Framework confinement of multi-metals within silica hollow spheres by one-pot synthesis process.

The control incorporation of metals in silica hollow spheres (SHSs) may bring new functions to silica mesoporous structures for applications including catalysis, sensing, molecular delivery, adsorption filtration, and storage. However, the strategies for incorporating metals, whether through pre-loading in the hollow interior or post-encapsulation in the mesoporous shell, still face challenges in achieving quantitative doping of various metals and preventing metal aggregation or channel blockage during usage. In this study, we explored the doping of different metals into silica hollow spheres based on the dissolution-regrowth process of silica. The process may promote the formation of more structural defects and functional silanol groups, which could facilitate the fixation of metals in the silica networks. With this simple and efficient approach, we successfully achieved the integration of ten diverse metal species into silica hollow sphere (SHS). Various single-metal, dual-metal, triple-metal, and quadruple-metal doped SHSs have been prepared, with the doped metals being stable and homogeneously dispersed in the structure. Based on the structural characterizations, we analyzed the influence of metal types on the morphology features of SHSs. The synergistic effects of multi-metals on the catalysis applications were also studied and compared.

Significance of this work: The control incorporation of metals in silica hollow spheres (SHSs) may bring new functions to silica mesoporous structures for applications including catalysis, sensing, molecular delivery, adsorption filtration, and storage. The incorporation of metals within SHSs is always either at the interior core or in the porous shells. The former method mainly utilizes metal nanoparticles as the core and regulates the synthesis of outer porous silica shells. The latter is primarily driven by the capillary force or intermolecular interactions with surface ligands to facilitate the post-loading of metal species in porous silica structures. The main problems associated with metal-doped SHSs include 1) controlled loading of different metals with a homogeneous distribution; 2) fixation of metal species in the structures to prevent aggregation during usage, particularly at high temperatures; 3) pore channel blockage after metal loading, which may hinder the loading of other external molecules. In this work, we developed the dissolution-regrowth of silica strategy for integrating various metals in porous SHSs (M@SHSs) by a one-pot hydrothermal process without using any anchoring molecules. Unlike other sol-gel formations, the growth rate of silica in this process is greatly reduced. It thus may bring more possibilities to introduce external metals within the silica frameworks instead of in the porous channels. By regulating the addition of metal salts in the silica nanoparticles dispersions, we have successfully synthesized stable and highly homogeneous single-metal, dual-metal, triple-metal, and quadruplemetal doped SHSs. Based on the structural characterizations, we analyzed the influence of metal types on the morphology features of SHSs. The synergistic effects of multi-metals on the catalysis applications were also studied and compared. Our results offer a facile and effective strategy for preparing multi-metals as nano-catalysts. Through proper design of the doped metals in SHSs, the structures should find more applications in catalysis, drug delivery, and adsorption with unique and enhanced properties.

EEG complexity correlates with residual consciousness level of disorders of consciousness.

BACKGROUND AND OBJECTIVE: Electroencephalography (EEG) and neuroimaging measurements have been highly encouraged to be applied in clinics of disorders of consciousness (DOC) to improve consciousness detection. We tested the relationships between neural complexity measured on EEG and residual consciousness levels in DOC patients. METHODS: Resting-state EEG was recorded from twenty-five patients with DOC. Lempel-Ziv complexity (LZC) and permutation Lempel-Ziv complexity (PLZC) were measured on the EEG, and their relationships were analyzed with the consciousness levels of the patients. RESULTS: PLZC and LZC values significantly distinguished patients with a minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/UWS), and healthy controls. PLZC was significantly correlated with the Coma Recovery Scale-Revised (CRS-R) scores of DOC patients in the global brain, particularly in electrodes locating in the anterior and posterior brain regions. Patients with higher CRS-R scores showed higher PLZC values. The significant difference in PLZC values between MCS and VS/UWS was mainly located in the bilateral frontal and right hemisphere regions. CONCLUSION: Neural complexity measured on EEG correlates with residual consciousness levels of DOC patients. PLZC showed higher sensitivity than LZC in the classification of consciousness levels.

Halomonas litopenaei sp. nov., a moderately halophilic, exopolysaccharide-producing bacterium isolated from a shrimp hatchery.

Two Gram-stain negative, moderately halophilic, exopolysaccharide-producing bacteria, designated strains SYSU ZJ2214T and SYSU XM8, were isolated from rearing water and larvae from shrimp hatcheries, respectively. Cells of the strains were aerobic, motile and short-rod-shaped. They grew at NaCl concentrations of 0.5-22 % (w/v), at 4-45 °C and at pH 6-9. Pairwise comparison of 16S rRNA gene sequences revealed that strains SYSU ZJ2214T and SYSU XM8 were most closely related to Halomonas denitrificans M29T (98.3 and 98.2 % similarity, respectively). Strains SYSU ZJ2214T and SYSU XM8 shared an average nucleotide identity of 99.9 % between them. The DNA G+C contents were calculated at 64.1 % for both strains from the draft genome information. The major cellular fatty acids (>5 %) were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and C12 : 0 3-OH, and the predominant respiratory quinone was ubiquinone Q-9. Their main polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, four unidentified phospholipids and three unidentified lipids. On the basis of phenotypic, genotypic and phylogenetic data, strains SYSU ZJ2214T and SYSU XM8 merit recognition as representatives of a novel species of the genus Halomonas, for which the name Halomonas litopenaei sp. nov. is proposed. The type strain is SYSU ZJ2214T (=NBRC 111829T=KCTC 42974T).

Synthesis, crystal structure, and biological evaluation of a series of phloretin derivatives.

A one-step synthesis of phloretin derivatives 2-11 from phloretin in good to excellent yields is reported. Their structures were characterized by 1H-NMR, 13C-NMR and MS, and the structures of 8 and 11 were determined by X-ray diffraction analysis. A mechanism for the formation of 9-11 is proposed. Compared with the anticancer drug docetaxel, phloretin, phloretin derivatives and phlorizin exhibited moderate cytotoxicity toward the MDA-MB-231, SPC-A1, A549, MCF-7 and EC109 cell lines. Among all of the tested compounds, 7 exhibited the strongest cytotoxicity toward the five cell lines and was more active than docetaxel in MDA-MB-231 cells. Our findings suggest that these derivatives hold great promise for further development as anticancer agents.

A case of treatment of multidrug-resistant intracranial Klebsiella pneumoniae infection by multichannel colistin sulfate.

The management of severe neurologic infections due to multidrug-resistant (MDR) Klebsiella pneumoniae infection remains a challenge. Limited antibiotic treatment regimens make treatment of severe MDR K. pneumoniae infection more difficult. We describe a patient who developed severe meningitis and ventriculitis after craniotomy caused by MDR K. pneumoniae and was effectively treated with the administration of multichannel applications (intravenous, intrathecal and aerosol inhalation) of colistin sulfate. This case provides clinical evidence that the intrathecal, intravenous and aerosol inhalation of colistin sulfate by multichannel application can be a last resort in refractory intracranial infection by MDR K. pneumoniae.

The anticonvulsant and neuroprotective effects of baicalin on pilocarpine-induced epileptic model in rats.

Baicalin, a flavonoid compound purified from plant Scutellaria baicalensis Georgi, has been reported to possess a wide variety of pharmacological properties including anti-oxidative, anti-apoptotic and neuroprotective properties. Oxidative stress can dramatically alter neuronal function and has been linked to status epilepticus (SE). However, the neuroprotective effect of baicalin on epilepsy is unclear. In this study we investigated whether Baicalin could exert anticonvulsant and neuroprotective effects in the pilocarpine-induced epileptic model in rats. To this end, we recorded the latency to first limbic seizure and SE and observed the incidence of SE and mortality. The changes of oxidative stress were measured 24 h after pilocarpine-induced SE. Nissl staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Fluoro-Jade B staining were performed to detect the neuronal loss, apoptosis and degeneration in hippocampus 72 h after pilocarpine-induced seizure. Pretreatment with baicalin significantly delayed the onset of the first limbic seizures and SE, reduced the mortality rate, and attenuated the changes in the levels of lipid peroxidation, nitrite content and reduced glutathione in the hippocampus of pilocarpine-treated rats. Furthermore, we also found that baicalin attenuated the neuronal cell loss, apoptosis, and degeneration caused by pilocarpine-induced seizures in rat hippocampus. Collectively, these results indicated remarkable anticonvulsant and neuroprotective effects of baicalin and should encourage further studies to investigate baicalin as an adjuvant in epilepsy both to prevent seizures and to protect against seizure induced brain injury.

Spinal cord stimulation modulates frontal delta and gamma in patients of minimally consciousness state.

Spinal cord stimulation (SCS) has been suggested as a therapeutic technique for treating patients with disorder of consciousness (DOC). Although studies have reported its benefits for patients, the underlying pathophysiological mechanisms remain unclear. The aim of this study was to measure the effects of SCS on the EEG of patients in a minimally conscious state (MCS), which would allow us to explore the possible workings underpinning of the approach. Resting state EEG was recorded before and immediately after SCS, using various frequencies (5Hz, 20Hz, 50Hz, 70Hz and 100Hz), for 11 patients in MCS. Relative power, coherence, S-estimator and bicoherence were calculated to assess the EEG changes. Five frequency bands (delta, theta, alpha, beta and gamma) and three regions (frontal, central and posterior) were divided in the calculation. The main findings of this study were that: (1) significantly altered relative power and synchronisation was found in delta and gamma bands after one SCS stimulation using 5Hz, 70Hz or 100Hz; (2) bicoherence showed that coupling within delta was significantly decreased after stimulation using 70Hz, while reduction of coupling between delta and gamma was found when using 5Hz and 100Hz. However, SCS of 20Hz, 50Hz and sham stimulation did not induce changes in any frequency band at any region. This study showed EEG evidence that SCS can modulate the brain function of MCS patients, speculatively by activating the formation-thalamus-cortex network.

Integrin αvß6 sustains and promotes tumor invasive growth in colon cancer progression.

AIM: To detect the mechanism by which colon tumor escapes the growth constraints imposed on normal cells by cell crowding and dense pericellular matrices. METHODS: An immunohistochemical study of integrin αvß6 and matrix metalloproteinase-9 (MMP-9) was performed on tissue microarrays of 200 spots, including 100 cases of colon tumors. RESULTS: High immunoreactivity for αvß6 (73.7%; 28/38) and MMP-9 (76.5%; 52/68) was observed in invasive tumor portions. Furthermore, the effects of integrin αvß6 on tumor invasive growth in nude mice were detected. Tumor invasive growth and high expression of both αvß6 and MMP-9 were only seen in tumors resulting from WiDr cells expressing αvß6 in the tumorigenicity assay. Flow cytometry was applied to analyze αvß6 expression in colon cancer WiDr and SW480 cells. The effects of cell density on αvß6 expression and MMP-9 secretion were also detected by Biotrak MMP-9 activity assay and gelatin zymography assay. High cell density evidently enhanced αvß6 expression and promoted MMP-9 secretion compared with low density. CONCLUSION: Integrin αvß6 sustains and promotes tumor invasive growth in tumor progression via a self-perpetuating mechanism. Integrin ανß6-mediated MMP-9 secretion facilitates pericellular matrix degradation at high cell density, which provides the basis of invasive growth.

Berberine exerts an anticonvulsant effect and ameliorates memory impairment and oxidative stress in a pilocarpine-induced epilepsy model in the rat.

Though new antiepileptic drugs are emerging, approximately a third of epileptic patients still suffer from recurrent convulsions and cognitive dysfunction. Therefore, we tested whether berberine (Ber), a vegetable drug, has an anticonvulsant property and attenuates memory impairment in a pilocarpine (Pilo)-induced epilepsy model in rats. The rats were injected with 400 mg/kg Pilo to induce convulsions, and Ber 25, 50, and 100 mg/kg were administrated by the intragastric route once daily 7 days before Pilo injection until the experiment was over. Convulsions were observed after Pilo injection. For the rats that developed status epilepticus (SE), malondialdehyde, glutathione levels, superoxide dismutase, and catalase activity in the hippocampus were measured 24 hours after SE. The rats received the Morris water-maze test 2 weeks after SE, and then were killed for fluoro-jade B staining to detect the degenerating neurons. We found Ber delayed latency to the first seizure and the time to develop SE in a dose-dependent manner. Malondialdehyde levels were decreased, while glutathione and catalase activity were strengthened in Ber-injected SE rats. In the Morris water-maze test, Ber decreased escape latency compared to saline-treated SE rats. Additionally, Ber reduced the number of fluoro-jade B-positive cells in the hippocampal CA1 region. Our data suggest that Ber exerts anticonvulsant and neuroprotective effects on Pilo-induced epilepsy in rats. Simultaneously, Ber attenuates memory impairment. The beneficial effect may be partly due to mitigation of the oxidative stress burden.

[Effect of realgar on induction of apoptosis in DLBCL cell line SU-DHL-4 and its possible mechanisms].

This study was aimed to explore the effect of realgar (As4S4) on growth inhibition and apoptosis induction of DLBCL cell line SU-DHL-4 and its mechanisms. The inhibitory effect of realgar on the cell growth were detected by MTT method. The morphological changes of SU-DHL-4 were observed by transmission electron microscopy (TEM). The apoptosis of SU-DHL-4 cells treated with realgar were detected by flow cytometry with Annexin V-FITC/PI double staining and DNA agarose gel electrophoresis. The cell cycle was examined by flow cytometry with PI staining. The expressions of apoptosis-related proteins (BCL-2 , Caspase-3,BAX) were detected by Western blot. The results showed that the realgar at the concentration of 20, 40, 80 µmol/L all could inhibit the proliferation of SU-DHL-4 (P < 0.05), and in a certain time and concentration range, the inhibition rate was enhanced in a time and dose dependent manner(r = 0.982). Flow cytometric test results showed that realgar could induce SU-DHL-4 cell apoptosis after treating for 48 hours, and the apoptosis rate increased with the increasing of drug concentration (P < 0.05). After treating SU-DHL-4 cells with Realgar for 48 h, the cell cycle was blocked in the S phase (P < 0.05). TEM results revealed that when treated with realgar for 48 h, the typically apoptosis morphology-apoptotic bodies were observed in all drug-treated group, furthermore, some necrotic cells in the 80 µmol/L group were observed. After intervened by realgar for 48 h, the DNA Ladder pattern was seen according to agarose gel electrophoresis. Western blot showed that the expression of Bcl-2 protein was down-regulated while the expressions of BAX and Caspase-3 protein were up-regulated when treating SU-DHL-4 cells with realgar for 48 h. It is concluded that realgar can inhibit cell growth and induce cell apoptosis, which may be related with up-regulation of Caspase-3 and BAX expression and down-regulation the of BCL-2 expression.

Fingolimod (FTY720) inhibits neuroinflammation and attenuates spontaneous convulsions in lithium-pilocarpine induced status epilepticus in rat model.

Accumulating evidence has shown that neuroinflammation plays a key role in epileptogenesis. However, the efficacy of anti-inflammatory agents for preventing epilepsy remains controversial. Fingolimod (FTY720), a sphingosine-1-phosphate (S1P) analog, has potent anti-inflammatory effects in multiple sclerosis (MS) patients and animal models. Here, we tested whether FTY720 could exert antiepileptogenic effects in an adult rat model of lithium-pilocarpine induced epilepsy. 24h after onset of status epilepticus (SE), the epileptic rats received saline or 1mg/kg FTY720 i.p. once daily for 14 consecutive days. Thereafter, spontaneous convulsions (SCs), mossy fiber sprouting (MFS), neuronal loss, activation of microglia and astrocytes, expressions of interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNFα) were evaluated in the SE rats. We found that FTY720 treatment reduced neuronal loss and decreased activation of microglia and astrocytes in hippocampus at four days post-SE. Simultaneously, abnormal expressions of IL-1ß and TNFα in hippocampus were restrained by FTY720 treatment. In addition, neuroprotective effects of FTY720 were demonstrated by increasing neuronal nuclei (NeuN)-positive cells and decreasing Fluoro-Jade B (FJB)-positive cells in the hippocampus. During 21-34days post-SE, the incidence, duration, frequency and severity of SCs significantly decreased in FTY720 treated rats compared with saline treated rats. Aberrant MFS was also attenuated by FTY720 administration. These results suggest that FTY720 exerts anti-inflammatory and antiepileptogenic effects in lithium-pilocarpine model of epilepsy and it may provide a new therapeutic approach for prevention of epileptogenesis.

Promotive effect of ginsenoside Rd on proliferation of neural stem cells in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng, the root of Panax ginseng C. A. MEYER (Araliaceae), is reputedly known for its nootropic and anti-aging functions and has been widely used to treat various diseases and enhance health for thousands of years in Asia. Recent studies revealed that ginsenoside, responsible for the pharmacological effects of ginseng, can prevent memory loss and improve spatial learning in mice, but underlying mechanisms are still largely unknown. Active neurogenesis in adult hippocampus is closely related to animals' learning and memory ability. The present study aimed to investigate the possible effects of ginsenoside Rd, one of the most effective ingredients in ginseng, on neurogenesis in vivo and in vitro. MATERIALS AND METHODS: Adult rats and cultured neural stem cells were treated with ginsenoside Rd at different doses, and the changes in the proliferation and differentiation of neural stem cells were examined by immunohistochemistry and immunocytochemistry. RESULTS: Ginsenoside Rd significantly increased the numbers of BrdU(+) and DCX(+) cells in the hippocampal dentate gyrus but did not affect the ratio of NeuN/BrdU double-labeled cells to the total number of BrdU(+) cells. For cultured neural stem cells, ginsenoside Rd promoted the size and number of neurospheres, increased the number of BrdU(+) and Ki67(+) cells but did not affect the differentiation of neural stem cells into neurons, astrocytes and oligodendrocytes. CONCLUSIONS: These results indicate that ginsenoside Rd can enhance the proliferation but not affect the differentiation of neural stem cells in vivo and in vitro.

Acetylsalicylic acid as an augmentation agent in fluoxetine treatment resistant depressive rats.

Clinical studies have reported that adjunctive acetylsalicylic acid (aspirin) therapy is beneficial for patients with treatment resistant depression (TRD). However, there still exist negative epidemiological data on the link between aspirin and depression. Therefore, this study aimed to further investigate whether aspirin can be used as an augmentation agent in fluoxetine treatment resistant depressive rats induced by chronic unpredictable mild stress (CUMS). In this study, the effects of CUMS regimen and antidepressant treatment were assessed by behavioral testing, hippocampal expression of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)). 4-week fluoxetine treatment reversed the behavioral changes in approximately 70-80% depressive rats. That is, 20-30% depressive rats were resistant to fluoxetine. In the hippocampus of fluoxetine treatment resistant depressive rats, a significant upregulation of COX-2 level and PGE(2) concentration was observed. However, in these rats adjunctive aspirin treatment significantly improved the depressive behaviors and downregulated the COX-2 level and PGE(2) concentration in the hippocampus. Thus, our results suggest that aspirin can be served as an effective adjunctive agent in the treatment resistant depression mediated by inhibition of the COX-2 level and PGE(2) concentration.

LPS inhibits the effects of fluoxetine on depression-like behavior and hippocampal neurogenesis in rats.

Depressed patients with increased inflammatory cytokines in peripheral blood have been reported to be more likely to exhibit treatment resistance. However, it is unknown whether the inflammation influences the action of antidepressant drugs. Here, we investigated the influence of lipopolysaccharide (LPS) on the antidepressant action of fluoxetine in depressive rats induced by chronic unpredictable mild stress (CUMS). In this study, we first modified the CUMS paradigm by administration of LPS daily before the stressor, and then investigated the influence of inflammation on the antidepressant action of fluoxetine. The effects of stress exposure and antidepressant treatment were assessed by behavioral testing (sucrose preference test, forced swimming test, novelty suppressed feeding test) and hippocampal BrdU labeling. The CUMS-induced behavioral changes can be reversed by 4-week fluoxetine treatment. Fluoxetine also increased the hippocampal neurogenesis in the depressive rats. Pretreatment with LPS, to mimic inflammation, had no significant effect on depressive behavior but attenuated the antidepressant action of fluoxetine significantly. Thus, our results suggest that the inflammation might play a certain role in the pathophysiology of antidepressant treatment resistance.