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The design of two-photon absorption (TPA) materials based on cocrystal engineering is an emerging strategy for constructing nonlinear materials. Here we observe that a prepared BDBT-TCNB cocrystal can retain well the TPA properties from the donor BDBT molecules, but the TPA properties of a BDBT-OFN cocrystal are inhibited upon using the same donor molecule but changing the acceptor molecule of the cocrystal. Via comparing the crystal structures and spectral data of the two cocrystals, we find that BDBT-TCNB cocrystals have obvious intermolecular charge transfer interactions, while the BDBT-OFN cocrystals exhibit totally different intermolecular arene–perfluoroarene interactions. Moreover, strong charge transfer interactions involving the BDBT-TCNB cocrystal also promote an enhancement of the fluorescence intensity and an increase in the lifetime and photoluminescence quantum yield (PLQY) relative to the monomers. Therefore, this example proves that intermolecular interactions involving cocrystals can be controlled via carefully selecting the donor and acceptor molecules, and then the TPA properties of the cocrystals can be selectively adjusted, promoting the development of TPA materials prepared via cocrystal engineering.

Aim: To discuss effects and mechanisms of allicin in hepatic fibrosis by vivo study. Materials and methods: Dividing 45 rats into 5 groups. Evaluating pathology and fibrosis by HE and Masson staining, measuring α-SMA, Collage III, Notch 1, p-AKT and p-mTOR protein expression by IHC assay and WB assay; LC 3B protein expression were evaluated by Immunofluorescence. Liver function were measured by Elisa assay. Results: With Allicin supplement, rats’ liver function, pathological and Collagen volume fraction were significantly improved with doses-dependent in liver tissues (P < 0.05, respectively); α-SMA, Collage III, Notch 1, p-AKT and p-mTOR protein expression were significantly suppressed with doses-dependent (P < 0.05, respectively); LC 3B protein expression was significantly increased with doses-dependent (P < 0.05, respectively). Conclusion: Allicin improved hepatic fibrosis by authophagy up regulation via regulation Notrch1/AKT/mTOR pathway by vivo study.

A new charge transfer cocrystal of 1,2,4,5-tetracyanobenzene (TCNB)-phenazine (PTC) was prepared by solvent evaporation method. The donor and acceptor molecules of cocrystal are stacked face to face with a mixed-stacking, implying a strong charge transfer (CT) interactions in the cocrystal system. The spectroscopic studies, single-crystal X-ray diffraction structure, density functional theory (DFT) and Hirschfield surfaces calculations are carried out to explore the relationship between structure and properties of cocrystal system, which show that the intermolecular interactions in PTC are stronger than those of single components, leading to the stability and photophysical behaviors of cocrystal different from their constitute units. This study will be helpful for the design and preparation of multifunctional cocrystal materials.

A new two-step enzymatic conversion process for the production of a novel mono-α-1,4-glucosylated rebaudioside A derivative (RA1G) was established via transglycosylation followed by hydrolyzation. In the transglycosylation reaction catalyzed by cyclodextrin glycosyltransferase, rebaudioside A (RA) was converted into glucosylated RA derivatives (RAGs), and the maximum conversion of 87.8% was obtained with the optimal conditions of 2 U/mL enzyme, 82.5 mg/mL β-cyclodextrin, and 82.5 mg/mL RA at 60 °C for 5 h. The obtained RAG solution was then directly used in hydrolyzation. Four amylases were screened for shortening the newly synthesized α-glucans of RAGs. A glucoamylase was found to produce RA1G as the single glucosylated product, and the maximum yield of 53.3% was achieved with the optimal conditions of adding 1.5 U/mL glucoamylase into RAG solution at 60 °C for 3 h. RA1G was identified as 13-[(2-O-β-D-glucopyranosyl-3-O-β-D-glucopyranosyl-β-D-glucopyranosyl) oxy] ent-kaur-16-en-19-oic acid-[(4-O-α-D-glucopyranosyl-β-D-glucopyranosyl) ester] by MS and NMR analysis and showed an improved sensory quality compared to RA.

Protection of totally unprotected β-D-gluco-, β-D-quinovo- and β-D-xylopyranosides with BzCN and Et3N as the catalyst afforded directly and regioselectively 3,6-di-O-benzoylated β-D-glucopyranosides or 3-O-benzoylated β-D-quinovo- and β-D-xylopyranosides, respectively. Furthermore, these trans–trans triol and tetrol systems could be regioselectively transformed into their corresponding 2-O-unprotected derivatives in the presence of BzCN as the benzoylating agent and a catalytic amount of 4-pyrrolidinopyridine as a base in one-pot reactions. Hence, BzCN in the presence of a catalytic amount of an amine base exhibits unique properties as an acylating agent, permitting the regioselective protection of all diol, triol and tetrol stereostructures occurring in the commonly found glycopyranosides. The convenient access and great value of some of the derived building blocks are shown through the concise synthesis of natural and unnatural saponins.

Herein, a novel organic material with high-efficiency charge transport ability and strong blue solid-state emission, referred to as 1,5-di(anthracen-2-yl)naphthalene (1,5-DAN), was designed and synthesized. Different from the common 2,6-position substituted molecules with high-efficiency charge-transport ability and strong blue emission, the 1,5-DAN displays a blue emission caused by the large torsion angle between the substituents and core. Moreover, the single-crystal mobility of 1,5-DAN is as high as 8.41 cm2 V−1 s−1 with a photoluminescence quantum yield up to 20.54%, which is one of the best records in this kind of emerging photoelectric organic semiconductor and shows the great potential in next-generation smart optoelectronics devices.

Three anthracene derivatives, referred to as 2-phenyl anthracene (Ph-Ant), 2-thiazole anthracene (TZ-Ant), and 2-pentafluorophenyl anthracene (F5Ph-Ant), were designed and synthesized to reveal the effects of the electron-withdrawing substituents on the molecular packing structure and photoelectric properties of the anthracene core. As the electron-withdrawing abilities of the substituents increased, the molecular structures of the three semiconductors showed a progressive deterioration in intermolecular interactions and molecular accumulation, and the photoelectric properties became worse. Interestingly, the energy levels of the three semiconductors showed gradually decreasing changes with an enhancement of the electron-withdrawing abilities of the substituents, indicating a possible strategy for fabricating n-type anthracene derivative semiconductor materials.

Organic semiconductors with long-range exciton diffusion length are highly desirable for optoelectronics but currently remain rare. Here, the estimated diffusion length of singlet excitons (LD ) in 2,6-diphenyl anthracene (DPA) crystals grown by solvent evaporation was shown to be up to approximately 124 nm. These crystals showed a previously unseen parallelogram morphology with layer-by-layer edge-on molecular stacking, isotropic optical waveguiding, radiation rate and non-radiation rate constants of 0.15 and 0.26 ns-1 respectively, as well as good field-effect transistor hole mobility and theoretically computed strong electronic couplings as high as 109 meV. Photoresponse experiments revealed that the photoconductivity of DPA crystals is surprisingly not related to the radiative pathway but associated with rapid exciton diffusion to the crystal surface for charge separation and carrier bimolecular recombination. Taken together, DPA was shown to be a promising semiconducting material for a new organic optoelectronics paradigm.

Ran Chen,1,2 Xiuying Lu,2 Zhen Li,2 Yajing Sun,2 Zhengxin He,3 Xiaoming Li1,2 1Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, People’s Republic of China; 3Department of Laboratory Medicine, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, People’s Republic of ChinaCorrespondence: Xiaoming LiDepartment of Otolaryngology Head and Neck Surgery, Hebei Medicial University, Shijiazhuang 050017, People’s Republic of China, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang 050082, People’s Republic of ChinaTel/ Fax + 86 311 8797 8418Email xmlmo@126.comBackground: Polarized M2 macrophages are an important type of tumor-associated macrophage (TAM), with roles in the growth, invasion, and migration of cancer cells in the tumor microenvironment. Dihydroartemisinin (DHA), a traditional Chinese medicine extract, has been shown to inhibit the progression and metastasis of head and neck squamous cell carcinoma (HNSCC); however, the effect of DHA on cancer prevention, and the associated mechanism, has not been investigated in the tumor microenvironment.Materials and Methods: First, human Thp-1 monocytes were induced and differentiated into M2 macrophages using phorbol 12-myristate 13-acetate (PMA), interleukin-6 (IL-6), and interleukin-4 (IL-4). Induction success was confirmed by cell morphology evaluation, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR). Then, DHA was applied to interfere with M2 macrophage polarization, and conditioned medium (CM), including conditioned medium from M2 macrophages (M2-CM) and conditioned medium from M2 macrophages with DHA (M2-DHA-CM), was obtained. CM was applied to Fadu or Cal-27 cells, and its effects on cancer invasion, migration, and angiogenesis wereevaluated using transwell, wound-healing, and tube formation assays, respectively. Finally, Western blotting was used to evaluate the relationship between signal transducer and activator of transcription 3 (STAT3) signaling pathway activation and M2 macrophage polarization.Results: Human Thp-1 monocytes were successfully polarized into M2-like TAMs using PMA, IL-6, and IL-4. We found that M2-like TAMs promoted the invasion, migration, and angiogenesis of HNSCC cells; however, DHA significantly inhibited IL-4/IL-6-induced M2 macrophage polarization. Additionally, as DHA induced a decrease in the number of M2-like TAMs, M2-DHA-CM inhibited the induction of invasion, migration, and angiogenesis of Fadu and Cal-27 cells. Finally, DHA inhibited M2 macrophage polarization by blocking STAT3 pathway activation in macrophages.Conclusion: DHA inhibits the invasion, migration, and angiogenesis of HNSCC by preventing M2 macrophage polarization via blocking STAT3 phosphorylation.Keywords: dihydroartemisinin, tumor-associated macrophages, HNSCC, STAT3, macrophage polarization

By introducing the naphthyl group into the 2,6-positions of anthracene, two different anthracene derivatives, 2,6-di(2-naphthyl)anthracene (2,6-di(2-Na)Ant) and 2,6-di(1-naphthyl)anthracene (2,6-di(1-Na)Ant) were synthesized. The tiny change in the substitution site of the naphthyl group leads to a significant difference in the molecular packing and further exerts a great impact on their optoelectronic properties. Thin film field-effect transistors for 2,6-di(2-Na)Ant show charge transport mobility up to 2.1 cm2 V−1 s−1, while 2,6-di(1-Na)Ant demonstrates no mobility. Moreover, thin film phototransistors of 2,6-di(2-Na)Ant show a photoresponsivity of 6.9 × 103 A W−1, a high photosensitivity of 2.6 × 106 and an excellent detectivity of 3.4 × 1016 Jones, which is one of the highest performances of thin film organic phototransistors reported to date.

Organic semiconductors (OSC) are generally considered intrinsic (undoped), an assumption which underpins our understanding of the charge transport in this promising class of materials. However, this premise conflicts with a variety of experimental observations, that suggest the presence of excess holes carriers in OSCs at room temperature. Here, using a low-power plasma de-doping method, we report that trace amounts (~1015 cm-3) of oxygen-induced organic radical cations (OIORCs) are inherent in the lattice of OSCs as innate hole carriers, and that this is the origin of the p-type characteristics exhibited by the majority of these materials. This finding clarifies previously unexplained organic electronics phenomena and provides a foundation upon which to re-understand charge transport in OSCs. Furthermore, the de-doping method can eliminate the trace OIORCs, resulting in the complete disappearance of p-type behavior, while re-doping (under light irradiation in O2), reverses the process. These methods can precisely modulate key electronic characteristics (e.g., conductivity, polarity, and threshold voltage) in a nondestructive way, expanding the explorable charge transport property space for all known OSC materials. Accordingly, we conclude that our tailorable OIORC doping strategy, requiring only off-the-shelf equipment and a glovebox, will become a core technology in the burgeoning organic electronics industry.

Hydroxylated polybrominated diphenyl ethers (OH-BDEs) are major transformation products of PBDEs that readily bioaccumulate in the marine food web. Although 6-OH-BDE-47 is frequently and abundantly detected in cetaceans, its potential toxic effects are largely unknown. We explored the toxicological pathways and mechanisms of OH-BDEs by exposing pygmy killer whale skin fibroblast cell lines (PKW-LWHT) to 6-OH-BDE-47 at concentrations ranging from 0.02, 0.2, 2 to 4 μM. The result showed that 6-OH-BDE-47 inhibited cell proliferation in a concentration- and time-dependent manner. The cell cycle data revealed that the cell cycle was arrest at the G0/G1 phase by 6-OH-BDE-47. Using qPCR and Western blot assay, we found that 6-OH-BDE-47 up-regulated the transcription and expression level of p21 and RB1 and down-regulated the expression level of Proliferating Cell Nuclear Antigen (PCNA), CDK2, CDK4, cyclin D1, cyclin E2, E2F1, and E2F3 and the cellular phosphorylated RB1. The results showed that 6-OH-BDE-47 was able to arrest the cell cycle of PKW-LWHT cells at G1 phase by changing the expression level of related regulatory genes in G1 stage, and finally inhibit cell proliferation.

Background Interferon-inducible 16 (IFI16)/caspase-1 inflammasome activates and secretes IL-1β. However, it is still unclear whether the IFI16 inflammasome is involved in human laryngeal squamous cell carcinoma. Autophagy directly removed inflammasome components and limited early IL-1β production. RalB is required for the crosstalk between inflammasome and autophagy in macrophages. Dihydroartemisinin (DHA), the main derived ingredient of artemisinin, has a variety of biological activities. The mechanism of DHA in regulating the crosstalk between IFI16 inflammasome and autophagy by inhibiting RalB expression was analyzed in order to provide clues for new therapeutic methods in laryngeal cancer. Methods The expression of IFI16 was analyzed by Oncomine and GEPIA databases and detected by Western blot and immunohistochemistry. The relationship between IFI16 inflammasome and autophagy was investigated by transmission electron microscopy, immunofluorescence assay, etc. in Hep-2, Cal-27 and HeLa cells treated with DHA. The xenograft tumor of hep-2 cell in nude mice were used to assess the effect of DHA on laryngeal cancer. Results It was reported for the first time in this study that IFI16 was overexpressed and positively correlated with caspase-1 in laryngeal carcinoma tissues. DHA significantly inhibited the activation of inflammasome and reduced IL-1β production in the microenvironment of Hep-2 cell xenograft tumor in nude mice. Mechanistically, we found that DHA degraded RalB, inhibited USP33 expression, and triggered autophagy. Meanwhile, enhanced autophagy can reduce the expression of RalB and USP33. Furthermore, DHA promotes autophagy, which suppresses the activation of IFI16/caspase-1 inflammasome and IL-1β production. Conclusions Therefore, our findings demonstrate that DHA may act as a RalB inhibitor to regulate the crosstalk between autophagy and IFI16/caspase-1 inflammasome, which inhibits IL-1β production in tumor microenvironment.

Few-layered arsenic-phosphorus alloys, AsxP(1-x), with a puckered structure have been recently synthesized and demonstrated with fully tunable band gaps and optical properties. It is predicted that the carrier mobility of monolayer AsP compounds is even higher than that of black phosphorene (b-P). The anisotropic and orthogonal electrical and thermal transport properties of the puckered group VA elements make them intriguing materials for thermoelectric applications. Herein, we investigated the thermal transport properties of AsP based on first-principles molecular dynamics and the Boltzmann transport equation. We reveal that monolayer AsP with three different chemical structures possesses thermal conductivities lower than b-P, but with increased anisotropy. Further, these structures behave profoundly different on heat conduction. This can be attributed to the distinct low-frequency optical modes associated with their bonding nature. Our results highlight the impact of atomic arrangement on the thermal conductivity of AsP, and the structure-property relationship established may guide the fabrication of thermoelectric materials via the engineered alloying method.

Monolayer arsenic is a newly emerging two-dimensional material in the VA group similar to its isologue, phosphorene. On the basis of first-principles calculations and Boltzmann transport theory, we investigated the electrical, thermal, and thermoelectric transport properties for two forms of monolayer arsenic, arsenene, featuring puckered and buckled structures, respectively. The two kinds of arsenene are both indirect band gap semiconductors possessing moderate to high charge carrier mobilities falling in the range 40–800 cm2 V–1 s–1. The puckered arsenene exhibits relatively low and anisotropic lattice thermal conductivities, with 9.6 W m–1 K–1 in the armchair and 30.7 W m–1 K–1 in the zigzag direction. More significantly, its preferential thermal transport direction is orthogonal to the electrical transport direction, which enhances the thermoelectric figure of merit in the armchair direction to 0.7 for p-doping and 1.6 for n-doping at room temperature.

A promising cocrystal material that acts as a rectifier was prepared by a simple procedure of solution volatilization. (E)-1,2-diphenylethene (STB) and 7,7',8,8'-tetracyanoquinodimethane (TCNQ) were used as donor and acceptor respectively, and aggregate in an ordered fashion in the stilbene-tetracyanoquinodimethane (STC) cocrystal that comprises 1 : 1 donor/acceptor mixed-stacked charge-transfer (CT) complexes. The strong CT interaction between the donor and acceptor is the main driving force for the self-assembly. The cocrystals show rectifying characteristics with a rectification ratio of 26. This result suggests that cocrystal engineering provides a great possibility to obtain rectifying materials from small, readily available organic molecules.

Kinsenoside is the major bioactive component from herbal medicine with a broad range of pharmacological functions. Goodyeroside A, an epimer of kinsenoside, remains less explored. In this report we chemically synthesized kinsenoside, goodyeroside A and their analogues with glycan variation, chirality inversion at chiral center(s), and bioisosteric replacement of lactone with lactam. Among these compounds, goodyeroside A and its mannosyl counterpart demonstrated superior anti-inflammatory efficacy. Furthermore, goodyeroside A was found to suppresses inflammatory through inhibiting NF-κB signal pathway, effectively. Structure-activity relationship is also explored for further development of more promising kinsenoside analogues as drug candidates.

Layered transition metal dichalcogenides (TMDs) have been found to exhibit the indirect-to-direct band gap transition when exfoliated from bulk to a single monolayer. Through first-principles calculations, we predict that such a transition can happen at bilayer for 2H-WSe2 and at tetralayer for 2H-WTe2. We find that the transition can be ascribed to the competition between spin–orbit coupling and interlayer coupling interactions, the former leading to appreciable splittings at the K point and the latter to splittings at the Γ point of the valence band. It is shown that stronger spin–orbit coupling tends to favor transition at a larger number of layers. These results provide insights into the valley degeneracy of the band edges and the valley-dependent optical transitions in few-layer TMDs for quantum control in valley-electronics.

Background Dihydroartemisinin (DHA) was one of the most potent anticancer artemisinin-like compounds that had been proved by many researchers, but its application was limited by its own characteristics. Purpose Magnetic DHA nano-liposomes (DHA-MLPs) were developed to improve the targeting antitumor efficiency and bioavailability of DHA, and their physical properties were characterized. Study design and methods Liposomes were prepared by thin film dispersion and orthogonal experimental design was used to optimize the formula. The magnetic targeting and antitumor effects of DHA-MLPs in the externally applied magnetic field was investigated in vitro and in vivo. Results The mean particle size of DHA-MLPs was 209.10 ± 4.92 nm, the charge potential was -37.13 ± 1.01 mV, the encapsulation efficiency (E.E.%) was 82.12 ± 0.91%, and the saturation magnetization at room temperature was 11.84 emu g−1. Targeting DHA-MLPs as well as free DHA could lead to cell cycle G1 block and apoptosis of HNSCC tumor cells in vitro. The tumor volumes of targeting DHA-MLPs treated mouse group were distinctly decreased than that in the control group, free DHA group and non-targeting DHA-MLPs group (P Conclusion This novelty liposome could strengthen the ability of DHA in tumor suppression, by increasing the targeted delivery of DHA and biocompatibility, optimize the bioefficacy of DHA.

Protection of 2,3,4- O-unprotected α-galacto- and α-fucopyranosides with BzCN and DMAP/DIPEA as the base afforded directly and regioselectively the 3- O-unprotected derivatives. The rationale for these studies was to take advantage of the eventual cooperativity of the "cyanide effect" and "the alkoxy group mediated diol effect". This way, even the totally unprotected α-galactopyranosides could be regioselectively transformed into the corresponding 2,4,6- O-protected derivatives. The great utility of these building blocks was demonstrated in efficient trisaccharide syntheses.

Objective:To study the interactive influence of implanted nano platinum black electrodes (as compared with pure platinum electrodes) on rabbit orbicularis oculi muscle morphology and function.Methods:The influence of the two types of electrode on the orbicularis oculi muscle was monitored in a rabbit model of facial paralysis. Biological electric current and exciting current were administered to biological tissue, and morphological and functional changes were identified. Changes in orbicularis oculi muscle contraction, electrode configuration and performance associated with long-term electrical stimulation were observed over 28 days of implantation.Results:The nano platinum black electrode was superior to the pure platinum electrode in the following aspects: morphology and functionality, electrical excitation function of the orbicularis oculi muscle (as assessed by electromyography), muscle contraction function and biological tissue changes. Furthermore, the nano platinum black electrode features had good stability.Conclusion:Microelectrode surface modification with nano platinum black can effectively increase the microelectrode surface area and improve electrode performance, and is associated with good tissue compatibility.

Paclitaxel (PTX) is one of the most useful chemotherapeutic agents approved for several cancers, including ovarian, breast, pancreatic, and non-small cell lung cancer. However, it causes systemic side effects when administered parenterally. Photodynamic therapy (PDT) is a new strategy for treating local cancers using light and photosensitizer. Unfortunately, PDT is often followed by recurrence, due to incomplete ablation of tumors. To overcome these problems, we prepared the far-red light-activatable prodrug of PTX by conjugating photosensitizer via singlet oxygen-cleavable aminoacrylate linker. Tubulin polymerization enhancement and cytotoxicity of prodrugs were dramatically reduced. However, once illuminated with far-red light, the prodrug effectively killed SKOV-3 ovarian cancer cells through the combined effects of PDT and locally released PTX. Ours is the first PTX prodrug that can be activated by singlet oxygen using tissue penetrable and clinically useful far-red light, which kills the cancer cells through the combined effects of PDT and site-specific PTX chemotherapy.

Limited availability of the n-3 fatty acids EPA and DHA have led to an interest in better understanding of the n-3 biosynthetic pathway and its regulation. The biosynthesis of alpha-linolenic acid to EPA and DHA involves several complex reaction steps including desaturation-, elongation- and peroxisomal beta-oxidation enzymes. The aims of the present experiments were to gain more knowledge on how this biosynthesis is regulated over time by different doses and fatty acid combinations. Hepatocytes isolated from salmon were incubated with various levels and combinations of oleic acid, EPA and DHA. Oleic acid led to a higher expression of the Δ6 fatty acid desaturase (fad) genes Δ6fad_a, Δ6fad_b, Δ6fad_c and the elongase genes elovl2 compared with cells cultured in medium enriched with DHA. Further, the study showed rhythmic variations in expression over time. Levels were reached where a further increase in specific fatty acids given to the cells not stimulated the conversion further. The gene expression of Δ6fad_a_and Δ6fad_b responded similar to fatty acid treatment, suggesting a co-regulation of these genes, whereas Δ5fad and Δ6fad_c showed a different regulation pattern. EPA and DHA induced different gene expression patterns, especially of Δ6fad_a. Addition of radiolabelled alpha-linolenic acid to the hepatocytes confirmed a higher degree of elongation and desaturation in cells treated with oleic acid compared to cells treated with DHA. This study suggests a complex regulation of the conversion process of n-3 fatty acids. Several factors, such as that the various gene copies are differently regulated, the gene expression show rhythmic variations and gene expression only affected to a certain level, determines when you get the maximum conversion of the beneficial n-3 fatty acids.

As one of the important thiazole derivatives, 2-aminobenzothiazole (2-ABT) has been widely used as a structural unit in the synthesis of antioxidants, anti-inflammatories, herbicides, antibiotics, and thermoplastic polymers. In this study, the interaction of 2-ABT with human serum albumin (HSA) was investigated in vitro under simulated physiological conditions, using multi-spectroscopic techniques and a molecular modeling study. The binding constant and binding sites were determined through fluorescence quenching spectra. The site-competitive replacement experiments revealed that the precise binding site of 2-ABT on HSA was site II (subdomain IIIA). Moreover, molecular docking results illustrated the electrostatic interaction between Glu 450 and 2-ABT, in accordance with the conclusions from the calculated thermodynamic parameters and the effect of ionic strength. The effect of 2-ABT on the conformational changes of HSA were evaluated by ultraviolet–visible (UV-Vis) absorption, three-dimensional (3D) fluorescence, synchronous fluorescence, and circular dichroism (CD) spectroscopy. This work facilitates comprehensive understanding of the binding of 2-ABT with HSA, contributing to evaluate the molecular transportation mechanism and biotoxicity of 2-aminobenzothiazole derivatives in vivo.

The toxic interaction of 2-aminobenzothiazole (2-ABT) with herring sperm DNA (hs-DNA) was investigated in vitro under simulated physiological conditions by multi-spectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated that 2-ABT interacted with hs-DNA in a minor groove binding mode. The binding constant and the number of binding sites were 7.2×103 L mol−1 and 0.95, respectively. Circular dichroism spectroscopy (CD) was employed to measure the conformation change of hs-DNA in the presence of 2-ABT, which verified the minor groove binding mode. The molecular modeling results illustrated that 2-ABT tended to bind in the region of rich A–T base pairs through the hydrogen bond between A 18 and amino group of 2-ABT. Sequence specificity was confirmed by comparison on the interactions of 2-ABT with four kinds of bases. This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the toxic interaction of small molecular pollutants and drugs with biomacromolecules, which contributes to clarify the molecular mechanism of toxicity or side effect in vivo.

Iron is often found to be of excessive concentrations in laying hens' diets, which may cause antagonistic interactions with other minerals. This study was conducted to investigate how to supplement Zn and Mn in the diets without Fe supplementation. In experiment 1, 420 18-week Lohmann Brown layers were fed a basal diet or a basal diet supplemented with 30-0, 65-30 and 100-60 mg/kg of Zn and Mn, respectively. In experiment 2, 360 40-week Lohmann Brown layers were fed a basal diet or a basal diet supplemented with 15-0, 35-0 and 55-15 mg/kg of Mn and Zn, respectively. Minerals were supplemented in the form of sulfate. Egg production was improved by supplementing 30 mg/kg Zn or 65 mg/kg Zn in combination with 30 mg/kg Mn in experiment one. In experiment two, a significant reduction of egg performance occurred with 35 mg/kg Mn supplementation. Mn and/or Zn supplementation increased eggshell thickness in experiment one, and decreased yolk cholesterol in both experiments. Mn and/or Zn supplementation increased Zn and Mn excretion in both experiments. Serum growth hormone (GH), thyroxine (T(4) ), and insulin levels, or alkaline phosphatase (AP) activity were not affected by treatments; serum estrogen (E(2) ) and triiodothyronine (T(3) ) were different but there was no consistency by dietary treatments. This study demonstrates that 30 mg/kg supplemental Zn is necessary to obtain maximal egg production, and there seems to be no need to supply Mn in this type of diet.

FV-429 is a newly synthesized flavonoid with a bis(2-hydroxyethyl) amino propoxy substitution. In this study, we investigate the anticancer effect of FV-429 both in vivo and in vitro. These data have shown that FV-429 could significantly inhibit tumor growth in mice inoculated with Heps hepatoma cells without evident toxicity. After the treatment of FV-429 (40 mg/kg), the inhibitory rate of tumor weight was 52.12%. Then, we performed diamidinophenylindole staining and annexin V/propidium iodide double-staining assay to investigate the apoptosis induced by FV-429 in HepG2 cells. Further research revealed that FV-429 induced apoptosis through the mitochondrial apoptotic pathway, as indicated by a change in Bax/Bcl-2 ratios, collapse of mitochondrial membrane potential, the transposition of apoptotic-inducing factor and cytochrome c, caspase-3 and caspase-9 activation, and degradation of poly (ADP-ribose) polymerase. The accumulation of reactive oxygen species induced by FV-429 in HepG2 cells was also observed. Moreover, the mitogen-activated protein kinases, the downstream effect of reactive oxygen species accumulation including c-Jun N-terminal kinase and p38 mitogen-activated protein kinases, could be activated by FV-429. Taken together, our results provided a mechanistic framework for further exploration of FV-429 as a novel chemotherapy for human tumors.

LFG-500 is a newly synthesized flavonoid with a piperazine and a benzyl group substitution. Here we investigated the antitumor effect of LFG-500 in vivo and in vitro. Firstly, the apoptosis induced by LFG-500 in HepG2 cells was characterized by diamidino-phenyl-indole (DAPI) staining and Annexin V/PI double staining. The accumulation of reactive oxygen species (ROS) was also observed. Data suggested that LFG-500 could induce the generation of reactive oxygen species, which could be partly inhibited by NAC (N-acetylcysteine), an ROS inhibitor. LFG-500 also induced ROS accumulation followed by a decrease in mitochondrial membrane potential (MMP), and finally activated caspase cascade. Pretreatment with Z-VAD-FMK, a caspase inhibitor, could partly block the apoptosis induced by LFG-500. We also found that the expression of Bcl-2 protein was decreased whereas that of Bax protein was increased, leading to an increase in Bax/Bcl-2 ratio. Meanwhile, the translocation of apoptotic inducing factor (AIF) from cytosol to nuclei and the release of cytochrome c (Cyt c) from mitochondria were also detected, indicating that LFG-500 induced apoptosis through an ROS-mitochondrial-mediated pathway. The significant suppression of tumor growth was also observed in Heps-bearing mice. After treatment with 30 mg/kg LFG-500, the inhibitory rate on tumor weight was 53.69%. Taken together, these results provided a mechanistic framework for further exploration of LFG-500 as a novel chemotherapy for human tumors.

The gene toxic interactions of toluidine blue (TB) with calf thymus DNA (ct-DNA) were examined in vitro with UV–visible absorption spectroscopy, fluorescence spectroscopy, fluorescence polarization and circular dichroism techniques. The experimental results showed that TB interacted with ct-DNA by two binding modes. At low TB concentrations, TB intercalated into the DNA base pairs. At higher TB concentrations, TB was attached to the negatively charged phosphate groups. For the intercalation binding mode and electrostatic binding mode, the binding constants were 1.76 × 10 6 L mol −1 and 6.18 × 10 5 L mol −1 and the number of binding sites was 0.48 and 0.79, respectively. Circular dichroism results showed that the two binding modes had different effects on the ct-DNA conformation. At high dye concentrations, Z-form DNA appears, while at low TB concentrations, a B to A form transition is observed.

We developed the photoactivatable prodrug of Paclitaxel (PTX) for the combinational treatment of chemo and photodynamic therapy (PDT). PTX causes dose-limiting side effects as other anticancer drugs when administered systemically. On the other hand, PDT suffers from incomplete ablation and subsequent reoccurrence in part due to the short half-life and poor diffusion rate of singlet oxygen. We prepared a conjugate of PTX with phthalocyanine via a singlet oxygen cleavable linker, as a unique prodrug of PTX, to overcome the problems of PDT and systemic chemotherapy. The PTX prodrug was evaluated for tubulin polymerization, the release rate of PTX from prodrug upon illumination at 690 nm, stability in complete media, and the combination effect in killing ovarian cancer cells in vitro (SKOV-3). The PTX prodrug did not enhance the tubulin polymerization unlike PTX. While it was stable in the media under dark, it rapidly released PTX upon illumination with far-red light: > 90% release in 30 min. The prodrug showed much lower dark toxicity compared to PTX. When illuminated with 690 nm at 5.6 mW/cm2, the prodrug showed very potent phototoxicity: IC50 = 3.9 nM, through the combinational effect of PDT and PTX. In conclusion, we found that the PTX prodrug have desired properties as light-activatable prodrug expressing the combinational effect of PDT and local PTX chemotherapy. Animal study is underway to evaluate the antitumor effect of the PTX prodrug. Citation Format: Pritam Thapa, Mengjie Li, Moses Bio, Pallavi Rajaputra, Yajing Sun, Sukyung Woo, Youngjae You. Progress in light activatable prodrug for the combinational treatment of PDT and site-specific chemotherapy: paclitaxel prodrugs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1361.

Autophagy is a tightly-regulated catabolic process that involves the degradation of intracellular components via lysosomes. Although the pivotal role of autophagy in cell growth, development, and homeostasis has been well understood, its function in cancer prevention and intervention remains to be delineated. The aim of this study was to investigate the function and mechanism of autophagy induced by oroxylin A, a natural mono-flavonoid extracted from Scutellariae radix. We found for the first time that oroxylin A induced Beclin 1-mediated autophagy in human hepatocellular carcinoma HepG2 cells. Time-lapse video microscopy and western blotting studies showed that treatment of cells with 80 μM oroxylin A resulted in the conversion of water soluble MAP-LC3 (LC3-I) to the lipidated and autophagosome-associated form (LC3-II) after 12 hours; then autophagosome-lysosome fusion and lysosome degradation after 24 hours was required in oroxylin A-mediated cell death. This induction was associated with the suppressing of PI3K-PTEN-Akt-mTOR signaling pathway by oroxylin A. Our results also showed that autophagy took place before noticeable apoptosis can be observed. It was further demonstrated that oroxylin A-triggered autophagy contributed to cell death using over-expression of autophagy-related gene (Atg5 and Atg7) and inhibition of autophagy by siBeclin 1 and 3-methyladenine (3-MA). In vivo study, oroxylin A inhibited xenograft tumor growth and induced obvious autophagy in tumors. Taken together, we conclude that oroxylin A exhibits autophagy-mediated antitumor activity in a dose and time-dependent manner in vivo and in vitro. These findings define and support a novel function of autophagy in promoting death of hepatocellular carcinoma cells.

A tightly regulated catabolic process named autophagy involves the degradation of intracellular components via lysosomes. Here we investigate the antitumor effect of E Platinum, a newly synthesized derivative of oxaliplatin, in vivo and in vitro. E Platinum exhibits growth inhibition of various tumor cells in a dose-dependent manner, but the mechanism underlying it is unclear. Based on theory introducing autophagy, we preliminarily investigate whether autophagy could contribute to the antitumor activity of E Platinum. Our results showed that autophagy induced by 12.5 μM E Platinum in gastric carcinoma BGC-823 cells was significantly characterized by the FITC-fluorescent microtubule associated protein 1 light chain 3 (MAP-LC3), lysosomal-rich/acidic compartments visualized with Lysotracker red (LTR-red) and an accumulation of numerous large autophagic vesicles within the cytoplasm, but not in the control cells. Meanwhile treatment of cells with 12.5 μM E Platinum resulted in conversion of water soluble LC3 (LC3-I) to lipidated and autophagosome-associated form (LC3-II) as well as increasing expression of autophagy protein Beclin 1. Activation of predominant lysosomal aspartic protease, LAMP-1 and cathepsin D, was demonstrated. Moreover, RNA interference targeting Beclin 1, inhibition of autophagy by 3-methyladenine (3-MA) and chloroquine significantly suppressed the above process as well as the BGC-823 cells growth inhibition triggered by 12.5 μM E Platinum. Studies of mechanism revealed that E Platinum suppressed activation of mTOR and p70S6K by decreasing phosphorylation of Akt, ERK1/2, JNK and p38 involved in mitogen-activated protein kinase signaling. We supported new evidences for E Platinum as a promising antitumor agent, involving with autophagy induction.

There is an obvious relationship among angiogenesis and inflammation. From previous study, we learn that oroxylin A possesses anti-angiogenic activity in vitro and in ovo. It also has an inhibitory effect on inflammation. But whether oroxylin A suppresses the inflammation-induced angiogenesis is still unknown. Our present study focuses on the role of oroxylin A in targeting LPS-induced angiogenesis, inflammatory and related pathways.The effects of oroxylin A on angiogenesis were investigated by transwell assay, tube formation assay, rat aortic ring assay and chorioallantoic membrane (CAM) model. Western blotting analysis was used to detect the expression of certain proteins.We found that oroxylin A inhibited LPS-induced migration and tube formation of human umbilical vein endothelial cells (HUVECs), as well as microvessel sprouting from rat aotric ring in vitro and the angiogenesis of chicken chorioallantoic membrane (CAM) model in ovo. The results also indicated that oroxylin A could inhibit the expression of LPS acceptor toll-like receptor 4 (TLR4) and the activities of its downstream mitogen-activated protein kinases (MAPKs), including reducing expressions of the phosphorylation of JNK, p38, and ERK. Moreover, oroxylin A prevented NF-κB dimers from translocating to the nucleus.Taken together, oroxylin A can suppress the angiogenesis induced by LPS and it may affect the LPS/TLR4 signaling pathway.

Flavonoid is an important group of natural products which exerted anticancer effects against various cancers. III-10 is a newly synthesized flavonoid with a pyrrolidinyl and a benzyl group substitution. It shares a same carbon skeleton with flavonoid which indicates that it may also have potential anticancer activity. To investigate whether III-10 could express anticancer effect on human U937 leukemia cells through differentiation induction, a series of experiments were processed. MTT and trypan-blue excluding assays showed that III-10 possessed growth and viability inhibition effects on U937 cells. Giemsa staining was implemented to observe the morphologic changes of U937 cells after III-10 treatment. Nitroblue tetrazolium (NBT) reduction assay and cell surface antigen flow cytometry were carried out to figure out the way III-10 induced U937 cells to differentiate. These experiments revealed that III-10 could induce U937 cells to differentiate into monocyte-like cells. Western blots and immunofluorescence were performed to inspect the possible underlying mechanism. The results revealed that differentiation-related proteins phospholipids scramblase 1 (PLSCR1) and promyelocytic leukemia protein (PML) were up-regulated after III-10 treatment. And III-10 stimulated PLSCR1 and PML probably through activation of protein kinase Cδ (PKCδ). All these results suggested that III-10 was a prospective anticancer compound and was requisite to be proceeded further investigation.

The toxic interaction of melamine with herring sperm DNA (hs-DNA) was investigated by using fluorescence and UV-vis absorption spectra techniques. The experimental results showed that the toxic interaction between melamine and hs-DNA occurred. Fluorescence quenching experiments indicated the existence of electrostatic binding between melamine and hs-DNA. The binding constants K(A) and the binding site numbers were calculated by means of the Stern-Volmer equation and were 9.8 × 10(4) L mol(-1) and 1.3, respectively. Both the results of fluorescence spectra and UV-vis absorption spectra verified that there are electrostatic binding between melamine and hs-DNA. The possibility in the presence of a classical intercalation binding mode could be ruled out by using DNA unwinding experiments.

By utilizing ultraviolet (UV)-visible absorption spectroscopy, circular dichroism (CD), resonance light scattering (RLS), and transmission electron microscope (TEM) techniques, the toxic interaction of methyl violet (MV) with calf thymus DNA (ctDNA) was investigated at the molecular level. The UV-visible absorption spectra results showed that MV intercalated into ctDNA base pairs at low MV concentrations, while MV was attached to the negative charged phosphate groups at higher concentrations and the binding constant ( Kθ25°C) was 1.80 × 103 L mol−1. The absorbency results showed that the genotoxic interaction of MV with ctDNA is under the electrostatic binding mode. MV had strong toxic interaction with ctDNA at 4.0 × 10−5 mol L−1 MV and pH 6.5. The toxic interaction of MV with ctDNA can result in the formation of massive aggregates and change of the ctDNA conformation, which showed a significant linear dose-response relationship.