Repurposing Iron- and 2-Oxoglutarate-Dependent Oxygenases to Catalyze Olefin Hydration.

Mononuclear nonheme iron(II) and 2-oxoglutarate (Fe/2OG)-dependent oxygenases and halogenases are known to catalyze a diverse set of oxidative reactions, including hydroxylation, halogenation, epoxidation, and desaturation in primary metabolism and natural product maturation. However, their use in abiotic transformations has mainly been limited to C-H oxidation. Herein, we show that various enzymes of this family, when reconstituted with Fe(II) or Fe(III), can catalyze Mukaiyama hydration-a redox neutral transformation. Distinct from the native reactions of the Fe/2OG enzymes, wherein oxygen atom transfer (OAT) catalyzed by an iron-oxo species is involved, this nonnative transformation proceeds through a hydrogen atom transfer (HAT) pathway in a 2OG-independent manner. Additionally, in contrast to conventional inorganic catalysts, wherein a dinuclear iron species is responsible for HAT, the Fe/2OG enzymes exploit a mononuclear iron center to support this reaction. Collectively, our work demonstrates that Fe/2OG enzymes have utility in catalysis beyond the current scope of catalytic oxidation.

A Polarization-Actuated Plasmonic Circulator.

A circulator for surface plasmon polaritons (SPPs) based on a plasmonic two-wire transmission-line (TWTL) structure is experimentally realized. A TWTL offers two distinct plasmon modes that can be independently excited, solely determined by the polarization of the laser field. Through controlled superposition of the two modes, TWTLs are exploited to enable polarization-actuated plasmonic circulators. In the first demonstration, the coupling antennas to the plasmonic circulator are designed to circulate SPPs sensitive to linearly polarized excitation. In the second design, the circulator reacts to the spin angular momenta carried by circularly polarized laser excitations. In both cases, the SPP circulation directions are directly controlled by the laser polarization, and the number of ports is easily expandable. Experimentally, a wide optical operational bandwidth of ∼100 nm is achieved. The results show a major step toward the realization of multifunctioning photonic nanocircuitry.

BCAS2, a protein enriched in advanced prostate cancer, interacts with NBS1 to enhance DNA double-strand break repair.

BACKGROUND: Breast cancer amplified sequence 2 (BCAS2) plays crucial roles in pre-mRNA splicing and androgen receptor transcription. Previous studies suggested that BCAS2 is involved in double-strand breaks (DSB); therefore, we aimed to characterise its mechanism and role in prostate cancer (PCa). METHODS: Western blotting and immunofluorescence microscopy were used to assay the roles of BCAS2 in the DSBs of PCa cells and apoptosis in Drosophila, respectively. The effect of BCAS2 dosage on non-homologous end joining (NHEJ) and homologous recombination (HR) were assayed by precise end-joining assay and flow cytometry, respectively. Glutathione-S-transferase pulldown and co-immunoprecipitation assays were used to determine whether and how BCAS2 interacts with NBS1. The expression of BCAS2 and other proteins in human PCa was determined by immunohistochemistry. RESULTS: BCAS2 helped repair radiation-induced DSBs efficiently in both human PCa cells and Drosophila. BCAS2 enhanced both NHEJ and HR, possibly by interacting with NBS1, which involved the BCAS2 N-terminus as well as both the NBS1 N- and C-termini. The overexpression of BCAS2 was significantly associated with higher Gleason and pathology grades and shorter survival in patients with PCa. CONCLUSION: BCAS2 promotes two DSB repair pathways by interacting with NBS1, and it may affect PCa progression.

No evidence from a systematic review for the use of probiotics to prevent otitis media.

AIM: This systematic review evaluates the current evidence for the use of probiotics in the prevention of acute otitis media (AOM) in children. METHODS: This study is registered with PROSPERO prior to commencement. PubMed, MEDLINE, EMBASE and Cochrane database were searched using relating keywords. All literature was screened to determine relatability to the topic. Review articles were also screened for additional literature. RESULTS: Thirteen studies were found on probiotics and their role in preventing AOM in children. They ranged in quality from poor to moderate. Half (2/4) of the studies that used nasal probiotic formulations showed a significant difference in reducing otitis media, while only a third (3/9) of the studies using oral formulations suggest benefit in reducing AOM. None of the studies demonstrated significant adverse effects from probiotics. CONCLUSION: The evidence for any effect of probiotics on the prevention of AOM is limited, and the overall low quality of studies makes it difficult to draw definitive conclusions. No serious adverse events were noted, and there is some evidence to suggest possible benefit with nasal probiotic administration.

The 10-Year Prognosis and Prevalence of Brugada-Type Electrocardiograms in Elderly Women: A Longitudinal Nationwide Community-Based Prospective Study.

BACKGROUND: Brugada syndrome is a disorder associated with sudden cardiac death and characterized by an abnormal electrocardiogram (ECG). Previous studies were predominantly conducted in men, and the data on long-term prognosis are limited. Information about women, especially elderly women, is lacking. OBJECTIVE: The aim of this study was to investigate the long-term prognosis of the Brugada ECG pattern in elderly women. METHOD: We investigated the 10-year prognosis of the Brugada ECG pattern in elderly women in a nationwide community-based population in Taiwan. Community-dwelling women older than 55 years were prospectively recruited from December 2008 to March 2013 by a stratified random sampling method. All enrolled individuals were followed up annually until April 2019, and the cause of death was documented by citizen death records. RESULTS: Among 2597 women, 60 (2.31%) had a Brugada-type ECG, and this prevalence was higher than the mean global prevalence of 0.23%. One woman had a type 1 ECG (0.04%), whereas 15 (0.58%) and 44 (1.70%) women had type 2 and type 3 ECG patterns, respectively. Cox survival analysis revealed that all-cause mortality and cardiac mortality were similar in the individuals with and without a Brugada-type ECG during a mean follow-up of 96.1 ± 20.5 months. CONCLUSIONS: Our findings suggest that Brugada ECG patterns are not infrequent in elderly women but are not associated with increased risk of mortality in long-term follow-up; these findings may help reduce unnecessary anxiety for physicians, nurses, allied health caregivers, and patients.

Modal Symmetry Controlled Second-Harmonic Generation by Propagating Plasmons.

A new concept for second-harmonic generation (SHG) in an optical nanocircuit is proposed. We demonstrate both theoretically and experimentally that the symmetry of an optical mode alone is sufficient to allow SHG even in centro-symmetric structures made of centro-symmetric material. The concept is realized using a plasmonic two-wire transmission-line (TWTL), which simultaneously supports a symmetric and an antisymmetric mode. We first confirm that emission of second-harmonic light into the symmetric mode of the waveguide is symmetry-allowed when the fundamental excited waveguide modes are either purely symmetric or antisymmetric. We further switch the emission into the antisymmetric mode when a controlled mixture of the fundamental modes is excited simultaneously. Our results open up a new degree of freedom into the designs of nonlinear optical components and should pave a new avenue toward multifunctional nanophotonic circuitry.

Pathway from N-Alkylglycine to Alkylisonitrile Catalyzed by Iron(II) and 2-Oxoglutarate-Dependent Oxygenases.

N-alkylisonitrile, a precursor to isonitrile-containing lipopeptides, is biosynthesized by decarboxylation-assisted -N≡C group (isonitrile) formation by using N-alkylglycine as the substrate. This reaction is catalyzed by iron(II) and 2-oxoglutarate (Fe/2OG) dependent enzymes. Distinct from typical oxygenation or halogenation reactions catalyzed by this class of enzymes, installation of the isonitrile group represents a novel reaction type for Fe/2OG enzymes that involves a four-electron oxidative process. Reported here is a plausible mechanism of three Fe/2OG enzymes, Sav607, ScoE and SfaA, which catalyze isonitrile formation. The X-ray structures of iron-loaded ScoE in complex with its substrate and the intermediate, along with biochemical and biophysical data reveal that -N≡C bond formation involves two cycles of Fe/2OG enzyme catalysis. The reaction starts with an FeIV -oxo-catalyzed hydroxylation. It is likely followed by decarboxylation-assisted desaturation to complete isonitrile installation.

An Ion-Exchangeable MOF with Reversible Dehydration and Dynamic Structural Behavior (NH4 )2 [Zn2 (O3 PCH2 CH2 COO)2 ]⋠5 H2 O (BIRM-1).

(NH4 )2 [Zn2 (O3 PCH2 CH2 COO)2 ]⋅5 H2 O (BIRM-1) is a new metal phosphonate material, synthesized through a simple hydrothermal reaction between zinc nitrate and 3-phosphonopropionic acid, using urea and tetraethylammonium bromide as the reaction medium. In common with other metal-organic framework materials, BIRM-1 has a large three-dimensional porous structure providing potential access to a high internal surface area. Unlike most others, it has the advantage of containing ammonium cations within the pores and has the ability to undergo cation exchange. Additionally, BIRM-1 also exhibits a reversible dehydration behavior involving an amorphization-recrystallization cycle. The ability to undergo ion exchange and dynamic structural behavior are of interest in their own right, but also increase the range of potential applications for this material. Here the crystal structure of this new metal phosphonate and its ion exchange behavior with K+ as an exemplar are studied in detail, and its unusual structure-reviving property reported.

Photoluminescence-Driven Broadband Transmitting Directional Optical Nanoantennas.

Optical nanoantennas mediate near and far optical fields. Operating a directional nanoantenna in transmitting mode is challenging because the antenna needs to be driven by a nanosized optical frequency generator, which must work at the antenna's resonance frequency and be precisely attached to the antenna's feed with correct polarization. Quantum emitters have been used as optical nanogenerators, but their precise positioning relative to the nanoantenna is technically challenging, setting up a barrier to the practical implementation. One unique source to drive nanoantenna is the photoluminescence from the material of the nanoantenna because the high operational frequency of the antenna reaches the regime for the electronic transitions in matter. Here, we exploit plasmon-modulated photoluminescence (PMPL) as an effective optical source to drive directional nanoantennas. We experimentally realize two technically challenging theoretical proposals, namely, an optical nanospectrometer based on Yagi-Uda nanoantennas and tunable broadband directional emission from log-periodic nanoantennas. Using photoluminescence from the nanoantenna as an optical source promotes practical implementation of transmitting optical nanoantennas.

Chemical Constituents of the Leaves of Peltophorum pterocarpum and Their Bioactivity.

Two new sesquiterpenoids peltopterins A and B (compounds 1 and 2) and fifty-two known compounds were isolated from the methanol extract of P. pterocarpum and their chemical structures were established through spectroscopic and mass spectrometric analyses. The isolates 40, 43, 44, 47, 48, 51 and 52 exhibited potential inhibitory effects of superoxide anion generation or elastase release.

[Diabetic Foot Neuropathy and Related Factors in Patients With Type 2 Diabetes Mellitus].

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) face a higher risk of diabetic foot neuropathy, which increases the risk of death. The early detection of factors that influence diabetic neuropathy reduces the risk of foot lesions, including foot ulcerations, lower extremity amputation, and mortality. PURPOSE: To explore the demographic, disease-characteristic, health-literacy, and foot-self-care-behavior factors that affect diabetic foot neuropathy in patients with T2DM. METHODS: A case-control study design was employed in which cases (Michigan Neuropathy Screening Instrument, MNSI) ≥ 2 were matched to controls based on age and gender in a medical center. A total of 114 patients diagnosed with T2DM in a medical center were recruited as participants. Data were collected using a structured questionnaire. The collected data were analyzed using Fisher's exact test, Mann-Whitney U test, and logistic regression. RESULTS: The results of multiple logistic regression showed that glycated hemoglobin (B = 1.696, p = .041) and communication and critical health literacy (B = -0.082, p = .034) were significant factors of diabetic foot neuropathy. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The findings of this study suggest that nurses should assess the health literacy of patients with T2DM before providing health education and should develop a specific foot-care intervention for individuals with poor glycemic control.

Optimization of nano-honeycomb structures for flexible w-LEDs.

This study presents the low cost fabrication of flexible white-light-emitting diodes (w-LEDs) with nano-honeycomb-structured phosphor films. Extending the dimensions of the nano-honeycomb structures improved the color uniformity of the flexible samples, and the 950-nm pattern sample demonstrated optimal color uniformity because this nano-pattern exhibited an excellent diffusion ability owing to its pitch size. In addition to color uniformity, the use of this nano-pattern improved the luminous efficiency. The 750-nm pattern exhibited the highest luminous efficiency (235.8 lm/W), which was approximately 7% higher than that exhibited by a non-patterned phosphor film sample. Thus, flexible w-LEDs with nano-honeycomb structure optimization have great potential to be used as next-generation lighting sources.

Cyclophosphamide promotes breast cancer cell migration through CXCR4 and matrix metalloproteinases.

Cyclophosphamide is indicated for the treatment of cancerous diseases such as breast cancer and cervical cancer. Recent studies have shown that cyclophosphamide may induce cancer metastasis, but the cause of this unexpected adverse effect is not fully understood. In this study, we investigate the effect of cyclophosphamide on cancer cell migration and its correlation to chemokine (C-X-C motif) receptor 4 (CXCR4), a biomarker for cancer metastasis. Two human cancer cell lines with significant difference in endogenous CXCR4 expression, the breast cancer cell line, MDA-MB-231, and the melanoma cell line, MDA-MB-435S, were treated with various concentrations of cyclophosphamide, followed by the assessment of CXCR4 expression and cell migration. We found that the migration ability of MDA-MB-231 cells was enhanced with increasing concentrations of cyclophosphamide, which induced the cell-surface expression of CXCR4, but had no effect on the overall amount of CXCR4. In MDA-MB-435S cells, in which CXCR4 was barely detectable, cyclophosphamide was unable to activate cell-surface CXCR4, and did not promote cell migration. Studies on the mRNA expression profile of matrix metalloproteinases (MMPs) in MDA-MB-231 cells further indicate that MMP9 and MMP13 may be involved in the action of cyclophosphamide. The protein expression of both MMP9 and MMP13 was increased in the presence of cyclophosphamide. Results from this study provide the molecular basis for the possible pathway of cyclophosphamide to induce cancer metastasis.

A Potential Wasteform for Cs Immobilization: Synthesis, Structure Determination, and Aqueous Durability of Cs2TiNb6O18.

Cs2TiNb6O18 is a potential ceramic wasteform for the long-term immobilization of radioactive cesium. Cs2TiNb6O18 was synthesized using the aqueous precursor method and a solid-state reaction, and its crystal structure was determined from the Rietveld refinement of synchrotron X-ray and neutron powder diffraction data. The structure is a pyrochlore analogue, space group P3̅m1 with Cs in 9-fold coordination. The calculated bond valence sum from analysis of neutron diffraction data of 0.84 and high coordination number suggest that Cs has a strong bonding environment. The chemical aqueous durability was investigated using the MCC-1 and PCT-B standard test methods. The measured Cs leach rates of 3.8 × 10-3 and 2.1 × 10-3 g m-2 day-1 obtained via the MCC-1 and PCT-B methods, respectively, demonstrate good promise of a safe long-term immobilization material comparable to, if not better than, hollandite-the material in the multiphase titanate ceramics (Synroc) targeted for cesium sequestration.

Utility of Ochrobactrum anthropi YC152 in a Microbial Fuel Cell as an Early Warning Device for Hexavalent Chromium Determination.

Fast hexavalent chromium (Cr(VI)) determination is important for environmental risk and health-related considerations. We used a microbial fuel cell-based biosensor inoculated with a facultatively anaerobic, Cr(VI)-reducing, and exoelectrogenic Ochrobactrum anthropi YC152 to determine the Cr(VI) concentration in water. The results indicated that O. anthropi YC152 exhibited high adaptability to pH, temperature, salinity, and water quality under anaerobic conditions. The stable performance of the microbial fuel cell (MFC)-based biosensor indicated its potential as a reliable biosensor system. The MFC voltage decreased as the Cr(VI) concentration in the MFC increased. Two satisfactory linear relationships were observed between the Cr(VI) concentration and voltage output for various Cr(VI) concentration ranges (0.0125-0.3 mg/L and 0.3-5 mg/L). The MFC biosensor is a simple device that can accurately measure Cr(VI) concentrations in drinking water, groundwater, and electroplating wastewater in 45 min with low deviations (<10%). The use of the biosensor can help in preventing the violation of effluent regulations and the maximum allowable concentration of Cr(VI) in water. Thus, the developed MFC biosensor has potential as an early warning detection device for Cr(VI) determination even if O. anthropi YC152 is a possible opportunistic pathogen.

Facet-Dependent and Light-Assisted Efficient Hydrogen Evolution from Ammonia Borane Using Gold-Palladium Core-Shell Nanocatalysts.

Au-Pd core-shell nanocrystals with tetrahexahedral (THH), cubic, and octahedral shapes and comparable sizes were synthesized. Similar-sized Au and Pd cubes and octahedra were also prepared. These nanocrystals were used for the hydrogen-evolution reaction (HER) from ammonia borane. Light irradiation can enhance the reaction rate for all the catalysts. In particular, Au-Pd THH exposing {730} facets showed the highest turnover frequency for hydrogen evolution under light with 3-fold rate enhancement benefiting from lattice strain, modified surface electronic state, and a broader range of light absorption. Finite-difference time-domain (FDTD) simulations show a stronger electric field enhancement on Au-Pd core-shell THH than those on other Pd-containing nanocrystals. Light-assisted nitro reduction by ammonia borane on Au-Pd THH was also demonstrated. Au-Pd tetrahexahedra supported on activated carbon can act as a superior recyclable plasmonic photocatalyst for hydrogen evolution.

A comparison of bioelectricity in microbial fuel cells with aerobic and anaerobic anodes.

Microbial fuel cells (MFCs) can, besides running on wastewater, also derive energy directly from certain aquatic plants. However, few studies have focussed on electricity generation using aerobic anodes. This study presents a comparison of the MFC performances of an anaerobic-anode MFC (ana-MFC) and an aerobic-anode MFC (aa-MFC), and shows their individual conditions for optimal operation. Results show that the maximum power density of 7.07 +/- 0.45 mW/m2 for the ana-MFC occurred at 500 omega, whereas the aa-MFC had a maximum power density of 2.34 +/- 0.16 mW/m2 at 2200 omega. The ana-MFC generally achieved high electricity generation, and the aa-MFC achieved relatively high electricity generation when fed with a diluted substrate. In the ana-MFC, the optimal substrate for electricity generation was glucose (fermentable substrate); however, glucose and acetic acid (non-fermentable substrate) were both suitable substrates for the aa-MFC. The optimal gas retention times of the ana-MFC and the aa-MFC were 9 and 120 s, respectively. This retention time is an important limiting factor of electricity generation for the ana-MFC. The aa-MFCs fed with different substrates exhibited non-significant differences between bacterial communities. We observed the relative diversities of bacterial communities in the ana-MFC fed with various substrates. The results of denaturing gradient gel electrophoresis analysis suggest that Ochrobactrum intermedium, Delftia acidovorans, and Citrobacterfreundii may be potential electrogenic bacteria. To our knowledge, this is the first study comparing the MFC performances of anaerobic and aerobic anodes.

Variation in biosynthesis and metal-binding properties of isonitrile-containing peptides produced by Mycobacteria versus Streptomyces.

A number of bacteria are known to produce isonitrile-containing peptides (INPs) that facilitate metal transport and are important for cell survival; however, considerable structural variation is observed among INPs depending on the producing organism. While non-heme iron 2-oxoglutarate dependent isonitrilases catalyze isonitrile formation, how the natural variation in INP structure is controlled and its implications for INP bioactivity remain open questions. Herein, total chemical synthesis is utilized with X-Ray crystallographic analysis of mycobacterial isonitrilases to provide a structural model of substrate specificity that explains the longer alkyl chains observed in mycobacterial versus Streptomyces INPs. Moreover, proton NMR titration experiments demonstrate that INPs regardless of alkyl chain length are specific for binding copper instead of zinc. These results suggest that isonitrilases may act as gatekeepers in modulating the observed biological distribution of INP structures and this distribution may be primarily related to differing metal transport requirements among the producing strains.

Mature neurons from iPSCs unveil neurodegeneration-related pathways in mucopolysaccharidosis type II: GSK-3ß inhibition for therapeutic potential.

Mucopolysaccharidosis (MPS) type II is caused by a deficiency of iduronate-2-sulfatase and is characterized by the accumulation of glycosaminoglycans (GAGs). Without effective therapy, the severe form of MPS II causes progressive neurodegeneration and death. This study generated multiple clones of induced pluripotent stem cells (iPSCs) and their isogenic controls (ISO) from four patients with MPS II neurodegeneration. MPS II-iPSCs were successfully differentiated into cortical neurons with characteristic biochemical and cellular phenotypes, including axonal beadings positive for phosphorylated tau, and unique electrophysiological abnormalities, which were mostly rescued in ISO-iPSC-derived neurons. RNA sequencing analysis uncovered dysregulation in three major signaling pathways, including Wnt/ß-catenin, p38 MAP kinase, and calcium pathways, in mature MPS II neurons. Further mechanistic characterization indicated that the dysregulation in calcium signaling led to an elevated intracellular calcium level, which might be linked to compromised survival of neurons. Based on these dysregulated pathways, several related chemicals and drugs were tested using this mature MPS II neuron-based platform and a small-molecule glycogen synthase kinase-3ß inhibitor was found to significantly rescue neuronal survival, neurite morphology, and electrophysiological abnormalities in MPS II neurons. Our results underscore that the MPS II-iPSC-based platform significantly contributes to unraveling the mechanisms underlying the degeneration and death of MPS II neurons and assessing potential drug candidates. Furthermore, the study revealed that targeting the specific dysregulation of signaling pathways downstream of GAG accumulation in MPS II neurons with a well-characterized drug could potentially ameliorate neuronal degeneration.