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Green fuel from water splitting is hardcore for future generations, and the limited source of fresh water (<1%) is a bottleneck. Seawater cannot be used directly as a feedstock in current electrolyzer techniques. Until now single atom catalysts were reported by many synthetic strategies using notorious chemicals and harsh conditions. A cobalt single-atom (CoSA) intruding cobalt oxide ultrasmall nanoparticle (Co 3 O 4 USNP)-intercalated porous carbon (PC) (CoSA-Co 3 O 4 @PC) electrocatalyst was synthesized from the waste orange peel as a single feedstock (solvent/template). The extended X-ray absorption fine structure spectroscopy (EXAFS) and theoretical fitting reveal a clear picture of the coordination environment of the CoSA sites (CoSA-Co 3 O 4 and CoSA-N 4 in PC). To impede the direct seawater corrosion and chlorine evolution the seawater has been desalinated (Dseawater) with minimal cost and the obtained PC is used as an adsorbent in this process. CoSA-Co 3 O 4 @PC shows high oxygen evolution reaction (OER) activity in transitional metal impurity-free (TMIF) 1 M KOH and alkaline Dseawater. CoSA-Co 3 O 4 @PC exhibits mass activity that is 15 times higher than the commercial RuO 2 . Theoretical interpretations suggest that the optimized CoSA sites in Co 3 O 4 USNPs reduce the energy barrier for alkaline water dissociation and simultaneously trigger an excellent OER followed by an adsorbate evolution mechanism (AEM)., (© 2023 Wiley-VCH GmbH.)

The multimodal non-identical generators having close frequency modes may complicate the design of subsynchronous damping controller. In this paper, the Band-Pass Filter (BPF) based Subsynchronous Damping Controller (SSDC) is designed with SSSC to damp multimode SSR. The system is adapted from IEEE First Benchmark Model (FBM) with two non-identical generators in parallel. One of the generators has a six-mass mechanical system and other has a four-mass mechanical system. The SSDC using reduced number of BPFs is proposed to enhance the damping of multimodal SSR while maintaining the frequency selectivity of filters. The proposed BPF based SSDC is designed to modulate the SSSC injected voltage so as to suppress the multimode components in the line. The DQ model is developed in MATLAB-Simulink using the differential and algebraic equations of the combined system. The analysis of SSR are carried out through damping torque, eigenvalue and transient simulation. The participation factor analysis is performed to identify the torsional modes of the generators. The eigenvalue analysis is used to select the number of BPFs. The BPFs with appropriate frequency selectivity are chosen to improve the damping of all critical torsional modes in the entire range of practical compensation level. The results show that, the peak negative damping at both generators is considerably reduced with the proposed SSDC in the entire range of torsional mode frequencies through practical compensation levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 ISA. Published by Elsevier Ltd. All rights reserved.)

In the field of nanotechnology, nanoadsorbents have emerged as a powerful tool for the purification of contaminated aqueous environments. Among the variety of nanoadsorbents developed so far, magnetite (Fe 3 O 4 ) nanoparticles have drawn particular interest because of their quick separation, low cost, flexibility, reproducibility, and environmentally benign nature. Herein, we describe a new strategy for the synthesis of Fe 3 O 4 nanoclusters, which is based on the use of naturally available edible mushrooms (Pleurotus eryngii) and environmentally benign propylene glycol as a solvent medium. By tuning the temperature, we successfully convert Fe 3 O 4 nanoparticles into Fe 3 O 4 nanoclusters via hydrothermal treatment, as evidenced by transmission electron microscopy. The Fe 3 O 4 nanoclusters are functionalized with an organic molecule linker (dihydrolipoic acid, DHLA) to remove hazardous Hg(II) ions selectively. Batch adsorption experiments demonstrate that Hg(II) ions are strongly adsorbed on the material surface, and X-ray photoelectron and Fourier transform infrared spectroscopy techniques reveal the Hg(II) removal mechanism. The DHLA@Fe 3 O 4 nanoclusters show a high removal efficiency of 99.2 % with a maximum Hg(II) removal capacity of 140.84 mg g -1 . A kinetic study shows that the adsorption equilibrium is rapidly reached within 60 min and follows a pseudo second-order kinetic model. The adsorption and separation system can be readily recycled using an external magnet when the separation occurs within 10 s. We have studied the effect of various factors on the adsorption process, including pH, concentration, dosage, and temperature. The newly synthesized superparamagnetic DHLA@Fe 3 O 4 nanoclusters open a new path for further development of the medical, catalysis, and environmental fields., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Several concerns exist on the performance and health attributes of sheep fed on complete replacements of the traditional feed ingredients with dried distillers' grain solubles (DDGS). The study intended to know the effect of DDGS on replacing the peanut cake (PNC) at 0%, 50%, 75%, and 100% in sheep fed Jowar stover-based diet. Replacing PNC with DDGS increased (P < 0.05) the final body weight and concentrate intake. The weight gain and average daily gain tended to increase (P = 0.086), whereas the feed conversion ratio tended to decrease (P = 0.092) with increased DDGS inclusion levels. The CP intake increased linearly (P < 0.01) with an increase in DDGS levels. However, the intakes of DM, OM, NDF, and ADF increased quadratically (P < 0.01) and showed a quadratic maximum at 75% replacements group. The in vitro dry matter digestibility and 24 h-gas (ml) production linearly increased (P < 0.05) with increased DDGS inclusion levels, while the CH 4 (% total gas) and CH 4 (ml) showed a quadratic increase (P < 0.05). The metabolisable energy, ammonia nitrogen, and volatile fatty acid concentrations were higher for DDGS diets. Further, the Gompertz curve fitting of the gas production data revealed higher asymptotic volume with lower constant of integration (b) and rate of production (k) of the DDGS incubations. No significant differences were observed for any of the carcass characteristics, except for leg weight, which showed a linear increase (P < 0.05). Increased tendency was observed for EBW, loin eye area at 12th rib, and edible portion of the sheep fed DDGS groups. Further, the visceral organs and carcass composition did not show any significant differences, except for kidney weight (linear, P < 0.05). The income over feed cost (IOFC) was higher for 100% DDGS group with lower feed cost and higher income per Kg mutton. Replacing the traditional peanut cake with DDGS in the crop residue-based diets of growing lambs contributes to higher yields for producers.

Two polycyclic heteroarene derivatives, namely, V-1 and V-2 , with a diphenanthro[9,10- b :9',10'-d]thiophene (DPT) core tethered with two diphenylaminophenyl or diphenylamino groups were first synthesized and used as hole-transporting materials (HTMs) in perovskite solar cell (PSC) fabrication. The novel HTMs exhibit appropriate energy-level alignment with the perovskite so as to ensure efficient hole transfer from the perovskite to HTMs. V-2 with the diphenylamino substituent on DPT exhibited impressive photovoltaic performance with a power conversion efficiency of 19.32%, which was higher than that of V-1 (18.60%) and the benchmark 2,2',7,7'-tetrakis-( N , N -di- p -methoxyphenyl-amine)-9,9'-spirobifluorene (spiro-OMeTAD) (17.99%), presumably because of a better hole extraction, higher hole mobility, and excellent film-forming ability, which were supported by steady-state photoluminescence (PL), time-resolved PL, the hole mobility experiment, scanning electron microscopy, and atomic force microscopy measurements. Meanwhile, V-2 -based PSCs exhibited better long-term durability than that with V-1 and the state-of-the-art spiro-OMeTAD, which is ascribable to the excellent surface morphology and hydrophobicity of the film. This systematic study suggests that DPT-based molecules are good potential candidates as HTMs for achieving high-performance PSCs.

The physical properties, packing, morphology, and semiconducting performance of a planar π-conjugated system can be effectively modified by introducing side chains and substituent groups, both of which can be complementary to the π framework in changing the intermolecular association, frontier molecular orbital energy, optical band gap, and others. We herein show that installation of end-capped electron-withdrawing groups (EWGs), such as dicyanovinyl (-DCV), 3-ethylrhodanine (-RD), and 2-(3-oxo-indan-1-ylidene)-malononitrile (-INCN), together with siloxane side chains to the backbones of dithienyldiketopyrrolopyrrole (DPPT), such as DPPT-Si-DCV , DPPT-Si-RD , and DPPT-Si-INCN , can greatly improve its solubility, air stability, and film morphology to serve as an n-channel in thin-film transistor fabrication. The EWGs attached to the DPPT core narrowed the optical band gap ( E g opt ) and changed the highest occupied molecular orbital and the lowest unoccupied molecular orbital energies ( E HOMO and E LUMO ), making them suitable for n-channel field-effect transistor (FET) applications. The benefits of introducing siloxane side chains to the DPPT core include enhanced solubility, low crystallization barrier, enantiotropic phase behavior, and much improved FET performance. The DPPT-Si-INCN film displayed low-lying HOMO (-5.82 eV) and LUMO (-4.60 eV) energy levels and an optical band gap as low as 1.22 eV, all of which suggest that this derivative can be quite resistant toward aerial oxidation. Thin films of these derivatives were prepared by the solution-shear method. A comparison of the solution-sheared films indicated that the molecular packing motif of DPPT-Si-INCN film was somehow different from that of DPPT-Si-DCV and DPPT-Si-RD , in which the π-π stacking tended to align orthogonally to the shearing direction. This specific π-π stacking alignment could have an impact on the electron mobility (μ e ) values in transistors based on the solution-sheared films.

A new class of polycyclic heteroarenes based on benzo[3,4]phenanthro[1,2- b ]benzo[3,4]phenanthro[2,1- d ]thiophene ( BPBPT ) was prepared from polyaryl thiophenes via regioselective Scholl reactions. The molecular frameworks of these compounds exhibited twisted bridges and near-cofacial packing motifs with oppositely or parallel π-stacked structures depending on the substituents on the periphery. Theoretical calculation of electronic coupling and charge mobility was carried out on the basis of the single-crystal structures. Single crystals of selected benzophenanthrothiophenes were used in p -channel field-effect transistor device fabrication, from which the highest mobility was measured as 2.03 cm 2 V -1 s -1 from Flu-BPBPT .

A series of tetra- and octa-substituted hexa-cata-hexabenzocoronenes (cata-HBCs) were synthesized from tetraryl olefins via iodine- and iron chloride-catalyzed oxidative cyclodehydrogenation reactions. The substitutions on the periphery of the parent HBC serve to modify the photophysical properties, highest occupied molecular orbital-lowest unoccupied molecular orbital gaps, and thermal stabilities of the respective derivatives. The crystal structures were determined to display multiple twists in the framework, resulting in different packing motifs depending on the position, type, and number of functional groups on the hexabenzocoronene framework. Nearly perfect co-facial packing to marginally or extensively shifted co-facial stacks were obtained due to substitution. The single crystals of parent HBC were used to fabricate single-crystal field-effect transistors, from which the highest p-channel mobility of 0.51 cm 2 V -1 s -1 was measured. Thin-film transistors of selected HBCs were also prepared, and 0.61 cm 2 V -1 s -1 was obtained for MeHBC-2. These results attest the potential of these materials as semiconducting materials.

The enormous ongoing industrial development has caused serious water pollution which has become a major crisis, particularly in developing countries. Among the various water pollutants, non-biodegradable heavy metal ions are the most prevalent. Thus, trace-level detection of these metal ions using a simple technique is essential. To address this issue, we have developed a fluorescent probe of Au/C nanodots (GCNDs-gold carbon nanodots) using an eco-friendly method based on an extract from waste onion leaves ( Allium cepa-red onions ). The leaves are rich in many flavonoids, playing a vital role in the formation of GCNDs. Transmission electron microscopy (TEM) and Scanning transmission electron microscopy-Energy-dispersive X-ray spectroscopy (STEM-EDS) elemental mapping clearly indicated that the newly synthesized materials are approximately 2 nm in size. The resulting GCNDs exhibited a strong orange fluorescence with excitation at 380 nm and emission at 610 nm. The GCNDs were applied as a fluorescent probe for the detection of Hg 2+ ions. They can detect ultra-trace concentrations of Hg 2+ with a detection limit of 1.3 nM. The X-ray photoelectron spectroscopy results facilitated the identification of a clear detection mechanism. We also used the new probe on a real river water sample. The newly developed sensor is highly stable with a strong fluorescent property and can be used for various applications such as in catalysis and biomedicine.

Because of their large surface area and conductivity, some inorganic materials have emerged as good candidates for the trace-level detection of pharmaceutical drugs. In the present work, we demonstrate the detection of an anticancer drug (regorafenib, REG) by using an electrochemical sensor based on a nanocomposite material. We synthesized a zirconia-nanoparticle-decorated reduced graphene oxide composite (ZrO 2 /rGO) using a one-pot hydrothermal method. Reduction of the graphene oxide supports of the Zr 2+ ions with hydrazine hydrate helped in preventing the agglomeration of the zirconia nanoparticles and in obtaining an excellent electrocatalytic response of the nanostructure ZrO 2 /rGO-based electrochemical sensor. Structural and morphological characterization of the nanostructure ZrO 2 /rGO was performed using various analytical methods. A novel regorafenib (REG) electrochemical sensor was fabricated by immobilizing the as-prepared nanostructure ZrO 2 /rGO on to a glassy carbon electrode (GCE). The resulting ZrO 2 /rGO/GCE could be used for the rapid and selective determination of REG in the presence of ascorbic acid and uric acid. The ZrO 2 /rGO/GCE showed a linear response for the REG analysis in the dynamic range 11-343 nM, with a remarkable lower detection limit and limit of quantifications of 17 and 59 nM, respectively. The newly developed sensor was used for the accurate determination of REG in both serum samples and pharmaceutical formulations, with satisfactory results., Competing Interests: The authors declare no competing financial interest.

New classes of nonlinear polyaromatics with extended conjugation at lateral and longitudinal directions from triphenylene, tetracene, and pentacene backbones are reported. These planar and twisted polyfused aromatics are obtained through specific and selective multifold Scholl reactions from predesigned polyaryls. These derivatives displayed shifted or perfect cofacial packing motifs. Single crystals of one derivative, phenanthro[9,10: b]triphenylene, were used as p-channel materials in fabricating transistor devices, which exhibited an average mobility of 0.38 cm 2 V -1 s -1 and a maximum mobility reaching 1.15 cm 2 V -1 s -1 .

Recently, active bubble-propelled micromotors have attracted great attention for fuel applications. However, for generating bubble-propelled micromotors, additional catalysts, such as Pt, Ag, and Ru, are required. These catalysts are expensive, toxic, and highly unstable for broad applications. To overcome these issues, in this study, we present an innovative methodology for the preparation of self-propelled motor machines using naturally occurring diatom frustules. This natural diatom motor shows effective motion in the presence of a very low concentration (0.8%) of H2O2 as a fuel at pH 7. Due to the unique 3D anisotropic shape of the diatom, the self-propelled motor exhibited unidirectional motion with a speed of 50 μm s-1 and followed pseudo first-order kinetics. It was found that a trace amount of iron oxide (Fe2O3) in the diatom was converted into Fe3O4, which can act as a catalyst to achieve the facile decomposition of H2O2. Interestingly, "braking" of the unidirectional motion was observed upon treatment with EDTA, which blocked the catalytically active site. These results illustrate that diatom catalytic micromotors have opened a new era in the field of catalysis and bioengineering applications.

Development of carbon-based materials has received tremendous attention owing to their multifunctional properties. Biomaterials often serve as an inspiration for the preparation of new carbon materials. Herein, we present a facile synthesis of a new bioinspired graphene oxide-like 2D-carbon flake (CF) using a natural resource, waste onion sheathing (Allium cepa). The 2D-CF was further decorated with crystalline Fe3O4 nanoparticles for applications. Superparamagnetic Fe3O4 nanoparticles (7 nm) were well-dispersed on the surface of the 2D-CF, which was characterized by X-ray diffractometry, X-ray photoelectron spectroscopy, Raman spectrometry, and transmission electron microscopy. Batch As(III) adsorption experiments showed that aqueous arsenic ions strongly adsorbed to the Fe3O4@2D-CF composite. The adsorption capacity of the Fe3O4@2D-CF composite for As(III) was 57.47 mg g(-1). The synergetic effect of both graphene oxide-like 2D-CF and Fe3O4 nanoparticles aided in excellent As(III) adsorption. An As(III) ion adsorption kinetics study showed that adsorption was very fast at the initial stage, and equilibrium was reached within 60 min following a pseudo-second-order rate model. Owing to the excellent superparamagnetic properties (52.6 emu g(-1)), the Fe3O4@2D-CF composite exhibited superb reusability with the shortest recovery time (28 s) among reported materials. This study indicated that Fe3O4@2D-CF composites can be used for practical applications as a global economic material for future generations.

Heavy metal ion removal from wastewater constitutes an important issue in the water treatment industry. Although a variety of nanomaterials have been developed for heavy metal removal via adsorption, the adsorption capacity, removal efficiency, and material recyclability still remain a challenge. Here, we present novel Fe3O4@DAPF core-shell ferromagnetic nanorods (CSFMNRs) for the removal of Pb(II) from aqueous solutions; they were prepared by the facile surface modification of twin-like ferromagnetic Fe3O4 nanorods using a 2,3-diaminophenol and formaldehyde (DAPF)-based polymer. The crystallinity and structure of the Fe3O4 nanorods were confirmed via X-ray diffraction (XRD). Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) revealed the core-shell morphology and composition of the materials. Pb(II) removal using the prepared Fe3O4@DAPF CSFMNRs was assessed, and comparable adsorption capacities (83.3 mg g(-1)) to the largest value were demonstrated. A thermodynamic study of the adsorption clearly indicated that the adsorption was exothermic and spontaneous. Due to the ferromagnetic properties with a high saturation magnetization value (56.1 emu g(-1)) of the nanorods, the nanorods exhibited excellent reusability with one of the fastest recovery times (25 s) among reported materials. Therefore, the Fe3O4@DAPF CSFMNRs can serve as recyclable adsorbent materials and as an alternative to commonly used sorbent materials for the rapid removal of heavy metals from aqueous solutions.

Mercury is considered one of the most notorious global pollutants due to its high toxicity and widespread use in industry. Although many materials have been developed for the removal of mercury for water purification, most of these materials are difficult to reuse, which may lead to an increase in the mercury handling expense. Therefore, new sustainable materials that can be easily recycled and are highly efficient for the removal of mercury are required. Herein, we report the surfactant-free green synthesis of Fe3O4 magnetic nanoparticles (MNPs) using a watermelon (Citrullus lanatus) rind extract. The Fe3O4 MNPs were further functionalized with 3,4-dihydroxyphenethylcarbamodithioate (DHPCT) and applied to the removal of Hg(ii). Evaluation of the mercury removal efficiency and the amount adsorbed by DHPCT@Fe3O4 MNPs demonstrated a high Hg(ii) removal efficiency (98%) with a maximum Hg(ii) adsorption capacity of 52.1 mg g(-1). Systematic studies of the adsorption mechanism and selectivity suggest that the soft ligand (DHPCT) can preferentially coordinate with the soft metal ion (Hg(ii)) resulting in selective mercury removal. The developed DHPCT@Fe3O4 MNPs were readily recycled several times using an external magnet by exploiting their ferromagnetic character, without a significant decline in the Hg(ii) removal efficiency. This study provides a new insight into the preparation of a highly efficient adsorbent for Hg(ii) removal by an eco-friendly method.

Stilbenes comprise a group of polyphenolic compounds, which exert inhibitory effects on various malignancies. The aim of this study was to evaluate the antitumor effects of a previously unreported stilbene derivative-3,3',4,4',5,5'-hexahydroxystilbene, termed M8-on human melanoma cells. Cell-cycle analysis of the metastatic melanoma cell line M24met showed that M8 treatment induces G(2)/M arrest accompanied with a dose- and time-dependent upregulation of p21 and downregulation of CDK-2 and leads to apoptosis. M8 induces the expression of phosphorylated p53, proteins involved in the mismatch repair machinery (MSH6, MSH2, and MLH1) and a robust tail moment in a comet assay. In addition, M8 inhibited cell migration in Matrigel assays. Shotgun proteomics and western analysis showed the regulation among others of paxillin, integrin-linked protein kinase, p21-activated kinase, and ROCK-1 indicating that M8 inhibits mesenchymal and amoeboid cell migration. These in vitro data were confirmed in vivo in a metastatic human melanoma severe combined immunodeficient (SCID) mouse model. We showed that M8 significantly impairs tumor growth. M8 also interfered with the metastatic process, as M8 treatment prevented the metastatic spread of melanoma cells to distant lymph nodes in vivo. In summary, M8 exerts strong antitumor effects with the potential to become a new drug for the treatment of metastatic melanoma.

Background: Digalloyl-resveratrol (di-GA) is a synthetic compound aimed to combine the biological effects of the plant polyhydroxy phenols gallic acid and resveratrol, which are both radical scavengers and cyclooxygenase inhibitors exhibiting anticancer activity. Their broad spectrum of activities may probably be due to adjacent free hydroxyl groups., Methods: Protein activation and expression were analysed by western blotting, deoxyribonucleoside triphosphate levels by HPLC, ribonucleotide reductase activity by (14)C-cytidine incorporation into nascent DNA and cell-cycle distribution by FACS. Apoptosis was measured by Hoechst 33258/propidium iodide double staining of nuclear chromatin and the formation of gaps into the lymphendothelial barrier in a three-dimensional co-culture model consisting of MCF-7 tumour cell spheroids and human lymphendothelial monolayers., Results: In HL-60 leukaemia cells, di-GA activated caspase 3 and dose-dependently induced apoptosis. It further inhibited cell-cycle progression in the G1 phase by four different mechanisms: rapid downregulation of cyclin D1, induction of Chk2 with simultaneous downregulation of Cdc25A, induction of the Cdk-inhibitor p21(Cip/Waf) and inhibition of ribonucleotide reductase activity resulting in reduced dCTP and dTTP levels. Furthermore, di-GA inhibited the generation of lymphendothelial gaps by cancer cell spheroid-secreted lipoxygenase metabolites. Lymphendothelial gaps, adjacent to tumour bulks, can be considered as gates facilitating metastatic spread., Conclusion: These data show that di-GA exhibits three distinct anticancer activities: induction of apoptosis, cell-cycle arrest and disruption of cancer cell-induced lymphendothelial disintegration.

Turmeric is a well recognized and highly recommended herb in ayurvedic systems of medicine and it has also been used for culinary purposes for thousands of years. Bis-O-demethylatedcurcumin (BDMC) was found to be more efficacious than curcumin and the increased potentcy was attributed to a higher number of phenolic groups in BDMC. A novel demethylatedcurcuminoid composition (DC) comprising minimum 95% of total demethylatedcurcuminoids (67.8% bisdemethylcurcumin, 20.7% demethylmonodemethoxycurcumin, 5.86% bisdemethoxycurcumin, 2.58% demethylcurcumin) was prepared (PCT/IN05/00337, dated October 13, 2005) starting from Curcuma longa extract containing 95% total curcuminoids (C95). DC exhibited superior neuroprotective and anti-inflammatory efficacy compared to C95 in a GeneChip study. Based on these interesting findings, this study sought to determine the broad-spectrum safety of DC. Acute oral, acute dermal, primary skin and eye irritation, and dose-dependent 90 day sub-chronic toxicity studies were conducted. The acute oral LD50 of DC was found to be > 5000 mg/kg in female SD rats. No changes in body weight or adverse effects were observed following necropsy. Acute dermal LD50 of DC was found to be > 2000 mg/kg. Based on the data from primary skin irritation test conducted on New Zealand Albino rabbits, DC was classified as minimally irritating. Similarly, primary eye irritation test was conducted with DC on rabbits and based on the test outcome DC was classified as mildly irritating to the eye. A dose-dependent 90-day sub-chronic toxicity study demonstrated no significant changes in selected organ weights and as percentages of body and brain weights. DC supplementation did not cause changes in hepatic DNA fragmentation. Hematology, clinical chemistry, and histopathological evaluations did not show any adverse effects in any of the organs tested. These results demonstrate the broad spectrum safety of DC.

A demethylated derivative of curcumin (DC; 67.8% bisdemethylcurcumin, 20.7% demethylmonodemethoxycurcumin, 5.86% bisdemethoxycurcumin, 2.58% demethylcurcumin) was prepared by using a 95% extract of curcumin (C(95); 72.2% curcumin, 18.8% monodemethoxycurcumin, 4.5% bisdemethoxycurcumin). DC increased glutathione and reduced reactive oxygen species (ROS) in HT4 neuronal cells. In a model of glutamate-induced death of HT4, DC was more effective than C(95) in neuroprotection. The protective effects of DC were retained even when DC was withdrawn from culture media after pretreatment. DC treatment, unlike an equal dose of C(95), completely spared glutamate-induced loss of cellular GSH. Both DC and C(95) prevented glutamate-induced elevation of cellular ROS but failed to attenuate glutamate-induced elevation of intracellular calcium. In human microvascular endothelial cells (HMECs) challenged with TNF-alpha, GeneChip analysis revealed that only a subcluster of 23 TNF-alpha-inducible genes were uniquely sensitive to C(95). In sharp contrast, 1,065 TNF-alpha-inducible genes were sensitive to DC but not to C(95), suggesting that DC was more effective in antagonizing the effects of TNF-alpha on HMECs. Functional analysis identified that the genes uniquely sensitive to DC belonged in four functional categories: cytokine-receptor interaction, focal adhesion, cell adhesion, and apoptosis. Real-time PCR as well as ELISA studies demonstrated that TNF-alpha-inducible CXCL10 and CXCL11 expression was sensitive to DC but not to C(95). Flow-cytometry studies recognized ICAM-1 and VCAM-1 as TNF-alpha-inducible adhesion molecules that were uniquely sensitive to DC. Taken together, DC exhibited promising neuroprotective and antiinflammatory properties that must be characterized in vivo.

Digalloylresveratrol (DIG) is a new synthetic ester of the naturally occurring polyhydroxyphenolic substances gallic acid and resveratrol which both exert anti-cancer activity in a number of tumor cell lines. The aim of the study was to identify the biochemical effects of DIG in HT-29 human colon cancer cells. DIG induced dose-dependently apoptosis after treatment for 72 h (40 microM DIG caused apoptosis in 45% of cells). DIG led to a substantial imbalance of deoxyribonucleoside triphosphates (dNTPs), the products of the enzyme ribonucleotide reductase (RR) and directly inhibited RR as it significantly reduced the incorporation of (14)C-labeled cytidine into the DNA of tumor cells. Furthermore, DIG affected the cell division and inhibited the transition from S to G2/M phase of the cell cycle. In contrast to resveratrol or gallic acid, DIG did not inhibit cyclooxygenases I and II. When HT-29 cells were simultaneously treated with DIG and 5-FU, the standard chemotherapeutic substance for colon cancer, additive growth inhibitory effects could be observed. With respect to the various biochemical and anti-proliferative effects of DIG in HT-29 cells, we regard DIG as a potential candidate for future treatment options of colon cancer and conclude that further preclinical and in vivo studies are warranted.

Intricatinol and intricatin, the two homoisoflavonoids isolated from Hoffmanosseggia intricata, and two analogs have been synthesized from pyrogallol in three steps. The spectral data of synthetic intricatinol are in good agreement with those of natural metabolite, but the spectral data of intricatin are not corroborative with those of the natural product. The structure of intricatin has been thus revised to 8-methoxybonducellin, a compound isolated from Caesalpinia pulcherrima. The antioxidant activity of all the four homoisoflavonoids was determined by superoxide (NBT) and DPPH free radical scavenging methods. The synthetic analog 7,8-dihydroxy-3-[(3,4-dihydroxyphenyl)methylene]chroman-4-one displayed excellent activity in both methods.

A series of four naturally occurring homoisoflavonoids and eight analogs have been synthesized starting from an appropriately substituted phenol through chroman-4-one, in four steps. The products were assigned as E-isomers based on NMR spectroscopic data. The E-isomers were converted into Z-isomers by photoisomerization. The E- and Z-isomers showed distinct chemical shifts and the differences between (E) and (Z)-homoisoflavonoids in the proton NMR spectra afford a useful method for ascertaining the stereochemistry. The antioxidant activity of homoisoflavonoids was determined by superoxide (NBT) and DPPH free radical scavenging methods. The analog 7-hydroxy-3-[(3,4,5-trihydroxyphenyl)methylene]chroman-4-one displayed excellent activity followed by sappanone A in both the methods and were several times potent than the commercial antioxidants like BHA, BHT, etc. These compounds were evaluated in vitro for their inhibitory activities against 5-lipoxygenase (5-LOX) enzyme. The analog 7-hydroxy-3-[(N,N-dimethylaminophenyl)methylene]chroman-4-one was found to possess potent inhibitory activity and was comparable to that of the standard, nordihydroguiaretic acid. These results suggest that these homoisoflavonoids, with their potent antioxidant and 5-LOX inhibitory activities, may have useful applications as antioxidants and lead compounds for asthma and inflammatory diseases.

A series of curcumin analogs (1-3, 5a-5t) was synthesized through the condensation of appropriately protected hydroxybenzaldehydes with acetylacetone, followed by deprotection. The antioxidant activity of these analogs was determined by superoxide free radical nitroblue tetrazolium and DPPH free radical scavenging methods and the polyhydroxycurcuminoids (5l-5s) displayed excellent antioxidant activity. These analogs showed cytotoxicity to lymphocytes and promising tumor-reducing activity on Dalton's lymphoma ascites tumor cells.

The role of the ErbB family in supporting the malignant phenotype was characterized by stable transfection of a single chain antibody (ScFv5R) against ErbB2 containing a KDEL endoplasmic reticulum retention sequence into GEO human colon carcinoma cells. The antibody traps ErbB2 in the endoplasmic reticulum, thereby down-regulating cell surface ErbB2. The transfected cells showed inactivation of ErbB2 tyrosine phosphorylation and reduced heterodimerization of ErbB2 and ErbB3. This resulted in greater sensitivity to apoptosis induced by growth deprivation and delayed tumorigenicity in vivo. Furthermore, decreased heterodimerization of ErbB2 and ErbB3 led to a reorganization in ErbB function in transfected cells as heterodimerization between epidermal growth factor receptor (EGFR) and ErbB3 increased, whereas ErbB3 activation remained almost the same. Importantly, elimination of ErbB2 signaling resulted in an increase in EGFR expression and activation in transfected cells. Increased EGFR activation contributed to the sustained cell survival in transfected cells.

3',4',6,7-Tetrahydroxyaurone (1a), an aurone isolated from Bidens frondosa, and five analogues (1b-1f) were synthesized from pyrogallol in three steps. The antioxidative activity of 1a-1f was determined by the superoxide free radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging methods.

Microfolicoumarin (1), a prenylcoumarin from Cedrelopsis microfoliata, was synthesized from 2,4,5-trimethoxybenzaldehyde in five steps. 1 did not show significant antioxidative activity, but the key intermediates, esculetin (3) and 5-prenylesculetin (6), exhibited strong antioxidative activity in both the superoxide-radical and 1,1-diphenyl-2-picrylhydrazyl radical-scavenging models.

4-[2-(3,5-Dimethoxyphenyl)ethenyl]-1,2-benzenediol (7), a stilbene isolated from Sphaerophysa salsula, was synthesized from 3,4-dihydroxybenzaldehyde (1) in five steps in an overall yield of 33%. The spectral data for synthetic 7 are in good agreement with those of the natural product. Hydroxystilbene 7 showed potent antioxidative activity.

Isoamoenylin (6), a dihydrostilbene from Dendrobium amoenum, was synthesised from 3,4,5-trimethoxybenzaldehyde (1) in four steps with an overall yield of 60%. The spectral data for synthetic 6 are in good agreement with those of the natural product. Isoamoenylin showed moderate antioxidative and weak antibacterial activities.

The aim of this study was to determine whether constitutive ErbB2 activation controls growth and apoptosis in colon cancer cells. Growth arrested GEO cells showed constitutive activation of ErbB2 in the absence of exogenous growth factors or serum supplementation. Higher levels of heregulin and ErbB2 activation were observed in the growth-arrested state and cell cycle re-entry was independent of exogenous growth factors. Blockade of ErbB2 activation by heregulin neutralizing antibodies and by AG879 resulted in prevention of cell cycle re-entry. This indicated that autocrine heregulin activity was responsible for growth factor independence and for cell cycle re-entry. Activation of ErbB2 was the result of heregulin mediated interaction with ErbB3 and generated downstream activation of the ERK and the PI3K/AKT pathways. Heregulin neutralizing antibody treatment of growth arrested GEO cells also generated apoptosis as reflected by PARP cleavage and DNA fragmentation indicating a cell survival signal was also induced by the constitutively activated ErbB2. The activation of AKT but not the MAPK pathway was responsible for cell survival in these cells.

In this study, we address whether TGFbeta signaling mediates vitamin D3 analog-induced growth inhibition in nonmalignant and malignant breast cells. Normal mammary epithelial cells (184), immortalized nonmalignant mammary epithelial cells (184A1 and MCF10A), and breast cancer cells (early passage MCF7: MCF7E) were sensitive to the inhibitory effects of vitamin D3 analogs (EB1089 and MC1288) while late passage MCF7 breast cancer (MCF7L) cells were relatively resistant. A similar pattern of sensitivity to TGFbeta was observed with these cells. Thus, the sensitivity to the vitamin D3 analogs correlated with the sensitivity to TGFbeta. MCF7L TGFbetaRII-transfected cells, which have autocrine TGFbeta activity, were more sensitive to EB1089 than MCF7L cells. TGFbeta neutralizing antibody was found to block the inhibitory effects of these analogs. These results are consistent with the idea that autocrine TGFbeta signaling mediates the anti-proliferative effects of the vitamin D3 analogs in these cells. The expression of TGFbeta isoforms and/or TGFbeta receptors was induced by the analogs in the vitamin D3 and TGFbeta sensitive cells. Vitamin D3 analogs did not induce TGFbeta or TGFbeta receptor expression in the resistant MCF7L cells. Therefore, EB1089 induces autocrine TGFbeta activity through increasing expression of TGFbeta isoforms and/or TGFbeta receptors. In addition, EB1089 induced nuclear VDR protein levels in the sensitive 184A1 cells but not in the resistant MCF7L cells. 184A1 cells were more sensitive to EB1089-induced VDR-dependent transactivation than MCF7L cells as measured by a luciferase reporter construct containing the VDRE, indicating a defect of VDR signaling in MCF7L cells. Smad3, a TGFbeta signaling mediator, coactivated VDR-dependent transactivation in 184A1 cells but not in MCF7L cells. These results indicate that Smad3 coactivates VDR to further enhance TGFbeta signaling and vitamin D3 signaling in the sensitive 184A1 cells. The results also indicate that Smad3 is not of itself sufficient to coactivate VDR in TGFbeta/vitamin D3 resistant MCF7L cells and other factors are required. We found that the PI 3-kinase pathway inhibitor LY29004 inhibited the synergy of TGFbeta and EB1089 on VDR-dependent transactivation activity. This indicates that the crosstalk between TGFbeta and vitamin D signaling is also PI 3-kinase pathway dependent., (Copyright 2001 Wiley-Liss, Inc.)

A general and staight forward total synthesis of 1,7-bis(4-hydroxyphenyl)-3-hydroxy-1,3-heptadiene-5-one (5) starting from 4-methoxycinnamic acid (6) via ethyl 5-(4-methoxyphenyl)-3-hydroxy-2.4-pentadienoate (14) was accomplished in 19% overall yield.

Transforming growth factor betas (TGF-betas) are a growth factor family with negative autocrine growth functions for most epithelial cells including colon carcinoma cell lines. Both type I (RI) and type II (RII) transmembrane TGF-beta receptors have been shown to be indispensable for TGF-beta-mediated cell growth regulation. Previous studies using different model systems have shown that both overexpression of TGF-beta1 and transfection of antisense TGF-beta1 to reduce TGF-beta1 expression could lead to increased tumorigenicity. These results are seemingly contradictory and suggest that effects of TGF-beta modulation on malignant properties of cancer cells may be contextual. This study addresses this issue using human colon carcinoma cells (CBS and FET) to determine the effects of modulation of the various components of the TGF-beta system on in vitro and in vivo growth properties in two independent isogenic models of colon carcinoma. Cells were stably transfected with a tetracycline-repressible RII expression vector (CBS4-RII), a tetracycline-repressible expression vector containing a truncated RII cDNA lacking the serine/threonine kinase domain (CBS4-deltaRII and FET6-deltaRII), or with a vector containing the TGF-beta1 cDNA (CBS4-beta1S and FET-beta1S). Expression of the truncated RII reduced TGF-beta sensitivity, whereas overexpression of RII increased TGF-beta sensitivity. TGF-beta overexpression did not affect TGF-beta response. In vivo tumorigenicity assays revealed that CBS4-RII cells had lower tumorigenicity than control cells, whereas CBS4-deltaRII and CBS4-beta1S had higher tumorigenicity than controls. The CBS4 cells are poorly tumorigenic in athymic mice, and the wild-type FET6 cells are nontumorigenic. FET6-deltaRII cells formed rapidly growing tumors, and FET-beta1S cells also formed tumors. These data illustrate the paradoxical tumor-promoting and -suppressing effects of TGF-beta signaling activity in two isogenic model systems from human colon carcinomas, thus demonstrating that the effects of modulation of TGF-beta expression or TGF-beta signaling capability affects malignancy in a contextual manner.

Several 7-(3R,4R-N,N'-dialkyl diaminopyrrolidinyl)-substituted quinolones were synthesized and evaluated for antibacterial activities. 5-Amino-7-(3R,4R-N,N'-dimethyldiamino-6,8-difluoro-1,4-dihydro-1-c yclopropyl -4-oxoquinoline-3-carboxylic acid was found to have potent antibacterial activity against gram +ve organisms.

We show that integrin alpha 5 subunit expression is stimulated when human fibrosarcoma HT1080 cells are released from quiescence. The alpha 5 subunit mRNA level in quiescent HT1080 cells was increased 24 hr after their release by 10% fetal bovine serum-containing medium reaching a maximum of 2.5 fold on day 2. Similar levels of induction of cell-surface alpha 5 subunit protein as well as beta 1 subunit protein were also observed. This resulted in a significant increase of cell attachment to fibronectin. The serum stimulation also increased alpha 5 subunit promoter activity by twofold which was protein synthesis independent. Subsequent deletion of alpha 5 subunit promoter DNA showed that the cis-element responsible for the activation is located between -92 bp and the transcription start site. The promoter activity was not induced until 12 hr after the release. Comparison of the effect of a serum-free medium and a 10% fetal bovine serum-supplemented medium revealed that both the DNA synthesis and alpha 5 subunit induction were independent of exogenous growth factors. The increased integrin alpha 5 beta 1 appears to function by reducing mitogenic activity since blockade of fibronectin binding to its receptor with a RGD peptide, a monoclonal anti-fibronectin antibody, or a monoclonal anti-alpha 5 subunit antibody during the release from quiescence significantly stimulated DNA synthesis. On the other hand, stable overexpression of the alpha 5 subunit resulted in decreased DNA synthesis.