FOXP3 promote the progression of glioblastoma via inhibiting ferroptosis mediated by linc00857/miR-1290/GPX4 axis.

The oncogenic properties of members belonging to the forkhead box (FOX) family have been extensively documented in different types of cancers. In this study, our objective was to investigate the impact of FOXP3 on glioblastoma multiforme (GBM) cells. By conducting a screen using a small hairpin RNA (shRNA) library, we discovered a significant association between FOXP3 and ferroptosis in GBM cells. Furthermore, we observed elevated levels of FOXP3 in both GBM tissues and cell lines, which correlated with a poorer prognosis. FOXP3 was found to promote the proliferation of GBM cells by inhibiting cell ferroptosis in vitro and in vivo. Mechanistically, FOXP3 not only directly upregulated the transcription of GPX4, but also attenuated the degradation of GPX4 mRNA through the linc00857/miR-1290 axis, thereby suppressing ferroptosis and promoting proliferation. Additionally, the FOXP3 inhibitor epirubicin exhibited the ability to impede proliferation and induce ferroptosis in GBM cells both in vitro and in vivo. In summary, our study provided evidences that FOXP3 facilitates the progression of glioblastoma by inhibiting ferroptosis via the linc00857/miR-1290/GPX4 axis, highlighting FOXP3 as a potential therapeutic target for GBM.

An immune signature to predict the prognosis of ATRX-wildtype glioma patients and guide immune checkpoint blockade therapy.

Immune and stromal cells contribute to glioma progression by infiltrating the tumor microenvironment. We used clinical characteristics, RNA sequencing data and the ESTIMATE algorithm to obtain stromal and immune scores for alpha thalassemia retardation syndrome X-linked (ATRX)-mutation-type (ATRX-mt) and ATRX-wildtype (ATRX-wt) glioma tissues from The Cancer Genome Atlas. To identify specific immune biomarkers of glioma, we compared the gene expression profiles of ATRX-wt glioma tissues with high vs. low immune/stromal scores, and discovered 162 differentially expressed genes. The protein-protein interaction network based on these results contained 80 interacting genes, of which seven (HOXA5, PTPN2, WT1, HOXD10, POSTN, ADAMDEC1 and MYBPH) were identified as key prognostic genes via LASSO and Cox regression analyses. A risk model constructed using the expression of these seven genes could predict survival for ATRX-wt glioma patients, but was ineffective for ATRX-mt patients. T cells and macrophages were more prevalent in low-risk than in high-risk glioma tissues. Immune checkpoint blockade treatment was highly beneficial for patients with low risk scores. High-risk gliomas were predicted to be more sensitive to rapamycin, dasatinib, 5-fluorouracil and gemcitabine. Thus, our model can be used for the diagnosis, prognostic prediction and treatment planning of ATRX-wt glioma patients.

Ar-turmerone inhibits the proliferation and mobility of glioma by downregulating cathepsin B.

Ar-turmerone, a compound isolated from turmeric seeds, has exhibited anti-malignant, anti-aging and anti-inflammatory properties. Here, we assessed the effects of ar-turmerone on glioma cells. U251, U87 and LN229 glioma cell lines were treated with different concentrations of ar-turmerone (0, 50, 100 and 200 µM), and their viability and mobility were evaluated using Cell Counting Kit 8, colony formation, wound healing and Transwell assays. The effects of ar-turmerone on U251 glioma cell proliferation were also assessed using a subcutaneous implantation tumor model. High-throughput sequencing, bioinformatic analyses and quantitative real-time polymerase chain reactions were used to identify the key signaling pathways and targets of ar-turmerone. Ar-turmerone reduced the proliferation rate and mobility of glioma cells in vitro and arrested cell division at G1/S phase. Cathepsin B was identified as a key target of ar-turmerone in glioma cells. Ar-turmerone treatment reduced cathepsin B expression and inhibited the cleavage of its target protein P27 in glioma cells. On the other hand, cathepsin B overexpression reversed the inhibitory effects of ar-turmerone on glioma cell proliferation, mobility progression in vitro and in vivo. In conclusion, ar-turmerone suppressed cathepsin B expression and P27 cleavage, thereby inhibiting the proliferation and mobility of glioma cells.

Preparation and properties of lignin-based dual network hydrogel and its application in sensing.

Ionic conductive hydrogels prepared from various biological macromolecules are ideal materials for the manufacture of human motion sensors from the perspective of resource regeneration and environmental sustainability. However, it is now difficult to develop conductive hydrogels including excellent self-healing and mechanical properties, mainly due to their inherent trade-off between dynamic cross-linked healing and stable cross-linked mechanical strength. In this work, alkali lignin-Polyvinyl alcohol-polyacrylic acid double network conductive hydrogels with high mechanical strength and good self-healing properties were prepared. We formed the primary network structure by hydrogen bonding interaction between polyvinyl alcohol, alkali lignin and polyacrylic acid, and the secondary network structure by coordination interaction with polyacrylic acid through the addition of Fe3+. The added lignin acts as a dynamic linkage bridge in a porous network mediated by multiple ligand bonds, imparting superior mechanical properties to the hydrogels. The relationships between the alkali lignin and iron ion dosage and the comprehensive properties of hydrogels (adhesion, antibacterial, self-healing, electrical conductivity and mechanical properties) were studied in detail. On this basis, the hydrogels explored the role of lignin in the regulation of hydrogels properties and revealed the self-healing and conductive mechanism.

Outer membrane protein A of Acinetobacter baumannii regulates pulmonary inflammation through the TLR2-NF-κB pathway.

Acinetobacter baumannii (A. baumannii) is characterized by a high prevalence of drug resistance; how to effectively treat it is still a major clinical challenge. Our previous experiments confirmed that ompA, which is one of the most well-characterized virulence factors, may be dependent on the caspase-1 pathway-stimulated expression of NLRP3 inflammasome to enhance inflammation. TLRs (i.e., TLR2, etc.) is the initiating signal for NLRP3 inflammasome activation; how it relates to ompA in its underlying pathogenic mechanism is not clear. In this study, we proofed that ompA promoted NLRP3 inflammasome activation while the TLR2-NF-κB pathway was also activated after A. baumannii infection. Additionally, the expression of NLRP3 inflammasome-associated proteins and genes was inhibited by silencing TLR2 and NLRP3. This indicated that ompA might depend on the TLR2-NF-κB pathway to assemble and activate the NLRP3 inflammasome. OmpA promoted the assembly of the NLRP3 inflammasome through the TLR2-NF-κB pathway and inhibited the degradation of caspase-1 by the proteasome so that a large number of mature IL-1ß/IL-18 and other proinflammatory factors were released extracellularly to enhance the body's inflammatory response. Taken together, the results of the joint pre-study confirmed a novel TLR2-NF-κB/NLRP3/caspase-1-modulated mechanism underpinning ompA activity, the NLRP3 inflammasome pathway may be as a potential immunomodulatory target against A. baumannii infections.

Fabrication of lignin reinforced hybrid hydrogels with antimicrobial and self-adhesion for strain sensors.

Ionic conductive hydrogels prepared from various biological macromolecules are ideal materials for the manufacture of human motion sensors from the perspective of resource regeneration and environmental sustainability. However, it is still challenging to prepare hydrogels with both high toughness and self-healing ability. In this study, lignin-based ß-CD-PVA (LCP) self-healing conductive hydrogels with high tensile properties were prepared by one-step method using alkali lignin as a plasticizer. Compared with PVA hydrogel, the maximum storage modulus and elongation were increased by 2.5 and 20.0 times, respectively. Uniform distribution of lignin can increase the fluidity and distance of polymer molecular chains, thus improving the viscoelastic and tensile properties of the LCP self-healing hydrogel. LCP hydrogels can maintain self-healing ability in both high (45 °C) and low temperature (0 °C) environments, and the self-healing ability is not affected by pH. Moreover, it also has good conductivity, anti-bacterial, thermostability, and anti-UV property, which has a good application prospect in the field of 3D printing and wearable electronic devices, which expands the efficient utilization of lignin in biorefinery.

Effects of Edaravone on Functional Recovery of a Rat Model with Spinal Cord Injury Through Induced Differentiation of Bone Marrow Mesenchymal Stem Cells into Neuron-Like Cells.

Edaravone can induce differentiation of bone marrow mesenchymal stem cells (BMSCs) into neuron-like cells and replace lost cells by transplanting neuron-like cells to repair spinal cord injury (SCI). In this study, BMSCs were derived from the bone marrow of male Wistar rats (4 weeks old) through density gradient centrifugation (1.073 g/mL), and the cell purity of BMSCs was up to 95%. The combined injection of basic fibroblast growth factor and edaravone was conducted to differentiate BMSCs into neuron-like cells. In this study, 120 male Wistar rats were used to establish the model of semitransverse SCI; on the seventh day, neuron-like cells were labeled by BrdU and then injected into the epicenter of the injury of rats. On the 14th day after cell transplantation, the biotin dextran amine (BDA) fluorescent agent was used to track the repair of nerve damage. At 7, 14, 21, and 30 days after SCI, the Basso, Beattie, and Bresnahan (BBB) locomotor scale method was used to measure the functional recovery of hind limbs in rats. Additionally, hematoxylin and eosin (H&E) staining, Nissl staining, immunohistochemistry, transmission electron microscopy (TEM), Western blotting, and Real-time quantitative reverse transcripion PCR (qRT-PCR) were used to observe the regeneration of nerve cells. In the edaravone+BMSC group, behavioral analysis of locomotor function showed that functional recovery was significantly enhanced after transplantation of the cells, BrdU-positive cells could be observed scattered in the injured area and extended to both the head and tail, and the BDA tracer shows that the edaravone+BMSC group emits more fluorescent signals. Additionally, H&E staining, Nissl staining, and immunohistochemistry revealed that the space of spinal cord tissue was attenuated and the neurons were increased. Western blotting and qRT-PCR showed that the expression levels of neuron-specific enolase (NSE), Nestin, and neurofilament 200 (NF) were increased, while the expression of glial fibrillary acidic protein (GFAP) was decreased. TEM showed that cytoplasmic edema was reduced, mitochondrial vacuoles were attenuated, and nuclear chromatin concentration was declined after transplantation of neuron-like cells. Moreover, with the extension of time of edaravone+BMSC transplantation, the structures of mitochondria and endoplasmic reticulum tended to be normal. In summary, the induced differentiation of BMSC transplantation can significantly promote the functional repair of SCI.

Preparation of a boronate-affinity monolithic column for adsorption of nucleosides.

Chitosan is a considerably versatile and promising biomaterial and can easily form a 3D hierarchical porous scaffold. In this work, a novel boronate-affinity monolithic column modified with a boronic acid-chitosan complex was prepared and characterized by different methods such as Fourier transform infrared spectroscopy, scanning electron microscopy, thermal gravimetric analysis, specific surface area analysis and pore size distribution analysis. The synthesized monolithic column was used for polymer monolithic microextraction combined with high performance liquid chromatography for the simultaneous determination of cytidine, uridine, inosine, and guanosine in milk powder samples. Several parameters affecting extraction efficiency, including the eluent proportion, eluent flow rate, sample flow rate, sample volume, and sample pH were investigated. The boronate-affinity monolithic column showed high enrichment ability due to the selective formation of cyclic borate esters between nucleosides and boronic acid groups at high pH and the release of cyclic borates at low pH values. Under the optimum operating conditions, the linear range was 0.1-50 µg mL-1, and the correlation coefficients were in the range of 0.9993-0.9994. The LOD and LOQ were in the range of 0.0027-0.0034 and 0.0090-0.011 µg mL-1, respectively. In addition, the results of recovery and relative standard deviation were satisfactory.

Secondary organic aerosol formation from 3C⁎-initiated oxidation of 4-ethylguaiacol in atmospheric aqueous-phase.

In this study, we investigated aqueous-phase triplet excited states (3C⁎)-induced photo-degradation of 4-ethylguaiacol (EG) under both simulated sunlight and ultraviolet (UV) light irradiations. Through quencher experiments, the relative contributions of reactive oxygen species (ROS, such as 1O2/O2-/·OH) and 3C⁎ were calculated and results showed three reactive species, e.g., 3C⁎, 1O2 and O2-, all seemed to play important roles in the photo-degradation of EG, but contribution from ·OH was relatively minor. High steady-state 1O2 concentration after 1 h irradiation further revealed the major contribution of 1O2 to photo-degradation under Xe light irradiation. The degradation experiment under three saturated gases (air, O2 and N2) showed that the degradation rate in air-saturated condition was the largest owing to synergistic effect of 1O2 and 3C⁎. Oxidative capacity of aqueous secondary organic aerosol (aqSOA) increased with reaction time by monitoring oxygen-to­carbon (O/C) ratio and carbon oxidation state (OSc) via an aerodyne soot particle aerosol mass spectrometer (SP-AMS). Moreover, aqSOA mass yields were calculated via SP-AMS data. The UV-vis spectral change suggested formation of light-absorbing organics at first stage under simulated sunlight irradiation. Based on the identified products and the reactive intermediates, we postulated that 3C⁎-induced oxidation might be attributed to direct reactions by 3C⁎ and 1O2, chemical reaction by ROS, as well as oligomerization via H-abstraction. To the best of our knowledge, this is the first time to explore systematically reaction pathways of 4-ethylguaiacol under 3C∗ radical on the basis of thorough analysis of products and reactive species. Our findings highlight the impacts of aqSOA from biomass burning emissions on air quality and climate change.

Dissipation, transformation and accumulation of triclosan in soil-earthworm system and effects of biosolids application.

Triclosan (TCS), widely used as an antimicrobial ingredient, is usually introduced into soil by biosolids application, and has presented potential risk in agro-ecosystem. The dissipation pathways of TCS in soil were analyzed in the presence and absence of earthworms (including Metaphire guillelmi and Eisenia fetida). Meanwhile the accumulation and transformation potentials of TCS in the two earthworms were evaluated. Results indicated that about 44% of initial TCS amount dissipated in sterile soil after 56-day incubation, which may mainly result from the bound-residues formation. In contrast, TCS in non-sterile soil dissipated more quickly with a t1/2 of 12 days, suggesting that microbial degradation was responsible for TCS dissipation. Triclosan was methylated to methyl triclosan (MTCS) in soil, which however contributed little for TCS dissipation. The presence of M. guillelmi accelerated TCS dissipation with the reduced t1/2 to 8 days, and inhibited MTCS formation in soil, while E. fetida had no significant (P > 0.05) effects on the fate of TCS. E. fetida accumulated more TCS than M. guillelmi, with bioaccumulation factors up to 11 vs. 0.6. It was also proved that methylation metabolism occurred in earthworms (including gut microorganisms), and M. guillelmi had higher metabolic efficiency compared to E. fetida. Even though eliminations of TCS and MTCS were rapid (except for TCS in M. guillelmi), the residues of the two compounds in both earthworms remained at high levels, having the potential to transfer in the terrestrial food web. In addition, results showed that biosolids application changed TCS persistence, as well as bioavailability dependent on earthworm species. When biosolids at 1% added, more residual TCS and MTCS in soil were observed, while TCS accumulation in E. fetida decreased, however, methylation metabolism in both earthworm species was not affected. The findings provide important information for a more precise risk assessment of biosolids land-application. CAPSULE: Triclosan dissipation, methylation and bioavailability in soils were affected by biosolids amendment and dependent on earthworm species with different accumulation and metabolic potentials.

A comprehensive investigation of aqueous-phase photochemical oxidation of 4-ethylphenol.

Secondary organic aerosol (SOA) species formed in atmospheric aqueous phases is recently recognized as an important contributor to fine aerosols, which is known to be a prominent human health risk factor internationally. This work, for the first time, systematically investigated aqueous-phase photochemical oxidation of 4-ethylphenol (4-EP) - a model compound from biomass burning and a surrogate of intermediate volatility organic compounds, under both ultraviolet (UV) (Hg lamp) and simulated sunlight (Xe lamp). We found that 4-EP could degrade upon hydroxal radical (OH) oxidation under UV light nearly 15 times faster than that under simulated sunlight, but large aqueous SOA (aqSOA) yields (108%-122%) were observed under both situations. AqSOA masses and oxidation states continuously increased under simulated sunlight, yet they increased first then decreased quickly under UV light. We proposed a reaction scheme based on identified products, showing that oligomerization, functionalization and fragmentation all can occur during 4-EP oxidation. Our results demonstrate that OH radical may suppress oligomerization and functionalization, but is favorable for fragmentation. Under UV light with H2O2 (high OH), fragmentation was dominant, producing more volatile and smaller molecules, and less aqSOA in later oxidation; Under simulated sunlight with H2O2 (moderate OH), functionalization that can form hydroxylated monomer was more important. Moreover, 4-EP oxidation by the organic triplet excited state (3C*) could form species with stronger visible light absorptivity than those from OH-mediated oxidation, and the absorptivity showed positive link with contents of humic-like substances.

Preparation of chiral-at-metal catalysts and their use in asymmetric photoredox chemistry.

Asymmetric catalysis is a powerful approach for the synthesis of optically active compounds, and visible light constitutes an abundant source of energy to enable chemical transformations, which are often triggered by photoinduced electron transfer (photoredox chemistry). Recently, bis-cyclometalated iridium(III) and rhodium(III) complexes were introduced as a novel class of catalysts for combining asymmetric catalysis with visible-light-induced photoredox chemistry. These catalysts are attractive because of their unusual feature of chirality originating exclusively from a stereogenic metal center, which offers the prospect of an especially effective asymmetric induction upon direct coordination of the substrate to the metal center. As these chiral catalysts contain only achiral ligands, special strategies are required for their synthesis. In this protocol, we describe strategies for preparing two types of chiral-at-metal catalysts, namely the Λ- and Δ-enantiomers (left- and right-handed propellers, respectively) of the iridium complex IrS and the rhodium complex RhS. Both contain two cyclometalating 5-tert-butyl-2-phenylbenzothiazoles in addition to two acetonitrile ligands and a hexafluorophosphate counterion. The two cyclometalated ligands set the propeller-shaped chiral geometry, but the acetonitriles are labile and can be replaced by substrate molecules. The synthesis protocol consists of three stages: first, preparation of the ligand 5-tert-butyl-2-phenylbenzothiazole; second, preparation of salicylthiazoline (used for iridium) and salicyloxazoline (used for rhodium) chiral auxiliaries; and third, the auxiliary-mediated synthesis of the individual enantiopure Λ- and Δ-configured catalysts. This class of stereogenic-only-at-metal complexes is of substantial value in the field of asymmetric catalysis, offering stereocontrolled radical reactions based on visible-light-activated photoredox chemistry. Representative examples of visible-light-induced asymmetric catalysis are provided.

Combining the catalytic enantioselective reaction of visible-light-generated radicals with a by-product utilization system.

We report an unusual reaction design in which a chiral bis-cyclometalated rhodium(iii) complex enables the stereocontrolled chemistry of photo-generated carbon-centered radicals and at the same time catalyzes an enantioselective sulfonyl radical addition to an alkene. Specifically, employing inexpensive and readily available Hantzsch esters as the photoredox mediator, Rh-coordinated prochiral radicals generated by a selective photoinduced single electron reduction are trapped by allyl sulfones in a highly stereocontrolled fashion, providing radical allylation products with up to 97% ee. The hereby formed fragmented sulfonyl radicals are utilized via an enantioselective radical addition to form chiral sulfones, which minimizes waste generation.

Enantioselective Alkynylation of Aromatic Aldehydes Catalyzed by a Sterically Highly Demanding Chiral-at-Rhodium Lewis Acid.

The enantioselective catalytic alkynylation of aromatic aldehydes is reported using a sterically highly hindered bis-cyclometalated rhodium-based Lewis acid catalyst featuring the octahedral metal as the only stereogenic center. Yields of 58-98% with 79-98% enantiomeric excess were achieved using 1-2 mol % of catalyst. This work complements previous work from our laboratory on the enantioselective alkynylation of 2-trifluoroacetyl imidazoles (Chem. - Eur. J. 2016, 22, 11977-11981) and trifluoromethyl ketones (J. Am. Chem. Soc. 2017, 139, 4322-4325) using catalysts with octahedral metal-centered chirality.

Investigation of submicron aerosol characteristics in Changzhou, China: Composition, source, and comparison with co-collected PM2.5.

Mass concentrations and chemical compositions of submicron particles (PM1) collected during July 2015 to April 2016 in Changzhou, a city in the Yangtze River Delta region, were systematically investigated for the first time. Specifically, an Aerodyne soot particle aerosol mass spectrometer (SP-AMS) was employed to characterize the water-soluble organic matter (WSOM). The average concentration of PM1 was 63.6 µg m-3, occupying ∼60% of co-collected PM2.5 mass. Water soluble inorganic ions (WSIIs) was the most abundant component with secondary ions (SO42-, NO3- and NH4+) as the dominant species. Organic matter (OM) accounted for 21.6% of PM1, with approximately 80% was water-soluble. Trace metals could constitute up to 3.0% of PM1 mass, and Fe, Al and Zn were the three most abundant ones. PAHs were predominated by ones with 5-6 rings, occupying over half of the PAHs mass; further analyses showed that fuel and coal combustion had significant contributions to PAHs. Positive matrix factorization of the WSOM data separated four factors: a traffic-related hydrocarbon-like OA (HOA), a local OA (LOA) likely associated with cooking and coal combustion emissions, etc., a secondary nitrogen-enriched OA (NOA) and an oxygenated OA (OOA). PCA analyses showed that crustal source was likely important for PM1 too. Back trajectory results implied that both PM1 and PM2.5 were mainly derived from local/regional emissions. Our findings present results regarding the PM1 chemistry and its relationship with the PM2.5 in Changzhou, which are valuable for the government to make effective policies to reduce the aerosol pollution in and near the city.

[Pollution Characteristics and Source Identification of PAHs in Atmospheric PM2.5 in Changzhou City].

A total of 55 ambient fine particle (PM2.5) samples were collected in Changzhou City from January to August 2016. The concentrations of 17 PM2.5-bound PAHs in the samples were analyzed by GC-MS. Results showed that seasonal average mass concentrations of PAHs in winter, spring, and summer were 140.24, 41.42, and 2.96 ng·m-3, respectively, which indicating that the pollution of PAHs in winter appeared more serious than in the other two seasons, and 4-6-ring high molecular weight PAHs were predominant in all three seasons. The average daily level of BaP was 3.64 ng·m-3 and the days it exceeded the permitted standard accounted for 41% of total days. PAH concentration had significant negative correlations with temperature (correlation coefficient: -0.643) and visibility (correlation coefficient: -0.466), whereas it had good positive correlations with atmospheric pressure (correlation coefficient: 0.544) and poor correlations with wind speed and relative humidity. PAH concentrations were higher at nighttime than at daytime, because of the influences of temperature difference, atmospheric stratification, as well as pollution sources. The results from the air backward trajectory model indicated that PM2.5-bound PAHs in Changzhou were mainly affected by local emission sources and short-distance transportation, whereas the contribution of long-distance transmission was small (only 11%). Based on analysis of characteristic ratios, PAHs were mainly sourced from coal burning, vehicle emissions, and biomass burning. An incremental lifetime cancer risk (ILCR) model was used to evaluate the health impact of PAHs via breathing exposure pathways. Results revealed that the ILCR of adults was higher than that of children. The ILCRs of the group for winter and spring were slightly higher than the risk threshold, but a difference was not obvious for summer.

Organocatalytic, Asymmetric Total Synthesis of (-)-Haliclonin†A.

The first total synthesis of the alkaloid (-)-haliclonin A is reported. The asymmetric synthesis relied on a novel organocatalytic asymmetric conjugate addition of nitromethane with 3-alkenyl cyclohex-2-enone to set the stereochemistry of the all-carbon quaternary stereogenic center. The synthesis also features a Pd-promoted cyclization to form the 3-azabicyclo[3,3,1]nonane core, a SmI2 -mediated intermolecular reductive coupling of enone with aldehyde to form the requisite secondary chiral alcohol, ring-closing alkene and alkyne metathesis reactions to build the two aza-macrocyclic ring systems, and an unprecedented direct transformation of enol into enone.

Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB.

High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM) of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g.) was administered daily for 12 weeks. We found that arsenic at dosages of 1, 3, and 10 mg/kg decreased body weight and increased the arsenic content in the brain. The object recognition LTM (tested 24 h after training) was disrupted by 3 mg/ kg and 10 mg/ kg, but not 1 mg/ kg arsenic exposure. Swimming exercise also prevented LTM impairment induced by 3 mg/ kg, but not with 10 mg/ kg, of arsenic exposure. The expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP-response element binding protein (pCREB) in the CA1 and dentate gyrus areas (DG) of the dorsal hippocampus were decreased by 3 mg/ kg and 10 mg/ kg, but not by 1 mg/ kg, of arsenic exposure. The decrease in BDNF and pCREB in the CA1 and DG induced by 3 mg/ kg, but not 10 mg/ kg, of arsenic exposure were prevented by swimming exercise. Arsenic exposure did not affect the total CREB expression in the CA1 or DG. Taken together, these results indicated that swimming exercise prevented the impairment of object recognition LTM induced by arsenic exposure, which may be mediated by BDNF and CREB in the dorsal hippocampus.

Complexity generation by chemical synthesis: a five-step synthesis of (-)-chaetominine from L-tryptophan and its biosynthetic implications.

We demonstrated, for the first time, that on the basis of chemistry principles, the hexacyclic peptidyl alkaloid (−)-chaetominine (1) can be synthesized in a straightforward manner from L-Trp. The approach features the efficient generation of molecular complexity via a tandem C3/C14 syn-selective epoxidation (dr = 3:2)­annulative ring-opening reaction and a regioselective epimerization at C14. The successful production of (−)-chaetominine (1) from L-Trp could be helpful for revealing how the configuration of L-tryptophan becomes inverted in the biosynthetic pathway of (−)-chaetominine (1).

The four-step total synthesis of (-)-chaetominine.

The total synthesis of the alkaloid (-)-chaetominine (1) has been achieved in four steps with an overall yield of 33.4%. Key features of our strategy include a one-pot cascade indole epoxidation - epoxide ring-opening cyclization - lactamization reaction sequence, and the use of a nitro group as a latent amino group for the one-pot construction of the quinazolinone ring. This constitutes a step economical, redox economical and protecting group-free total synthesis.