Regulation of HOX gene expression in AML.

As key developmental regulators, HOX cluster genes have varied and context-specific roles in normal and malignant hematopoiesis. A complex interaction of transcription factors, epigenetic regulators, long non-coding RNAs and chromatin structural changes orchestrate HOX expression in leukemia cells. In this review we summarize molecular mechanisms underlying HOX regulation in clinical subsets of AML, with a focus on NPM1 mutated (NPM1mut) AML comprising a third of all AML patients. While the leukemia initiating function of the NPM1 mutation is clearly dependent on HOX activity, the favorable treatment responses in these patients with upregulation of HOX cluster genes is a poorly understood paradoxical observation. Recent data confirm FOXM1 as a suppressor of HOX activity and a well-known binding partner of NPM suggesting that FOXM1 inactivation may mediate the effect of cytoplasmic NPM on HOX upregulation. Conversely the residual nuclear fraction of mutant NPM has also been recently shown to have chromatin modifying effects permissive to HOX expression. Recent identification of the menin-MLL interaction as a critical vulnerability of HOX-dependent AML has fueled the development of menin inhibitors that are clinically active in NPM1 and MLL rearranged AML despite inconsistent suppression of the HOX locus. Insights into context-specific regulation of HOX in AML may provide a solid foundation for targeting this common vulnerability across several major AML subtypes.

Iron/vanadium co-doped tungsten oxide nanostructures anchored on graphitic carbon nitride sheets (FeV-WO3@g-C3N4) as a cost-effective novel electrode material for advanced supercapacitor applications.

In this work, we studied the effect of iron (Fe) and vanadium (V) co-doping (Fe/V), and graphitic carbon nitride (g-C3N4) on the performance of tungsten oxide (WO3) based electrodes for supercapacitor applications. The lone pair of electrons on nitrogen can improve the surface polarity of the g-C3N4 electrode material, which may results in multiple binding sites on the surface of electrode for interaction with electrolyte ions. As electrolyte ions interact with g-C3N4, they quickly become entangled with FeV-WO3 nanostructures, and the contact between the electrolyte and the working electrode is strengthened. Herein, FeV-WO3@g-C3N4 is fabricated by a wet chemical approach along with pure WO3 and FeV-WO3. All of the prepared samples i.e., WO3, FeV-WO3, and FeV-WO3@g-C3N4 were characterized by XRD, FTIR, EDS, FESEM, XPS, Raman, and BET techniques. Electrochemical performance is evaluated by cyclic voltammetry (CV), galvanic charge/discharge (GCD), and electrochemical impedance spectroscopy (EIS). It is concluded from electrochemical studies that FeV-WO3@g-C3N4 exhibits the highest electrochemical performance with specific capacitance of 1033.68 F g-1 at scan rate 5 mV s-1 in the potential window range from -0.8 to 0.25 V, that is greater than that for WO3 (422.76 F g-1) and FeV-WO3 (669.76 F g-1). FeV-WO3@g-C3N4 has the highest discharge time (867 s) that shows it has greater storage capacity, and its coulombic efficiency is 96.7%, which is greater than that for WO3 (80.1%) and FeV-WO3 (92.1%), respectively. Furthermore, excellent stability up to 2000 cycles is observed in FeV-WO3@g-C3N4. It is revealed from EIS measurements that equivalent series resistance and charge transfer values calculated for FeV-WO3@g-C3N4 are 1.82 Ω and 0.65 Ω, respectively.

Chitosan nanoparticles as a smart nanocarrier for gefitinib for tackling lung cancer: Design of experiment and in vitro cytotoxicity study.

Due to its poor solubility and systemic side effects, gefitinib (Gef) has limited application in treatment of lung cancer. In this study, we used design of experiment (DOE) tools to gain the necessary knowledge for the synthesis of high-quality gefitinib loaded chitosan nanoparticles (Gef-CSNPs) capable of delivering and concentrating Gef at A549 cells, thereby increasing therapeutic effectiveness while decreasing adverse effects. The optimized Gef-CSNPs were characterized by SEM, TEM, DSC, XRD, and FTIR analyses. The optimized Gef-CSNPs had a particle size of 158±3.6 nm, an entrapment efficiency of 93±1.2 %, and a release of 97±0.6 % after 8 h. The in vitro cytotoxicity of the optimized Gef-CSNPs was found to be significantly higher than pure Gef (IC50 = 10.08 ± 0.76 µg/mL and IC50 = 21.65 ± 0.32 µg/mL), respectively. In the A549 human cell line, the optimized Gef-CSNPs formula outperformed pure Gef in terms of cellular uptake (3.286 ± 0.12 µg/mL and 1.777 ± 0.1 µg/mL) and apoptotic population (64.82 ± 1.25 % and 29.38 ± 1.11 %), respectively. These findings explain why researchers are so interested in using natural biopolymers to combat lung cancer, and they paint an optimistic picture of their potential as a promising tool in the fight against lung cancer.

Recent Advances in the Pharmaceutical and Biomedical Applications of Cyclodextrin-Capped Gold Nanoparticles.

The real problem in pharmaceutical preparation is drugs' poor aqueous solubility, low permeability through biological membranes, and short biological t1/2. Conventional drug delivery systems are not able to overcome these problems. However, cyclodextrins (CDs) and their derivatives can solve these challenges. This article aims to summarize and review the history, properties, and different applications of cyclodextrins, especially the ability of inclusion complex formation. It also refers to the effects of cyclodextrin on drug solubility, bioavailability, and stability. Moreover, it focuses on preparing and applying gold nanoparticles (AuNPs) as novel drug delivery systems. It also studies the uses and effects of cyclodextrins in this field as novel drug carriers and targeting devices. The system formulated from AuNPs linked with CD molecules combines the advantages of both CD and AuNPs. Cyclodextrins benefit in increasing aqueous drug solubility, loading capacity, stability, and size control of gold NPs. Also, AuNPs are applied as diagnostic and therapeutic agents because of their unique chemical properties. Plus, AuNPs possess several advantages such as ease of detection, targeted and selective drug delivery, greater surface area, high loading efficiency, and higher stability than microparticles. In the present article, we tried to present the potential pharmaceutical applications of CD-derived AuNPs in biomedical applications including antibacterial, anticancer, gene-drug delivery, and various targeted drug delivery applications. Also, the article highlighted the role of CDs in the preparation and improvement of catalytic enzymes, the formation of self-assembling molecular print boards, the fabrication of supramolecular functionalized electrodes, and biosensors formation.

Application of ZnO-NRs@Ni-foam substrate for electrochemical fingerprint of arsenic detection in water.

Arsenic (As3+) is the most carcinogenic and abundantly available heavy metal present in the environment. Vertically aligned ZnO nanorod (ZnO-NR) growth was achieved on metallic nickel foam substrate via a wet chemical route and it was used as an electrochemical sensor towards As(iii) detection in polluted water. Crystal structure confirmation, surface morphology observation and elemental analysis of ZnO-NRs were conducted using X-ray diffraction, field-emission scanning electron microscopy and energy-dispersive X-ray spectroscopy, respectively. Electrochemical sensing performance of ZnO-NRs@Ni-foam electrode/substrate was investigated via linear sweep voltammetry, cyclic voltammetry and electrochemical impedance spectroscopy in a carbonate buffer solution of pH = 9 and at different As(iii) molar concentrations in solution. Under optimum conditions, the anodic peak current was found proportional to the arsenite concentration from 0.1 µM to 1.0 µM. The achieved values for limit of detection and limit of quantification were 0.046 ppm and 0.14 ppm, respectively, which are far lower than the recommended limits for As(iii) detection in drinking water as suggested by the World Health Organization. This suggests that ZnO-NRs@Ni-foam electrode/substrate can be effectively utilized in terms of its electrocatalytic activity towards As3+ detection in drinking water.

Boosting the Activity of the Oxygen Evolution Reaction through an Electrospun Nickel Manganese-Based Bimetallic Zeolite Imidazolate Framework Fibrous System in Alkaline Medium.

Developing cost-efficient and noble metal free electrocatalysts is vastly anticipated for the oxygen evolution reaction (OER). Therefore, in this study, to lift the thermodynamic and kinetic activity of the OER, we attempted to synthesize a bimetallic nickel and manganese-based zeolite imidazolate framework system in a fiber form. For this synthesis, a bottom-up approach has been followed through wet chemical analysis, and electrospinning was utilized for fiber formation. The resultant fiber has shown a lesser overpotential of 256 mV at a benchmarking current density of 10 mA cm-2 under 1 M KOH conditions. As expected, the attained Tafel slope and charge transfer resistance values are lesser. The observed results reveal that the synergism between the Ni and Mn nodes on the imidazolate framework successfully promotes the thermodynamic formation of *O and *OOH intermediates, which significantly helps to improve the faster OER kinetics at the electrode-electrolyte interface.

In vitro and in vivo synergistic wound healing and anti-methicillin-resistant Staphylococcus aureus (MRSA) evaluation of liquorice-decorated silver nanoparticles.

The multi-drug resistant Staph. aureus strain, Methicillin-resistant Staphylococcus aureus (MRSA), is an emerging pathogen that could penetrate skin cuts and wounds, causing a life-threatening condition. The green biosynthesis of silver nanoparticles with liquorice extract has been demonstrated over several years for anticancer and antioxidant effects, as well as antibacterial effect against both Gram-positive and Gram-negative bacteria. The study was designed to evaluate the synergistic in vivo and in vitro wound healing and anti-MRSA activity of decorated liquorice silver nanoparticles (LD-AgNPs). The LD-AgNPs were prepared by thoroughly mixing diluted liquorice extract with AgNO3 at room temperature. The prepared nanoparticles were characterized by size measurement, IR spectroscopy, TEM imaging, and X-ray diffraction. The in vitro and in vivo antibacterial and wound healing testing were also performed. The obtained LD-AgNPs were spherical in shape and had a hydrodynamic size of about 50.16 ± 5.37 nm. Moreover, they showed potent antibacterial activity against Gram-positive and Gram-negative resistant bacteria, produced a significantly higher level of procollagen type I compared to either liquorice extract or standard silver sulfadiazine, and promoted the wound healing process in rabbits. The formulation of silver nanoparticles with liquorice extract showed synergetic effects in enhancing the treatment of wounds, with significant antibacterial activity against E. coli and MRSA.

Bias-Modified Schottky Barrier Height-Dependent Graphene/ReSe2 van der Waals Heterostructures for Excellent Photodetector and NO2 Gas Sensing Applications.

Herein, we reported a unique photo device consisting of monolayer graphene and a few-layer rhenium diselenide (ReSe2) heterojunction. The prepared Gr/ReSe2-HS demonstrated an excellent mobility of 380 cm2/Vs, current on/off ratio ~ 104, photoresponsivity (R ~ 74 AW-1 @ 82 mW cm-2), detectivity (D* ~ 1.25 × 1011 Jones), external quantum efficiency (EQE ~ 173%) and rapid photoresponse (rise/fall time ~ 75/3 µs) significantly higher to an individual ReSe2 device (mobility = 36 cm2 V-1s-1, Ion/Ioff ratio = 1.4 × 105-1.8 × 105, R = 11.2 AW-1, D* = 1.02 × 1010, EQE ~ 26.1%, rise/fall time = 2.37/5.03 s). Additionally, gate-bias dependent Schottky barrier height (SBH) estimation for individual ReSe2 (45 meV at Vbg = 40 V) and Gr/ReSe2-HS (9.02 meV at Vbg = 40 V) revealed a low value for the heterostructure, confirming dry transfer technique to be successful in fabricating an interfacial defects-free junction. In addition, HS is fully capable to demonstrate an excellent gas sensing response with rapid response/recovery time (39/126 s for NO2 at 200 ppb) and is operational at room temperature (26.85 °C). The proposed Gr/ReSe2-HS is capable of demonstrating excellent electro-optical, as well as gas sensing, performance simultaneously and, therefore, can be used as a building block to fabricate next-generation photodetectors and gas sensors.

Synthesis of Cyano-Benzylidene Xanthene Synthons Using a Diprotic Brønsted Acid Catalyst, and Their Application as Efficient Inhibitors of Aluminum Corrosion in Alkaline Solutions.

Novel cyano-benzylidene xanthene derivatives were synthesized using one-pot and condensation reactions. A diprotic Brønsted acid (i.e., oxalic acid) was used as an effective catalyst for the promotion of the synthesis process of the new starting xanthene-aldehyde compound. Different xanthene concentrations (ca. 0.1-2.0 mM) were applied as corrosion inhibitors to control the alkaline uniform corrosion of aluminum. Measurements were conducted in 1.0 M NaOH solution using Tafel extrapolation and linear polarization resistance (LPR) methods. The investigated xanthenes acted as mixed-type inhibitors that primarily affect the anodic process. Their inhibition efficiency values were enhanced with inhibitor concentration, and varied according to their chemical structures. At a concentration of 2.0 mM, the best-performing studied xanthene derivative recorded maximum inhibition efficiency values of 98.9% (calculated via the Tafel extrapolation method) and 98.4% (estimated via the LPR method). Scanning electron microscopy (SEM) was used to examine the morphology of the corroded and inhibited aluminum surfaces, revealing strong inhibitory action of each studied compound. High-resolution X-ray photoelectron spectroscopy (XPS) profiles validated the inhibitor compounds' adsorption on the Al surface. Density functional theory (DFT) and Monte Carlo simulations were applied to investigate the distinction of the anticorrosive behavior among the studied xanthenes toward the Al (111) surface. The non-planarity of xanthenes and the presence of the nitrile group were the key players in the adsorption process. A match between the experimental and theoretical findings was evidenced.

Correction: Electrocatalytic hydrogen generation using tripod containing pyrazolylborate-based copper(ii), nickel(ii), and iron(iii) complexes loaded on a glassy carbon electrode.

[This corrects the article DOI: 10.1039/D1RA08530A.].

Electrocatalytic hydrogen generation using tripod containing pyrazolylborate-based copper(ii), nickel(ii), and iron(iii) complexes loaded on a glassy carbon electrode.

Three transition metal complexes (MC) namely, [TpMeMeCuCl(H2O)] (CuC), [TpMeMeNiCl] (NiC), and [TpMeMeFeCl2(H2O)] (FeC) {TpMeMe = tris(3,5-dimethylpyrazolyl)borate} were synthesized and structurally characterized. The three complexes CuC, NiC, and FeC-modified glassy carbon (GC) were examined as molecular electrocatalysts for the hydrogen evolution reaction (HER) in alkaline solution (0.1 M KOH). Various GC-MC electrodes were prepared by loading different amounts (ca. 0.2-0.8 mg cm-2) of each metal complex on GC electrodes. These electrodes were used as cathodes in aqueous alkaline solutions (0.1 M KOH) to efficiently generate H2 employing various electrochemical techniques. The three metal complexes' HER catalytic activity was assessed using cathodic polarization studies. The charge-transfer kinetics of the HER at the (GC-MC)/OH- interface at a given overpotential were also studied using the electrochemical impedance spectroscopy (EIS) technique. The electrocatalyst's stability and long-term durability tests were performed employing cyclic voltammetry (repetitive cycling up to 5000 cycles) and 48 h of chronoamperometry measurements. The catalytic evolution of hydrogen on the three studied MC surfaces was further assessed using density functional theory (DFT) simulations. The GC-CuC catalysts revealed the highest HER electrocatalytic activity, which increased with the catalyst loading density. With a low HER onset potential (E HER) of -25 mV vs. RHE and a high exchange current density of 0.7 mA cm-2, the best performing electrocatalyst, GC-CuC (0.8 mg cm-2), showed significant HER catalytic performance. Furthermore, the best performing electrocatalyst required an overpotential value of 120 mV to generate a current density of 10 mA cm-2 and featured a Tafel slope value of -112 mV dec-1. These HER electrochemical kinetic parameters were comparable to those measured here for the commercial Pt/C under the same operating conditions (-10 mV vs. RHE, 0.88 mA cm-2, 108 mV dec-1, and 110 mV to yield a current density of 10 mA cm-2), as well as the most active molecular electrocatalysts for H2 generation from aqueous alkaline electrolytes. Density functional theory (DFT) simulations were used to investigate the nature of metal complex activities in relation to hydrogen adsorption. The molecular electrostatic surface potential (MESP) of the metal complexes was determined to assess the putative binding sites of the H atoms to the metal complex.

Prussian blue analogue derived cobalt-nickel phosphide/carbon nanotube composite as electrocatalyst for efficient and stable hydrogen evolution reaction in wide-pH environment.

Transition metal phosphides, especially bimetallic phosphides, are promising noble-metal-free electrocatalysts for hydrogen evolution reaction (HER). However, their inferior charge transfer ability constrains further performance improvement. In this work, a facile strategy is reported to fabricate Co2P/Ni2P/carbon nanotube (CNT) composite from a precursor Co-Ni Prussian blue analogue. The combination of Co2P/Ni2P and CNT endows Co2P/Ni2P/CNT with improved electrical conductivity and a richer electrochemically active surface area. As a result, the Co2P/Ni2P/CNT composite exhibits desirable HER activities across a wide pH range, delivering a benchmark current density of 10 mA cm-2 at overpotentials as low as 151 and 202 mV in 0.5 M H2SO4 and 1 M KOH electrolytes, respectively, as well as remarkable electrocatalytic stabilities over 48 h in both electrolytes. This strategy enables the design of high-performance electrocatalysts for efficient and stable hydrogen generation.

Diaryl Sulfide Derivatives as Potential Iron Corrosion Inhibitors: A Computational Study.

The present work aimed to assess six diaryl sulfide derivatives as potential corrosion inhibitors. These derivatives were compared with dapsone (4,4'-diaminodiphenyl sulfone), a common leprosy antibiotic that has been shown to resist the corrosion of mild steel in acidic media with a corrosion efficiency exceeding 90%. Since all the studied compounds possess a common molecular backbone (diphenyl sulfide), dapsone was taken as the reference compound to evaluate the efficiency of the remainder. In this respect, two structural factors were examined, namely, (i) the effect of replacement of the S-atom of diaryl sulfide by SO or SO2 group, (ii) the effect of the introduction of an electron-withdrawing or an electron-donating group in the aryl moiety. Two computational chemical approaches were used to achieve the objectives: the density functional theory (DFT) and the Monto Carlo (MC) simulation. First, B3LYP/6-311+G(d,p) model chemistry was employed to calculate quantum chemical descriptors of the studied molecules and their geometric and electronic structures. Additionally, the mode of adsorption of the tested molecules was investigated using MC simulation. In general, the adsorption process was favorable for molecules with a lower dipole moment. Based on the adsorption energy results, five diaryl sulfide derivatives are expected to act as better corrosion inhibitors than dapsone.

Novel Optical Biosensor Based on a Nano-Gold Coated by Schiff Base Doped in Sol/Gel Matrix for Sensitive Screening of Oncomarker CA-125.

The urge for sensitive, facile, minimally invasive, and fast detection method of CA-125, a significant and crucial biomarker in ovarian malignancy, is currently substantial. This paper describes the detailed construction and characterization of a newly designed optical nano-biosensor to detect CA-125 accurately and sensitively. The fabricated sensor consists of a nano-gold thin film doped into a matrix of sol-gel, exhibiting a centered fluorescence band at 423 nm when excited at 340 nm. The quantification of CA-125 relies on its quenching ability of this fluorescence signal. The sensor was challenged to evaluate its sensitivity and specificity in detecting CA-125 present in samples collected from ovarian cancer diagnosed patients and compared to samples from healthy women as a control. Our findings revealed that the developed biosensor had a sensitivity of 97.35% and a specificity of 94.29%. Additionally, a wide linearity range over 2.0-127.0 U mL-1 for CA-125 was achieved with a detection limit of 1.45 U mL-1. Furthermore, the sensor could successfully discriminate samples between healthy and diseased people, which demonstrates its suitability in CA-125 assessment.

Tb3+-atorvastatin doped in poly(ethylene glycol) optical biosensor for selective determination of progesterone and testosterone in serum samples.

An innovative, simple and cost effective Tb3+-atorvastatin photo probe was designed and used as a core for a spectrofluorometric approach to sensitively determine two vital biological compounds in serum samples. Tb3+-atorvastatin complex displays a characteristic electrical band with λ em at 545 nm with significant luminescence intensity, which is quenched in the presence of progesterone and testosterone at two variant sets of pH; 6.2 and 7.5, respectively. The conditions were optimized and the best solvent for operation was found to be acetonitrile with λ ex at 320 nm. Progesterone and testosterone were assessed in serum samples using the same optimal conditions within concentration ranges of 2 × 10-9 to 2.9 × 10-6 and 3.1 × 10-9 to 4.8 × 10-6 mol L-1, respectively. The proposed luminescence method was validated in accordance to ICH guidelines and found to be accurate, precise and specific and free from any interference. The cost effectiveness and applicability of the method make it a good choice for routine analysis of the two compounds and early diagnosis of chronic diseases associated with abnormalities in their physiological levels.

Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors.

There is a need to formulate oral cetuximab (CTX) for targeting colorectal cancer, which is reported to express somatostatin receptors (SSTRs). Therefore, coating CTX with a somatostatin analogue such as octreotide (OCT) is beneficial. Alginate was used to coat CTX to facilitate delivery to the gastrointestinal tract (GIT). This study aimed to deliver CTX conjugated with OCT in the form of microparticles as a GIT-targeted SSTR therapy. Both CTX and OCT were conjugated using a solvent evaporation method and the conjugated CTX-OCT was then loaded onto Ca-alginate-beads (CTX-OCT-Alg), which were characterized for drug interactions using differential scanning calorimetry (DSC), and Fourier transform infrared spectra (FTIR). Moreover, the morphology of formulated beads was examined using a scanning electron microscope (SEM). The drug content and release profile were studied using UV spectroscopy. Finally, in vitro cytotoxicity of all compounds was evaluated. The results showed homogenous conjugated CTX-OCT with a diameter of 0.4 mm. DSC showed a delay in the OCT peak that appeared after 200 °C due to small polymer interaction that shifted the OCT peak. Moreover, FTIR showed no prominent interaction. SEM showed clear empty cavities in the plain Ca-alginate-beads, while CTX-OCT-Alg showed occupied beads without cavities. CTX-OCT-Alg had a negligible release in 0.1 N HCl, while the CTX-OCT was completely released after 300 min in phosphate buffer pH 7.4. All formulations showed good antiproliferative activity compared with free drugs. The formulated CTX-OCT-Alg are a promising platform for targeting colorectal cancer through GIT.

Antagonism between the dynein and Ndc80 complexes at kinetochores controls the stability of kinetochore-microtubule attachments during mitosis.

Chromosome alignment and segregation during mitosis require kinetochore-microtubule (kMT) attachments that are mediated by the molecular motor dynein and the kMT-binding complex Ndc80. The Rod-ZW10-Zwilch (RZZ) complex is central to this coordination as it has an important role in dynein recruitment and has recently been reported to have a key function in the regulation of stable kMT attachments in Caenorhabditis elegans besides its role in activating the spindle assembly checkpoint (SAC). However, the mechanism by which these protein complexes control kMT attachments to drive chromosome motility during early mitosis is still unclear. Here, using in vitro total internal reflection fluorescence microscopy, we observed that higher concentrations of Ndc80 inhibited dynein binding to MTs, providing evidence that Ndc80 and dynein antagonize each other's function. High-resolution microscopy and siRNA-mediated functional disruption revealed that severe defects in chromosome alignment induced by depletion of dynein or the dynein adapter Spindly are rescued by codepletion of the RZZ component Rod in human cells. Interestingly, rescue of the chromosome alignment defects was independent of Rod function in SAC activation and was accompanied by a remarkable restoration of stable kMT attachments. Furthermore, the chromosome alignment rescue depended on the plus-end-directed motility of centromere protein E (CENP-E) because cells codepleted of CENP-E, Rod, and dynein could not establish stable kMT attachments or align their chromosomes properly. Our findings support the idea that dynein may control the function of the Ndc80 complex in stabilizing kMT attachments directly by interfering with Ndc80-MT binding or indirectly by controlling the Rod-mediated inhibition of Ndc80.

Aluminum Titania Nanoparticle Composites as Nonprecious Catalysts for Efficient Electrochemical Generation of H2.

In this paper, we demonstrated, for the first time, aluminum titania nanoparticle (Al-TiO2 NP) composites with variable amounts of TiO2 NPs as nonprecious active catalysts for the electrochemical generation of H2. These materials were synthesized by mixing desired amounts of hydrogen titanate nanotubes (TNTs), fabricated here by a cost-effective approach at moderate hydrothermal conditions, with aluminum powder (purity 99.7%; size 35 µm). The mixture was compacted under an applied uniaxial stress of 300 MPa followed by sintering at 500 °C for 1 h. After sintering had been completed, all TNTs were found to convert to TiO2 NPs (average particle size 15 nm). Finally, Al-xTiO2 NP nanocomposites (x = 1, 3, 5, and 10) were obtained and characterized by scanning electron microscopy/energy-dispersive X-ray, X-ray diffraction, and X-ray photoelectron spectroscopy. The hydrogen evolution reaction (HER) activity of these materials was studied in 0.5 M H2SO4 at 298 K using polarization and impedance measurements. The nanocomposite of chemical composition Al-5% TiO2 NPs showed the best catalytic performance for the HER, with an onset potential (EHER), a Tafel slope (ßc), and an exchange current density (j0) of -100 mV (RHE), 59.8 mV decade(-1), and 0.14 mA cm(-2), respectively. This HER activity is not far from that of the commercial platinum/carbon catalyst (EHER = 0.0 mV, ßc = 31 mV dec(-1), and j0 = 0.78 mA cm(-2)). The best catalyst also exhibited good stability after 10000 repetitive cycles with negligible loss in current.

Nucleoporin Nup188 is required for chromosome alignment in mitosis.

Most cancer cells are aneuploid, which could be caused by defects in chromosome segregation machinery. Nucleoporins (Nup) are components of the nuclear pore complex, which is essential for nuclear transport during interphase, but several nucleoporins are also known to be involved in chromosome segregation. Here we report a novel function of Nup188, one of the nucleoporins regulating chromosome segregation. Nup188 localizes to spindle poles during mitosis, through the C-terminal region of Nup188. In Nup188-depleted mitotic cells, chromosomes fail to align to the metaphase plate, which causes mitotic arrest due to the spindle assembly checkpoint. Both the middle and the C-terminal regions were required for chromosome alignment. Robust K-fibers, microtubule bundles attaching to kinetochores, were hardly formed in Nup188-depleted cells. Significantly, we found that Nup188 interacts with NuMA, which plays an instrumental role in focusing microtubules at centrosomes, and NuMA localization to spindle poles is perturbed in Nup188-depleted cells. These data suggest that Nup188 promotes chromosome alignment through K-fiber formation and recruitment of NuMA to spindle poles.