Tissue distribution of gold and silver after subacute intravenous injection of co-administered gold and silver nanoparticles of similar sizes.

Gold (AuNPs, 12.8 nm) and silver nanoparticles (AgNPs, 10 nm), mixed or separate, were injected into the caudal vein of male Sprague-Dawley rats for 4 weeks. The rats were allowed to recover for further 4 weeks to examine the differences in AuNP/AgNP tissue distribution and clearance. The size distribution of injected AuNPs and AgNPs were not statistically different. The dose groups (five males per group for the administration and three males for the recovery) consisted of seven divisions, i.e., control, AgNPs (with a low dose of 10 µg/kg/day, and, a high dose of 100 µg/kg/day), AuNPs (with a low dose of 10 µg/kg/day, and, a high dose of 100 µg/kg/day), as well as mixed AgNPs/AuNPs (with a low dose of 10/10 µg/kg/day, and a high dose of 100/100 µg/kg/day). The AgNPs accumulated in a dose-dependent manner in the liver, spleen, kidneys, lung, brain, testis or blood. Au concentration increased also in a dose-dependent manner in the liver, kidneys, spleen and lungs, but not in the brain, testis and blood. Ag concentration in the tissues increased dose-dependently after 4 weeks of AgNP/AuNP mixed administration, but to a much lower extent than those observed when they were administered separately. Ag concentration in the tissues after 4 weeks of AgNP/AuNP mixed administration cleared dose-dependently after 4 weeks of recovery. Au concentration in the tissues increased dose-dependently after 4 weeks of AgNp/AuNP mixed administration, while Au concentration in the tissues did not clear as seen in Ag after 4 weeks recovery. Au concentration showed biopersistency or accumulation in the liver, kidneys, spleen and brain of the 4 weeks of recovery. In conclusion, AgNPs and AuNPs showed different toxicokinetic properties and the mixed administration of AgNPs with AuNPs resulted in mutual reduction of their tissue distribution which appeared to be due to competitive inhibition. Furthermore, this subacute intravenous injection study has suggested that these nanoparticles were distributed to the organs in particulate instead of ionic forms.

Enhanced Antioxidant Activity of Bioactives in Colored Grains by Nano-Carriers in Human Lens Epithelial Cells.

The use of phytochemicals for preventing chronic diseases associated with oxidative stress such as cataracts is hindered by their low bioavailability. The effects of nano-carriers on the antioxidant activities of extracts of black rice with giant embryo (BRGEx) and soybeans (SBx) have been determined in human lens epithelial B3 cells. Scanning (SEM) and transmission electron microscopy (TEM) demonstrated that rGO (reduced graphene oxide) has a flat surface unlike GO (graphene oxide), which has a distinctive wrinkled structure with defects. UPLC analysis revealed 41.9 µg/100 g of γ-oryzanols in water extract of BRGE, and 111.8 µg /100 g of lutein, 757.7 µg/100 g of γ-tocotrienol, 4071.4 µg/100 g of γ-tocopherol in 40% ethanol extract of soybeans, respectively. Even though a low concentration of BRGEx alone did not show any antioxidant activity in B3 cells, co-treatment of BRGEx with rGO together substantially reduced hydrogen peroxide and methylglyoxal-induced DNA damage, as determined by phosphorylated γH2AX. In addition, SBx with rGO also attenuated DNA damage. Furthermore, intracellular reactive oxygen species were significantly decreased by combining extracts of these colored grains with rGO. These results suggest a potential application of nanocarriers for enhancing the bioavailability of phytochemicals.

Whole slurry saccharification and fermentation of maleic acid-pretreated rice straw for ethanol production.

We evaluated the feasibility of whole slurry (pretreated lignocellulose) saccharification and fermentation for producing ethanol from maleic acid-pretreated rice straw. The optimized conditions for pretreatment were to treat rice straw at a high temperature (190 °C) with 1 % (w/v) maleic acid for a short duration (3 min ramping to 190 °C and 3 min holding at 190 °C). Enzymatic digestibility (based on theoretical glucose yield) of cellulose in the pretreated rice straw was 91.5 %. Whole slurry saccharification and fermentation of pretreated rice straw resulted in 83.2 % final yield of ethanol based on the initial quantity of glucan in untreated rice straw. These findings indicate that maleic acid pretreatment results in a high yield of ethanol from fermentation of whole slurry even without conditioning or detoxification of the slurry. Additionally, the separation of solids and liquid is not required; therefore, the economics of cellulosic ethanol fuel production are significantly improved. We also demonstrated whole slurry saccharification and fermentation of pretreated lignocellulose, which has rarely been reported.

Rational design of a structural framework with potential use to develop chemical reagents that target and modulate multiple facets of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by multiple, intertwined pathological features, including amyloid-ß (Aß) aggregation, metal ion dyshomeostasis, and oxidative stress. We report a novel compound (ML) prototype of a rationally designed molecule obtained by integrating structural elements for Aß aggregation control, metal chelation, reactive oxygen species (ROS) regulation, and antioxidant activity within a single molecule. Chemical, biochemical, ion mobility mass spectrometric, and NMR studies indicate that the compound ML targets metal-free and metal-bound Aß (metal-Aß) species, suppresses Aß aggregation in vitro, and diminishes toxicity induced by Aß and metal-treated Aß in living cells. Comparison of ML to its structural moieties (i.e., 4-(dimethylamino)phenol (DAP) and (8-aminoquinolin-2-yl)methanol (1)) for reactivity with Aß and metal-Aß suggests the synergy of incorporating structural components for both metal chelation and Aß interaction. Moreover, ML is water-soluble and potentially brain permeable, as well as regulates the formation and presence of free radicals. Overall, we demonstrate that a rational structure-based design strategy can generate a small molecule that can target and modulate multiple factors, providing a new tool to uncover and address AD complexity.

Heat shock protein 27 phosphorylation is involved in epithelial cell apoptosis as well as epithelial migration during corneal epithelial wound healing.

We reported the expression of phosphorylated HSP27 during epithelial wound healing in murine corneas (Jain et al., 2012) in July of 2012. This in vivo investigation demonstrated that the expression levels of phosphorylated HSP27 were greater in wounded corneal epithelial cells than in unwounded controls and that the localization of phosphorylated HSP27 was in the basal and superficial epithelia three days following corneal epithelial wounding. We suggested that phosphorylated HSP27 had a role in the early phase of corneal epithelial wound healing. The purpose of this study was to investigate the exact role of heat shock protein 27 (HSP27) phosphorylation for the wound healing of cultured human corneal epithelial cells (HCECs). HSP27-specific siRNAs and control-siRNAs, with no known homologous targets in HCECs, were created. The cultured HCECs were divided into two groups: Scrambled control-siRNA-transfected group vs. HSP27-specific siRNA-transfected group. The scratch-induced directional wounding assay, Western blotting, using antibodies against non-phosphorylated and phosphorylated HSP27, non-phosphorylated and phosphorylated Akt, and Bcl-2-associated X protein (Bax), immunofluorescence staining to determine the filament actin, flow cytometry to measure apoptosis, and proliferation assay were performed to determine the role of HSP27. Western blot assay showed that the expression of phosphorylated HSP27 significantly increased at 5, 10, and 30 min after scratch wounding, compared with those in unwounded HCECs (all p < 0.05). Western blot assay also showed HSP27-specific siRNAs effectively blocked the expression of non-phosphorylated HSP27. The HSP27-specific siRNA-transfected group had more Bax expression, less phosphorylated Akt expression, and less non-phosphorylated and phosphorylated HSP27 expression (all p < 0.05). The scratch-induced directional wounding assay showed the HSP27-specific siRNA-transfected group with a less migrating cell number than the control-siRNA-transfected group (p < 0.05). Immunofluorescence staining showed that reorganization of actin cytoskeleton prominently decreased in the HSP27-specific siRNA-transfected group, compared with the control siRNA-tranfected group. Flow cytometry revealed that the HSP27-specific siRNA-transfected group had more HCEC apoptosis. Proliferation assay showed no difference between the two groups. In conclusion, the role of HSP27 in corneal epithelial wound healing can be epithelial cell apoptosis, as well as epithelial migration. HSP27 is involved in HCEC migration by the reorganization of actin cytoskeleton.

Electrochemical flow-based solution-solid growth of the Cu2O nanorod array: potential application to lithium ion batteries.

The catalyzed solution-liquid-solid (SLS) growth has been well developed to synthesize semiconductor nanowires with controlled diameters. The SLS growth occurs in the longitudinal direction of nanowires, due to the directional anisotropy driven by the metal catalysts where chemical precursors are introduced. In the present study, we report a selective, template-free, and environmentally-friendly electrochemical flow-based solution-solid (electrochemical flow-SS) growth of the Cu2O nanorod array. The anisotropy for directional growth without any catalysts is generated by the electrical field in a flowing electrolyte of ultra-dilute CuSO4. The filamentary anisotropy originates from electric field enhancement on pyramidal nanocrystals in the electrolyte of low ionic conductivity (13 µS cm(-1)). The Cu2O and Cu nanorods are able to be selectively synthesized by controlling the electrolyte pH and oxygen dissolution into the electrolyte. The synthesized Cu2O nanorod array shows excellent electrochemical properties as an anode material for lithium-ion batteries; the specific capacities increase from 323 to 1206 mA h g(-1) during 500 cycles. The capacity enhancement is due to the phase transformation from Cu2O to CuO, nano-restructuring of nanorods into fragmented nanoparticles, and the progressive generation of an electroactive polymeric gel-like layer on the surface of the nanoparticles. The electrochemical flow-SS growth of Cu2O nanorods is expected to contribute to further development of other functional nanorods.

Remarkable solvent, porphyrin ligand, and substrate effects on participation of multiple active oxidants in manganese(III) porphyrin catalyzed oxidation reactions.

The participation of multiple active oxidants generated from the reactions of two manganese(III) porphyrin complexes containing electron-withdrawing and -donating substituents with peroxyphenylacetic acid (PPAA) as a mechanistic probe was studied by carrying out catalytic oxidations of cyclohexene, 1-octene, and ethylbenzene in various solvent systems, namely, toluene, CH(2) Cl(2) , CH(3) CN, and H(2) O/CH(3) CN (1:4). With an increase in the concentration of the easy-to-oxidize substrate cyclohexene in the presence of [(TMP)MnCl] (1a) with electron-donating substituents, the ratio of heterolysis to homolysis increased gradually in all solvent systems, suggesting that [(TMP)Mn-OOC(O)R] species 2a is the major active species. When the substrate was changed from the easy-to-oxidize one (cyclohexene) to difficult-to-oxidize ones (1-octene and ethylbenzene), the ratio of heterolysis to homolysis increased a little or did not change. [(F(20) TPP)Mn-OOC(O)R] species 2b generated from the reaction of [(F(20) TPP)MnCl] (1b) with electron-withdrawing substituents and PPAA also gradually becomes involved in olefin epoxidation (although to a much lesser degree than with [(TMP)Mn-OOR] 2a) depending on the concentration of the easy-to-oxidize substrate cyclohexene in all aprotic solvent systems except for CH(3) CN, whereas Mn(V)=O species is the major active oxidant in the protic solvent system. With difficult-to-oxidize substrates, the ratio of heterolysis to homolysis did not vary except for 1-octene in toluene, indicating that a Mn(V)=O intermediate generated from the heterolytic cleavage of 2b becomes a major reactive species. We also studied the competitive epoxidations of cis-2-octene and trans-2-octene with two manganese(III) porphyrin complexes by meta-chloroperbenzoic acid (MCPBA) in various solvents under catalytic reaction conditions. The ratios of cis- to trans-2-octene oxide formed in the reactions of MCPBA varied depending on the substrate concentration, further supporting the contention that the reactions of manganese porphyrin complexes with peracids generate multiple reactive oxidizing intermediates.

Biopersistence of silver nanoparticles in tissues from Sprague-Dawley rats.

Silver nanoparticles are known to be distributed in many tissues after oral or inhalation exposure. Thus, understanding the tissue clearance of such distributed nanoparticles is very important to understand the behavior of silver nanoparticles in vivo. For risk assessment purposes, easy clearance indicates a lower overall cumulative toxicity. Accordingly, to investigate the clearance of tissue silver concentrations following oral silver nanoparticle exposure, Sprague-Dawley rats were assigned to 3 groups: control, low dose (100 mg/kg body weight), and high dose (500 mg/kg body weight), and exposed to two different sizes of silver nanoparticles (average diameter 10 and 25 nm) over 28 days. Thereafter, the rats were allowed to recover for 4 months. Regardless of the silver nanoparticle size, the silver content in most tissues gradually decreased during the 4-month recovery period, indicating tissue clearance of the accumulated silver. The exceptions were the silver concentrations in the brain and testes, which did not clear well, even after the 4-month recovery period, indicating an obstruction in transporting the accumulated silver out of these tissues. Therefore, the results showed that the size of the silver nanoparticles did not affect their tissue distribution. Furthermore, biological barriers, such as the blood-brain barrier and blood-testis barrier, seemed to play an important role in the silver clearance from these tissues.

Preparation of an aqueous suspension of stabilized TiO2 nanoparticles in primary particle form.

To prepare stabilized TiO2 nanoparticles (TiO2 NPs) in aqueous media as a suspension of the primary particles, we attempted to optimize the conditions for dispersing stable, aggregated TiO2 NPs (A-TiO2 NPs) in aqueous HCl/NaOH solutions or 5 mM pH buffered aqueous solutions. The A-TiO2 NPs with a hydrodynamic diameter (or DLS size) of 150 +/- 20 nm could be dispersed at high concentration (63.5 +/- 0.5 mg/ml) in a 5 mM phosphate buffer (PB) solution of pH 8, and a primary TiO2 (P-TiO2) NP suspension (1.2 +/- 0.3 mg/ml) with DLS size of 30 +/- 5 nm could be separated from the highly concentrated A-TiO2 NP suspension by sonication and subsequent centrifugation. It was observed by comparing the UV-Vis absorption spectra of the A-TiO2 and P-TiO2 NP suspensions that the extinction coefficient of the TiO2 NPs in the aqueous suspension depended on the degree of aggregation. The stabilized P-TiO2 NP suspension in aqueous solution can be used to study nanotoxicity as well as to characterize the physicochemical properties of TiO2 NPs.

Gene expression profiling of kidneys from Sprague-Dawley rats following 12-week inhalation exposure to silver nanoparticles.

The specific properties of silver nanoparticles (AgNPs), such as antimicrobial activity and electrical conductivity, allow them to be used in many fields. However, their expanding application is also raising health, environmental and safety concerns. Previous in vivo AgNP toxicity studies have indicated a gender-different accumulation of silver in the kidneys, with 2-3 times more silver in female kidneys compared to male kidneys. However, no other studies have further addressed this gender difference. Accordingly, the current study investigated the gender-dependent effect of AgNPs on the kidney gene level based on toxicogenomic studies of kidneys obtained from rats exposed to AgNPs via inhalation for 12 weeks. When compared with the fresh air control, the silver nanoparticle-exposed kidneys included 104 genes with a more than 1.3-fold expression increase. For the male rat kidneys exposed to a low or high dose of silver nanoparticles, 96 genes exhibited expression changes, where six genes changed with both the low and high dose; four increased and two decreased. Meanwhile, for the female rat kidneys exposed to a low or high dose of silver nanoparticles, 66 genes exhibited expression changes, where 11 genes changed with both the low and high dose; nine increased and two decreased. Gender-dependent gene expression changes of more than 2-fold were linked to 163 genes, with 79 genes in the male kidneys and 84 genes in the female kidneys, plus gender-dependent gene expression changes of more than 5-fold were linked to 21 genes. However, no genes involved in apoptosis or the cell cycle were activated by the 12-week silver nanoparticle inhalation exposure. Overall, the male rat kidneys showed a higher expression of genes involved in xenobiotic metabolism, while the female rat kidneys showed a higher expression of genes involved in extracellular signaling.

Cera-Glow, ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201, improves skin barrier function in clinical study.

BACKGROUND: Ceramides are essential lipids in stratum corneum for skin permeability barrier function in that they retain the skin moisture and protect from the invasion of foreign pathogens. Previously, we demonstrated that ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201 enhanced ceramide production in human epidermal keratinocytes. Furthermore, for comprehensive knowledge of this effect, in vitro experiments and multi-omics analysis were conducted to explore the underlying mechanisms. AIMS: This study was designed to identify whether a cosmetic sample (i.e., Cera-Glow) containing the lysates improves the skin barrier function in clinical trials. PATIENTS/METHODS: Twenty-four female participants (45.46 ± 9.78 years) had been enrolled in the transepidermal water loss (TEWL) measurement for 5 days and 21 female participants (50.33 ± 5.74 years) had undergone a skin hydration evaluation for 4 weeks. TEWL and skin hydration were evaluated using a Tewameter and the Epsilon Permittivity Imaging System, respectively. After applying the Cera-Glow sample, all participants recorded a satisfaction survey questionnaire (e.g., satisfaction, efficacy, and adverse reactions). RESULTS: Application of Cera-Glow significantly improved transepidermal water loss induced by 1% (w/v) sodium lauryl sulfate (p < 0.05-0.01) and increased skin hydration (p < 0.01). Metabolic analysis suggested that Cera-Glow should contain beneficial gradients for skin barrier function. According to the questionnaire, most of participants were satisfied with the skin hydration improvement and efficacy of Cera-Glow. CONCLUSIONS: Cera-Glow, ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201, can significantly improve skin barrier function.

NaCl-Assisted Temperature-Dependent Controllable Growth of Large-Area MoS2 Crystals Using Confined-Space CVD.

Due to its semiconducting nature, controlled growth of large-area chemical vapor deposition (CVD)-grown two-dimensional (2D) molybdenum disulfide (MoS2) has a lot of potential applications in photodetectors, sensors, and optoelectronics. Yet the controllable, large-area, and cost-effective growth of highly crystalline MoS2 remains a challenge. Confined-space CVD is a very promising method for the growth of highly crystalline MoS2 in a controlled manner. Herein, we report the large-scale growth of MoS2 with different morphologies using NaCl as a seeding promoter for confined-space CVD. Changes in the morphologies of MoS2 are reported by variation in the amount of seeding promoter, precursor ratio, and the growth temperature. Furthermore, the properties of the grown MoS2 are analyzed using optical microscopy, scanning electron microscopy (SEM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDX), and atomic force microscopy (AFM). The electrical properties of the CVD-grown MoS2 show promising performance from fabricated field-effect transistors. This work provides new insight into the growth of large-area MoS2 and opens the way for its various optoelectronic and electronic applications.

Robust and efficient amide-based nonheme manganese(III) hydrocarbon oxidation catalysts: substrate and solvent effects on involvement and partition of multiple active oxidants.

Two new mononuclear nonheme manganese(III) complexes of tetradentate ligands containing two deprotonated amide moieties, [Mn(bpc)Cl(H(2)O)] (1) and [Mn(Me(2)bpb)Cl(H(2)O)]⋅CH(3)OH (2), were prepared and characterized. Complex 2 has also been characterized by X-ray crystallography. Magnetic measurements revealed that the complexes are high spin (S = 5/2) Mn(III) species with typical magnetic moments of 4.76 and 4.95 µ(B), respectively. These nonheme Mn(III) complexes efficiently catalyzed olefin epoxidation and alcohol oxidation upon treatment with MCPBA under mild experimental conditions. Olefin epoxidation by these catalysts is proposed to involve the multiple active oxidants Mn(V)=O, Mn(IV)=O, and Mn(III)-OO(O)CR. Evidence for this approach was derived from reactivity and Hammett studies, KIE (k(H)/k(D)) values, H(2)(18)O-exchange experiments, and the use of peroxyphenylacetic acid as a mechanistic probe. In addition, it has been proposed that the participation of Mn(V)=O, Mn(IV)=O, and Mn(III)-OOR could be controlled by changing the substrate concentration, and that partitioning between heterolysis and homolysis of the O-O bond of a Mn-acylperoxo intermediate (Mn-OOC(O)R) might be significantly affected by the nature of solvent, and that the O-O bond of the Mn-OOC(O)R might proceed predominantly by heterolytic cleavage in protic solvent. Therefore, a discrete Mn(V)=O intermediate appeared to be the dominant reactive species in protic solvents. Furthermore, we have observed close similarities between these nonheme Mn(III) complex systems and Mn(saloph) catalysts previously reported, suggesting that this simultaneous operation of the three active oxidants might prevail in all the manganese-catalyzed olefin epoxidations, including Mn(salen), Mn(nonheme), and even Mn(porphyrin) complexes. This mechanism provides the greatest congruity with related oxidation reactions by using certain Mn complexes as catalysts.

Development of multiplexed analysis for the photocatalytic activities of nanoparticles in aqueous suspension.

A multiplexed assay technique to measure the photocatalytic activity (PCA) of nanoparticles (NPs) in aqueous suspension was developed based on the observation of TiO(2) NPs-photocatalytic oxidation rate of NADH by monitoring the fluorescence intensities. 96 sample solutions of a small volume (<150 µL) could be assayed in a single run without separation of NPs within 15 min. PCA values can be measured with high sensitivity and low experimental uncertainties through the observation at various concentrations of photocatalyst, substrate, aqueous protons and pH buffer ions in a short measurement time.

Mass imaging of iron oxide nanoparticles inside cells for in vitro cytotoxicity.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging analysis was performed on murine macrophage cells treated with various concentrations of iron oxide (Fe3O4) nanoparticles, which are used as MRI contrast agents. First, murine macrophage cells were seeded on a slide glass for 24 hrs and treated with varying concentrations of Fe3O4 nanoparticles for 24 hrs. To expose a cross section of each cell and obtain a distribution of the nanoparticles inside the cells, the cells were sputtered using Bi ions after which the cross section of each cell was scanned and imaged using the focused cluster ion beam with a spatial resolution of 300 nm. Fe3O4 nanoparticles were found mainly in the cytoplasm region of the cells, not in the nucleus region of cells, suggesting that the uptake of the Fe3O4 nanoparticles were into the cytoplasm of cell, not into the nucleus of cell. Based on these observations, our protocol using mass imaging analysis would be a useful addition to the study of in vitro nanoparticle cytotoxicity.

Generation of continuous-wave single-frequency 1.5 W 378 nm radiation by frequency doubling of a Ti:sapphire laser.

We have generated continuous-wave single-frequency 1.5 W 378 nm radiation by frequency doubling a high-power Ti:sapphire laser in an external enhancement cavity. An LBO crystal that is Brewster-cut and antireflection coated on both ends is used for a long-term stable frequency doubling. By optimizing the input coupler's reflectivity, we could generate 1.5 W 378 nm radiation from a 5 W 756 nm Ti:sapphire laser. According to our knowledge, this is the highest CW frequency-doubled power of a Ti:sapphire laser.

Protection against amyloid beta cytotoxicity by sulforaphane: role of the proteasome.

The 26S proteasome plays a major role in degradation of abnormal proteins within the cell. The indirect antioxidant including sulforaphane (SFN) protects cells from oxidative damage by increasing the expression of Nrf2-target genes. It has been observed that the expression of multiple subunits of the proteasome was up-regulated by indirect antioxidants through the Nrf2 pathway. In the current study, the role of SFN in amyloid beta(1-42) (Abeta(1-42))-induced cytotoxicity has been investigated in murine neuroblastoma cells. Treatment with SFN protected cells from Abeta(1-42)-mediated cell death in Neuro2A and N1E 115 cells. Inhibition of proteasome activities by MG132 could abolish the protective effect of SFN against Abeta(1-42). Neuro2A cells, which were stably overexpressing the catalytic subunit of the proteasome PSMB5, showed an elevated resistance toward Abeta(1-42) toxicity compared to control cells. Furthermore, the in vitro assay demonstrated that the Abeta(1-42) peptide is degraded by the proteasome fraction. These results suggest that proteasome-inducing indirect antioxidants may facilitate the removal of the Abeta(1-42) peptide and lead to the amelioration of abnormal protein-associated etiologies.

Pretreatment and enzymatic saccharification of oak at high solids loadings to obtain high titers and high yields of sugars.

Production of high-titer sugar from lignocellulose is important in terms of process economics of bio-based product industry. In this study, to obtain high titers and yields of sugars, we combined pretreatment and saccharification steps, both at high solids loadings. First, pretreatment of oak was optimized at a 30% (w/w) solids loading. The whole slurry of the pretreated oak was subjected to a fed-batch saccharification step at the final solids loading of 30%, to minimize loss of fermentable sugars and simplify the processes. As a result, high-titer sugars (157.5 g/L) consisting of 120.2 g/L of glucose and 37.3 g/L of xylose were obtained at 75.9% and 58.6%, respectively, of theoretical maximum yields, based on the initial glucan and xylan contents. Thus, through proper optimization processes of oak, the combination of pretreatment and saccharification at high solids loadings was effective in obtaining both high titers and high yields of sugars from lignocellulose.

Periodicity of cerebral flow velocity during sleep and its association with white-matter hyperintensity volume.

Impaired sleep-related activation of the cerebral waste-clearance system might be related with the brain aging process. We hypothesized that cerebral blood-flow pattern changes during sleep might reflect the activation of the cerebral waste-clearance system and investigated its association with the cerebral white-matter hyperintensity (WMH) volume. Fifty healthy volunteers were prospectively recruited. In addition to the baseline transcranial Doppler parameters, the mean flow velocity (MFV) of the middle cerebral artery was monitored during waking and short-term non-REM sleep. Spectral density analysis was performed to analyze the periodic MFV variation patterns. For the aged subgroup (>50 years, n = 25), the WMH volumes in the total, subcortical, and periventricular regions were measured. The MFV periodic pattern during sleep was substantially augmented over that in the waking status. Spectral density analysis of MFV showed a noticeable peak in the very-low-frequency (VLF) band during sleep status (sleep/waking ratio 2.87 ± 2.71, P < 0.001). In linear regression analysis in the aged subgroup, the sleep/waking ratio of the VLF peak was inversely associated with total (P = 0.013) and subcortical (P = 0.020) WMH volumes. Sleep-related amplification of the cerebral flow-velocity periodicity might reflect the activation of cerebral waste clearance system during sleep, and be related to the pathogenesis of cerebral WMH.

Role of the Nrf2-antioxidant system in cytotoxicity mediated by anticancer cisplatin: implication to cancer cell resistance.

The treatment of alkylating cytotoxic drug cisplatin is often limited by high incidence rate of resistance. In the present study, the potential involvement of the transcription factor Nrf2 in determination of cisplatin cytotoxicity has been investigated. Nrf2-deficient murine embryonic fibroblasts showed increased cell death, cytotoxicity, and apoptosis in response to cisplatin treatment compared to wild-type cells. Cisplatin-resistant human ovarian cancer SK-OV cells, which are retaining 25-fold higher levels of GSH than murine fibroblasts, could be sensitized by inhibition of Nrf2. Transfection with Nrf2 siRNA into SK-OV cells resulted in severe degree of GSH depletion and exacerbated cytotoxicity following cisplatin treatment compared to scrambled RNA control. In conclusion, we propose that the Nrf2 pathway, which plays a protective role in normal cells, can be a potential target to control cancer cell resistance to oxidants, cytotoxic chemicals, and radiation.