MALT1 accelerates proatherogenic vascular smooth muscle cell growth, invasion and synthetic phenotype switching via nuclear factor­κB signaling­dependent way.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) modulates T helper cell differentiation and nuclear factor-κB (NF-κB) pathway-mediated inflammation and potentially regulates lipid metabolism, which are all critical factors involved in atherosclerosis. The present study aimed to investigate the effect of MALT1 on the cellular functions of proatherogenic vascular smooth muscle cells (VSMCs). Therefore, to establish a human proatherogenic VSMC model, VSMCs were treated with different doses of oxidized low-density lipoprotein (oxLDL). Subsequently, the effect of MALT1 overexpression or knockdown in proatherogenic VSMCs treated with or without NF-κB activator was also explored. The results showed that treatment of proatherogenic VSMCs with oxLDL significantly elevated the mRNA and protein expression levels of MALT1 in a dose-dependent manner. Furthermore, MALT1 overexpression enhanced cell viability, invasion and phenotype switching and reduced apoptosis in proatherogenic VSMCs. However, MALT1 knockdown exerted the opposite effect on the above cellular functions. Additionally, the results revealed that MALT1 could positively regulate the NF-κB pathway in proatherogenic VSMCs. Moreover, treatment of proatherogenic VSMCs with NF-κB activator not only exacerbated the dysregulation of cellular functions, but also hampered the effect of MALT1 knockdown on attenuating cell growth, invasion and synthetic phenotype switching, thus suggesting that NF-κB was essential for the regulation of MALT1-triggered functions in proatherogenic VSMCs. In conclusion, the current study suggested that MALT1 could exacerbate cell viability, mobility and synthetic phenotype switching of proatherogenic VSMCs in a NF-κB signaling-dependent manner. Therefore, MALT1 could be considered as a potential therapeutic target for atherosclerosis.

Potential antibacterial ethanol-bridged purine azole hybrids as dual-targeting inhibitors of MRSA.

A new class of antibacterial ethanol-bridged purine azole hybrids as potential dual-targeting inhibitors was developed. Bioactivity evaluation showed that some of the target compounds had prominent antibacterial activity against the tested bacteria, notably, metronidazole hybrid 3a displayed significant inhibitory activity against MRSA (MIC = 6 µM), and had no obvious toxicity on normal mammalian cells (RAW 264.7). In addition, compound 3a also did not induce drug resistance of MRSA obviously, even after fifteen passages. Molecular modeling studies showed that the highly active molecule 3a could insert into the base pairs of topoisomerase IA-DNA as well as topoisomerase IV-DNA through hydrogen bonding. Furthermore, a preliminary study on the antibacterial mechanism revealed that the active molecule 3a could rupture the bacterial membrane of MRSA and insert into MRSA DNA to block its replication, thus possibly exhibiting strong antibacterial activity. These results strongly indicated that the highly active hybrid 3a could be used as a potential dual-targeting inhibitor of MRSA for further development of valuable antimicrobials.

One-Pot Synthesis of 2,4-Diacyl Thiophenes from α-Oxo Ketene Dithioacetals and Propargylic Alcohols.

Although thiophenes having various functionalities are the basic structural units in numerous bioactive compounds and optoelectronic materials, synthetic routes to acylated thiophenes from aliphatic sulfur-containing starting materials are still rare. In particular, there have been no reports concerning the straightforward synthesis of 2,4-diacylthiophenes from alkynes. Herein, we describe a highly efficient and metal-free three-step one-pot synthetic approach to tetrasubstituted 2,4-diacylthiophenes from propargylic alcohols and α-oxo ketene dithioacetals. This research features a relay catalysis system that integrates Brønsted acid-catalyzed propargylation, molecular iodine-mediated electrophilic cyclization, and visible light-induced deiodinative oxygenation. The 2,4-diacylthiophenes serving as the key starting materials are readily synthesized, enabling facile construction of analogues of related biologically active compounds and the modular assembly of tetrasubstituted thienothiophenes.

Knockdown of long noncoding RNA DLEU1 suppresses the progression of renal cell carcinoma by downregulating the Akt pathway.

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are involved in the tumorigenesis and progression of various types of cancer. The lncRNA deleted in lymphocytic leukemia 1 (DLEU1) has been reported to be dysregulated in cancer cells and thus associated with tumor development; however, the role of DLEU1 in renal cell carcinoma (RCC) remains unclear. In the present study, DLEU1 was knocked down using small interfering RNA in the RCC cell lines KETR3 and 786­O to determine the role of DLEU1. Cell Counting Kit­8, colony formation, Transwell and flow cytometry assays were performed to assess the effects of DLEU1 on cell proliferation, migration, invasion and apoptosis in KETR3 and 786­O cells. The protein expression levels of factors associated with apoptosis and epithelial­mesenchymal transition (EMT) were examined by western blot. The results demonstrated that silencing DLEU1 decreased the growth capacity, migration and invasion of KETR3 and 786­O cells. Additionally, loss of DLEU1 was observed to stimulate the mitochondrial pathway of cell apoptosis via regulation of the expression of Bcl­2/Bax, cleaved caspase­3 and cleaved caspase­9 in KETR3 and 786­O cells. Furthermore, DLEU1 knockdown significantly inhibited the protein kinase B (Akt) pathway by downregulating the expression of phosphorylated­Akt, cyclin  D1 and P70S6 kinase. In addition, depletion of DLEU1 was observed to impair the process of EMT in RCC cells via the upregulation of E­cadherin, and downregulation of N­cadherin and vimentin. Collectively, these results indicated a pro­oncogenic role of DLEU1 in the progression and development of RCC via modulation of the Akt pathway and EMT phenotype.

Direct-Indirect Transition of Pressurized Two-Dimensional Halide Perovskite: Role of Benzene Ring Stack Ordering.

Two-dimensional (2D) hybrid organic-inorganic metal halide perovskites (HOIPs) with considerably hydrophobic phenyl ethylammonium (PEA) organic cations have been used in highly efficient solar cells and LEDs, which are stable and enjoy a long lifetime, even when exposed to moisture. Different from other 2D HOIPs with alkyl amine cations, a benzene ring is present in the PEA cation. Until recently, an understanding of the effects of PEA on the structural, electronic, and optical properties of 2D HOIPs under pressure has remained limited. We find that there is a direct-indirect band gap transition at around 5.8 GPa and that the direct band gap recovers when the pressure is released. The stacking order of the benzene rings in the PEA cation plays a critical role in the mechanical and electronic properties. Our present work demonstrates that 2D HOIPs with organic cations containing benzene rings prove highly attractive for use in flexible optoelectronics.

Hypoxia induced microRNA-301b-3p overexpression promotes proliferation, migration and invasion of prostate cancer cells by targeting LRP1B.

Prostate cancer is a high burden on society worldwide due to its high morbidity and mortality. Growing evidence has implicated microRNAs (miRNAs or miRs) in the occurrence and progression of prostate cancer. The present study was conducted with main emphasis put on the possible effect of hypoxia-induced miR-301b-3p on prostate cancer by targeting low-density lipoprotein receptor-related protein 1B (LRP1B). Firstly, the differentially expressed genes were identified by conducting microarray-based gene expression profiling of prostate cancer. Next, the expression of miR-301b-3p in prostate cancer cells was examined in cells treated with 1% oxygen or dimethyloxalylglycine (DMOG), and the cell line with the highest miR-301b-3p expression was selected for subsequent experiments. Subsequently, the target relationship between miR-301b-3p and LRP1B was identified. The effect of miR-301b-3p and LRP1B on cell proliferation, migration and invasion as well as tumorigenicity of transfected cells was examined using the gain- and loss-of-function approaches. Hypoxia induced miR-301b-3p was highly expressed while LRP1B was poorly expressed in prostate cancer. Moreover, miR-301b-3p could down-regulate LRP1B by interacting with LRP1B, which acted to promote the proliferation, migration and invasion abilities of prostate cancer cells in addition to tumor growth in vivo. In addition, up-regulation of LRP1B can reverse the promoting effect of miR-301b-3p on the aforementioned factors. Collectively, up-regulation of miR-301b-3p induced by hypoxia could potentially accelerate proliferation, migration and invasion of prostate cancer cells via the inhibitory effect on LRP1B expression, highlighting that miR-301b-3p may be instrumental for the therapeutic targeting of prostate cancer.

Access to Multisubstituted Furan-3-carbothioates via Cascade Annulation of α-Oxo Ketene Dithioacetals with Isoindoline-1,3-dione-Derived Propargyl Alcohols.

A Brønsted acid-promoted, unprecedented formal (3 + 2) annulation strategy for the synthesis of multisubstituted furan-3-carbothioates is reported. This transformation represents the first regioselective annulation of α-oxo ketene dithio-acetals as 1,3-bis-nucleophiles in a cascade manner. The choice of isoindoline-1,3-dione-derived propargyl alcohols is crucial to the uncommon annulation mode between an alkyne-type bis-electrophile and a 1,3-bis-nucleophile under metal-free conditions. The scale-up of the synthesis and several interesting transformations of an as-synthesized product were further investigated. A Nazarov-like cyclization is proposed for the ring-closure process according to the experimental observations.

Correlated High-Pressure Phase Sequence of VO2 under Strong Compression.

Understanding how the structures of a crystal behave under compression is a fundamental issue both for condensed matter physics and for geoscience. Traditional description of a crystal as the stacking of a unit cell with special symmetry has gained much success on the analysis of physical properties. Unfortunately, it is hard to reveal the relationship between the compressed phases. Taking the family of metal dioxides (MO2) as an example, the structural evolution, subject to fixed chemical formula and highly confined space, often appears as a set of random and uncorrelated events. Here we provide an alternative way to treat the crystal as the stacking of the coordination polyhedron and then discover a unified structure transition pattern, in our case VO2. X-ray diffraction (XRD) experiments and first-principles calculations show that the coordination increase happens only at one apex of the V-centered octahedron in an orderly fashion, leaving the base plane and the other apex topologically intact. The polyhedron evolves toward increasing their sharing, indicating a general rule for the chemical bonds of MO2 to give away the ionicity in exchange for covalency under pressure.

Metal-free phosphonation of heteroarene N-oxides with trialkyl phosphite at room temperature.

A new protocol is described for the conversion of heteroarene N-oxides to heteroarylphosphonates through in situ activation with bromotrichloromethane. The N-oxides of isoquinoline, quinoline, quinoxaline and 1,10-phenanthroline were fast transformed into the corresponding heteroarylphosphonates in up to 92% yield under mild conditions in the absence of solvent and metal catalysts. The good functional group tolerance, low cost, feasibility of scale up, and wide availability of reagents make this method a prominent complement to the Hirao coupling.

Giant Pressure-Driven Lattice Collapse Coupled with Intermetallic Bonding and Spin-State Transition in Manganese Chalcogenides.

Materials with an abrupt volume collapse of more than 20 % during a pressure-induced phase transition are rarely reported. In such an intriguing phenomenon, the lattice may be coupled with dramatic changes of orbital and/or the spin-state of the transition metal. A combined in situ crystallography and electron spin-state study to probe the mechanism of the pressure-driven lattice collapse in MnS and MnSe is presented. Both materials exhibit a rocksalt-to-MnP phase transition under compression with ca. 22 % unit-cell volume changes, which was found to be coupled with the Mn(2+) (d(5) ) spin-state transition from S=5/2 to S=1/2 and the formation of Mn-Mn intermetallic bonds as supported by the metallic transport behavior of their high-pressure phases. Our results reveal the mutual relationship between pressure-driven lattice collapse and the orbital/spin-state of Mn(2+) in manganese chalcogenides and also provide deeper insights toward the exploration of new metastable phases with exceptional functionalities.

Unusual Mott transition in multiferroic PbCrO3.

The Mott insulator in correlated electron systems arises from classical Coulomb repulsion between carriers to provide a powerful force for electron localization. Turning such an insulator into a metal, the so-called Mott transition, is commonly achieved by "bandwidth" control or "band filling." However, both mechanisms deviate from the original concept of Mott, which attributes such a transition to the screening of Coulomb potential and associated lattice contraction. Here, we report a pressure-induced isostructural Mott transition in cubic perovskite PbCrO3. At the transition pressure of ∼3 GPa, PbCrO3 exhibits significant collapse in both lattice volume and Coulomb potential. Concurrent with the collapse, it transforms from a hybrid multiferroic insulator to a metal. For the first time to our knowledge, these findings validate the scenario conceived by Mott. Close to the Mott criticality at ∼300 K, fluctuations of the lattice and charge give rise to elastic anomalies and Laudau critical behaviors resembling the classic liquid-gas transition. The anomalously large lattice volume and Coulomb potential in the low-pressure insulating phase are largely associated with the ferroelectric distortion, which is substantially suppressed at high pressures, leading to the first-order phase transition without symmetry breaking.

Developments in time-resolved high pressure x-ray diffraction using rapid compression and decompression.

Complementary advances in high pressure research apparatus and techniques make it possible to carry out time-resolved high pressure research using what would customarily be considered static high pressure apparatus. This work specifically explores time-resolved high pressure x-ray diffraction with rapid compression and/or decompression of a sample in a diamond anvil cell. Key aspects of the synchrotron beamline and ancillary equipment are presented, including source considerations, rapid (de)compression apparatus, high frequency imaging detectors, and software suitable for processing large volumes of data. A number of examples are presented, including fast equation of state measurements, compression rate dependent synthesis of metastable states in silicon and germanium, and ultrahigh compression rates using a piezoelectric driven diamond anvil cell.

Nanoarchitectured materials composed of fullerene-like spheroids and disordered graphene layers with tunable mechanical properties.

Type-II glass-like carbon is a widely used material with a unique combination of properties including low density, high strength, extreme impermeability to gas and liquid and resistance to chemical corrosion. It can be considered as a carbon-based nanoarchitectured material, consisting of a disordered multilayer graphene matrix encasing numerous randomly distributed nanosized fullerene-like spheroids. Here we show that under both hydrostatic compression and triaxial deformation, this high-strength material is highly compressible and exhibits a superelastic ability to recover from large strains. Under hydrostatic compression, bulk, shear and Young's moduli decrease anomalously with pressure, reaching minima around 1-2 GPa, where Poisson's ratio approaches zero, and then revert to normal behaviour with positive pressure dependences. Controlling the concentration, size and shape of fullerene-like spheroids with tailored topological connectivity to graphene layers is expected to yield exceptional and tunable mechanical properties, similar to mechanical metamaterials, with potentially wide applications.

Carbon coated face-centered cubic Ru-C nanoalloys.

Carbon-encapsulated ruthenium-carbon (Ru-C) nanoalloys were synthesized by dynamic shocks. The Ru-C alloy shows a new fcc structure different from the original hcp structure of metal Ru. This fcc phase is assigned to a Ru32C4 solid solution with a lattice parameter of 3.868(2) Å and a bulk modulus KT0 of 272(12) GPa. The small amount of carbon in the solid solution enhances the thermodynamic and chemical stabilities with respect to pure Ru, as well as induces changes in the electronic properties, which have direct applications in improving the material's catalytic activity and selectivity.

Novel high-pressure monoclinic metallic phase of V2O3.

Vanadium sesquioxide, V2O3, is a prototypical metal-to-insulator system where, in temperature-dependent studies, the transition always coincides with a corundum-to-monoclinic structural transition. As a function of pressure, V2O3 follows the expected behavior of increased metallicity due to a larger bandwidth for pressures up to 12.5 GPa. Surprisingly, for higher pressures when the structure becomes unstable, the resistance starts to increase. Around 32.5 GPa at 300 K, we observe a novel pressure-induced corundum-to-monoclinic transition between two metallic phases, showing that the structural phase transition can be decoupled from the metal-insulator transition. Using x-ray Raman scattering, we find that screening effects, which are strong in the corundum phase, become weakened at high pressures. Theoretical calculations indicate that this can be related to a decrease in coherent quasiparticle strength, suggesting that the high-pressure phase is likely a critical correlated metal, on the verge of Mott-insulating behavior.

Enhanced electron transport in Nb-doped TiO2 nanoparticles via pressure-induced phase transitions.

Anatase TiO2 is one of the most important energy materials but suffers from poor electrical conductivity. Nb doping has been considered as an effective way to improve its performance in the applications of photocatalysis, solar cells, Li batteries, and transparent conducting oxide films. Here, we report the further enhancement of electron transport in Nb-doped TiO2 nanoparticles via pressure-induced phase transitions. The phase transition behavior and influence of Nb doping in anatase Nb-TiO2 have been systematically investigated by in situ synchrotron X-ray diffraction and Raman spectroscopy. The bulk moduli are determined to be 179.5, 163.3, 148.3, and 139.0 GPa for 0, 2.5, 5.0, and 10.0 mol % Nb-doped TiO2, respectively. The Nb-concentration-dependent stiffness variation has been demonstrated: samples with higher Nb concentrations have lower stiffness. In situ resistance measurements reveal an increase of 40% in conductivity of quenched Nb-TiO2 in comparison to the pristine anatase phase. The pressure-induced conductivity evolution is discussed in detail in terms of the packing factor model, which provides direct evidence for the rationality of the correlation of packing factors with electron transport in semiconductors. Pressure-treated Nb-doped TiO2 with unique properties surpassing those in the anatase phase holds great promise for energy-related applications.

Pressure-induced amorphization in single-crystal Ta2O5 nanowires: a kinetic mechanism and improved electrical conductivity.

Pressure-induced amorphization (PIA) in single-crystal Ta2O5 nanowires is observed at 19 GPa, and the obtained amorphous Ta2O5 nanowires show significant improvement in electrical conductivity. The phase transition process is unveiled by monitoring structural evolution with in situ synchrotron X-ray diffraction, pair distribution function, Raman spectroscopy, and transmission electron microscopy. The first principles calculations reveal the phonon modes softening during compression at particular bonds, and the analysis on the electron localization function also shows bond strength weakening at the same positions. On the basis of the experimental and theoretical results, a kinetic PIA mechanism is proposed and demonstrated systematically that amorphization is initiated by the disruption of connectivity between polyhedra (TaO6 octahedra or TaO7 bipyramids) at the particular weak-bonding positions along the a axis in the unit cell. The one-dimensional morphology is well-preserved for the pressure-induced amorphous Ta2O5, and the electrical conductivity is improved by an order of magnitude compared to traditional amorphous forms. Such pressure-induced amorphous nanomaterials with unique properties surpassing those in either crystalline or conventional amorphous phases hold great promise for numerous applications in the future.

Measurement of the energy dependence of X-ray-induced decomposition of potassium chlorate.

We report the first measurements of the X-ray induced decomposition of KClO3 as a function of energy in two experiments. KClO3 was pressurized to 3.5 GPa and irradiated with monochromatic synchrotron X-rays ranging in energy from 15 to 35 keV in 5 keV increments. A systematic increase in the decomposition rate as the energy was decreased was observed, which agrees with the 1/E(3) trend for the photoelectric process, except at the lowest energy studied. A second experiment was performed to access lower energies (10 and 12 keV) using a beryllium gasket; suggesting an apparent resonance near 15 keV or 0.83 Ǻ maximizing the chemical decomposition rate. A third experiment was performed using KIO3 to ascertain the anionic dependence of the decomposition rate, which was observed to be far slower than in KClO3, suggesting that the O-O distance is the critical factor in chemical reactions. These results will be important for more efficiently initiating chemical decomposition in materials using selected X-ray wavelengths that maximize decomposition to aid useful hard X-ray-induced chemistry and contribute understanding of the mechanism of X-ray-induced decomposition of the chlorates.

Charge transfer in spinel Co3O4 at high pressures.

Charge transfer in cobalt oxide Co(3)O(4) in the spinel structure is evidenced by experimental results using x-ray diffraction (XRD), x-ray absorption near edge structure (XANES) spectroscopy, and Raman scattering at high pressures up to 42.1, 24.6 and 35.1 GPa, respectively. While the cubic structure was found to persist under pressure up to 42.1 GPa based on the XRD and Raman results, the mode Grüneisen parameter was calculated according to our Raman measurements. Our structural data refinement revealed a structural transition from the normal spinel structure at low pressures to a partially inverse spinel structure at pressures above 17.7 GPa. This transition may be caused by the interaction of charges between tetrahedral and octahedral sites via a charge transfer process. Evidence for the charge transfer process is further supported by changes of the pre-edge features in the XANES data.

Note: Experiments in hard x-ray chemistry: in situ production of molecular hydrogen and x-ray induced combustion.

We have successfully loaded H(2) into a diamond anvil cell at high pressure using the synchrotron x-ray induced decomposition of NH(3)BH(3). In a second set of studies, radiation-assisted release of O(2) from KCLO(3), H(2) release from NH(3)BH(3), and reaction of these gases in a mixture of the reactants to form liquid water using x-rays at ambient conditions was observed. Similar observations were made using a KCLO(3) and NaBH(4) mixture. Depending on reaction conditions, an explosive or far slower reaction producing water was observed.