In vitro antitumor activity of novel benzimidazole-based Cu(II) complexes.

Four benzimidazole-based Cu(II) complexes: Cu2(p-2-bmp)2Br4 (1), Cu2(p-2-bmp)2Cl4 (2), Cu2(p-2-bmb)2(DMF)2Br4·(CHCl3) (3), and Cu(p-2-bmb)(NO3)2·(CHCl3) (4) were isolated and characterized, where p-2-bmp is 1-((2-(pyridine-2-yl)-1H-benzoimidazol-1-yl)methyl)-1H-pyridine and p-2-bmb is 1-((2-(pyridin-2-yl)-1-benzoimidazol-1-yl)methyl)-1H-benzotriazole. Complexes 1 and 2 have binuclear configurations, 3 has a mononuclear structure, and 4has a one-dimensional (1-D) chain skeleton. To evaluate their potential anticancer effects on human carcinoma cells, anti-proliferation, DNA binding and cleavage, and apoptosis elicitation were examined. Compared with complexes 2, 3, and 4, complex 1 exhibited potent in vitro cytotoxicity toward four cell lines (MCF7, EC109, SH-SY5Y and QBC939), with SH-SY5Y cells demonstrating the most sensitivity. Therefore, further in-depth investigations were performed using complex 1. Absorption titration experiments, circular dichroism spectroscopic studies, and ethidium bromide displacement assays suggested that complex 1 binds to DNA through intercalation, significantly cleaves supercoiled pBR322 DNA, and inhibits DNA transcription. Cell cycle analysis revealed that SH-SY5Y cells were arrested in the G2/M phase after treatment with complex 1. Membrane permeability analysis and nuclear staining of SH-SY5Y cells showed that complex 1 could induce apoptosis.

Piezoelectric Outputs of Electrospun PVDF Web as Full-Textile Sensor at Different Mechanical Excitation Frequencies.

With the increasing application of electrospun PVDF webs in piezoelectric sensors and energy-harvesting devices, it is crucial to understand their responses under complex mechanical excitations. However, the dependence of the piezoelectric effect on mechanical excitation properties is not fully comprehended. This study aims to investigate the piezoelectric output of randomly oriented electrospun PVDF nanofiber webs fabricated through different electrospinning processes at various mechanical excitation frequencies. The electrospun PVDF web was sandwiched between two textile electrodes, and its piezoelectric output as a full-textile sensor was measured across a frequency range from 0.1 Hz to 10 Hz. The experimental results revealed that the piezoelectric output of the electrospun PVDF web exhibited a nearly linear increase at excitation frequencies below 1.0 Hz and then reached an almost constant value thereafter up to 10 Hz, which is different from the hybrid PVDF or its copolymer web. Furthermore, the dependency of the piezoelectric output on the excitation frequency was found to be influenced by the specific electrospinning process employed, which determined the crystalline structure of electrospun PVDF nanofibers. These findings suggest that determining an appropriate working frequency for randomly oriented electrospun PVDF nanofiber webs is essential before practical implementation, and the piezoelectric response mode in different mechanical activation frequency ranges can be used to detect different human physiological behaviors.

The Interconnecting Process and Sensing Performance of Stretchable Hybrid Electronic Yarn for Body Temperature Monitoring.

Flexible and stretchable electronic yarn containing electronic components (i.e., hybrid electronic yarn) are essential for manufacturing smart textile garments or fabrics. Due to their low stretchability and easy interconnection fracture, previously reported hybrid electronic sensing yarns have poor mechanical durability and washability. In order to address this issue, a stretchable hybrid electronic yarn for body temperature monitoring was designed and prepared using a spandex filament as the core yarn and a thin enameled copper wire connected with a thermal resistor as the wrapping fiber. The temperature sensing performance of different hybrid electronic yarn samples was evaluated using the following three types of interconnection methods: conductive adhesive bonding, melt soldering, and hot pressure bonding. The optimal interconnection method with good sensing performance was determined. Furthermore, in order to improve the mechanical durability of the hybrid electronic yarn made using the optimal interconnection method, the interconnection area was encapsulated with polymers, and the effect of polymer materials and structures on the temperature-sensing properties was evaluated. The results show that traditional wrapping combined with hot pressing interconnection followed by tube encapsulating technology is beneficial for achieving high stretchability and good temperature-sensing performance of hybrid electronic yarn.

Influence of heat treatment before and/or after high-pressure homogenization on the structure and emulsification properties of soybean protein isolate.

This study investigates the effects of heat treatment before high-pressure homogenization (HHPH) and heat treatment after high-pressure homogenization (HPHH) at different pressures (20, 60, and 100 MPa) on the structural and emulsification properties of soy protein isolate (SPI). The results indicate that HHPH treatment increases the surface hydrophobicity (H0) of the SPI, reduces ß-fold and irregular curls, leading to the formation of soluble aggregates, increased adsorbed protein content, and subsequent improvements in emulsification activity index (EAI) and emulsion stability index (ESI). In contrast, the HPHH treatment promoted the exchange of SH/SS bonds between protein molecules and facilitated the interaction of basic peptides and ß-subunits, leading to larger particle sizes of the soluble aggregates compared to the HHPH-treated samples. However, excessive aggregation in HPHH-treated aggregates leads to decreased H0 and adsorbed protein content, and increased interfacial tension, negatively affecting the emulsification properties. Compared to the HPHH treatment, HHPH treatment at homogenization pressures of 20 to 100 MPa increases EAI and ESI by 5.81-29.6 % and 5.31-25.9 %, respectively. These findings provide a fundamental basis for soybean protein manufacturers to employ appropriate processing procedures aimed at improving emulsification properties.

Fabrication and Seamless Integration of Insensitive-Bending Fully Printed All-in-One Fabric-Based Supercapacitors Based on Cost-Effective MWCNT Electrodes.

All-in-one supercapacitors are considered to be promising due to their advantages of flexibility and structure stability. However, the sophisticated and precise manufacturing processes and difficulty of series/parallel integration hinder their application and development. Herein, cost-effective all-in-one fabric-based supercapacitors (all-in-one FSCs) are fabricated by utilizing the facile screen-printing technique and multiwalled carbon nanotube (MWCNT) electrodes. The MWCNT electrodes are constructed on the gel-electrolyte-soaked fabric that simultaneously serves as separator and electrode substrates. The as-prepared all-in-one FSC exhibits better capacitive behavior and rate capability and lower internal resistance than traditional sandwiched fabric-based supercapacitors (sandwiched FSCs). Moreover, due to the simplified structure and interface interaction, the all-in-one FSC shows excellent flexibility and stability even under dynamic bending cycles with a relatively high strain rate of 20% s-1. This work also demonstrates the seamless series/parallel integration scheme of all-in-one supercapacitors by designing the screen-printing patterns instead of using metal wires. The proposed fabrication process and series/parallel integration scheme definitely improve the portability of integrated supercapacitors and potentially contribute to the large-scale production and application on wearable electronics.

Thiosemicarbazone N-Heterocyclic Cu(II) complexes inducing nuclei DNA and mitochondria damage in hepatocellular carcinoma cells.

The α-N-Heterocyclic thiosemicarbazones and their metal complexes have been widely investigated as anticancer and antibacterial agents for their broad spectrum of pharmacological properties. Thus, two thiosemicarbazone-based Cu(II) complexes, [Cu2(ptpc)I2] (1) and [Cu(qtpc)I] (2) with thiosemicarbazone ligand (ptpc = 2-(di(pyridin-2-yl)methylene)-N-(2-(trifluoromethyl)phenyl)-hydrazine-1-carbothioamide, qtpc = 2-(quinolin-8-ylmethylene)-N-(2-(trifluoromethyl)phenyl)hydrazine-1-carbothioamide) were synthesized and evaluated for their biological activities. Complexes 1 and 2 are superior to cisplatin in vitro antiproliferative activities toward hepatocellular carcinoma cell line with the half maximal inhibitory concentration value of 0.2 and 2 µM, respectively. A series of spectroscopic assays and the DNA cleavage experiments showed that both complexes can change and distort the conformation of DNA. Molecular docking experiment further demonstrated that complex 1 binds to DNA mainly in groove mode. Meanwhile, benefiting from their good liposolubility, complexes 1 and 2 could easily enter cells, which further triggers cell cycle arrest and apoptosis. Moreover, complexes 1 and 2 caused serious mitochondrial damage, associating with increased the level of reactive oxygen species (ROS) and Ca2+, decreased adenosine triphosphate (ATP) content and mitochondrial membrane potential (Δψm), and transformed mitochondrial morphology. These findings indicated that complexes 1 and 2 might exert their anticancer activity by inducing DNA and mitochondrial damage simultaneously.

Amlexanox-modified platinum(IV) complex triggers apoptotic and autophagic bimodal death of cancer cells.

Platinum(IV) prodrugs c,c,t-[PtCl2(NH3)2(OH)(amlexanox)] (MAP) and c,c,t-[PtCl2(NH3)2(amlexanox)2] (DAP) were synthesized by reacting amlexanox with oxoplatin and characterized by NMR, HR-MS, HPLC, and elemental analysis. The complexes could be reduced to platinum(II) species and amlexanox to exert antitumor activity. Generally, MAP was more potent than DAP and cisplatin towards various human cancer cell lines; particularly, it was active in cisplatin-resistant Caov-3 ovarian cancer and A549/DDP lung cancer cells. MAP induced serious damage to DNA, remarkable change in mitochondrial morphology, decrease in mitochondrial membrane potential, release of cytochrome c from mitochondria, and up-regulation of pro-apoptotic protein Bax in Caov-3 cells, thereby leading to evident apoptosis. Meanwhile, MAP markedly promoted the autophagic flux, including affecting the expression of microtubule-associated protein light chain 3 (LC3) and autophagy adaptor protein p62 in Caov-3 cells, with an increase in the ratio of LC3-II/LC3-I and a decrease in p62, thus trigging the occurrence of autophagy. The MAP-induced bimodal cell death mode is uncommon for platinum complexes, which presents a new possibility to invent anticancer drugs with unique mechanism of action.

Bis{µ-1,3-bis-[(2-methyl-1H-benzimid-azol-1-yl)meth-yl]benzene-κN:N}bis-(diiodidocadmium).

In the title compound, [Cd(2)I(4)(C(24)H(22)N(4))(2)], the 1,3-bis-[(2-methyl-1H-benzimidazol-1-yl)meth-yl]benzene ligand bridges two CdI(2) units, forming a centrosymmetric dinuclear complex. The Cd(II) atom adopts a distorted tetra-hedral coordination geometry. In the crystal, complex mol-ecules are linked into columns parallel to [101] by π-π stacking inter-actions, with centroid-centroid distances of 3.558 (2) Å.

Construction of a Ag(12) high-nuclearity metallamacrocyclic 3D framework.

An unprecedented high-nuclearity metallamacrocycle-based 3D silver framework with formula {[Ag(2)(C(25)H(27)N(6)O)(2)](CH(3)OH)(H(2)O)(0.17)}(n) (1), built on the basis of dodecanuclear silver building blocks, has been synthesized and characterized, and it shows strong phosphorescence emission at 10 K, which is a consequence of the presence of intersystem crossing from singlet to triplet caused by the heavy-atom effect of silver ions.

Influence of the introduction of a triphenylphosphine group on the anticancer activity of a copper complex.

Aiming at obtaining new copper complexes with good cytotoxicity against cancer cells, triphenylphosphine (TPP) was introduced to obtain insight into the influence of the co-ligands. In this paper, two copper complexes, Cu(2-pbmq)(CH3OH)Br2 (1) and [Cu(2-pbmq)(TPP)Br]2 (2) were designed, synthesized, and characterized by X-ray crystallography, 2-((2-(pyrazin-2-yl)-1H-benzo[d]imidazol-1-yl)methyl))quinolone (2-pbmq), to investigate the influence of the TPP group on the anticancer activity of the metal complex. Although the presence of the TPP group diminished the intensity of the interaction properties of the complex with DNA, the in vitro anticancer activity and cellular uptake of the TPP-containing complex were markedly superior to those of its TPP-lacking counterpart. Detailed studies on the more potently cytotoxic complex 2 revealed that it accumulated in nucleus, arrested the cell cycle at the G0-G1 phase, causing mitochondrial dysfunction, involving the potential simultaneous mitochondrial membrane collapse, cellular ATP level depletion, and Ca2+ leakage, eventually inducing cell apoptosis. In summary, the introduction of a TPP group enhances the biological activity and cytotoxicity of the complex.

UV Curable Conductive Ink for the Fabrication of Textile-Based Conductive Circuits and Wearable UHF RFID Tags.

Textile is a kind of emerging substrate for wearable printed electronics to realize recyclable smart products by versatile and low-cost screen printing. The high temperature sintering step is necessary to get high surface electrical conductivity, whereas most of the common fabrics have poor temperature endurance. Meanwhile, both rough surface and porous structure of fabrics are not beneficial to obtain high-resolution and high-quality circuits. In this work, the ultraviolet (UV) curable conductive inks with low-temperature and short-time curing were developed for screen-printing e-textiles, and the rheological behavior of conductive inks with different polymer contents was characterized in order to determine the ink formulation suitable for screen printing on fabrics. To demonstrate the usability of the developed ink in fabricating e-textiles, the conductive lines with different widths as well as the antenna for UHF RFID tags were screen-printed on plain nylon-woven fabrics. The geometric morphology and the electrical properties of the printed conductive lines were evaluated. The results showed that the screen-printed conductive lines have a minimum line width of 0.2 mm, highest conductivity of 6.02 × 106 S m-1, and good bending endurance at a bending radius of 5 mm. Also, the feasibility of UV curable conductive ink for a fabric-based electronic device was confirmed by the screen-printed antenna of UHF RFID tags, and the reading distance after five cycles of washing is still over 3.0 m. Generally, this work developed a kind of low-temperature curing ink characterized by direct screen printing on common fabrics and high electrical conductivity after curing, and it will facilitate the use of textiles as the screen-printed substrates for flexible and wearable electronic devices.

A wearable fiber-shaped supercapacitor based on a poly(lactic acid) filament and high loading polypyrrole.

There is a growing interest in fiber-shaped supercapacitors, which are likely to meet the demands of wearable electronics. However, the loading of active material is so small that the energy density of fiber supercapacitors is low. In this research, a graphene oxide/poly(pyrrole) (GO/PPy) hybrid was applied as the active material and a novel method to accomplish a high loading of the active material on poly(lactic acid) (PLA) filaments is proposed. Iron ions, as positive ions, are intercalated into GO sheets to form complexes which can be absorbed on the surface of the PLA. Furthermore, iron ions can be used as initiators to initiate pyrrole polymerization. Using complexes in which iron ions are intercalated into GO, instead of pure GO, then coated onto PLA and then polymerized using pyrrole, this method could effectively increase the loading of PPy. As a result, the active material loading is 0.121 mg cm-1, and the weight gain rate even reached 72.4%. A high areal specific capacitance of 158.8 mF cm-2 and energy density of 3.5 µW h cm-2 are achieved using the proposed fiber-shaped supercapacitor. Meanwhile, it shows great potential for textile shaped electronics because of its fiber format.

Synthesis and anticancer evaluation of benzo-N-heterocycles transition metal complexes against esophageal cancer cell lines.

Three novel transition metal complexes, Cu(p-2-bmq)Cl2 (1), Zn(p-2-bmq)Cl2 (2) and [Co(p-2-bmq)Cl2]2 (3) (where p-2-bmq = 2-((1-(pyridin-2-yl)-1H-benzoimidazol-2-yl)methyl) quinolone, have been synthesized. The complexes were detected for their cytotoxicity in vitro against four human esophageal cancer cell lines (SMMC7721, BGC823, HCT116 and HT29) by MTT assay. The results showed that they all have anti-tumor cell proliferation activity. E specially, complex 1 exhibited significant cytotoxicity with IC50 value of 15.89 µM against SMMC7721 cells for 72 h. The morphological changes of nuclei by fluorescence staining methods proved that complex 1 could induce intracellular DNA damage. The flow cytometry analysis revealed that the treatment of SMMC7721 cells with complex 1 induced intracellular ROS increased, mitochondrial potential collapse, G2/M-phase arrest, and even apoptosis. These studies should highly valuable for the development of transition metal-based compounds to the potential anticancer medicinal applications.

Chemical biology suggests pleiotropic effects for a novel hexanuclear copper(ii) complex inducing apoptosis in hepatocellular carcinoma cells.

A novel hexanuclear copper(ii)-based complex, [Cu6(tpbb)2(NO3)12] (1), was synthesized, which shows potent cytotoxicity to hepatoma carcinoma cells by inducing apoptosis and apoptosis-related processes. Furthermore, mechanistic investigations based on proteomes revealed that the induced apoptosis was mediated by acting on several targets and multiple pathways in a pleiotropic way.

Cation exchange induced tunable properties of a nanoporous octanuclear Cu(II) wheel with double-helical structure.

A double-helical octanuclear Cu(II) wheel 1 with 2.88 nm diameter was prepared through the reaction of a clinical medicine, telmisartan, with copper sulfate. Central copper ions can be partially replaced by bivalent zinc and cobalt ions and fully exchanged by trivalent iron ions. The properties of central metal ion-exchanged variants are much different from those of 1. Central metal ion exchange might be regarded as a powerful and effective method to modify properties from one crystalline material to another only by varying central metal ions under moderate conditions.

Serological thymidine kinase 1 (STK1) indicates an elevated risk for the development of malignant tumours.

BACKGROUND: The role of serum tumour markers is to reveal tumours not yet visible by imaging techniques. Here we examine the use of serum thymidine kinase 1 protein (STK1) in health screening. PATIENTS AND METHODS: Persons (n = 11,880) participating in health screening programs in China, during 2005-2007, were tested for STK1. STK1 was measured by a sensitive chemiluminescence dot-blot assay. Medical examination of participants was carried out in parallel. RESULTS: The proportion of STK1-positive (> 2 pM) individuals was 0.5%, corresponding to the cancer incidence rate of China. No malignant cases were found in the STK1-negative group, but two pre-malignant and one malignant case were found in the STK1-positive group. The low frequency of malignancies found was probably due to the relatively young population (mean age 40.4 +/- 13.4 years). In the STK1-positive group, there were 24% of persons with benign diseases (breast, liver, kidney), 37% with proliferative tissues (breast, prostate), 13% with fatty liver, 9% with inflammatory reactions/virus infections (three hepatitis B virus-positive persons) and 17% showed other types of physiological changes not directly related to proliferation. In the STK1-positive group, a significantly (p < 0.001) higher proportion of persons with proliferation of breast and prostate tissues were found (37%), as compared to the STK1-negative group (18%). Furthermore, the mean ages among the groups of persons with STK1-positive values were between 5-8 years higher, as compared to the STK1 negative group, due to higher mean ages of persons with proliferative breast and prostate tissues. Thus, 83% of the STK1-positive persons had diseases (benign, proliferation tissues, fatty liver, helicobacter pylori-positive and hepatitis B virus-positive) related to malignancies. CONCLUSION: STK1-values > 2 pM may indicate an early risk for development of malignancies years later.

DNA interactions and in vitro anticancer evaluations of pyridine-benzimidazole-based Cu complexes.

Copper is an essential element and has redox potential, thus copper complexes have been developed rapidly with the hope of curing cancer. To further develop anticancer agents and investigate their anticancer mechanisms, two Cu complexes, [Cu(bpbb)0.5·Cl·SCN]·(CH3OH) (1) and [Cu2(bpbb)·Br3·(OH)] n (2), were synthesized and characterized using 4,4'-bis((2-(pyridin-2-yl)-1H-benzo[d]imidazol-1-yl)methyl)biphenyl (bpbb), with associated Cu(ii) salts. Complex 1 is a binuclear structure, whereas 2 is a one-dimensional complex. Compared with 2, complex 1 exhibited potent in vitro cytotoxicity toward four cell lines (HCT116, BGC823, HT29, and SMMC7721), and was most effective against HCT116 cells. Therefore, further in-depth investigation was carried out using complex 1. Absorption spectral titration experiments, ethidium bromide displacement assays, and circular dichroism spectroscopic studies suggested that complex 1 binds strongly to DNA by intercalation. Complex 1 exhibited a clear concentration-dependent pBR322 DNA cleavage activity. Inductively coupled plasma mass spectrometry testing implied that complex 1 could enter cells and that DNA was one important target. Cellular level assays suggested that complex 1 activates the generation of intracellular reactive oxygen species, causing DNA damage, promoting cell cycle arrest and mitochondria dysfunction, and inducing cellular apoptosis.

Cytotoxicity, dual-targeting apoptosis induction evaluation of multinuclear cu complexes based on pyrazine-benzimidazole derivative.

To investigate the cytotoxicity and mechanism of action of multinuclear Cu complexes against tumor cell lines, two complexes, Cu6(bpbib)4Br8 (1) and Cu2(bpbib)2(BF4)2Cl2 (2) (bpbib = 1,4-bis((2-(pyrazin-2-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzene) were synthesized and characterized. Both Cu complexes showed high selectivity toward cancer and not normal cells, and the SMMC7721 cell line showed most sensitivity toward both complexes. Complex 1 exhibited more potent cytotoxicity and enhanced cellular uptake, and therefore, was comprehensively investigated. Complex 1 exhibited dual effects in the inhibition of tumor cell proliferation of SMMC7721 cells, causing nuclear DNA damage and mitochondrial dysfunction involving simultaneous reactive oxygen species (ROS) generation and Ca2+ increase. DNA binding studies suggest that intercalation might be the most probable binding mode. Fluorescence spectrometry also detected a medium affinity of complex 1 to bovine serum albumin (BSA) at distinct temperatures and resulted in BSA fluorescence static quenching.

The control of beads diameter of bead-on-string electrospun nanofibers and the corresponding release behaviors of embedded drugs.

Bead-on-string nanofibers, with appropriate control of the beads diameter, are potential fibrous structures for efficient encapsulation of particle drugs in micron scales and could achieve controlled drug release for tissue engineering applications. In this study, the beads diameter of electrospun bead-on-string nanofibers was controlled by adjusting the concentration of spinning polymer, poly (lactic-co-glycolic acid) (PLGA), and the solvent ratio of chloroform to acetone. The images of the scanning electron microscopy (SEM) suggested that bead-on-string nanofibers could be successfully obtained only with a certain range of PLGA solution concentration. Moreover, with the decrease in the solvent ratio of chloroform to acetone, the range was left-shifted towards a smaller concentration. In addition, increase in the PLGA solution concentration within the range the beads diameter became greater and the shape of the beads changed from oval to slender when increasing the PLGA concentration within the range. The bead-on-string nanofibers with different beads diameter were further used to load micro-particle drugs of tetracycline hydrochloride, as a model drug, to examine the release behavior of nanofibers scaffold. The release profiles of drug loaded bead-on-string nanofibers demonstrated the possibility to alleviate the burst drug release by means of beads diameter control.

Responses of cutaneous mechanoreceptors within fingerpad to stimulus information for tactile softness sensation of materials.

Softness sensation is one of primitive tactile textures. While the psychophysical characteristics of softness sensation have been thoroughly studied, it is lack of a deep understanding of the underlying neuromechanical principles. On the stimulus-response processes of human fingerpad touching fabrics and the physiological properties of slowly adapting type I (SAIs) cutaneous mechanoreceptors within fingerpad, a fabric-skin-receptor coupling model was built and validated. By the fabric-skin-receptor model a series of numerical experiments was conducted, and how the evoked neural responses of cutaneous mechanoreceptors change with the composite compliance of both fingerpad skin and the materials in contact was investigated. The results indicated that the evoked neural responses of populations of cutaneous mechanoreceptors by the physical stimulus from fabrics were nearly proportional to the perceived softness magnitude, and nonlinearly increased and then decreased with the effective elastic modulus of fabrics or the relative elastic modulus of fabrics to soft tissues within fingerpad, where the nonlinear inflection point depended on the touching force level. Therefore, it concluded that the tactile judgment of the physical information for softness sensation of objects was an encoding of neural responses of populations of SAIs cutaneous mechanoreceptors, and the physical information depended on the mechanical interaction of fingerpad and objects in contact.