Environmentally relevant concentrations of microplastics modulated the immune response and swimming activity, and impaired the development of marine medaka Oryzias melastigma larvae.

Microplastics (MPs), due to their impacts on the ecosystem and their integration into the food web either through trophic transfer or ingestion directly from the ambient environment, are an emerging class of environmental contaminants posing a great threat to marine organisms. Most reports on the toxic effects of MPs exclusively focus on bioaccumulation, oxidative stress, pathological damage, and metabolic disturbance in fish. However, the collected information on fish immunity in response to MPs is poorly defined. In particular, little is known regarding mucosal immunity and the role of mucins. In this study, marine medaka (Oryzias melastigma) larvae were exposed to 6.0 µm beads of polystyrene microplastics (PS-MPs) at three environmentally relevant concentrations (102 particles/L, 104 particles/L, and 106 particles/L) for 14 days. The experiment was carried out to explore the developmental and behavioural indices, the transcriptional profiles of mucins, pro-inflammatory, immune, metabolism and antioxidant responses related genes, as well as the accumulation of PS-MPs in larvae. The results revealed that PS-MPs were observed in the gastrointestinal tract, with a concentration- and exposure time-dependent manner. No significant difference in the larval mortality was found between the treatment groups and the control, whereas the body length of larvae demonstrated a significant reduction at 106 particles/L on 14 days post-hatching. The swimming behaviour of the larvae became hyperactive under exposure to 104 and 106 particles/L PS-MPs. In addition, PS-MP exposure significantly up-regulated the mucin gene transcriptional levels of muc7-like and muc13-like, however down-regulated the mucin gene expression levels of heg1, muc2, muc5AC-like and muc13. The immune- and inflammation and metabolism-relevant genes (jak, stat-3, il-6, il-1ß, tnf-а, ccl-11, nf-κb, and sod) were significantly induced by PS-MPs at 104 and 106 particles/L compared to the control. Taken together, this study suggests that PS-MPs induced inflammation response and might obstruct the immune functions and retarded the growth of the marine medaka larvae even at environmentally relevant concentrations.

Microplastic pollution in wild commercial nekton from the South China Sea and Indian Ocean, and its implication to human health.

Marine biota, especially commercially important species, serves as a basis for human nutrition. However, millions of tons of plastic litter are produced and enter the marine environment every year, with potential adverse impacts on marine organisms. In the present study, we investigated the occurrence and characteristics of microplastic (MP) pollution in the digestive tracts of 13 species of wild nektons from 20 stations sampled in the South China Sea (SCS) and the Indian Ocean (IO), and assessed the human health risks of MPs. The detection rate of MPs ranged from 0.00% to 50.00% from the SCS, which was dramatically lower than that from the IO (10.00-80.00%). The average abundance of MP was 0.18 ± 0.06 items g wet weight-1 (ww-1) in the SCS, which was significantly lower than that in the IO with a concentration of 0.70 ± 0.16 items g ww-1. Most MPs were fibers in type, black in color, and polyester (PES) in polymer composition in both the SCS and IO. Interestingly, distinct profiles of MP pollution were found between the benthic and pelagic nektons: 1) The predominant MP composition was PES in the benthic nektons, whereas polyamide (PA) accounted for a larger part of the total MP count in the pelagic nektons within the SCS; 2) The abundance of MP in the benthic nektons (0.52 ± 0.24 items individual-1) was higher than that in the pelagic nektons (0.30 ± 0.11 items individual-1). Accordingly, the mean hazard score of MPs detected in the benthic nektons (220.66 ± 210.75) was higher than that in the pelagic nektons (49.53 ± 22.87); 3) The mean size of the MP in the pelagic nektons (0.84 ± 0.17 mm) was larger than that in the benthic nektons (0.49 ± 0.09 mm). Our findings highlight the need to further investigate the ecological impacts of MPs on wild nekton, especially commercially important species, and its potential implications for human health.

Microplastics negatively impact embryogenesis and modulate the immune response of the marine medaka Oryzias melastigma.

Microplastic (MP) pollution is an emerging contaminant in aquatic environments worldwide. Nonetheless, the developmental toxicity of MPs in the early life stages of fish and the mechanisms involved are not yet fully understood. The present study investigated the effects of different concentrations of polystyrene (PS) MPs on the early development of the marine model fish the medaka Oryzias melastigma. Our results showed that waterborne exposure to PS MPs significantly delayed the hatching time, altered the heartbeat and decreased the hatching rate of embryos. Furthermore, the genes involved in cardiac development, encoding for embryo-hatching enzymes, as well as inflammatory responses were significantly upregulated. The transcriptome results showed that mainly the pathways involved in metabolism, immune response, genetic information processing and diseases were significantly enriched. These results demonstrate that PS MPs negatively impact embryogenesis and the immune response of O. melastigma.

Design of an InSb thermoradiative system for harvesting low-grade waste heat.

We propose a thin-film InSb-based thermoradiative system (TRS) and assess its performance characteristics by using a parametric design at low-grade waste heat. We consider the effects of several loss mechanisms on system performance, including optical, sub-gap radiation, and non-radiative losses. Our results predict that the 50 nm thick InSb TRS operating with a hot (cold) source at 500 K (300 K) may yield a power density of 113 Wm-2 and an efficiency limit of 10.5%. To enhance the system performance, more efforts should be paid to optimize the layer thickness, enhance optical radiation, improve surface passivation, and fabricate an Ag back-reflective mirror and an optical filter for frequency-dependent photon recycling. This Letter provides new insights, to the best of our knowledge, for optimal designs and energy loss mechanisms, thus paving a route towards the development of practical TRS at a low temperature of around 500 K.

Ruthenium(II) salicylate complexes inducing ROS-mediated apoptosis by targeting thioredoxin reductase.

Thioredoxin reductase (TrxR), a major component of the thioredoxin system, makes a critical role in regulating cellular redox signaling and is found to be overexpressed in many human cancer cells. TrxR has become an attractive target for anticancer agents. In this work, three Ru(II) complexes with salicylate as ligand, [Ru(phen)2(SA)] (phen = 1,10-phenanthroline, SA = salicylate, 1), [Ru(dmb)2(SA)] (dmb = 4,4'-dimethyl-2,2'-bipyridine, 2) and [Ru(bpy)2(SA)] (bpy = 2,2'-bipyridine, 3), were synthesized and characterized. The anticancer effect exerted by them was evaluated. Complex 1 was found to exhibit obvious anticancer activity, in comparison with cisplatin, against cancer cell lines, while displaying low toxicity to the normal cell line BEAS-2B. The mechanism of complex 1 cancer cell growth suppress was investigated in A549 cells. Complex 1 exerted its anticancer through inducing apoptosis and triggering cell cycle arrest at the G0/G1 phase. Complex 1 can selectively inhibit TrxR activity and thus promote the generation and accumulation of reactive oxygen species (ROS), which subsequently trigger mitochondrial dysfunction and DNA damage, activate oxidative stress-sensitive mitogen activated protein kinase (MAPK), and suppress the protein kinase B (PKB or AKT) signal pathway, resulting in apoptosis in A549 cells.

Photoelectric converters with quantum coherence.

Photon impingement is capable of liberating electrons in electronic devices and driving the electron flux from the lower chemical potential to higher chemical potential. Previous studies hinted that the thermodynamic efficiency of a nanosized photoelectric converter at maximum power is bounded by the Curzon-Ahlborn efficiency η_{CA}. In this study, we apply quantum effects to design a photoelectric converter based on a three-level quantum dot (QD) interacting with fermionic baths and photons. We show that, by adopting a pair of suitable degenerate states, quantum coherences induced by the couplings of QDs to sunlight and fermion baths can coexist steadily in nanoelectronic systems. Our analysis indicates that the efficiency at maximum power is no longer limited to η_{CA} through manipulation of carefully controlled quantum coherences.

The studies on the cytotoxicity in vitro, cellular uptake, cell cycle arrest and apoptosis-inducing properties of ruthenium methylimidazole complex [Ru(MeIm)4(p-cpip)](2.).

A new ruthenium methylimidazole complex [Ru(MeIm)4(p-cpip)](2+) (Ru1, p-cpip=2-(4-chlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, MeIm=1-methylimidazole) has been synthesized and characterized. The cellular uptake, in vitro cytotoxicities, cell cycle arrest and apoptosis-inducing mechanism of this Ru(II) complex have been extensively explored by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, Comet assay, inverted fluorescence microscope as well as Western blotting experimental techniques. Notably, Ru1 displayed relatively high cytotoxic activity against lung cancer A549 cells and had high selectivity between tumor and normal cells in comparison with cisplatin. Further studies showed that Ru1 caused cell cycle arrest at G0/G1 phase and induced apoptosis via the mitochondrial pathway, which involved reactive oxygen species (ROS) accumulation, mitochondrial dysfunction and Bcl-2 and caspase correlative family member activation. For providing more information about the possible antitumor mechanism, the in vitro DNA binding studies have been also investigated by different spectrophotometric methods, thermal denaturation and viscosity measurements.

Exploration of the binding mode between (-)-zampanolide and tubulin using docking and molecular dynamics simulation.

The binding mode of (-)-zampanolide (ZMP) to tubulin was investigated using docking, molecular dynamics (MD) simulation, and binding free-energy calculations. The docking studies validated the experimental results indicating that the paclitaxel site is the binding site for (-)-ZMP. The 18 ns MD simulation shows the docking mode has changed a lot, whereas it offers more reliable binding data. MM-PBSA binding free-energy calculations further confirmed the results of the MD simulation. The study revealed that hydrophobic interactions play an important role in stabilizing the binding, and the strong hydrogen bond formed with Asp224 enhances the affinity for tubulin. Meanwhile, the results support the assumption that (-)-ZMP can be attacked by His227, leading to a nucleophilic reaction and covalent binding. These theoretical results lead to a greater understanding of the mechanism of action of binding to tubulin, and will therefore aid the design of new compounds with higher affinities for tubulin.

Docking and molecular dynamics studies of the binding between Peloruside A and tubulin.

The molecular docking, MD simulation and binding free energy calculation were performed to explore the probable binding modes between PLA and tubulin. Through docking study, three possible binding sites for PLA were speculated as follows: the taxane site, the alternative site and a new site in α-tubulin. Then, 12.0 ns MD simulations show that these binding modes predicted by docking have been changed more or less, whereas the MD simulations offer more reliable binding details. The MM-PBSA binding free-energy calculations reasonably identify that the taxane site is the most favorable binding site of PLA and the alternative site is the secondary one, which can be used to explain some experimental facts. These studies theoretically resolve the priority of binding sites for PLA and offer the reliable binding modes between PLA and tubulin, and thus help to understanding the action mechanism for this kind of inhibitor.

Theoretical studies on DNA-photocleavage efficiencies of Ru(II) polypyridyl complexes.

Theoretical studies on the DNA-photocleavage efficiencies of Ru(II) polypyridyl complexes 1-4 have been carried out using density functional theory (DFT). First, an evaluation of the computational accuracy of the redox potentials for [Ru(bpy)(3)](2+) in the ground state and the excited state was tested by different computational methods. Secondly, the redox potentials of complexes 1-4 in the excited state were accurately computed. Finally, the trend in the DNA-photocleavage efficiencies (φ) of complexes 1-4, i.e., φ(4) > φ(3) > φ(2) > φ(1), were reasonably explained by the excited-state reduction potentials and the electron-transfer activation energies. In particular, the DNA-photocleavage efficiencies of two new Ru(II) complexes 3 and 4 were predicted.

Theoretical studies on DNA-photocleavage efficiencies and mechanisms of Ru(II) polypyridyl complexes.

Theoretical studies on the DNA-photocleavage efficiencies and mechanisms of Ru(II) complexes [Ru(bpy)(2)(L)](2+) (bpy = 2,2'-bipyridine; L: dppz = dipyrido[3,2-a:2',3'-c]phenazine; mitatp = 5-methoxy-isatino[1,2-b]-1,4,8,9-tetraazatriphenylene; nitatp = 5-nitro-isatino [1,2-b]-1,4,8,9-tetraazatriphenylene) 1-3 were carried out using density functional theory (DFT). First, the accuracies of redox potentials computed for [Ru(bpy)(3)](2+) in the ground state and the excited state by different computational methods were tested, and then the redox potentials of complexes 1-3 in their excited states were computed accurately. Secondly, the trend in the DNA-photocleavage efficiencies (ϕ) of complexes 1-3 [i.e., ϕ(2) > ϕ(3) > ϕ(1)] was reasonably well explained by their excited-state reduction potentials and their electron-transfer activation energies. Finally, the photoinduced oxidation-reduction mechanism utilized by these complexes was explored, and the DNA-photocleavage process was explained rationally.

Binding conformations and QSAR of CA-4 analogs as tubulin inhibitors.

A theoretical study on the binding conformations and the quantitative structure-activity relationship (QSAR) of combretastatin A4 (CA-4) analogs as inhibitors toward tubulin has been carried out using docking analysis and comparative molecular field analysis (CoMFA). The appropriate binding orientations and conformations of these compounds interacting with tubulin were revealed by the docking study; and a 3D-QSAR model showing significant statistical quality and satisfactory predictive ability was established, in which the correlation coefficient (R(2)) and cross-validation coefficient (q(2)) were 0.955 and 0.66, respectively. The same model was further applied to predict the pIC(50) values for 16 congeneric compounds as external test set, and the predictive correlation coefficient R(2)(pred) reached 0.883. Other tests on additional validations further confirmed the satisfactory predictive power of the model. In this work, it was very interesting to find that the 3D topology structure of the active site of tubulin from the docking analysis was in good agreement with the 3D-QSAR model from CoMFA for this series of compounds. Some key structural factors of the compounds responsible for cytotoxicity were reasonably presented. These theoretical results can offer useful references for understanding the action mechanism and directing the molecular design of this kind of inhibitor with improved activity.

A theoretical study on the hydrolysis process of two Keppler-type antitumor complexes [TzH][trans-RuCl4(Tz)2] and [2-NH2TzH][trans-RuCl4(2-NH2Tz)2].

The hydrolysis processes of two Keppler-type antitumor ruthenium(III) complexes of [TzH][trans-RuCl4(Tz)2] (TzICR) and [2-NH2TzH][trans-RuCl4(2-NH2Tz)2] ((2-NH2)TzICR) have been investigated by using density functional theory (DFT) method, and the solvent effect was also considered and calculated by conductor-like polarizable calculation model (CPCM). The structural characteristics and the detailed energy profiles for the hydrolysis processes of title complexes have been obtained. The analysis of thermodynamic and kinetic characteristics of hydrolysis reaction suggests the following: For the 1st hydrolysis step, the complex TzICR has a lower hydrolysis rate than the reported drug [ImH][trans-RuCl4Im2](ICR, Im=imidazole). However, complex (2-NH2)TzICR has obviously a higher hydrolysis rate than TzICR and ICR. The result is in good agreement with the experimental one and the related regularity was further explained in theory. For the 2nd hydrolysis step, it is very significant to find that the formation of cis-diaqua products is thermodynamically preferred to that of trans isomers. Combining with the hydrolysis action mechanism of cisplatin, this is related to the so-called "cis effect", in which the cis-diaqua products are advantageous to binding to pertinent biomolecular targets. Therefore, the cis-diaqua products can be expected to be important precursors for the biological actions. These theoretical results would help to understand the action mechanism of these potential drugs with the pertinent biomolecular target.

A bioaccumulative cyclometalated platinum(II) complex with two-photon-induced emission for live cell imaging.

The cyclometalated platinum(II) complex [Pt(L)Cl], where HL is a new cyclometalating ligand 2-phenyl-6-(1H-pyrazol-3-yl)pyridine containing C(phenyl), N(pyridyl), and N(pyrazolyl) donor moieties, was found to possess two-photon-induced luminescent properties. The two-photon-absorption cross section of the complex in N,N-dimethylformamide at room temperature was measured to be 20.8 GM. Upon two-photon excitation at 730 nm from a Ti:sapphire laser, bright-green emission was observed. Besides its two-photon-induced luminescent properties, [Pt(L)Cl] was able to be rapidly accumulated in live HeLa and NIH3T3 cells. The two-photon-induced luminescence of the complex was retained after live cell internalization and can be observed by two-photon confocal microscopy. Its bioaccumulation properties enabled time-lapse imaging of the internalization process of the dye into living cells. Cytotoxicity of [Pt(L)Cl] to both tested cell lines was low, according to MTT assays, even at loadings as high as 20 times the dose concentration for imaging for 6 h.

Binding to DNA purine base and structure-activity relationship of a series of structurally related Ru(II) antitumor complexes: a theoretical study.

The thermodynamics of the binding of a series of structurally related Ru(II) antitumor complexes, that is, alpha-[Ru(azpy)2Cl2] 1, beta-[Ru(azpy)2Cl2] 2, alpha-[Ru(azpy)(bpy)Cl2] 3, and cis-[Ru(bpy)2Cl2] 4 to DNA purine bases (gunine, adenine at N7 site) has been studied by using the DFT method. The binding of imine form of 9-methyladenine (9-MeAde) to the Ru(II) moiety in a didentate fashion via its N6 and N7 atoms was also considered. The geometrical structures of the DNA model base adducts were obtained at the B3LYP/(LanL2DZ + 6-31G(d)) level in vacuo. The following exact single-point energy calculations were performed at the B3LYP/(LanL2DZ(f)+6-311+G(2d, 2p)) level both in vacuo and in aqueous solution using the COSMO model. The bond dissociation enthalpies and free energies, reaction enthalpies and free energies both in the gas phase and in aqueous solution for all considered Ru(II)-DNA model base adducts were obtained from the computations. The calculated bond dissociation enthalpies and free energies allow us to build a binding affinity order for the considered Ru(II)-DNA model base adducts. The theoretical results show that the guanine N7 is a preferred site for this series of complexes and support such an experimental fact that alpha-[Ru(azpy)(bpy)(9-EtGua)H2O](2+) (3-(9-EtGua)) is isomerized to alpha'-[Ru(azpy)(bpy)(9-EtGua)H2O](2+) (3'-(9-EtGua)). On the basis of structural and thermodynamical characteristics, the possible structure-activity relationship was obtained, and the distinct difference in cytotoxicities of this series of structurally related antitumor complexes was explained theoretically.

QSAR, action mechanism and molecular design of flavone and isoflavone derivatives with cytotoxicity against HeLa.

The quantitative structure-activity relationship (QSAR) of 32 flavone and isoflavone derivatives with cytotoxicity expressed as pGC50, which is defined as the negative value of the logarithm of necessary molar concentration of this series of compounds to cause 50% growth inhibition against the human cervical epithelioid carcinoma cell line (HeLa), has been studied by using the density functional theory (DFT), molecular mechanics (MM2) and statistical methods. In order to obtain QSAR model with high predictive ability, the original dataset was randomly divided into a training set comprising 26 compounds and a test set comprising the rest 6 compounds. An optimal model for the training set with significant statistical quality (RA2=0.852) and predictive ability (q2=0.818) was established. The same model was further applied to predict pGC50 values of the 6 compounds in the test set, and the resulting predictive correlation coefficient Rpred2 reaches 0.738, further showing that this QSAR model has high predictive ability. It is very interesting to find that the cytotoxicities of these compounds against HeLa appear to be mainly governed by two quantum-chemical factors, i.e., the energy (ELUMO) of the lowest unoccupied molecular orbital (LUMO) and the net charges of C atom at site 6 on aromatic rings (QC6). Here the possible action mechanism of these compounds was analyzed and discussed in detail, in particular, the fact why the flavone derivatives have considerably higher cytotoxicity than isoflavone derivatives was reasonably explained. Based on this QSAR equation, 5 new compounds with higher cytotoxicity have been theoretically designed. Such results can offer useful theoretical references for experimental works.

Synthesis, characterization, DNA-binding and spectral properties of complexes [Ru(L)4(dppz)]2+ (L=Im and MeIm).

Two new Ru(II) complexes [Ru(L)(4)(dppz)](2+) (L=imidazole (Im), 1-methylimidazole (MeIm); dppz=dipyrido[3,2-a:2',3'-c]phenazine), have been synthesized and characterized in detail by elemental analysis, (1)H NMR, Electrospray ionization mass spectrometry (ESI-MS) and UV-visible (UV-Vis) spectroscopic techniques. The interaction of these complexes with calf thymus DNA (CT-DNA) has been explored by using electronic absorption titration, competitive binding experiment, circular dichroism (CD), thermal denaturation and viscosity measurements. The experimental results show that: both the two complexes can bind to DNA in an intercalation mode; the DNA-binding affinity of complex [Ru(Im)(4)(dppz)](2+)1 (K(b)=2.5 x 10(6)M(-1)) is greater than that of complex [Ru(MeIm)(4)(dppz)](2+)2 (K(b)=1.1 x 10(6)M(-1)). Moreover, it is very interesting to find that the circular dichroic spectrum of DNA-complex 1 adduct, in which both bands centered at 277 nm and 236 nm are all negative, is very different from those of DNA-complex 2 adduct and other Ru(II) complexes binding to DNA in general intercalation mode. It may be due to the hydrogen-bonding effect or the contribution of induced CD signals of complex 1. Another interesting finding is that the hypochromism of the complexes is not linear relation to their DNA-binding affinities. In order to deeply study these experimental phenomena and trends, the density functional theory (DFT) and time-dependent DFT (TDDFT) computations were carried out, and on the basis of the DFT/TDDFT results and the frontier molecular orbital theory, the trend in DNA-binding affinities, the spectral properties as well as the interesting phenomena of larger extent of hypochromism but relatively smaller K(b) values for the title complexes have been reasonably explained.

Anion-selective interaction and colorimeter by an optical metalloreceptor based on ruthenium(II) 2,2'-biimidazole: hydrogen bonding and proton transfer.

A new anion sensor [Ru(bpy)2(H2biim)](PF6)2 (1) (bpy = 2,2'-bipyridine and H2biim = 2,2'-biimidazole) has been developed, in which the Ru(II)-bpy moiety acts as a chromophore and the H2biim ligand as an anion receptor via hydrogen bonding. A systematic investigation shows that 1 is an eligible sensor for various anions. It donates protons for hydrogen bonding to Cl-, Br-, I-, NO3-, HSO4-, H2PO4-, and OAc- anions and further actualizes monoproton transfer to the OAc- anion, changing color from yellow to orange brown. The fluoride ion has a high affinity toward the N-H group of the H2biim ligand for proton transfer, rather than hydrogen bonding, because of the formation of the highly stable HF2- anion, resulting in stepwise deprotonation of the two N-H fragments. These processes are signaled by vivid color changes from yellow to orange brown and then to violet because of second-sphere donor-acceptor interactions between Ru(II)-H2biim and the anions. The significant color changes can be distinguished visually. The processes are not only determined by the basicity of anion but also by the strength of hydrogen bonding and the stability of the anion-receptor complexes. The design strategy and remarkable photophysical properties of sensor 1 help to extend the development of anion sensors.

Density functional theory/time-dependent DFT studies on the structures, trend in DNA-binding affinities, and spectral properties of complexes [Ru(bpy)2(p-R-pip)]2+ (R = -OH, -CH3, -H, -NO2).

Studies on the electronic structures and trend in DNA-binding affinities of a series of Ru(II) complexes [Ru(bpy)2(p-R-pip)]2+ (bpy = 2,2-bipyridine; pip = 2-phenylimidazo[4,5-f] [1,10]-phenanthroline; R = -OH, -CH3, -H, -NO2) 1-4 have been carried out, using the density functional theory (DFT) at the B3LYP/LanL2DZ level. The electronic absorption spectra of these complexes were also investigated using time-dependent DFT (TDDFT) at the B3LYP//LanL2DZ/6-31G level. The computational results show that the substituents on the parent ligand (pip) have a significant effect on the electronic structures of the complexes, in particular, on the energies of the lowest unoccupied molecular orbital (LUMO) and near some unoccupied molecular orbitals (LUMO+x, x = 1-4). With the increase in electron-withdrawing ability of the substituent in this series, the LUMO+x (x = 0-4) energies of the complexes are substantially reduced in order, for example, epsilon(LUMO)(1) approximately epsilon(LUMO)(2) > epsilon(LUMO)(3) > epsilon(LUMO)(4), whereas the pi-component populations of the LUMO+x (x = 0-4) are not substantially different. Combining the consideration of the bigger steric hindrance of complex 2, the trend in DNA-binding affinities (K(b)) of the complexes, that is, K(b)(2) < K(b)(1) < K(b)(3) < K(b)(4) can be reasonably explained. In addition, the experimental singlet metal-to-ligand charge transfer ((1)MLCT) spectra of these complexes can be well simulated and discussed by the TDDFT calculations.