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A new neolignan, (-)-(7S, 8R)-3‑methoxy-4', 7-epoxy-8, 5'-neolignane-5, 9, 3', 9′-tetraol (1) and a new biphenylpropanoid, 1, 2-epoxy-1-(3', 4'-dihydroxyphenyl-)-3-(2'', 3'', 5''-trihydroxyphenyl-) propane (2), together with eight known compounds (3-10), were isolated from the 95% EtOH extract of the leaves of Cupressus funebris Endl. Their structures were determined by spectroscopic methods including NMR, circular dichroism (CD) spectra and comparison of the NMR data with reported in references. The antioxidant activities of all compounds were evaluated by DPPH, ABTS, and FRAP methods. Compounds 2 (IC50: 33.98 ± 0.11 μM), 3 (IC50: 32.97 ± 0.63 μM), 8 (IC50: 32.07 ± 1.57 μM), and 9 (IC50: 33.30 ± 2.29 μM) showed stronger DPPH free radical scavenging activity than l -ascorbic acid (IC50: 64.31 ± 1.32 μM). Except for 4, the other compounds showed ABTS radical scavenging abilities comparable to l -ascorbic acid (54.91 ± 1.18 μM) with the IC50 ranged from 24.42 ± 1.78 μM to 138.70 ± 13.58 μM. Compound 3 (0.72 ± 0.02 mmol/g) showed the same ferric reducing antioxidant power (FRAP) as l -ascorbic acid (0.83±0.02 mmol/g).

Meeting the demand for fresh water and energy is among the major challenges to the development of human civilization. Herein, we report the concept of a covalent organic framework hydrogel (named CPP) as a synergistic platform for seawater desalination and uranium extraction. In natural seawater, CPP shows an exceptional evaporation rate (0.744 kg m−2 h−1) and uranium extraction capacity (4.15 mg g−1), which benefits from the hydrophilic 3D hydrogel network and capillary microporous channels of CPP providing adequate water transport, improving the mass transfer of uranyl ions, and increasing the binding sites of uranyl ions. In addition, CPP exploits interfacial solar heating to limit heat, increases solar energy utilization, and further accelerates the coordination between uranium and binding sites. The excellent photocatalytic effects endow CPP with high anti-biofouling activity, achieving long-term solar desalination and highly efficient uranium extraction. The connection between freshwater and nuclear energy is realized in a new material providing an opportunity to meet the growing needs of mankind.

Extracting uranium from seawater with a chemically stable adsorbent is one of the most promising strategies for challenges originating from sustainable nuclear energy industries. Covalent organic f...

Mercury is one of the most toxic elements in the environment. Recently, a number of covalent organic frameworks (COFs) were developed for simultaneous detection and removal of mercury. They rely on...

Uranium is a key element in the nuclear industry and also a global environmental contaminant with combined highly toxic and radioactive. Currently, the materials based on post-modification of amidoxime have been developed for uranium detection and adsorption. However, the affinity of amidoxime group for vanadium is stronger than that of uranium, which is the main challenge hindering the practical application of amidoxime-based adsorbents. Herein, we synthesized a fluorescent covalent organic framework (TFPPy-BDOH) through integrating biphenyl diamine and pyrene unit into the π-conjugated framework. TFPPy-BDOH has an excellent selectivity to uranium due to the synergistic effect of nitrogen atom in the imine bond and hydroxyl groups in conjugated framework. It can achieve ultra-fast fluorescence response time (2 s) and ultra-low detection limit (8.8 nM), which may be attributed to its intrinsic regular porous channel structures and excellent hydrophilicity. More excitingly, TFPPy-BDOH can chemically reduce soluble U (VI) to insoluble U (IV), and release the binding site to adsorb additional U (VI), achieving high adsorption capacity of 982.6 ± 49.1 mg g-1. Therefore, TFPPy-BDOH can overcome the challenges faced by current amidoxime-based adsorbents, making it as a potential adsorbent in practical applications.

Energy and fresh water are essential for the sustainable development of human society, and both could be obtained from seawater. Herein, we explored the first covalent organic framework (COF) sponge (named BHMS) by in situ loading the benzoxazole-linked COF (DBD-BTTH) onto a porous polymer scaffold (polydimethylsiloxane) as a synergistic platform for efficient solar desalination and selective uranium recovery. In natural seawater, BHMS shows a high evaporation rate (1.39 kg m-2 h-1) and an exceptional uranium recovery capacity (5.14 ± 0.15 mg g-1) under 1 sun, which are due to its desirable inbuilt structural hierarchy and elastic macroporous open cells providing adequate water transport, increased evaporation sites of seawater, and selective binding sites of uranyl. Besides, the excellent photothermal performance and photocatalytic activity endow the BHMS with high solar desalination efficiency and excellent anti-biofouling activity and promote selective coordination of uranyl.

We propose a high sensitivity optical fiber sensor for detecting the acoustic emission generated by the partial discharge in gas-insulated-switchgear (GIS). A model is established to investigate the effects of the cylinder coil on the sensitivity, the bandwidth, and the detection limit. After that, the proposed sensor was modified based on the effects. The average sensitivity of the optimized acoustic emission (AE) optical fiber sensor is 32 dB higher than that of the conventional lead zirconate titanate (PZT) in the frequency range from 20 kHz to 100 kHz. Moreover, the experimental results show that the detectable partial discharge initial voltage for the proposed optical system is 17.1% lower than that for the PZT system, and the amplitude of the signal detected by the proposed optical system is 525% higher than that detected by the PZT system.

Online dissolved gas analysis (DGA) is an effective technique to obtain the health status information of insulation oil in power transformers. The typical hydrocarbon gases (methane, ethyne, ethene, ethane) decomposed from insulation oil, are the key indicators to diagnose the fault type and severity. To realize contactless and field measurement, a multi-gas detection system based on tunable diode laser absorption spectrum (TDLAS) is proposed in this paper. Critical technique problems on the light source, long path gas cell, and the topology for multi-gas detection are investigated. Individual central wavelengths of hydrocarbon gases are set at as 1653.72 nm for methane, 1530.37 nm for ethyne, 1620.04 nm for ethene and 1679.06 nm for ethane in the near infrared band. A 10.13 m long multi-pass gas cell is developed with the advantage of anti-vibration design. To share the optical absorption path, an optical switch is adopted to merge the multi-gas detection system. The high sensitivity of the TDLAS multi-gas detection system was demonstrated in the laboratory calibrations, with ethyne detection reaching sub-parts per million level, and the other hydrocarbon gases achieving ppm level. Furthermore, the comparison detection in the real 220 kV power transformer gave evidence to the effective monitoring of DGA, proving it an alternative approach to online detection of multiple gases in power transformer oil.

Cassiae Semen is a widely used herbal medicine and a popular edible variety in many dietary or health beverage. Emerging evidence disclosed that improper administration of Cassiae Semen could induce obvious liver injury, which is possibly attributed to emodin, one of the bioactive anthraquinone compounds in Cassiae Semen, which caused hepatotoxicity, but the underlying mechanisms are not completely understood. Hence, the present study firstly explored the possible role of oxidative stress-mediated mitochondrial dysfunction and ER stress in emodin-cause apoptosis of L02 cells, aiming to elaborate possible toxic mechanisms involved in emodin-induced hepatotoxicity. Our results showed that emodin-induced ROS activated ER stress and the UPR via the BiP/IRE1α/CHOP signaling pathway, followed by ER Ca2+ release and cytoplasmic Ca2+ overloading. At the same time, emodin-caused redox imbalance increased mtROS while decreased MMP and mitochondrial function, resulting in the leaks of mitochondrial-related proapoptotic factors. Interestingly, blocking Ca2+ release from ER by 2-APB could inhibit emodin-induced apoptosis of L02, but the restored mitochondrial function did not reduce the apoptosis rates of emodin-treated cells. Besides, tunicamycin (TM) and doxorubicin (DOX) were used to activate ER stress and mitochondrial injury at a dosage where obvious apoptosis was not observed, respectively. We found that cotreatment with TM and DOX significantly induced apoptosis of L02 cells. Thus, all the results indicated that emodin-induced excessive ROS generation and redox imbalance promoted apoptosis, which was mainly associated with BiP/IRE1α/CHOP signaling-mediated ER stress and would be enhanced by oxidative stress-mediated mitochondrial dysfunction. Altogether, this finding has implicated that redox imbalance-mediated ER stress could be an alternative target for the treatment of Cassiae Semen or other medicine-food homologous varieties containing emodin-induced liver injury.

The inherent features of covalent organic frameworks (COFs) make them highly attractive for uranium recovery applications. A key aspect yet to be explored is how to improve the selectivity and efficiency of COFs for recovering uranium from seawater. To achieve this goal, a series of robust and hydrophilic benzoxazole-based COFs is developed (denoted as Tp-DBD, Bd-DBD, and Hb-DBD) as efficient adsorbents for photo-enhanced targeted uranium recovery. Benefiting from the hydroxyl groups and the formation of benzoxazole rings, the hydrophilic Tp-DBD shows outstanding stability and chemical reduction properties. Meanwhile, the synergistic effect of the hydroxyl groups and the benzoxazole rings in the π-conjugated frameworks significantly decrease the optical band gap, and improve the affinity and capacity to uranium recovery. In seawater, the adsorption capacity of uranium is 19.2× that of vanadium, a main interfering metal in uranium extraction.

Uranium is a key element in the nuclear industry, but its unintended leakage has caused health and environmental concerns. Here we report a sp2 carbon-conjugated fluorescent covalent organic framework (COF) named TFPT-BTAN-AO with excellent chemical, thermal and radiation stability is synthesized by integrating triazine-based building blocks with amidoxime-substituted linkers. TFPT-BTAN-AO shows an exceptional UO22+ adsorption capacity of 427 mg g−1 attributable to the abundant selective uranium-binding groups on the highly accessible pore walls of open 1D channels. In addition, it has an ultra-fast response time (2 s) and an ultra-low detection limit of 6.7 nM UO22+ suitable for on-site and real-time monitoring of UO22+, allowing not only extraction but also monitoring the quality of the extracted water. This study demonstrates great potential of fluorescent COFs for radionuclide detection and extraction. By rational designing target ligands, this strategy can be extended to the detection and extraction of other contaminants., Porous materials for uranium capture have been developed in the past, but materials for simultaneous uranium capture and detection are scarce. Here the authors develop a stable covalent organic framework capable of adsorbing and detecting uranyl ions.

Capturing of uranium from the natural seawater is considered to be one of the most promising methods to meet the current demand for nuclear energy. Herein, we prepared a reduced graphene oxide-based (rGO-based) covalent organic framework hydrogel (KTG) with three-dimensional porous structure as a platform for enhancing uranium capture capacity through photothermal desalination. Under light irradiation, the KTG produces a local heat that can be used to generate steam while promoting the rapid diffusion of uranium inside the hydrogel 3D network, thereby increasing the adsorption efficiency and capacity of uranium. KTG can achieve exceptional uranium capture capacity (521.6 mg g−1) under one sun irradiation, which is 42.4% higher than that under dark conditions. In addition, excellent photocatalytic activity and mechanical properties make KTG possess high anti-biofouling activity, good reusability, and achieving continuous uranium capture and solar distillation.

To overcome the low sensitivity of power transformer partial discharge (PD) detection by a lead zirconate titanate (PZT) sensor, we propose a novel PD detection system based on phase-shifted fiber Bragg gratings (PS-FBG). Compared with the conventional method, the proposed sensor can be installed inside the power transformer, which takes the advantage of the optical fiber status as an insulator. Distributed PD detection is achieved using wavelength and time-division multiplexing. Frequency response experiments indicate that the sensitivity of the PS-FBG is 8.46 dB higher than that of the conventional ultrasonic sensor. Moreover, a PD detection experiment shows that the PD sensitivity of the PS-FBG immersed in oil is 17.5 times higher than that of the PZT sensor. Furthermore, the multiplexing and the feasibility of defect localization of the proposed distributed PD detection system are demonstrated.

Methane is one of the indicative gases in power transformer oil, and the detection of methane dissolved in oil with high accuracy is of great importance for dissolved gases analysis and fault diagnosis inside power transformers. Based on the Beer–Lambert spectral absorption law, dissolved methane detection with tunable diode laser absorption spectrum (TDLAS) is proposed in this paper for the advantages of high sensitivity and resolution. On the basis of wavelength modulation spectroscopy, a specialized TDLAS system was established. To meet the actual needs of field testing, the anti-vibration design of an integrated Herriott cell and a gas pressure (P)/temperature (T) setting are worked out. Photodetector, collimator, and Herriott cell are integrated into one component to reduce the effects of vibration. It is investigated that the temperature has little effect on the second harmonic amplitude in the range of 30 °C ~ 50 °C, and the vacuum pressure is reasonably set at about 1 kPa. Experimental results showed that the resolution of sensitivity could be reached as 6.8 mV/( $\mu$ L/L), the maximum deviation was less than $\pm 4~\mu$ L/L, and the response time is less than 5 min. In the end, field application was also carried out, proving it is a prospective online sensing technique to serve oil-immersed power transformers better.

Self-assembly reaction of Pb(NO3)2 with thiophene-2, 5-dicarboxylic acid (H2TDC) led to an acentric three-dimensional (3D) metal-organic framework under solvothermal conditions, namely, Pb(TDC) (1). The 3D framework of 1 is a pillared-layer structure with the I2O1 type which is composed of a 2D inorganic Pb–O–Pb substructural layer and two independent μ6-TDC2- anions pillars. This 3D framework shows a six-connected pcu topological net according to the topological analysis. Compound 1 crystallizes in an acentric space group and displays potential ferroelectric property which could be due to the swing of the thiophene rings. The remnant polarization (Pr), coercive field (Ec) and saturation spontaneous polarization (Ps) of 1 are ca. 0.034 μC cm−2, 15.7 kV cm−1 and 0.0997 μC cm−2, respectively. Among the H2TDC-based MOFs, the present compound is the first example which shows ferroelectric property. In addition, 1 also exhibits photoluminescent property which can be attributed to ligand-to-metal charge transfer.

So far, it remains a challenge to synthesize uranium adsorbents with robust stability, high adsorption capacity, excellent photocatalytic activity and easy regeneration. Herein, we report the first example of vinylene-linked covalent organic framework (Tp-TMT) with enhanced uranium adsorption through combined selective ligand binding, chemical reduction and photocatalytic reduction. The unique structure and excellent photocatalytic activity of Tp-TMT make it very suitable for photo-enhanced uranium adsorption through three synergistic mechanisms, thus exhibiting an outstanding uranium adsorption capacity (2362.4 mg g−1). In the dark, a large number of hydroxyl groups in the Tp-TMT framework serve as selective binding sites for uranium, and reduce part of U(VI) to U(IV), thereby greatly improving the adsorption capacity. Meanwhile, the synergistic effect of the triazine units and hydroxyl groups in the highly conjugated framework greatly decreases the optical band gap of Tp-TMT, and an additional U(VI) photocatalytic reduction process can occur under light irradiation, further increasing the adsorption kinetics and capacity. This work explored the structural and functional design of covalent organic frameworks for the adsorption and reduction of uranium in nuclear industry wastewater.

Highly effective and reliable adsorbents for uranium extraction are vital significant for environmental protection and social development. Herein, inspired by the interaction between imidazole affinity ligand of histidine and uranium, a series of varying degree hydroxylation imidazole linked covalent organic polymers were developed for the first time via one step facile reaction without any post treatment between 2,4,6-triformylphloroglucinol (Tp), 2,4,6-triformylresorcinol (Bd), 2,4,6-triformylphenol (Hb) and 3,3′-diaminobenzidine (DAB), denoted as TpDAB, BdDAB, and HbDAB, respectively. Benefiting from the hierarchical structure of the covalent organic polymer and synergistic effects originating from hydroxyl groups and imidazole linkages, TpDAB, BdDAB, and HbDAB displayed as the promising adsorbents for uranium extraction with high extraction ability and fast capture kinetics. X-ray photoelectron spectroscopy results revealed that both nitrogen atoms in imidazole and oxygen atom in hydroxyl took part in uranium coordination. With the increasing of hydroxyl group amounts, TpDAB achieved highest extraction capacity of uranium. Furthermore, TpDAB with imidazole affinity group possessed eminent selectivity for uranium in the multiple metal ions solution, and especially overcome the unavoidable problem of vanadium interfering with amidoxime adsorption uranium. This work provided a promising uranium extraction strategy with high selectivity and easy preparation for environmental protection and human health.

The authors describe a voltammetric method for the determination of arsenite [As(III)] based on an As(III)-specific binding probe DNA (SBP DNA; a single-stranded DNA) and the electrochemical indicator Methylene Blue (MB). The SBP DNA was first hybridized with a capture probe (CP) DNA on the surface of a gold electrode. Then, MB was intercalated into the SBP/CP hybrid on the electrode. On addition of As(III), it specifically binds to the SBP DNA, and this results in a conformational change and the dissociation of the SBP DNA from the electrode into solution. Consequently, the amount of MB remaining on the modified electrode is reduced, and this decreases the peak current of MB (best measured at −0.28 V vs. SCE). The findings are exploited in an assay for As(III) that has a linear response in the 0.1 to 200 ppb concentration range and a detection limit as low as 75 ppt. Conceivably, this method can be extended by designing various specific ssDNA oligonucleotides for other heavy metal ions or for small molecules.

We report the exploration of the stabilization effect of the in situ generated N-alkylated DABCO (DABCO = 1,4-diazabicyclo[2.2.2]octane) cation in the family of bromoplumbates and a 1-D bromoplumbate, (Et2DABCO)2n(Pb3Br10)n (1), has been prepared by solvothermal conditions. Optical diffuse reflectance determination shows the band gap of 1 is 3.69 eV, which manifests that 1 is a wide-band-gap semiconductor. Compared with the band gap of bulk PbBr2 (3.84 eV) [1, 2], 1 exhibits 0.15 eV red shift of absorption edge. While for the reported iodo analogs of this compound, (MPDA)2n(Pb3I10)n and (Et2DABCO)2n(Pb3I10)n [3], they exhibit 0.53 and 0.47 eV blue shift of the energy gaps compared with the measured value of 2.30 eV for bulk PbI2, respectively. The photoluminescent study of 1 shows that it exhibits a broad emission band centered at 697 nm upon photoexcitation by 345 nm (amount to 3.59 eV). The calculated density of states manifests the theoretical value of the band gap of 1 is 3.422 eV and the origination of photoluminescence can be ascribed to the transition of bonding electrons of Br– anion to the empty orbits of Pb(II) ion.

Tanshinone IIA (Tan IIA) is a pharmacologically active substance extracted from the rhizome of Salvia miltiorrhiza Bunge (also known as the Chinese herb Danshen), and is widely used to treat atherosclerosis. The pregnane X receptor (PXR) is a nuclear receptor that is a key regulator of xenobiotic and endobiotic detoxification. Tan IIA is an efficacious PXR agonist that has a potential protective effect on endothelial injuries induced by xenobiotics and endobiotics via PXR activation. Previously numerous studies have demonstrated the possible effects of Tan IIA on human umbilical vein endothelial cells, but the further mechanism for its exerts the protective effect is not well established. To study the protective effects of Tan IIA against hydrogen peroxide (H₂O₂) in human umbilical vein endothelial cells (HUVECs), we pretreated cells with or without different concentrations of Tan IIA for 24 h, then exposed the cells to 400 μM H₂O₂ for another 3 h. Therefore, our data strongly suggests that Tan IIA may lead to increased regeneration of glutathione (GSH) from the glutathione disulfide (GSSG) produced during the GSH peroxidase-catalyzed decomposition of H₂O₂ in HUVECs, and the PXR plays a significant role in this process. Tan IIA may also exert protective effects against H₂O₂-induced apoptosis through the mitochondrial apoptosis pathway associated with the participation of PXR. Tan IIA protected HUVECs from inflammatory mediators triggered by H₂O₂ via PXR activation. In conclusion, Tan IIA protected HUVECs against H₂O₂-induced cell injury through PXR-dependent mechanisms.

The purpose of this work was to study the influences of Realgar-Indigo naturalis(RIF) and its principal element realgar on 4 main cytochrome P450 enzymes activities in rats. A simple and efficient cocktail method was developed to detect the four probe drugs simultaneously. In this study, Wistar rats were administered intragastric RIF and realgar for 14 days; mixed probe drugs were injected into rats by caudal vein. Through analyzing the pharmacokinetic parameter of mixed probe drugs in rats, we can calculate the CYPs activities. The results showed that RIF could inhibit CYP1A2 enzyme activity and induce CYP2C11 enzyme activity significantly. Interestingly, in realgar high dosage group, CYP3A1/2 enzyme activity was inhibited significantly, and different dosage of realgar manifested a good dose-dependent manner. The RIF results indicated that drug coadministrated with RIF may need to be paid attention in relation to drug-drug interactions (DDIs). Realgar, a toxic traditional Chinese medicine (TCM), does have curative effect on acute promyelocytic leukemia (APL). Its toxicity studies should be focused on. We found that, in realgar high dosage group, CYP3A1/2 enzymes activity was inhibited. This phenomenon may explain its potential toxicity mechanism.

Dissolved gas analysis (DGA)in power transformers is related to the degradation of insulation materials and dissolved methane (CH 4 )is a symbol gas of low energy electrical or thermal faults in power transformer oil. Conventional online DGA equipment suffers from problems such as cross sensitivity, electromagnetic compatibility and reliability. Based on tunable diode laser absorption spectroscopy (TDLAS) technique, a novel optical method is proposed to detect dissolved methane in transformer oil. Oil samples with fault gases are prepared and dissolved methane detection has been carried out in the laboratory. 1653.72 nm is selected as the central wavelength of tunable diode laser, moreover, a multipass gas cell and wavelength modulation strategy is utilized to trace methane dissolved in oil. Results show that the resolution of detection reaches 0.28 µL/L, and accuracy is less than 2 µL/L at low concentration. In addition, the detection cycle is so time-saving, less than 5 minutes. The proposed measurement method shows tremendous advantages, such as immediate response to concentration changes, no cross interference, no carrier gases, which is proved to be a promising maintain-free technique instead of conventional DGA equipment.

Neurotrophic factors can promote the survival of degenerating retinal cells through the activation of STAT3 pathway. Thus, augmenting STAT3 activation in the retina has been proposed as potential therapy for retinal dystrophies. On the other hand, aberrant activation of STAT3 pathway is oncogenic and implicated in diverse human diseases. Furthermore, the STAT3/SOCS3 axis has been shown to induce the degradation of rhodopsin during retinal inflammation. In this study, we generated and used mice with constitutive activation of STAT3 pathway in the retina to evaluate the safety and consequences of enhancing STAT3 activities in the retina as a potential treatment for retinal degenerative diseases. We show that long-term activation of the STAT3 pathway can induce retinal degenerative changes and also exacerbate uveitis and other intraocular inflammatory diseases. Mechanisms underlying the development of vision impairment in the STAT3c-Tg mice derived in part from STAT3-mediated inhibition of rhodopsin and overexpression of SOCS3 in the retina. These results suggest that much caution should be exercised in the use of STAT3 augmentation therapy for retinal dystrophies.

OsSPL14, identified as IDEAL PLANT ARCHITECTURE1 (IPA1) or WEALTHY FARMER’S PANICLE (WFP) gene, plays a critical role in regulating rice plant architecture. Here, the study showed that OsSPL14-overexpression transgenic rice plants had shorter growth period, short-narrow flag leaves, and thick-green leaves. Compared with wild type plant ‘MH86’, transgenic plants had higher chlorophyll a (Ca), chlorophyll b (Cb) and carotenoid (Cx) content at both seedling and maturity stage. Meanwhile, transcriptome analysis identified 473 up-regulated and 103 down-regulated genes in transgenic plant. The expression of differentially expressed genes (DEGs) involved in carotenoid biosynthesis, abscisic acid (ABA) metabolism and lignin biosynthesis increased significantly. Most of DEGs participated in “plant hormone signal transduction” and “starch and sucrose metabolism” are also up-regulated in transgenic plant. In addition, there were higher levels of ABA and gibberellin acid (GA3) in OsSPL14-overexpression transgenic plants. Moreover, the content of culm lignin, cellulose, silicon and potassium all increased dramatically. Thus, these results demonstrate that overexpression of OsSPL14 has influence on leaf development, hormone level and culm composition in rice, which provide more insight into understanding the function of OsSPL14. Highlight OsSPL14-overexpression transgenic plants showed shorter growth period, short-narrow flag leaves, and thick-green leaves. Transcript profile, abscisic acid (ABA) and gibberellin acid (GA3) level, and culm composition also changed obviously.

Pyruvate is a well-known scavenger of reactive oxygen species (ROS) like hydrogen peroxide and could prevent cells from oxidative damage. A pyruvate-requiring marine bacterium, Pyruvatibacter mobilis CGMCC 1.15125T (=KCTC 42509T), was isolated from the culture broth of a photosynthetic marine microalga. Here we report the complete genome sequence of Pyruvatibacter mobilis, which contained a circular chromosome of 3,333,914 bp with a mean G + C content of 63.9%. Through genomic analysis, we revealed that strain CGMCC 1.15125T encodes genes for some antioxidants like superoxide dismutase, glutathione, rubrerythrin and globin to relieve cellular oxidative stress, while pyruvate added to the medium may reduce extracellular ROS. The genome features of P. mobilis provide further insights into the antioxidant activities of bacteria surviving in oxygen-enriched habitats.

The solubility of valsartan in ethyl acetate + (butanone, isopropyl ether) binary solvent mixtures was measured at temperatures T = 278.15–323.15 K and pressure p = 0.1 MPa with a laser monitoring dynamic technique by a synthetic method. The experimental data were regressed by the modified Apelblat equation, the general single model and the hybrid model. The experimental data are well correlated with the above models because the mean deviations (MDs) are less than 3.79%. The mole fraction solubility of valsartan increases with increase in temperature and enrichment in butanone content, while it decreases with increased mole fraction of isopropyl ether at constant temperature. In addition, thermodynamic studies, including Gibbs energy, entropy and enthalpy, were calculated by van’t Hoff analysis. The results showed that the dissolution of valsartan in mixed solvents is endothermic, spontaneous and entropy-driven.

Pregnane X receptor (PXR) is a nuclear receptor that regulates a number of genes encoding drug metabolism enzymes and transporters and plays a key role in xeno- and endobiotic detoxification. Ginkgolide B has shown to increase the activity of PXR. Here we examined whether ginkgolide B activated PXR and attenuated xenobiotic-induced injuries in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were treated with ginkgolide B. The expression of PXR, CYP3A4, MDR1, VCAM-1, E-selectin and caspase-3 were quantified with qRT-PCR and Western blot analysis. Cell apoptosis was analyzed with flow cytometry. Fluorescently labeled human acute monocytic leukemia cells (THP-1 cells) were used to examine cell adhesion. Ginkgolide B (30–300 μmol/L) did not change the mRNA and protein levels of PXR in the cells, but dose-dependently increased nuclear translocation of PXR protein. Ginkgolide B increased the expression of CYP3A4 and MDR1 in the cells, which was partially reversed by pretreatment with the selective PXR signaling antagonist sulforaphane, or transfection with PXR siRNA. Functionally, ginkgolide B dose-dependently attenuated doxorubicin- or staurosporine-induced apoptosis, which was reversed by transfection with PXR siRNA. Moreover, ginkgolide B suppressed TNF-α-induced THP-1 cell adhesion and TNF-α-induced expression of vascular adhesion molecule 1 (VCAM-1) and E-selectin in the cells, which was also reversed by transfection with PXR siRNA. Ginkgolide B exerts anti-apoptotic and anti-inflammatory effects on endothelial cells via PXR activation, suggesting that a PXR-mediated endothelial detoxification program may be important for protecting endothelial cells from xeno- and endobiotic-induced injuries.

Liquid methanol and methanol clusters have been comprehensively studied to reveal their local structure and hydrogen bond networks. However, our understanding of the crystal forms of methanol is rather limited. The known crystal structures of solid methanol, α, β, and γ, are composed of infinite hydrogen bond chains in their unit cell. The structural diversity of solid methanol is much less than that of liquid methanol, in which both chain and ring structures exist and have been confirmed by experiments. In this study, we employed ab initio random structure searching (AIRSS) to study possible solid methanol structures. AIRSS predicted known solid methanol phases as well as various ring structures that have not been considered. A new possible candidate structure for the δ phase was also discovered. The relative stability of known solid methanol phases and our newly discovered structures were also investigated through dispersion corrected density functional theory. The density functional calculation provides reliable phase transition pressures between the known phases and the searched structures compared with experimental suggestions. In addition, the simulation result indicated that CH⋯O hydrogen bonds play a major role in stabilizing the methanol crystals under high pressures.

Metabolite differences between sexes have rarely been observed in a global manner, but it has recently been made possible by the advancement in metabolomics techniques. In this study, untargeted ultraperformance liquid chromatography coupled to time-of-flight mass spectrometry and an in-house software platform were used for a rapid comparison of sex differences in urinary metabolites in humans and in urinary and serum metabolites in Sprague Dawley (SD) rats. In addition, the species differences of urinary metabolites between humans and SD rats were also observed. Principle component analysis showed that all the observed metabolite sex differences were more distinct in SD rats than in humans, indicating that the sex differences of human urinary metabolites is small compared with that of SD rats. In SD rats, the observed metabolite sex differences were more distinct in urine than in serum, indicating the importance of urine analysis for metabolomics studies. The species differences in the urinary metabolites of humans and SD rats were much more distinct than any of the observed sex differences. Many sex- and species-related markers were discovered and putatively identified. In both humans and SD rats, steroid metabolites appeared to constitute a major sex difference in urinary metabolites. This provides new proof of the special importance of steroid metabolites in sex differences from an untargeted metabolomics investigation, which is rare for sex differences. Contrary patterns involving adrenocortical activity appeared to exist between rodents and humans, which agrees with previous reports. In the serum metabolites of SD rats, sex differences in ascorbic acid or its isomer and pantothenic acid or its isomer, but not in steroid metabolites, were prominent. Human-specific α- N-phenylacetyl-L-glutamine and androsterone glucuronide were among the putative identities of the markers discriminating humans and SD rats. This study demonstrated the feasibility of an in-house software platform and provides metabolite-related information on sex and species differences.

The problem of surface charge accumulation on gas-insulator interface is one of the critical factors for the development of DC Gas Insulated transmission Lines (GIL). In order to solve this problem, researchers have proposed a variety of mathematical models in which the volume conductivity of SF6 was assumed to be constant for calculating the distribution of surface charge. However, the conductivity of SF6 was inconstant, affected by electric field strength. In this paper, a gas model is developed, taking into account the generation, recombination and motion of charge carriers in SF6 of DC-GIL. The surface charge density and the electric field distribution on the insulator surface under DC voltage were simulated. Afterwards, the electric conduction through the volume of the insulator was proved to be the dominating accumulation mechanism. In order to improve the insulation performance, the influence of practical insulator shape on the electric field distribution in DC-GIL was studied. Three different shapes of insulator which were disc insulator, conical insulator and obtuse conical insulator were introduced and compared. The simulation results indicate the obtuse conical insulator was the most suitable configuration for DC-GIL.

Phase transition in thermoelectric (TE) material is a double-edged sword-it is undesired for device operation in applications, but the fluctuations near an electronic instability are favorable. Here, Sb doping is used to elicit a spontaneous composition fluctuation showing uphill diffusion in GeTe that is otherwise suspended by diffusionless athermal cubic-to-rhombohedral phase transition at around 700 K. The interplay between these two phase transitions yields exquisite composition fluctuations and a coexistence of cubic and rhombohedral phases in favor of exceptional figures-of-merit zT. Specifically, alloying GeTe by Sb

A facile strategy has been constructed for the highly efficient discrimination of single nucleotide polymorphisms (SNPs) based on magnetic functionalized graphene oxide (GO@Fe3O4) modified poly(dimethylsiloxane) microchip system coupled with electrochemical detection. A methylene blue-labeled single stranded DNA (P1) can complete complementary with target mircoRNA-21 (T1) to form a perfectly matched DNA/RNA heteroduplex (P1T1), while the hybridization of the P1 with single-base mismatched sequence of mircoRNA-21 (M1) can form a loose DNA/ms-RNA heteroduplex (P1M1). The π-stacking interaction between the loose DNA/ms-RNA heteroduplex and the GO is much stronger than that of the perfectly matched DNA/RNA heteroduplex. Moreover, GO can enhance the unwinding of unstable DNA/ms-RNA through strong interaction between GO and single stranded DNA (ssDNA) and consequently increase the retention time of single-base mismatch microRNA-21 in the GO@Fe3O4-based microchip system. Therefore, the GO@Fe3O4-based microchip system exhibited high performance for the separation and detection of microRNA-21 and single-base mismatch microRNA-21, which provide a powerful protocol for SNPs discrimination within a short analytical time. More importantly, this platform can be used for other small molecules and proteins assay in various systems by simply changing the sequence of the probe DNA.

Psoralea corylifolia L. is a traditional Chinese medicine for the treatment of various skin diseases such as psoriasis, vitiligo and chronic graft-versus-host. Bakuchiol, isolated from the seeds of P. corylifolia L., is one of the most important active compounds. To study the metabolic fate of bakuchiol in rats, an ultra performance liquid chromatography/electrospray ionization-photo diode array-quadrupole time of flight-mass spectrometry (UPLC/ESI-PDA-QTOF-MS) combined with MetaboLynx XS software was used, peak area-time curves of major metabolites in plasma from bakuchiol were determined. A total of 11 metabolites were identified after a single oral administration of bakuchiol, including 6 in plasma, 10 in bile, 8 in urine and 2 in feces, the metabolic transformation pathways of bakuchiol in rats included oxidation, hydroxylation, methylation, O-glucuronide conjugation and O-sulfate conjugation. In conclusion, this study expands our knowledge about the metabolism of bakuchiol which will be conducive to reveal its in vivo pharmacological and toxicological material basis, in addition, UPLC/ESI-PDA-QTOF-MS coupled with MetaboLynx XS software can be adopted as a useful tool for quick detection and identification of metabolites from medicine in vivo.

Objective Phosphodiesterase (PDE) plays an important role in the pathogenesis of Alzheimer's disease (AD). Ferulic acid (FA) has a therapeutic benefit in the treatment of AD. We investigated whether this therapeutic effect is based on the modulation of the PDE/cyclic adenosine monophosphate (cAMP) pathway. In the present study, we investigated whether FA could abrogate Aβ25-35- and lipopolysaccharide-induced cellular damage. Materials and methods Cell viability, superoxide production, and the levels of inflammatory factors were investigated. We further investigated the intracellular levels of cAMP and Ca2+, both of which are associated with PDE activity. Furthermore, molecular docking was used to identify the binding mode between phosphodiesterase 4B2 (PDE4B2) and FA. Results Pretreatment with FA significantly maintained cell viability, increased the levels of superoxide dismutase, and inhibited production of TNF-α and IL-1β induced by Aβ25-35. Moreover, pretreatment with FA increased the intracellular levels of cAMP and decreased the intracellular levels of Ca2+. The docking results also showed that FA has the potential to inhibit PDE4B2 activity. Conclusions Taken together, our results suggested that one of the therapeutic effects of FA on AD was potentially mediated by modulating the PDE/cAMP pathway.

Ethnopharmacological relevance Inflammatory bowel disease (IBD) is associated with chronic inflammation of the intestinal tract. Piperine (1-peperoylpiperidine), the primary lipophilic component in black pepper (Piper nigrum) and long pepper (Piper longum), has been reported to be effective for anti-inflammatory. Rencently, several ethnopharmacological purity compounds, such as baicalin and artemisinin, are reported to have potentially therapeutic role in treating IBD. In the present study, the effects of piperine on pregnane X receptor (PXR)-mediated CYP3A expression and its therapeutic role in IBD were investigated. Materials and methods LS174T cells and C57BL/6J mice were treated by the piperine. Gene expressions were analyzed by real-time PCR, Western blot analysis, transient transfections assay and histological analysis. Results Data indicated that treatment of LS174T cells with piperine markedly increased both CYP3A4 and PXR mRNA and protein. Transient transfection experiments indicated that transcriptional activation of the CYP3A4 gene via piperine was PXR-dependent. Data show that pre-administration of piperine decreased clinical hallmarks of colitis in DSS-treated PXR mice as measured by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. Inflammatory mediators (CCR2, ICAM-1, IL-1β, IL-6, IL-10, iNOS, MCP-1, and TNFα) after DSS treatment were significantly decreased in mice pretreated with piperine but corresponding conditions did not occur in mice with down-regulation of PXR by small interfering RNA (siRNA). Conclusion Piperine is a potential agonist of PXR and an inducer of PXR, which may induce CYP3A4 gene expression at the mRNA and protein levels. These results establish that piperine may contribute to prevention or reduction of colonic inflammation.

Three-dimensional (3D) flower-like cubic Ni3S4 nanoplates with single crystalline nature were successfully prepared through decomposing bis(thiourea) nickel(II) chloride crystals (BTNC). The samples were characterized by X-ray diffraction, scanning electron microscope, transmission electron microscope, selected area electron diffraction and Raman spectroscopy. Results show that the as-prepared products are pure cubic Ni3S4 and stable in range of 180–220°C with single crystal nature providing high surface areas, and higher reaction temperature leads to lower surface areas. Typical Raman peaks of the as-synthesized 3D flower-like cubic Ni3S4 at 200°C are located at 239, 286, 337, 379, 423, 478 and 630 cm−1. Magnetization measurement indicates that single crystalline Ni3S4 nanoplates prepared at 200°C displays antiferromagnetic behaviour.

Pure cubic pyrite flake-like nickel disulfide nanocrystallites have been successfully synthesized by thermal decomposition approach under open-air conditions at 280 °C using bis(thiourea) nickel (II) chloride crystals as precursors. The crystallinity and morphology of the products were found to be dependent on the reaction temperature. Raman spectroscopy study indicates that peak of flake-like nickel disulfide located at 478.7 cm −1 should correspond to a stretching vibration with an A g mode. Magnetization measurement indicates that as-prepared product at 280 °C under open-air condition displays anomalous magnetic property at room temperature and shows weak ferromagnetic. The present thermal approach in a complex system may allow synthesizing other metal chalcogenides by decomposing under open-air conditions.

‘Wangkumbae’ pear (Pyrus pyrifolia Nakai) was used as material and genes encoding enzymes involved in lignin biosynthesis were cloned: two of 4-coumarate:coenzyme A ligase (4CL) genes Pp4CL1 and Pp4CL2, another two cinnamyl alcohol dehydrogenase (CAD) genes PpCAD1 and PpCAD2, and four peroxidase (POD) genes PpPOD1, PpPOD2, PpPOD3 and PpPOD4. The result of real-time PCR analysis showed a similar expression pattern of PpPAL1 and PpPAL2 with higher accumulation of transcripts at fruit developing early stage and low accumulation at late stage. The expression of PpPAL1 and PpPAL2 revealed down-regulation in gibberellin (GA)-treated fruit. The accumulations of Pp4CL1 and Pp4CL2 transcripts were higher in fruit developing early stage compared with those in late stage, and Pp4CL2 expression level was higher than Pp4CL1. Pp4CL1 and Pp4CL2 expression levels in GA-treated fruit were lower compared with in the control fruit. The relative expression level of PpCAD2 showed higher than PpCAD1 and reached a peak at 53 day after blooming. The expressions of PpCAD2 in GA-treated fruit was significantly lower compared with those in the control fruit in early developmental stage, which was consistent with developmental dynamics of sclereid and dynamic changes in lignin contents during the development. The expression of PpPOD4 gene was significantly higher than PpPOD1, PpPOD2 and PpPOD3 during developmental stages. The expressions of PpPOD1, PpPOD2, and PpPOD4 increased firstly and then decreased during the development of the control fruit. PpPOD1 expression in GA-treated fruit was lower than that in the control fruit, which was consistent with the changes in lignin contents.

Platelet-derived growth factor (PDGF)-C is a member of the PDGF family and is critical for neuronal survival in the central nervous system. We studied the possible survival and antiapoptotic effects of PDGF-C on focal retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) on C57BL/6N [Crb1(rd8)] (DKO rd8) background mice, a model for progressive and focal retinal degeneration. We found no difference in transcript and protein expression of PDGF-C in the retina between DKO rd8 mice and wild type (WT, C57BL/6N). Recombinant PDGF-CC protein (500 ng/eye) was injected intravitreally into the right eye of DKO rd8 mice with phosphate-buffered saline as controls into the left eye. The retinal effects of PDGF-C were assessed by fundoscopy, ocular histopathology, A2E levels, apoptotic molecule analysis, and direct flat mount retinal vascular labeling. We found that the PDGF-CC-treated eyes showed slower progression or attenuation of the focal retinal lesions, lesser photoreceptor and retinal pigment epithelial degeneration resulting in better-preserved photoreceptor structure. Lower expression of apoptotic molecules was detected in the PDGF-CC-treated eyes than in controls. In addition, no retinal neovascularization was observed after PDGF-CC treatment. Our results demonstrate that PDGF-C potently ameliorates photoreceptor degeneration via the suppression of apoptotic pathways without inducing retinal angiogenesis. The protective effects of PDGF-C suggest a novel alternative approach for potential age-related retinal degeneration treatment.

The eighteen incompatible medicaments is an important theory in traditional Chinese medicine. The theory suggests that drugs in the eighteen incompatible medicaments can be toxic when used together.Veratrum nigrumL. andRadix paeoniae albabelong to the eighteen incompatible medicaments and have been prohibited for thousands of years. This study offers preliminary insight into the mechanism and chemical constituents responsible for the incompatibility and toxicity of these two agents. Specifically, we performed toxicology studies to identify and quantify the constituent substances of the two agents. Experiments revealed that acute toxicity increases when the dose ofV. nigrumL. is higher than, or equal to, RPA. UPLC-TOF-MS analysis showed that, although the volumes ofV. nigrumL. were the same, the content of some veratrum alkaloids changed significantly and had a trend toward a highly positive correlationr≥0.8with toxicity. This suggests that the increased toxicity of theV. nigrumL. and RPA combination was due mainly to increased content of the special veratrum alkaloids. The cytotoxicity of veratridine in SH-SY5Y cells was decreased with increasing paeoniflorin concentrations. This study provides insight into the mechanism behind the incompatibility theory of TCM.

This research used bagasse as raw material, through xylanase biological treatment process, preparative bagasse dissolving pulp. The optimum process conditions of sulfuric acid pre-hydrolysis were as below: Acid dosage 0.10%, 150°C, 90min. After pre-hydrolysis, cellulose content of the raw materials increased 18.45%, and pentosan decreased 14.49%. The fiber quality analysis showed fiber length and width were reduced, the tiny fiber content was decreased after acid pre-hydrolysis; HPLC analysis showed the optimum acid pre-hydrolysis process which can reduce the inevitable cellulose degradation effectively,hemicelluloses were hydrolyzed furthest at the same time; FTIR spectrum analysis showed acid pre-hydrolysis process can dissolve a lot of hemicelluloses.

To evaluate whether Shenfu injection (SFI) protects against cardiac myocyte injury induced by Fupian injection (FPI) in vitro.H9c2 cells were separately treated with FPI, Renshen injection (RSI) and SFI. Cell viability, lactate dehydrogenase (LDH) release, spontaneous beating rate of primative cardical cells, caspase-3/7 activity, cell apoptosis, and cytochrome P450 2J3 (CYP2J3) mRNA expression were analyzed.The viability of H9c2 cells treated with SFI (37 and 75 mg/mL) was significantly higher than that of H9c2 cells treated with FPI (25 and 50 mg/mL) (P0.05, P0.01, respectively). LDH activity of H9c2 cells treated with SFI (75 mg/mL) was significantly decreased (P0.01) compared with that of H9c2 cells treated with FPI (50 mg/mL). SFI (150 mg/mL) significantly attenuated FPI (100 mg/mL)-induced spontaneous beating rate decrease in primary myocardial cells after 4-hour treatment. Compared with FPI (12 and 25 mg/mL), SFI (18 and 37 mg/mL) treatment could effectively reverse the change of caspase-3/7 activity (P0.01 and P0.01, respectively). Compared with FPI (6 and 25 mg/mL), apoptotic cells decreased significantly (P0.05, P0.01, respectively) when H9c2 cells were incubated with SFI (9 and 37 mg/mL). The expression of CYP2J3 mRNA was down-regulated by FPI, while RSI and SFI could up-regulate the expression of CYP2J3 (P0.01), which suggested the potential mechanism of protection of RSI against cardiac myocyte damage induced by FPI treatment.These observations indicate that SFI has the potential to exert cardioprotective effects against FPI toxicity. The effect was possibly correlated with the activation of CYP2J3.

Sc-doped barium titanate (BaTiO3) nanopowders and ceramics were prepared by a sol–gel method for the first time. The polymorphism, microstructure and dielectric properties were investigated. Pseudo-cubic Sc-doped BaTiO3 nanopowders with a particle size of 30–40 nm have been achieved at low temperature of 800 °C. A phase diagram for the solid solution system BaTi1−xScxO3−δ was obtained. The limit of pseudo-cubic Sc-doped BaTiO3 solid solution (BTss) and the stable hexagonal phase have a large dependence on temperatures. The dopant of Sc3+ can also dramatically refine the grain size of BaTiO3 to 300 nm when x = 0.10. For different Sc3+ content in BaTiO3 ceramics, two types of impedance response appeared, and the resistivity of ceramics was dominated by bulk resistance or grain boundary resistance. Curie temperature (TC) and dielectric constant decreased by increasing the Sc3+ content. Relaxor behaviour occurs below room temperature when x = 0.10.

A new polyoxomolybdate (C6H6)4[H4GeMo12O40]·1.5H2O (1) has been isolated under hydrothermal condition and characterized by IR spectroscopy, elemental analysis and thermal stability. Single crystal X-ray structure analysis revealed that 1 crystallized in monoclinic space group P21/n with a = 10.9070(8) A, b = 20.9582(11) A, c = 11.4607(8) A, β = 109.983(4)o, V = 2,462.1(3) A3, Z = 2. The most significant feature of 1 is that the benzene rings are derived from the bis(carboxyethylgermanium) sesquoxide (H2E2Ge2O3) ligands via in situ reaction. A new polyoxomolybdate (C6H6)4[H4GeMo12O40].1.5H2O (1) has been obtained from in situ reaction by using H2E2Ge2O3 ligands in the presence of molybdates. The formation of compound 1 involves the in situ reaction occurred in H2E2Ge2O3 ligand in the presence of molybdates via the doubly dehydrogenative coupling reaction.

To identify the chemical differences which lead to the different therapeutic effects of dried rehmannia root (DRR) and prepared rehmannia root (PRR), we compared the chemical composition of decoctions of randomly purchased DRR and PRR using ultra performance liquid chromatography (UPLC) coupled with time-of-flight mass spectrometry and high performance liquid chromatography (HPLC) coupled with evaporative light scattering detection (ELSD) with the aid of multivariate statistical analysis. Both approaches clearly revealed compositional and quantitative differences between DRR and PRR. UPLC-MS data indicated stachyose, rehmaionoside A (or rehmaionoside B), acteoside (or forsythiaside, or isoacteoside), 6-O-coumaroylajugol (or 6-O-E-feruloylajugol, or 6-O-Z-feruloylajugol) as important discriminators between DRR and PRR decoctions. HPLC-ELSD analysis showed that the content of fructose in the decoctions of PRR was about four times greater than that of DRR (P

Microcapsules were prepared using the complex coacervation method with nano anatase TiO2 as the core material, gelatin/Arabia gum as the wall material, while dispersing TiO2 into the reaction solution using the ultrasonic. The prepared microcapsules can be finished into textiles such as the polypropylene nonwovens, and the microcapsules in the textiles gradually fracture and the anatase TiO2 was released, which would facilitate photo-degradation of the polypropylene nonwovens when exposed in sunlight. The microcapsules size was used as the process optimization evaluation index, and the quadratic general revolving combination design was used to conduct the experiments for obtaining the optimum ultrasonic conditions, and the other progress parameters were the same that used in our early microcapsule preparation. The obtained optimal process for ultrasound is: ultrasonic time is 17min; ultrasonic power is 74W and ultrasound temperature 60 °C.

We acquired the Raman spectra of adenine in powder and aqueous phase using excitation lasers with 532, 633, and 785 nm wavelengths for the region between 300 and 1500 cm–1. In comparison to the most distinct peak at 722 cm–1, the peaks between 1200 and 1500 cm–1 exhibited a characteristic increase in cross-section with decreasing excitation wavelength in both phases. This trend can be reproduced by different density functional theory (DFT) calculations for the adenine molecule in the gas phase as well as in the aqueous phase. Furthermore, from the calculation on the π-stacked dimer, hydrogen-bonded dimer, and trimer, we find that this trend toward excitation laser wavelength is not sensitive to the packing. When comparing the Raman spectra given by different excitation wavelength, one should take care in analyzing the cross-section, and present day DFT calculations are able to capture general trends in the excitation laser wavelength dependence of the Raman activity.

Phosphodiesterase 4 (PDE4) isozymes are involved in different functions, depending on their patterns of distribution in the brain. The PDE4 subtypes are distributed in different inflammatory cells, and appear to be important regulators of inflammatory processes. In this study we examined the effects of ferulic acid (FA), a plant component with strong anti-oxidant and anti-inflammatory activities, on lipopolysaccharide (LPS)-induced up-regulation of phosphodiesterase 4B (PDE4B) in PC12 cells, which in turn regulated cellular cAMP levels and the cAMP/cAMP response element binding protein (CREB) pathway in the cells.PC12 cells were treated with LPS (1 μg/mL) for 8 h, and the changes of F-actin were detected using laser scanning confocal microscopy. The levels of pro-inflammatory cytokines were measured suing ELISA kits, and PDE4B-specific enzymatic activity was assessed with a PDE4B assay kit. The mRNA levels of PDE4B were analyzed with Q-PCR, and the protein levels of CREB and phosphorylated CREB (pCREB) were determined using immunoblotting. Furthermore, molecular docking was used to identify the interaction between PDE4B2 and FA.Treatment of PC12 cells with LPS induced thick bundles of actin filaments appearing in the F-actin cytoskeleton, which were ameliorated by pretreatment with FA (10-40 μmol/L) or with a PDE4B inhibitor rolipram (30 μmol/L). Pretreatment with FA dose-dependently inhibited the LPS-induced production of TNF-α and IL-1β in PC12 cells. Furthermore, pretreatment with FA dose-dependently attenuated the LPS-induced up-regulation of PDE4 activity in PC12 cells. Moreover, pretreatment with FA decreased LPS-induced up-regulation of the PDE4B mRNA, and reversed LPS-induced down-regulation of CREB and pCREB in PC12 cells. The molecular docking results revealed electrostatic and hydrophobic interactions between FA and PDE4B2.The beneficial effects of FA in PC12 cells might be conferred through inhibition of LPS-induced up-regulation of PDE4B and stimulation of cAMP/CREB signaling pathway. Therefore, FA may be a potential therapeutic intervention for the treatment of neuroinflammatory diseases such as AD.

3D in vitro toxicity testing model was developed by magnetic levitation method for culture of the human hepatoma cell line HepG2 and applied to evaluate the drug hepatotoxicity. After formation of stable 3D structure for HepG2 cells, their glycogen storage capacity under 2D and 3D culture conditions were detected by immunohistochemistry technology, and the mRNA expression levels of phase Ⅰ and Ⅱ drug metabolism enzymes, drug transporters, nuclear receptors and liver-specific marker albumin(ALB) were compared between 2D and 3D culture conditions by using RT-PCR method. Immunohistochemistry results showed that HepG2 cells had abundant glycogen storage capacity under 3D culture conditions, which was similar to human liver tissues. The mRNA expression levels of major drug metabolism enzymes, drug transporters, nuclear receptors and ALB in HepG2 cells under 3D culture conditions were up-regulated as compared with 2D culture conditions. For drug hepatotoxicity evaluation, the typical hepatotoxic drug acetaminophen(APAP), and most reported drugs Polygonum multiflorum Thunb.(Chinese name He-shou-wu) and Psoraleae corylifolia L.(Chinese name Bu-gu-zhi) were selected for single dose and repeated dose(7 d) exposure. In the repeated dose exposure test, 3D HepG2 cells showed higher sensitivity. This established 3D HepG2 cells model with magnetic levitation 3D culture techniques was more close to the human liver tissues both in morphology and functions, so it was a better 3D hepatotoxicity evaluation model.