Incarvine C and its analogues inhibit the formation of cell cytoskeleton by targeting Rac1.

Ras-related C3 botulinum toxin substrate 1 (Rac1) has emerged as a key regulator in the treatment of cancer metastasis because of its involvement in the formation of cell plate pseudopods and effects on cell migration. In this study, we found that incarvine C, a natural product isolated from Incarvillea sinensis, and its seven analogues exhibited antitumour activity by inhibiting cell cytoskeleton formation, with moderate cytotoxicity. Accordingly, these compounds inhibited the cytoskeleton-mediated migration and invasion of MDA-MB-231 cells, with inhibition rates ranging from 37.30 % to 69.72 % and 51.27 % to 70.90 % in vitro, respectively. Moreover, they induced G2/M phase cell cycle arrest in MDA-MB-231 cells. A pull-down assay revealed that the interaction between Rac1 and its downstream effector protein PAK1 was inhibited by these compounds and that the compound Ano-6 exhibited substantial activity, with an inhibition rate of more than 90 %. Molecular docking showed that incarvine C and its analogues could bind to the nucleotide-binding pocket of Rac1, maintaining high levels of inactivated Rac1. As Ano-6 exhibited significant activity in vitro, its anti-cancer activity was tested in vivo. Four weeks of oral treatment with Ano-6 was well-tolerated in mice, and it induced a potential anti-tumour response in xenografts of MDA-MB-231 cells. Further studies demonstrated that Ano-6 was enriched in tumour tissues after 2 h of administration and induced an increase in the number of dead tumour cells. In summary, these findings not only reveal the mechanism of incarvine C but also provide a new molecular template for Rac1 inhibitors and identify a promising candidate for breast cancer treatment.

How do taxi drivers expose to fine particulate matter (PM2.5) in a Chinese megacity: a rapid assessment incorporating with satellite-derived information and urban mobility data.

BACKGROUND: Taxi drivers in a Chinese megacity are frequently exposed to traffic-related particulate matter (PM2.5) due to their job nature, busy road traffic, and urban density. A robust method to quantify dynamic population exposure to PM2.5 among taxi drivers is important for occupational risk prevention, however, it is limited by data availability. METHODS: This study proposed a rapid assessment of dynamic exposure to PM2.5 among drivers based on satellite-derived information, air quality data from monitoring stations, and GPS-based taxi trajectory data. An empirical study was conducted in Wuhan, China, to examine spatial and temporal variability of dynamic exposure and compare whether drivers' exposure exceeded the World Health Organization (WHO) and China air quality guideline thresholds. Kernel density estimation was conducted to further explore the relationship between dynamic exposure and taxi drivers' activities. RESULTS: The taxi drivers' weekday and weekend 24-h PM2.5 exposure was 83.60 µg/m3 and 55.62 µg/m3 respectively, 3.4 and 2.2 times than the WHO's recommended level of 25 µg/m3. Specifically, drivers with high PM2.5 exposure had a higher average trip distance and smaller activity areas. Although major transportation interchanges/terminals were the common activity hotspots for both taxi drivers with high and low exposure, activity hotspots of drivers with high exposure were mainly located in busy riverside commercial areas within historic and central districts bounded by the "Inner Ring Road", while hotspots of drivers with low exposure were new commercial areas in the extended urbanized area bounded by the "Third Ring Road". CONCLUSION: These findings emphasized the need for air quality management and community planning to mitigate the potential health risks of taxi drivers.

Retinoic acid signalling inhibits myogenesis by blocking MYOD translation in pig skeletal muscle cells.

Vitamin A is an essential nutrient in animals, playing important roles in animal health. In the pig industry, proper supplementation of vitamin A in the feed can improve pork production performance, while deficiency or excessive intake can lead to growth retardation or disease. However, the specific molecular mechanisms through which vitamin A operates on pig skeletal muscle growth as well as muscle stem cell function remain unexplored. Therefore, in this study, we isolated the pig primary skeletal muscle stem cells (pMuSCs) and treated with retinoic acid (RA), the natural metabolite of vitamin A, and then examined the myogenic capacity of pMuSCs via immunostaining, real-time PCR, CCK8 and western-blot analysis. Unexpectedly, the RA caused a significant decrease in the proliferation and differentiation of pMuSCs. Mechanistically, the RA addition induced the activation of retinoic acid receptor gamma (RARγ), which inhibited the myogenesis through the blockage of protein translation of the master myogenic regulator myogenic differentiation 1 gene (MYOD). Specifically, RARγ inactivate AKT kinase (AKT) signalling and lead to dephosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1), which in turn repress the eukaryotic translation initiation factor 4E (eIF4E) complex and block mRNA translation of MYOD. Inhibition of AKT could rescue the myogenic defects of RA-treated pMuSCs. Our findings revealed that retinoid acid signalling inhibits the skeletal muscle stem cell proliferation and differentiation in pigs. Therefore, the vitamin A supplement in the feedstuff should be cautiously optimized to avoid the potential adverse consequences on muscle development associated with the excessive levels of retinoic acid.

Motion screening of fiducial marker for improved localization precision and resolution in SMLM.

Single-molecule localization microscopy (SMLM) provides unmatched high resolution but relies on accurate drift correction due to the long acquisition time for each field of view. A popular drift correction is implemented via referencing to fiducial markers that are assumed to be firmly immobilized and remain stationary relative to the imaged sample. However, there is so far lack of efficient approaches for evaluating other motions except sample drifting of immobilized markers and for addressing their potential impacts on images. Here, we developed a new approach for quantitatively assessing the motions of fiducial markers relative to the sample via mean squared displacement (MSD) analysis. Our findings revealed that over 90% of immobilized fluorescent beads in the SMLM imaging buffer exhibited higher MSDs compared to stationary beads in dry samples and displayed varying degrees of wobbling relative to the imaged field. By excluding extremely high-MSD beads in each field from drift correction, we optimized drift correction and experimentally measured localization precision. In SMLM experiments of cellular microtubules, we also found that including only relatively low-MSD beads for drift correction significantly improved the image resolution and quality. Our study presents a simple and effective approach to assess the potential relative motions of fiducial markers and emphasizes the importance of pre-screening fiducial markers for improved image quality and resolution in SMLM imaging.

A New Monoterpene Alkaloid from Incarvillea sinensis with Migration Inhibitory Activity on Cancer Cell.

A novel monoterpene alkaloid, named incarvine G, was isolated from the Incarvillea sinensis Lam. Its chemical structure was elucidated using comprehensive spectroscopic methods. Incarvine G is an ester compound comprised of a monoterpene alkaloid and glucose. This compound showed evident inhibition on cell migration, invasion, and cytoskeleton formation of human MDA-MB-231 with low cytotoxicity.

Recent Advances in Electrocatalytic Hydrogen Evolution Using Nanoparticles.

Hydrogen fuel is considered as the cleanest renewable resource and the primary alternative to fossil fuels for future energy supply. Sustainable hydrogen generation is the major prerequisite to realize future hydrogen economy. The electrocatalytic hydrogen evolution reaction (HER), as the vital step of water electrolysis to H2 production, has been the subject of extensive study over the past decades. In this comprehensive review, we first summarize the fundamentals of HER and review the recent state-of-the-art advances in the low-cost and high-performance catalysts based on noble and non-noble metals, as well as metal-free HER electrocatalysts. We systemically discuss the insights into the relationship among the catalytic activity, morphology, structure, composition, and synthetic method. Strategies for developing an effective catalyst, including increasing the intrinsic activity of active sites and/or increasing the number of active sites, are summarized and highlighted. Finally, the challenges, perspectives, and research directions of HER electrocatalysis are featured.

ARP2/3 Regulates Fatty Acid Synthesis by Modulating Lipid Droplets' Motility.

The breakdown of lipid droplets (LDs) provides energy and contributes to the proliferation and migration of cancer cells. Recent studies have suggested that motility plays a key role in LD breakdown. However, the molecular mechanisms underlying LD motility were poorly characterized. In this study, we examined the function of microfilament-associated proteins 2 and 3 (ARP2 and ARP3) in regulating LDs' motility in Hela cells. ARP2/3 mediated the LDs' physical contact with F-actin and promoted the recruitment of Myosin Heavy Chain 9 (MYH9). MYH9 regulated the LD content by binding with LDs and ARP2/3. The number of LDs and TG content was increased after MYH9 interfered. The genes related to FA-related genes and neutral lipid synthesis-related genes were significantly increased (p < 0.05) when ARP2 and ARP3 were overexpressed. Bioinformatic analysis indicated that the high expression of ARP2/3 was associated with a poorer prognosis in cervical squamous cell carcinoma (CSCC). This study showed the effect of cytoskeletal filaments on LD metabolism in cancer cells.

Motility Plays an Important Role in the Lifetime of Mammalian Lipid Droplets.

The lipid droplet is a kind of organelle that stores neutral lipids in cells. Recent studies have found that in addition to energy storage, lipid droplets also play an important role in biological processes such as resistance to stress, immunity, cell proliferation, apoptosis, and signal transduction. Lipid droplets are formed at the endoplasmic reticulum, and mature lipid droplets participate in various cellular processes. Lipid droplets are decomposed by lipase and lysosomes. In the life of a lipid droplet, the most important thing is to interact with other organelles, including the endoplasmic reticulum, mitochondria, peroxisomes, and autophagic lysosomes. The interaction between lipid droplets and other organelles requires them to be close to each other, which inevitably involves the motility of lipid droplets. In fact, through many microscopic observation techniques, researchers have discovered that lipid droplets are highly dynamic organelles that move quickly. This paper reviews the process of lipid droplet motility, focusing on explaining the molecular basis of lipid droplet motility, the factors that regulate lipid droplet motility, and the influence of motility on the formation and decomposition of lipid droplets. In addition, this paper also proposes several unresolved problems for lipid droplet motility. Finally, this paper makes predictions about the future research of lipid droplet motility.

SEIPIN: A Key Factor for Nuclear Lipid Droplet Generation and Lipid Homeostasis.

Lipid homeostasis is essential for normal cell physiology. Generally, lipids are stored in a lipid droplet (LD), a ubiquitous organelle consisting of a neutral lipid core and a single layer of phospholipid membrane. It is thought that LDs are generated from the endoplasmic reticulum and then released into the cytosol. Recent studies indicate that LDs can exist in the nucleus, where they play an important role in the maintenance of cell phospholipid homeostasis. However, the details of nuclear lipid droplet (nLD) generation have not yet been clearly characterized. SEIPIN is a nonenzymatic protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene. It is associated with lipodystrophy diseases. Many recent studies have indicated that SEIPIN is essential for LDs generation. Here, we review much of this research in an attempt to explain the role of SEIPIN in nLD generation. From an integrative perspective, we conclude by proposing a theoretical model to explain how SEIPIN might participate in maintaining homeostasis of lipid metabolism.

Covalent capture of supramolecular species in an aqueous solution of water-miscible small organic molecules.

Since an early report in the 1970s, the mesoscale inhomogeneities formed in an aqueous solution of water-miscible small organic molecules have been debated for over forty years with a variety of explanations. Although it was recently established that these inhomogeneities are supramolecular species caused by trace impurities, the structure of the supramolecular species and the mechanism behind their formation are not yet clear. By means of covalent capture, we herein disclose that the formation mechanism of the supramolecular species consists of a two-step self-assembly process: the small molecules first assemble into primary micelles with a trace amount of impurity, and the formed dynamic ultra-small micelles aggregate further through hydrogen bonding to achieve a buildup of thermodynamic mesoscale inhomogeneities. Based on this finding, supramolecular species have been used as elements for pH-responsive size-changeable drug carriers, which respond to the acidic tumour extracellular milieu and decompose into small particles for deep tumour penetration and effective distribution.

Combination of Suspension Array and Mycelial Growth Assay for Detecting Multiple-Fungicide Resistance in Botrytis cinerea in Hebei Province in China.

To provide a high-throughput, efficient, and accurate method to monitor multiple-fungicide resistance of Botrytis cinerea in the field, we used the suspension array, sequencing, and mycelial growth assay in our research. Discriminating-dose bioassays for detecting carbendazim, diethofencarb, boscalid, and iprodione resistance (CarR, DieR, BosR, and IprR, respectively) were used to analyze 257 isolates collected from Hebei Province in China during 2016 and 2017. High resistance frequencies to carbendazim (100%), diethofencarb (92.08%), and iprodione (86.59%) were detected. BosR isolates accounted for 11.67% of the total. In addition, 103 isolates were randomly selected for phenotype and genotype detection. The high-throughput suspension array was utilized to detect eight genotypes simultaneously, including BenA-E198, BenA-198A, SdhB-H272, SdhB-272Y, BcOS1-I365, BcOS1-365S, erg27-F412, and erg27-412S, which were associated with resistance toward carbendazim or diethofencarb, boscalid, iprodione, and fenhexamid (FenR), respectively. Most of the benzimidazole-resistant isolates (81.55%) possessed the E198V mutation in the BenA gene. Ninety-three isolates with dual resistance to carbendazim and diethofencarb showed the E198V/K mutation. All BosR isolates carried the H272R mutation in the SdhB gene. The I365S and Q369P+N373S (66.99%) mutations in the BcOS1 gene were more frequently observed. No mutation was detected in the erg27 gene in Hebei isolates. There were 13 resistance profile phenotypes. Phenotypes with triple resistance were the most common (83.50%), and CarRDieRBosSIprRFenS was the major type. CarR isolates that carried E198V/K/A were all highly resistant (HR) and only one F200Y mutant was moderately resistant (MR) to carbendazim. Isolates that possessed E198V/K were MR or HR to diethofencarb. BosR isolates that possessed H272R mutation were lowly resistant (LR). IprR isolates were all LR or MR. The distribution of half maximal effective concentrations of CarR isolates with E198V/K mutations and IprR isolates with Q369P+N373S mutations significantly increased from 2016 to 2017. Combined with our observations, a combination method of the high-throughput suspension array and the mycelial growth assay was suggested to accurately monitor multiple resistance of B. cinerea in the field.

Macrophage migration inhibitory factor contributes to the pathogenesis of benign lymphoepithelial lesion of the lacrimal gland.

BACKGROUND: Benign Lymphoepithelial Lesion (BLEL) is a rare disease observed in the adult population. Despite the growing numbers of people suffering from BLEL, the etiology and mechanisms underlying its pathogenesis remain unknown. METHODS: In the present study, we used gene and cytokines expression profiling, western blot and immunohistochemistry to get further insight into the cellular and molecular mechanisms involved in the pathogenesis of BLEL of the lacrimal gland. RESULTS: The results showed that Macrophage Migration Inhibitory Factor (MIF) was the most highly expressed cytokine in BLEL, and its expression positively correlated with the expression of Th2 and Th17 cells cytokines. MIF was found to regulate biological functions and pathways involved in BLEL pathogenesis, such as proliferation, resistance to apoptosis, MAPK and PI3K/Akt pathways. We also found that MIF promotes fibrosis in BLEL by inducing BLEL fibroblast differentiation into myofibroblasts as well as the synthesis and the deposit of extracellular matrix in BLEL tissues. CONCLUSIONS: Our findings demonstrate the contribution of MIF to the pathogenesis of BLEL of the lacrimal gland and suggested MIF as a promising therapeutic target for its treatment.

TLR7 and TLR8 agonist resiquimod (R848) differently regulates MIF expression in cells and organs.

Since its first description in 1966, macrophage migration inhibitory factor (MIF) was found to play a critical role in inflammatory and immune responses as well as in disease pathogenesis especially in tumor pathogenesis and cancer progression. MIF is expressed in different cell types and is associated with many disease severity and tumor pathogenesis. Here, we investigated the influence of TLR7 and TLR8 agonist resiquimod (R848), an immune response inducer used as a prophylactic agent for several infectious diseases as well as anticancer agents and vaccine adjuvant on MIF expression in cells and organs. Humans, mice and rats cell lines from different tissues (blood, retinal, nasopharynx, brain and liver) and C57BL/6J mice organs (brain, liver and spleen) were used for this investigation. In vitro, R848 induced MIF gene overexpression except in brain and liver cells. Furthermore, it enhanced cells ability to release soluble MIF and differently regulated mRNA expression of MIF-related receptors (CD74, CXCR4, CXCR2 and CD44). Its influence on MIF gene expression and MIF proteins release was more consistent in cancer cells. In vivo, a strong positive expression of MIF was observed in different regions in brain and spleen in response to R848 treatment; however in liver, increased MIF expression was observed in hepatocytes only. On the other hand, R848 treatment had induced a slight enhancement of MIF concentration in the plasma of C57BL/6J mice. Taken together, these data suggest that R848 differently regulates MIF mRNA expression depending on organ types and could influence MIF concentration in cellular microenvironment.

Ethanol production from a biomass mixture of furfural residues with green liquor-peroxide saccarified cassava liquid.

BACKGROUND: As the most abundant renewable resources, lignocellulosic materials are ideal candidates as alternative feedstock for bioethanol production. Cassava residues (CR) are byproducts of the cassava starch industry which can be mixed with lignocellulosic materials for ethanol production. The presence of lignin in lignocellulosic substrates can inhibit saccharification by reducing the cellulase activity. Simultaneous saccharification and fermentation (SSF) of furfural residues (FR) pretreated with green liquor and hydrogen peroxide (GL-H2O2) with CR saccharification liquid was investigated. The final ethanol concentration, yield, initial rate, number of live yeast cells, and the dead yeast ratio were compared to evaluate the effectiveness of combining delignificated lignocellulosic substrates and starchy substrates for ethanol production. RESULTS: Our results indicate that 42.0 % of FR lignin removal was achieved on FR using of 0.06 g H2O2/g-substrate and 9 mL GL/g-substrate at 80 °C. The highest overall ethanol yield was 93.6 % of the theoretical. When the ratio of 0.06 g/g-H2O2-GL-pretreated FR to CR was 5:1, the ethanol concentration was the same with that ratio of untreated FR to CR of 1:1. Using 0.06 g/g-H2O2-GL-pretreated FR with CR at a ratio of 2:1 resulted in 51.9 g/L ethanol concentration. Moreover, FR pretreated with GL-H2O2 decreased the concentration of byproducts in SSF compared with that obtained in the previous study. CONCLUSIONS: The lignin in FR would inhibit enzyme activity and GL-H2O2 is an advantageous pretreatment method to treat FR and high intensity of FR pretreatment increased the final ethanol concentration. The efficiency of ethanol fermentation of was improved when delignification increased. GL-H2O2 is an advantageous pretreatment method to treat FR. As the pretreatment dosage of GL-H2O2 on FR increased, the proportion of lignocellulosic substrates was enhanced in the SSF of the substrate mixture of CR and FR as compared with untreated FR. Moreover, the final ethanol concentration was increased with a high ethanol yield and lower byproduct concentrations.

Inhibition of c-Jun N-terminal kinase signaling suppresses skin flap apoptosis in a rat ischemia and/or reperfusion model.

BACKGROUND: The goals of this study were to validate the role of c-Jun N-terminal kinase (JNK) activation in skin flap apoptosis in a rat model of abdomen skin ischemia and/or reperfusion (IR) and to compare the protective effect of SP600125 and hydrogen-rich saline in skin IR injury. METHODS: Male Sprague-Dawley rats were divided into five groups: one sham surgery group and four surgery groups. Before undergoing 3 h of IR management, the surgery groups were treated with normal saline (IR), dimethyl sulfoxide, SP600125 (SP), and hydrogen-rich saline (H). On the third postoperative day, blood perfusion of the flap was measured using Laser Doppler flowmeters. Hematoxylin and eosin staining was used to observe morphologic changes. Early apoptosis was observed using TdT-mediated dUTP-X nick end-labeling staining. pASK-1, pJNK, Bcl-2, and Bax were examined by immunodetection. Caspase-3 activity was also measured 24 h after reperfusion. RESULTS: Compared to the IR group and the dimethyl sulfoxide group, the SP group and the H group had larger skin flap survival area, more blood perfusion and lower levels of caspase-3 activity. The SP and the H groups had high expression levels of Bcl-2 and low expression levels of pASK-1 and pJNK. Bax was significantly decreased in the SP group. In addition, cell apoptosis was decreased in both the sham surgery and the H groups. CONCLUSIONS: IR-induced JNK phosphorylation was reduced by SP600125, indicating that JNK mediates the apoptosis pathways in rat skin. In the SP and the H groups, the apoptotic factors measured showed similar expression levels, indicating that JNK inhibition during IR may be associated with H-mediated protection against skin IR apoptosis.

Diblock Polyelectrolytic Copolymers Containing Cationic Iron and Cobalt Sandwich Complexes: Living ROMP Synthesis and Redox Properties.

Diblock metallopolymer polyelectrolytes containing the two redox-robust cationic sandwich units [CoCp'Cp](+) and [FeCp'(η(6)-C6 Me6)](+) (Cp = η(5)-C5 H5; Cp' = η(5)-C5H4-) as hexafluorophosphate ([PF6](-)) salts are synthesized by ring-opening metathesis polymerization using Grubbs' third generation catalyst. Their electrochemical properties show full chemical and electrochemical reversibilities allowing fine determination of the copolymer molecular weight using Bard-Anson's electrochemical method by cyclic voltammetry.

Redox-Robust Pentamethylferrocene Polymers and Supramolecular Polymers, and Controlled Self-Assembly of Pentamethylferricenium Polymer-Embedded Ag, AgI, and Au Nanoparticles.

We report the first pentamethylferrocene (PMF) polymers and the redox chemistry of their robust polycationic pentamethylferricenium (PMFium) analogues. The PMF polymers were synthesized by ring-opening metathesis polymerization (ROMP) of a PMF-containing norbornene derivative by using the third-generation Grubbs ruthenium metathesis catalyst. Cyclic voltammetry studies allowed us to determine confidently the number of monomer units in the polymers through the Bard-Anson method. Stoichiometric oxidation by using ferricenium hexafluorophosphate quantitatively and instantaneously provided fully stable (even in aerobic solutions) blue d(5) Fe(III) metallopolymers. Alternatively, oxidation of the PMF-containing polymers was conducted by reactions with Ag(I) or Au(III) , to give PMFium polymer-embedded Ag and Au nanoparticles (NPs). In the presence of I2 , oxidation by using Ag(I) gave polymer-embedded Ag/AgI NPs and AgNPs at the surface of AgI NPs. Oxidation by using Au(III) also produced an Au(I) intermediate that was trapped and characterized. Engineered single-electron transfer reactions of these redox-robust nanomaterial precursors appear to be a new way to control their formation, size, and environment in a supramolecular way.

Hyperbaric oxygen preconditioning inhibits skin flap apoptosis in a rat ischemia-reperfusion model.

BACKGROUND: Hyperbaric oxygen (HBO) improves skin flap function and inhibits partial necrosis induced by ischemia-reperfusion (I/R) injury. Our study aimed to evaluate the mechanism underlying HBO regulation of the antiapoptosis factors associated with I/R injury of skin flaps. METHODS: The rats were divided into sham surgery, I/R, and HBO groups. Rats from the HBO group received HBO preconditioning followed by I/R surgery. Blood perfusion of the skin flaps was measured with laser Doppler flowmeters. Tissue morphology and apoptosis were subsequently assessed based on hematoxylin-eosinhe and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. Protein expression of phosphorylated apoptosis signal-regulating kinase 1 (pASK-1), phosphorylated c-Jun N-terminal kinase (pJNK), B-cell lymphoma-2 (Bcl-2), and Bcl2-associated X protein (Bax) was examined by immunodetection, and Bcl-2 messenger RNA expression was detected by quantitative polymerase chain reaction. In addition, caspase-3 activity was also measured. RESULTS: The result of microcirculation analysis showed that the survival and blood perfusion rates significantly increased in the skin flap after HBO exposure. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining revealed that cell apoptosis was significantly attenuated in the HBO group. Furthermore, HBO preconditioning increased the expression of Bcl-2 and inhibited pASK-1, pJNK, and Bax expression as determined by both immunohistochemistry and Western blot. Caspase-3 activity and the Bax/Bcl-2 ratio declined in the HBO group. CONCLUSIONS: HBO preconditioning effectively ameliorates I/R injury by regulating the apoptosis signal-regulating kinase 1 and/or c-Jun N-terminal kinase pathway and anti- and proapoptosis factors.

Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats.

Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75mg/kg body weight (1/20 LD50) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity.

"Click" chemistry mildly stabilizes bifunctional gold nanoparticles for sensing and catalysis.

A large family of bifunctional 1,2,3-triazole derivatives that contain both a polyethylene glycol (PEG) chain and another functional fragment (e.g., a polymer, dendron, alcohol, carboxylic acid, allyl, fluorescence dye, redox-robust metal complex, or a ß-cyclodextrin unit) has been synthesized by facile "click" chemistry and mildly coordinated to nanogold particles, thus providing stable water-soluble gold nanoparticles (AuNPs) in the size range 3.0-11.2 nm with various properties and applications. In particular, the sensing properties of these AuNPs are illustrated through the detection of an analogue of a warfare agent (i.e., sulfur mustard) by means of a fluorescence "turn-on" assay, and the catalytic activity of the smallest triazole-AuNPs (core of 3.0 nm) is excellent for the reduction of 4-nitrophenol in water.