Ball billing induced highly dispersed nano-MgO in biochar for glucose isomerization at low temperatures.

The isomerization of glucose is a crucial step for biomass valorization to downstream chemicals. Herein, highly dispersed MgO doped biochar (BM-0.5@450) was prepared from rice straw via a solvent-free ball milling pretreatment and pyrolysis under nitrogen conditions. The nano-MgO doped biochar demonstrated enhanced conversion of glucose in water at low temperatures. A 31 % yield of fructose was obtained from glucose over BM-0.5@450 at 50 °C with 80.0 % selectivity. At 60 °C for 140 min, BM-0.5@450 achieved a 32.5 % yield of fructose. Compared to catalyst synthesized from conventional impregnation method (IM@450), the BM-0.5@450 catalyst shows much higher fructose yields (32.5 % vs 25.9 %), which can be attributed to smaller crystallite size of MgO (11.32 nm vs 19.58 nm) and homogenous distribution. The mechanism study shows that the activated MgOH+·OH- group by water facilitated the deprotonation process leading to the formation of key intermediate enediol.

Relationship between the cGAS-STING and NF-κB pathways-role in neurotoxicity.

Neurotoxicity can cause a range of symptoms and disorders in humans, including neurodegenerative diseases, neurodevelopmental disorders, nerve conduction abnormalities, neuroinflammation, autoimmune disorders, and cognitive deficits. The cyclic guanosine-adenosine synthase (cGAS)-stimulator of interferon genes (STING) pathway and NF-κB pathway are two important signaling pathways involved in the innate immune response. The cGAS-STING pathway is activated by the recognition of intracellular DNA, which triggers the production of type I interferons and pro-inflammatory cytokines, such as tumor necrosis factor, IL-1ß, and IL-6. These cytokines play a role in oxidative stress and mitochondrial dysfunction in neurons. The NF-κB pathway is activated by various stimuli, such as bacterial lipopolysaccharide, viral particle components, and neurotoxins. NF-κB activation may lead to the production of pro-inflammatory cytokines, which promote neuroinflammation and cause neuronal damage. A potential interaction exists between the cGAS-STING and NF-κB pathways, and NF-κB activation blocks STING degradation by inhibiting microtubule-mediated STING transport. This review examines the progress of research on the roles of these pathways in neurotoxicity and their interrelationships. Understanding the mechanisms of these pathways will provide valuable therapeutic insights for preventing and controlling neurotoxicity.

Carrier-free self-assembled nanomedicine based on celastrol and galactose for targeting therapy of hepatocellular carcinoma via inducing ferroptosis.

Triggering ferroptosis is a potential therapeutic pathway and strategy for the prospective treatment of lethal hepatocellular carcinoma (HCC). The asialo-glycoprotein receptor (ASGPR) is an over-expressed receptor on the membranes of hepatocellular carcinoma cells (HCCs) and binds specifically to galactose (Gal) ligand. Celastrol (CE) is a potent anticancer natural product, but its poor water solubility and severe toxicity restrict its clinical application. In this study, a carrier-free self-assembled nanoparticles, CE-Gal-NPs, were designed and prepared by nanoprecipitation method, which could recognize ASGPR receptor by active targeting (Gal ligand) and passive targeting (EPR effect), access to the cell through the clathrin pathway and finally internalize to lysosomes. CE-Gal-NPs triggered reactive oxygen species (ROS)-mediated ferroptosis pathway and exerted anti-HCC effects in vitro and in vivo by down-regulating GPX4 and up-regulating COX-2 expression, depleting glutathione (GSH) levels, and increasing lipid peroxidation levels in cells and tumor tissues. In the H22 xenograft mouse model, the CE-Gal-NPs group exhibited dramatically superior tumor inhibition than the CE group, while Gal conjugating diminished the systemic toxicity of CE. Consequently, this study presented a promising strategy for CE potentiation and toxicity reduction, as well as a potential guideline for the development of clinically targeted therapeutic agents for HCC.

De Novo Design of Imidazopyridine-Tethered Pyrazolines That Target Phosphorylation of STAT3 in Human Breast Cancer Cells.

In breast cancer (BC), STAT3 is hyperactivated. This study explored the design of imidazopyridine-tethered pyrazolines as a de novo drug strategy for inhibiting STAT3 phosphorylation in human BC cells. This involved the synthesis and characterization of two series of compounds namely, 1-(3-(2,6-dimethylimidazo [1,2-a]pyridin-3-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-(4-(substituted)piperazin-1-yl)ethanone and N-substituted-3-(2,6-dimethylimidazo[1,2-a]pyridin-3-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazoline-1-carbothioamides. Compound 3f with 2,3-dichlorophenyl substitution was recognized among the tested series as a lead structure that inhibited the viability of MCF-7 cells with an IC50 value of 9.2 µM. A dose- and time-dependent inhibition of STAT3 phosphorylation at Tyr705 and Ser727 was observed in MCF-7 and T47D cells when compound 3f was added in vitro. Calculations using density functional theory showed that the title compounds HOMOs and LUMOs are situated on imidazopyridine-pyrazoline and nitrophenyl rings, respectively. Hence, compound 3f effectively inhibited STAT3 phosphorylation in MCF-7 and T47D cells, indicating that these structures may be an alternative synthon to target STAT3 signaling in BC.

Nano-Zirconium Dioxide Catalyzed Multicomponent Synthesis of Bioactive Pyranopyrazoles That Target Cyclin Dependent Kinase 1 in Human Breast Cancer Cells.

Small molecules are being used to inhibit cyclin dependent kinase (CDK) enzymes in cancer treatment. There is evidence that CDK is a drug-target for cancer therapy across many tumor types because it catalyzes the transfer of the terminal phosphate of ATP to a protein that acts as a substrate. Herein, the identification of pyranopyrazoles that were CDK inhibitors was attempted, whose synthesis was catalyzed by nano-zirconium dioxide via multicomponent reaction. Additionally, we performed an in-situ analysis of the intermediates of multicomponent reactions, for the first-time, which revealed that nano-zirconium dioxide stimulated the reaction, as estimated by Gibbs free energy calculations of spontaneity. Functionally, the novel pyranopyrazoles were tested for a loss of cell viability using human breast cancer cells (MCF-7). It was observed that compounds 5b and 5f effectively produced loss of viability of MCF-7 cells with IC50 values of 17.83 and 23.79 µM, respectively. In vitro and in silico mode-of-action studies showed that pyranopyrazoles target CDK1 in human breast cancer cells, with lead compounds 5b and 5f having potent IC50 values of 960 nM and 7.16 µM, respectively. Hence, the newly synthesized bioactive pyranopyrazoles could serve as better structures to develop CDK1 inhibitors against human breast cancer cells.

Improvement Strategies for Stability and Efficiency of Perovskite Solar Cells.

Recently, perovskites have garnered great attention owing to their outstanding characteristics, such as tunable bandgap, rapid absorption reaction, low cost and solution-based processing, leading to the development of high-quality and low-cost photovoltaic devices. However, the key challenges, such as stability, large-area processing, and toxicity, hinder the commercialization of perovskite solar cells (PSCs). In recent years, several studies have been carried out to overcome these issues and realize the commercialization of PSCs. Herein, the stability and photovoltaic efficiency improvement strategies of perovskite solar cells are briefly summarized from several directions, such as precursor doping, selection of hole/electron transport layer, tandem solar cell structure, and graphene-based PSCs. According to reference and analysis, we present our perspective on the future research directions and challenges of PSCs.

Voacamine is a novel inhibitor of EGFR exerting oncogenic activity against colorectal cancer through the mitochondrial pathway.

Colorectal cancer (CRC), among the most aggressive and prevailing neoplasms, is primarily treated with chemotherapy. Voacamine (VOA), a novel bisindole natural product, possesses a variety of conspicuous pharmacological activities. Within the current research, we evaluated in vitro and in vivo the anticancer efficacy of VOA against CRC and its potential mechanisms. Our results illustrated that VOA concentrationdependently suppressed the proliferation and migration of CT26 and HCT116 cells as correspondingly indicated by IC50 values of 1.38 ± 0.09 µM and 4.10 ± 0.14 µM. Furthermore, treatment of VOA also suppressed tumor cell colony formation, escalated the late-stage apoptosis rate of tumor cells, and evoked cell cycle of CT26 and HCT116 cells arrest inhibition in G2-M and G0-G1 phases, respectively. Meanwhile, VOA markedly disrupted the mitochondrial membrane potential eliciting mitochondrial dysfunction, decreased ATP production, and intermediated an enhanced accumulation of intracellular reactive oxygen species with a concentration-dependent pattern, accompanied by elevated expression levels of pro-apoptotic related protein Bax, Cyt-C, cleaved caspases 3/8/9 and by diminished Bcl-2, Bid, PRAP and caspases 3/8/9 expression. Further mechanistic studies revealed VOA treatment suppressed the EGFR/PI3K/Akt pathway with the evidence of the decreased phosphorylation proteins of EGFR, PI3K, Akt, and downstream proteins of p-mTOR, p-NF-kB, and p-P70S6. Additionally, molecular dynamics simulations further displayed VOA could enter the EGFR pocket followed by multiple mutual interaction effects. Interestingly, the EGFR activator (NSC228155) could slack the inhibitory capability of VOA on the EGFR/PI3K/Akt pathway as well as VOA-induced impairment of mitochondrial function. Finally, administration of VOA (15, 30 mg/kg every 2 days, i.p., for 16 days) in CT26 syngeneic mice dose-dependently suppressed the neoplastic development without appreciable organ toxicities. Taken together, our study demonstrated that VOA may be a prospective therapeutic agent for the treatment of CRC.

Highly Efficient Transfer Hydrogenation of Biomass-Derived Furfural to Furfuryl Alcohol over Mesoporous Zr-Containing Hybrids with 5-Sulfosalicylic Acid as a Ligand.

The catalytic transfer hydrogenation of biomass-derived furfural to furfuryl alcohol under mild conditions is an attractive topic in biorefinery. Herein, mesoporous Zr-containing hybrids (Zr-hybrids) with a high surface area (281.9−291.3 m2/g) and large pore volume (0.49−0.74 cm3/g) were prepared using the biomass-derived 5-sulfosalicylic acid as a ligand, and they were proven to be highly efficient for the Meerwein−Ponndorf−Verley reduction of furfural to furfuryl alcohol at 110 °C, with the highest furfuryl alcohol yield reaching up to 97.8%. Characterizations demonstrated that sulfonic and carboxyl groups in 5-sulfosalicylic acid molecules were coordinated with zirconium ions, making zirconium ions fully dispersed, thus leading to the formation of very fine zirconia particles with the diameter of <2 nm in mesoporous Zr-hybrids. The interaction between the 5-sulfosalicylic acid ligands and zirconium ions endowed mesoporous Zr-hybrids with relatively higher acid strength but lower base strength, which was beneficial for the selective reduction of furfural to furfuryl alcohol. A recycling study was performed over a certain mesoporous Zr-hybrid, namely meso-Zr-SA15, demonstrating that the yield and selectivity of furfuryl alcohol remained almost unchanged during the five consecutive reaction cycles. This study provides an optional method to prepare hybrid catalysts for biomass refining by using biomass-derived feedstock.

Solvent-Free Synthesis of MgO-Modified Biochars for Phosphorus Removal from Wastewater.

Adsorption is an efficient technology for removing phosphorus from wastewater to control eutrophication. In this work, MgO-modified biochars were synthesized by a solvent-free ball milling method and used to remove phosphorus. The MgO-modified biochars had specific surface areas 20.50-212.65 m2 g-1 and pore volume 0.024-0.567 cm3 g-1. The as-prepared 2MgO/BC-450-0.5 had phosphorus adsorption capacities of 171.54 mg g-1 at 25 °C and could remove 100% of phosphorus from livestock wastewater containing 39.51 mg L-1 phosphorus. The kinetic and isotherms studied show that the pseudo-second-order model (R2 = 0.999) and Langmuir models (R2 = 0.982) could describe the adoption process well. The thermodynamic analysis indicated that the adsorption of phosphorus on the MgO-modified biochars adsorbent was spontaneous and endothermic. The effect of pH, FTIR spectra and XPS spectra studies indicated that the phosphorus adsorption includes a protonation process, electrostatic attraction and precipitation process. This study provides a new strategy for biochar modification via a facile mechanochemical method.

Development of 1-(4-(Substituted)piperazin-1-yl)-2-((2-((4-methoxybenzyl)thio)pyrimidin-4-yl)oxy)ethanones That Target Poly (ADP-Ribose) Polymerase in Human Breast Cancer Cells.

A number of uracil amides cleave poly (ADP-ribose) polymerase and therefore novel thiouracil amide compounds were synthesized and screened for the loss of cell viability in a human-estrogen-receptor-positive breast cancer cell line. The synthesized compounds exhibited moderate to significant efficacy against human breast cancer cells, where the compound 5e IC50 value was found to be 18 µM. Thouracil amide compounds 5a and 5e inhibited the catalytical activity of PARP1, enhanced cleavage of PARP1, enhanced phosphorylation of H2AX, and increased CASPASE 3/7 activity. Finally, in silico analysis demonstrated that compound 5e interacted with PARP1. Hence, specific thiouracil amides may serve as new drug-seeds for the development of PARP inhibitors for use in oncology.

Construction of multi-substituted pyrazoles via potassium carbonate-mediated [3 + 2] cycloaddition of in situ generated nitrile imines with cinnamic aldehydes.

A highly efficient potassium carbonate-mediated [3 + 2] cycloaddition reaction of hydrazonoyl chlorides with cinnamic aldehydes to furnish multi-substituted pyrazoles under nontoxic and mild conditions has been developed. A plausible stepwise cycloaddition reaction mechanism is proposed. This protocol featured broad substrate coverage, good functional group tolerance, wide scalability, and operational simplicity, as well as conveniently constructed pyrazole scaffolds.

Activation of mitochondrial-associated apoptosis signaling pathway and inhibition of PI3K/Akt/mTOR signaling pathway by voacamine suppress breast cancer progression.

BACKGROUND: Breast cancer is one of the malignant tumors with the highest morbidity and mortality rate. Numerous efficient anti-breast cancer drugs are being derived from the development of natural products. Voacamine (VOA), a bisindole alkaloid isolated from Voacanga africana Stapf, possesses various pharmacological and biological activities. PURPOSE: In this study, we investigated the efficacy of VOA against breast cancer cells and elucidated the underlying mechanisms in vitro and in vivo. METHODS: Human breast cancer cell line MCF-7 and mouse breast cancer cell line 4T1 were used to study the underlying anti-cancer mechanisms of VOA. The proliferation was detected by MTT, colony formation, cell proliferation and wound-healing migration assays. Flow cytometry was utilized to determine the level of reactive oxygen species (ROS) cell-cycle, apoptosis and mitochondrial membrane potential. The target proteins were analyzed by Western blot. Molecular docking was performed and scored by AutoDock. Subcutaneous cancer models in mice were established to evaluate the anticancer effects in vivo. RESULT: Our results demonstrated that VOA selectively suppressed breast cancer MCF-7 and 4T1 cells proliferation with IC50 values of 0.99 and 1.48 µM, and significantly inhibited the migration and colony formation of tumor cells. Furthermore, the cell cycle was arrested in the S phase with the decreased expression levels of CDK2, Cyclin A and Cyclin E. Additionally, exposure to VOA dose-dependently brought about dose-dependently the loss of mitochondrial membrane potential (Δψm) and amassment of reactive oxygen species (ROS), resulting in the initiation of the intrinsic apoptotic pathway. Western blot analysis unveiled that VOA significantly activated mitochondrial-associated apoptosis and obviously suppress the PI3K/Akt/mTOR pathway via modulation of related protein expression levels in both tumor cell lines. In tumor-bearing mouse models, administration of VOA dose-dependently inhibited the tumor growth without causing apparent toxicities. CONCLUSION: These findings revealed the novel properties of VOA in promoting apoptosis of breast cancer cells by activating mitochondrial-associated apoptosis signaling pathway and inhibiting PI3K/Akt/mTOR signaling pathway and significantly decreasing tumor size without detecting appreciable toxicity. In summary, the present results demonstrated VOA could be an encouraging drug candidate to cure breast cancer, exhibiting an effective method to exploit unique drugs from natural components.

Design and Activity of Novel Oxadiazole Based Compounds That Target Poly(ADP-ribose) Polymerase.

Novel PARP inhibitors with selective mode-of-action have been approved for clinical use. Herein, oxadiazole based ligands that are predicted to target PARP-1 have been synthesized and screened for the loss of cell viability in mammary carcinoma cells, wherein seven compounds were observed to possess significant IC50 values in the range of 1.4 to 25 µM. Furthermore, compound 5u, inhibited the viability of MCF-7 cells with an IC50 value of 1.4µM, when compared to Olaparib (IC50 = 3.2 µM). Compound 5s also decreased cell viability in MCF-7 and MDA-MB-231 cells with IC50 values of 15.3 and 19.2 µM, respectively. Treatment of MCF-7 cells with compounds 5u and 5s produced PARP cleavage, H2AX phosphorylation and CASPASE-3 activation comparable to that observed with Olaparib. Compounds 5u and 5s also decreased foci-formation and 3D Matrigel growth of MCF-7 cells equivalent to or greater than that observed with Olaparib. Finally, in silico analysis demonstrated binding of compound 5s towardsthe catalytic site of PARP-1, indicating that these novel oxadiazoles synthesized herein may serve as exemplars for the development of new therapeutics in cancer.

Synthesis of sulfonated lignin-derived ordered mesoporous carbon for catalytic production of furfural from xylose.

Sulfonated lignin-derived ordered mesoporous carbon (OMC-SO3H) solid acid was synthesized through solvent evaporation induced self-assembly (EISA) method followed by sulfonation, using lignin as carbon precursor and glyoxal as cross-linking agent during the preparation process. The as-synthesized OMC-SO3H exhibited a typical 2D hexagonal meso-structure (space group p6mm) and showed a good catalytic performance for the catalytic conversion of hemicellulose-derived xylose to furfural. A highest furfural yield of 76.7% with 100% xylose conversion was achieved at 200 °C for 45 min in γ-valerolactone (GVL)-water (85:15 v/v%) mixture. The lignin-derived OMC-SO3H solid acid catalyst showed superior stability and reusability, and was also applicable to the catalytic production of furfural from xylan. This work provides a promising strategy for the synthesis of ordered mesoporous carbon solid acid from green and sustainable lignin biomass resource, which has wide range of applications in the utilization of cellulose and hemicellulose.

LDOC1 Suppresses Microbe-Induced Production of IL-1ß in Human Normal and Cancerous Oral Cells through the PI3K/Akt/GSK-3ß Axis.

Poor oral hygiene (POH) is associated with oral squamous cell carcinoma (OSCC). Oral microbes often proliferate due to POH. Array data show that LDOC1 plays a role in immunity against pathogens. We investigated whether LDOC1 regulates the production of oral microbe-induced IL-1ß, an oncogenic proinflammatory cytokine in OSCC. We demonstrated the presence of Candida albicans (CA) in 11.3% of OSCC tissues (n = 80). CA and the oral bacterium Fusobacterium nucleatum stimulate higher levels of IL-1ß secretion by LDOC1-deficient OSCC cells than by LDOC1-expressing oral cells. CA SC5314 increased OSCC incidence in 4-NQO (a synthetic tobacco carcinogen) and arecoline-cotreated mice. Loss and gain of LDOC1 function significantly increased and decreased, respectively, CA SC5314-induced IL-1ß production in oral and OSCC cell lines. Mechanistic studies showed that LDOC1 deficiency increased active phosphorylated Akt upon CA SC5314 stimulation and subsequent inhibitory phosphorylation of GSK-3ßS9 by activated Akt. PI3K and Akt inhibitors and expression of the constitutively active mutant GSK-3ßS9A significantly reduced the CA SC5314-stimulated IL-1ß production in LDOC1-deficient cells. These results indicate that the PI3K/Akt/pGSK-3ß signaling pathway contributes to LDOC1-mediated inhibition of oral microbe-induced IL-1ß production, suggesting that LDOC1 may determine the pathogenic role of oral microbes in POH-associated OSCC.

Complete dechlorination of lindane over N-doped porous carbon supported Pd catalyst at room temperature and atmospheric pressure.

Transfer hydrogenation is highly effective for dechlorinating priority organic pollutants in wastewater. Lindane could be completely dechlorinated at room temperature and atmospheric pressure via transfer hydrogenation, in which Pd (3.1 wt%) supported on chitosan-derived porous carbon (3.1Pd@A600) and formic acid (FA) were used as catalyst and hydrogen source, respectively. Favorable catalytic activity of 3.1Pd@A600 is attributed to pyridinic N of the support that allowed Pd nanoparticles to be well-dispersed in the solid and to pyridinic N-Pd interactions that enhanced FA decomposition over that observed for commercial carbon supported Pd catalyst (5Pd@AC). In the reaction system containing 3.1Pd@A600 and FA, 99.7% lindane conversion and 100% dechlorination efficiency could be achieved at 25 °C and atmospheric pressure within 60 min. Benzene and cyclohexane were identified as end-products of lindane dechlorination. The transfer hydrogenation strategy developed in this study has wide application to chlorinated organic pollutants contained in actual waste streams.

Coupled Pretreatment with Liquid Nitrogen and Ball Milling for Enhanced Cellulose Hydrolysis in Water.

A key problem in the conversion of cellulose into chemicals and fuels is the low product yield from cellulose due to its robust structure. In this work, for the first time, cellulose was pretreated with coupling of liquid nitrogen and ball milling (LN-BM) for cellulose hydrolysis. After the LN-BM treatment, the glucose yield from cellulose by HCl in water increased by almost 2 times and yield of formic acid catalyzed by H2SO4-NaVO3 was more than 3-fold that obtained from untreated cellulose. The yields were also much higher than that from the individually ball-milled cellulose. The structure variation of cellulose indicated that reduction of both crystallinity index and molecular weight contributed to improving the conversion efficiency, but the former was the dominant factor. The combination of liquid nitrogen and ball milling developed in this work is an effective and environment-friendly approach for cellulose pretreatment.

Novel STAT3 Inhibitor LDOC1 Targets Phospho-JAK2 for Degradation by Interacting with LNX1 and Regulates the Aggressiveness of Lung Cancer.

Meta-analysis revealed that Leucine Zipper Down-Regulated In Cancer 1 (LDOC1) increased methylation more in people with lung tumors than in those who were healthy and never smoked. Quantitative methylation-specific PCR revealed that cigarette smoke condensate (CSC) exposure drives LDOC1 promoter hypermethylation and silence in human bronchial cells. Immunohistochemistry studies showed that LDOC1 downregulation is associated with poor survival of patients with lung cancer. Loss and gain of LDOC1 functions enhanced and attenuated aggressive phenotypes in lung adenocarcinoma A549 and non⁻small cell lung carcinoma H1299 cell lines, respectively. We found that LDOC1 deficiency led to reinforcing a reciprocal loop of IL-6/JAK2/STAT3, through which LDOC1 mediates the cancer progression. LDOC1 knockdown considerably augmented tumorigenesis and the phosphorylation of JAK2 and STAT3 in vivo. Results from immunoprecipitation and immunofluorescent confocal microscopy indicated that LDOC1 negatively regulates JAK2 activity by forming multiple protein complexes with pJAK2 and E3 ubiquitin-protein ligase LNX1, and in turn, LDOC1 targets pJAK2 to cause ubiquitin-dependent proteasomal degradation. LDOC1 deficiency attenuates the interactions between LNX1 and pJAK2, leading to ineffective ubiquitination of pJAK2, which activates STAT3. Overall, our results elucidated a crucial role of LDOC1 in lung cancer and revealed how LDOC1 acts as a bridge between tobacco exposure and the IL-6/JAK2/STAT3 loop in this human malignancy.

Nitrogen-doped porous carbon derived from chitosan for the enhanced dehydrochlorination of lindane under mild conditions.

Dehydrochlorination of lindane is commonly conducted in homogeneous alkaline solutions, possessing a series of problems such as corrosion and poor recyclability. In order to overcome the pervasive problems concerning homogeneous catalysts, heterogeneous catalysts have been increasingly employed in the applications. In this study, nitrogen-doped porous carbons (NPCs) were developed by a simple way in which chitosan and ZnCl2 were employed as the precursor and activation agent, respectively. NPCs exhibited high surface area (1111-1497 m2/g) and large porosity (0.464-0.621 cm3/g), resulting in a great adsorption affinity to lindane and the by-products. As solid bases, NPCs displayed an enhanced catalytic activity on lindane dehydrochlorination. This was closely related to the amount of pyridinic nitrogen on the pore surface, which could be tuned by the synthesis temperature. The optimal removal efficiency of lindane was up to 99.9% in presence of A800 (a NPC catalyst) at moderate pH (9.0) and mild temperature (45 °C) after incubation for 24 h. The rate constant for A800 suspension was improved by 2-3 orders of magnitude in comparison with that obtained in homogeneous solution at moderate pH (9.0) and mild temperatures (25-45 °C). The reusability of the material was evaluated by cycling for three times without noticeably reduced catalytic activity. This study provides a novel strategy to achieve partial dechlorination of chlorinated organic pollutants.

The inhibitory activity of gallic acid against DNA methylation: application of gallic acid on epigenetic therapy of human cancers.

Epigenome aberrations have been observed in tobacco-associated human malignancies. (-)-epigallocatechin-3-gallate (EGCG) has been proven to modulate gene expression by targeting DNA methyltransferases (DNMTs) through a proposed mechanism involving the gallate moiety of EGCG. We show that gallic acid (GA) changes the methylome of lung cancer and pre-malignant oral cell lines and markedly reduces both nuclear and cytoplasmic DNMT1 and DNMT3B within 1 week. GA exhibits stronger cytotoxicity against the lung cancer cell line H1299 than EGCG. We found that GA reactivates the growth arrest and DNA damage-inducible 45 (GADD45) signaling pathway may through the demethylation of CCNE2 and CCNB1 in H1299 cells. To improve the epigenetic anti-cancer activities of oolong tea, we identified a fungus, Aspergillus sojae which can efficiently increase the GA content in oolong tea via a 2-week fermentation process. The fungus dramatically increased GA up to 44.8 fold in the post-fermentation oolong tea extract (PFOTE), resulting in enhanced demethylation effects and a significant reduction in the nuclear abundances of DNMT1, DNMT3A, and DNMT3B in lung cancer cell lines. PFOTE also showed stronger anti-proliferation activities than oolong tea extract (OTE) and increased sensitivity to cisplatin in H1299 cells. In summary, we demonstrate the potent inhibitory effects of GA on the activities of DNMTs and provide a strong scientific foundation for the use of specialized fermented oolong tea high in GA as an effective dietary intervention strategy for tobacco-associated cancers.