild-type (WT) mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS). Seizure susceptibility was compared among mouse groups in response to intraperitoneal injection of pentylenetetrazole (PTZ). Brain tissues were assayed for proinflammatory gene and protein expression, and immunofluorescence staining was used to estimate the proportion of activated microglia. RESULTS: Increased susceptibility to PTZ-induced seizures following sepsis was significantly attenuated in gp91phox-/- and p47phox-/- mice compared with WT mice. Both gp91phox-/- and p47phox-/- mice exhibited reduced microglia activation and lower brain induction of multiple proconvulsive cytokines, including TNFα, IL-1ß, IL-6, and CCL2, compared with WT mice. Administration of DPI following LPS injection significantly attenuated the increased susceptibility to PTZ-induced seizures and reduced both microglia activation and brain proconvulsive cytokine concentrations compared with vehicle-treated controls. DPI also inhibited the upregulation of gp91phox transcripts following LPS injection. CONCLUSIONS: Our results indicate that NADPH oxidases contribute to the development of increased seizure susceptibility in mice after sepsis. Pharmacologic inhibition of NOX may be a promising therapeutic approach to reducing sepsis-associated neuroinflammation, neuronal hyperexcitability, and seizures.

Enhanced Catalytic Activity of Aluminum Complexes for the Ring-Opening Polymerization of ε-Caprolactone.

A series of dinuclear aluminum (Al2Pyr2) complexes bridged by two pyrazole ligands were synthesized, and their catalytic activity toward ring-opening polymerization of ε-caprolactone (CL) was investigated. Different types of the Al-N-N-Al-N-N skeletal ring were found among these Al2Pyr2 complexes. The butterfly form, LThio2Al2Me4, exerted the highest catalytic activity for CL polymerization. κ2-CL coordination with both Al centers within the butterfly form LThio2Al2Me4 facilitates the initiation process. Generally speaking, the Al2Pyr2 complexes exhibited substantially higher catalytic activity for CL polymerization than literature examples such as ß-diketiminate- or traiaza-bearing aluminum complexes. In fact, the Al2Pyr2 complexes can even carry out CL polymerization at room temperature.

Reactivity Study of Unsymmetrical ß-Diketiminato Copper(I) Complexes: Effect of the Chelating Ring.

ß-Diketiminato copper(I) complexes play important roles in bioinspired catalytic chemistry and in applications to the materials industry. However, it has been observed that these complexes are very susceptible to disproportionation. Coordinating solvents or Lewis bases are typically used to prevent disproportionation and to block the coordination sites of the copper(I) center from further decomposition. Here, we incorporate this coordination protection directly into the molecule in order to increase the stability and reactivity of these complexes and to discover new copper(I) binding motifs. Here we describe the synthesis, structural characterization, and reactivity of a series of unsymmetrical N-aryl-N'-alkylpyridyl ß-diketiminato copper(I) complexes and discuss the structures and reactivity of these complexes with respect to the length of the pyridyl arm. All of the aforementioned unsymmetrical ß-diketiminato copper(I) complexes bind CO reversibly and are stable to disproportionation. The binding ability of CO and the rate of pyridyl ligand decoordination of these copper(I) complexes are directly related to the competition between the degree of puckering of the chelate system and the steric demands of the N-aryl substituent.

Synthesis of Sodium Complexes Supported with NNO-Tridentate Schiff Base Ligands and Their Applications in the Ring-Opening Polymerization of L-Lactide.

A series of sodium complexes bearing NNO-tridentate Schiff base ligands with an N-pendant arm were synthesized and used as catalysts for the ring-opening polymerization of L-lactide (L-LA). Electronic effects of ancillary ligands coordinated by sodium complexes substantially influence the catalysis, and ligands with electron-donating groups increase the catalytic activity of the sodium complexes for catalyzing L-LA polymerization. In particular, a sodium complex bearing a 4-methoxy group has the highest activity with conversion up to 95% within 30 s at 0 °C and a low polydispersity index of 1.13, whereas the 4-bromo group showed the poorest performance with regard to the catalytic rate of L-LA polymerization in the presence of benzyl alcohol (BnOH). (1)H NMR pulsed-gradient spin-echo diffusion experiments and single-crystal X-ray analyses showed that sodium complexes [L(H)Na(THF)]2 and [L(4-Cl)Na(THF)]2 were dinuclear species in both solution and the solid state. The kinetic results indicated a first-order dependence on each of [[L(4-Cl)Na]2], [l-LA], and [BnOH].