Insights into the structure-function relationship of the NorQ/NorD chaperones from Paracoccus denitrificans reveal shared principles of interacting MoxR AAA+/VWA domain proteins.

BACKGROUND: NorQ, a member of the MoxR-class of AAA+ ATPases, and NorD, a protein containing a Von Willebrand Factor Type A (VWA) domain, are essential for non-heme iron (FeB) cofactor insertion into cytochrome c-dependent nitric oxide reductase (cNOR). cNOR catalyzes NO reduction, a key step of bacterial denitrification. This work aimed at elucidating the specific mechanism of NorQD-catalyzed FeB insertion, and the general mechanism of the MoxR/VWA interacting protein families. RESULTS: We show that NorQ-catalyzed ATP hydrolysis, an intact VWA domain in NorD, and specific surface carboxylates on cNOR are all features required for cNOR activation. Supported by BN-PAGE, low-resolution cryo-EM structures of NorQ and the NorQD complex show that NorQ forms a circular hexamer with a monomer of NorD binding both to the side and to the central pore of the NorQ ring. Guided by AlphaFold predictions, we assign the density that "plugs" the NorQ ring pore to the VWA domain of NorD with a protruding "finger" inserting through the pore and suggest this binding mode to be general for MoxR/VWA couples. CONCLUSIONS: Based on our results, we present a tentative model for the mechanism of NorQD-catalyzed cNOR remodeling and suggest many of its features to be applicable to the whole MoxR/VWA family.

Development and Evaluation of a Cost-Effective, Carbon-Based, Extended-Release Febuxostat Tablet.

This study outlines the development of a cost-effective, extended-release febuxostat (FEB) tablet using activated charcoal as an adsorbent to enhance drug release. FEB, a BCS Class II drug, presents formulation challenges due to low solubility and high lipophilicity. We evaluated eight formulations with varying FEB-to-charcoal ratios using FTIR and DSC for physical interactions and followed USP standards for overall assessment. The optimal 1:0.25 FEB-to-charcoal ratio demonstrated a consistent 12 h zero-order release pattern. In vivo studies indicated a significantly extended plasma profile compared to immediate-release tablets. The optimal tablets demonstrated acceptable hardness and disintegration times. This innovative approach enhances patient compliance, improves bioavailability, and reduces production costs, offering a promising solution for controlled FEB delivery.

Cryptococcus tetragattii Meningitis Associated with Travel, Taiwan.

Meningitis caused by Cryptococcus tetragattii fungus is rare and has been found in specific geographic regions. We report a case of meningitis caused by C. tetragattii (molecular type VGIV) in an immunocompetent patient in Taiwan. The patient had traveled to Egypt and was positive for granulocyte-macrophage colony-stimulating factor autoantibody.

Early Introduction and Community Transmission of SARS-CoV-2 Omicron Variant, New York, New York, USA.

The Omicron variant of SARS-CoV-2 has become dominant in most countries and has raised significant global health concerns. As a global commerce center, New York, New York, USA, constantly faces the risk for multiple variant introductions of SARS-CoV-2. To elucidate the introduction and transmission of the Omicron variant in the city of New York, we created a comprehensive genomic and epidemiologic analysis of 392 Omicron virus specimens collected during November 25-December 11, 2021. We found evidence of 4 independent introductions of Omicron subclades, including the Omicron subclade BA.1.1 with defining substitution of R346K in the spike protein. The continuous genetic divergence within each Omicron subclade revealed their local community transmission and co-circulation in New York, including both household and workplace transmissions supported by epidemiologic evidence. Our study highlights the urgent need for enhanced genomic surveillance and effective response planning for better prevention and management of emerging SARS-CoV-2 variants.

Electronic Structure and Chemical Bonding of the First-, Second-, and Third-Row-Transition-Metal Monoborides: The Formation of Quadruple Bonds in RhB, RuB, and TcB.

Boron presents an important role in chemistry, biology, and materials science. Diatomic transition-metal borides (MBs) are the building blocks of many complexes and materials, and they present unique electronic structures with interesting and peculiar properties and a variety of bonding schemes which are analyzed here. In the first part of this paper, we present a review on the available experimental and theoretical studies on the first-row-transition-metal borides, i.e., ScB, TiB, VB, CrB, MnB, FeB, CoB, NiB, CuB, and ZnB; the second-row-transition-metal borides, i.e., YB, ZrB, NbB, MoB, TcB, RuB, RhB, PdB, AgB, and CdB; and the third-row-transition-metal borides, i.e., LaB, HfB, TaB, WB, ReB, OsB, IrB, PtB, AuB, and HgB. Consequently, in the second part, the second- and third-row MBs are studied via DFT calculations using the B3LYP, TPSSh, and MN15 functionals and, in some cases, via multi-reference methods, MRCISD+Q, in conjunction with the aug-cc-pVQZ-PPM/aug-cc-pVQZB basis sets. Specifically, bond distances, dissociation energies, frequencies, dipole moments, and natural NPA charges are reported. Comparisons between MB molecules along the three rows are presented, and their differences and similarities are analyzed. The bonding of the diatomic borides is also described; it is found that, apart from RhB(X1Σ+), which was just recently found to form quadruple bonds, RuB(X2Δ) and TcB(X3Σ-) also form quadruple σ2σ2π2π2 bonds in their X states. Moreover, to fill the gap existing in the current literature, here, we calculate the TcB molecule.

Seroprevalence of SARS-Cov-2 Antibodies in Adults, Arkhangelsk, Russia.

Population-based data on coronavirus disease in Russia and on the immunogenicity of the Sputnik V vaccine are sparse. In a survey of 1,080 residents of Arkhangelsk 40-75 years of age, 65% were seropositive for IgG. Fifteen percent of participants had been vaccinated; of those, 97% were seropositive.

Comparison of Complications after Coronavirus Disease and Seasonal Influenza, South Korea.

We conducted a retrospective cohort study using claims data to determine the number and types of complications from coronavirus disease (COVID-19) that patients experience and which patients are more vulnerable to those complications compared with complications in patients with influenza. Among the cohort, 19.6% of COVID-19 patients and 28.5% of influenza patients had >1 new complication. In most complications, COVID-19 patients had lower or similar relative risk compared with influenza patients; exceptions were hair loss, heart failure, mood disorder, and dementia. Young to middle-aged adult COVID-19 patients and patients in COVID-19 hotspots had a higher risk for complications. Overall, COVID-19 patients had fewer complications than influenza patients, but caution is necessary in high-risk groups. If the fatality rate for COVID-19 is reduced through vaccination, management strategies for this disease could be adapted, similar to those for influenza management, such as easing restrictions on economic activity or requirements for close-contact isolation.

Public Acceptance of and Willingness to Pay for Mosquito Control, Texas, USA.

Mosquito control is essential to reduce vectorborne disease risk. We surveyed residents in Harris, Tarrant, and Hidalgo Counties, Texas, USA, to estimate willingness-to-pay for mosquito control and acceptance of control methods. Results show an unmet demand for expanded mosquito control that could be funded through local taxes or fees.

SARS-CoV-2 B.1.619 and B.1.620 Lineages, South Korea, 2021.

We report the rapid emergence of severe acute respiratory syndrome coronavirus 2 lineages B.1.619 and B.1.620 in South Korea. The surge in frequency in a relatively short time emphasizes the need for ongoing monitoring for new lineages to track potential increases in transmissibility and disease severity and reductions in vaccine efficacy.

Dirac State in the FeB2 Monolayer with Graphene-Like Boron Sheet.

By introducing the commonly utilized Fe atoms into a two-dimensional (2D) honeycomb boron network, we theoretically designed a new Dirac material of FeB2 monolayer with a Fermi velocity in the same order of graphene. The electron transfer from Fe atoms to B networks not only effectively stabilizes the FeB2 networks but also leads to the strong interaction between the Fe and B atoms. The Dirac state in FeB2 system primarily arises from the Fe d orbitals and hybridized orbital from Fe-d and B-p states. The newly predicted FeB2 monolayer has excellent dynamic and thermal stabilities and is also the global minimum of 2D FeB2 system, implying its experimental feasibility. Our results are beneficial to further uncovering the mechanism of the Dirac cones and providing a feasible strategy for Dirac materials design.

Segregation of a haplotype encompassing FEB1 with genetic epilepsy with febrile seizures plus in a Colombian family.

Febrile seizures and epilepsy are believed to be linked and some forms of epilepsy are associated with a history of febrile seizures (FS). Linkage analysis to seven known loci for FS and/or genetic epilepsy with febrile seizures plus (GEFS plus) was performed in a small Colombian family. Short tandem repeat (STR) markers were genotyped and two-point linkage analysis and haplotype reconstruction were conducted. A maximum LOD score of 0.75 at marker D8S533 for FEB1 at a recombination fraction (θ) of 0 and a segregating haplotype were identified. FEB1 was the first locus to be associated with FS and this is the second report to describe this association. Two genes in this region, CRH and DEPDC2, are good putative candidate genes that may play a role in FS and/or GEFS plus.

Mild construction of an Fe-B-O based flexible electrode toward highly efficient alkaline simulated seawater splitting.

It is essential to construct self-supporting electrodes based on earth-abundant iron borides in a mild and economical manner for grid-scale hydrogen production. Herein, a series of highly efficient, flexible, robust, and scalable Fe-B-O@FeBx modified on hydrophilic cloth (denoted as Fe-B-O@FeBx/HC, 10 cm × 10 cm) are fabricated by mild electroless plating. The overpotentials and Tafel slope values for the hydrogen and oxygen evolution reactions are 59 mV and 57.62 mV dec-1 and 181 mV and 65.44 mV dec-1, respectively; only 1.462 V is required to achieve 10 mA cm-2 during overall water splitting (OWS). Fe-B-O@FeBx/HC maintains its high catalytic activity for more than 7 days at an industrial current density (400 mA cm-2), owing to the loosened popcorn-like Fe-B-O@FeBx that is firmly loaded on a 2D-layered and mechanically robust substrate along with its fast charge and mass transfer kinetics. The chimney effect of core-shell borides@(oxyhydro)oxides enhances the OWS performance and protects the inner metal borides from further corrosion. Moreover, the flexible Fe-B-O@FeBx/HC electrode has a low cost for grid-scale hydrogen production ($2.97 kg-1). The proposed strategy lays a solid foundation for universal preparation, large-scale hydrogen production and practical applications thereof.

Analysis of Diffusion Coefficients of Iron Monoboride and Diiron Boride Coating Formed on the Surface of AISI 420 Steel by Two Different Models: Experiments and Modelling.

In the present work, two mathematical diffusion models have been used to estimate the growth of the iron monoboride and diiron boride coating formed on AISI 420 steel. The boronizing of the steel was carried out with the solid diffusion packing method at a boronizing temperature of 1123 K-1273 K. Experimental results show the two-coating system consists of an outer monoboride and an inner diiron boride coating with a predominantly planar structure at the propagation front. The depth of the boride coating increases according to temperature and treatment time. A parabolic curve characterizes the propagation of the boride coatings. The two proposed mathematical models of mass transfer diffusion are founded on the solution corresponding to Fick's second fundamental law. The first is based on a linear boron concentration-penetration profile without time dependence, and the second model with time dependence (exact solution). For both models, the theoretical law of parabolic propagation and the average flux of boron atoms (Fick's first fundamental law) at the growth interfaces (monoboride/diiron boride and diiron boride/substrate) are considered to estimate the propagation of the boride coatings (monoboride and diiron boride). To validate the mathematical models, a programming code is written in the MATLAB program (adaptation 7.5) designed to simulate the growth of the boride coatings (monoboride and diiron boride). The following parameters are used as input data for this computer code: (the layer thicknesses of the FeB and Fe2B phases, the operating temperature, the boronizing time, initial formation time of the boride coating, the surface boron concentration limits, FeB/Fe2B and Fe2B/Fe growth interfaces, and the mass transfer diffusion coefficient of boron in the iron monoboride and diiron boride phases). The outputs of the computer code are the constants εFeB and εFe2B. The assessment of activation energies of AISI 420 steel for the two mathematical models of mass transfer is coincident (QFeB=221.9 kJ∙mol-1 and QFe2B=209.1 kJ∙mol-1). A numerical analysis was performed using a standard Taylor series for clarification of the proximity between the two models. SEM micrographs exhibited a strong propensity toward a flat-fronted composition at expansion interfaces of the iron monoboride and diiron boride coating, confirmed by XRD analysis. Tribological characterizations included the Vickers hardness test method, pin-on-disc, and Daimler-Benz Rockwell-C indentation adhesion tests. After thorough analysis, the energies were compared to the existing literature to validate our experiment. We found that our models and experimental results agreed. The diffusion models we utilized were crucial in gaining a deeper understanding of the boronizing behavior of AISI 420 steel, and they also allowed us to predict the thicknesses of the iron monoboride and diiron boride coating. These models provide helpful approaches for predicting the behavior of these steels.

Rational design, synthesis and structural characterization of peptides and peptidomimetics to target Hsp90/Cdc37 interaction for treating hepatocellular carcinoma.

Heat shock protein 90 (Hsp90) and cell division cycle 37 (Cdc37) work together as a molecular chaperone complex to regulate the activity of a multitude of client protein kinases. These kinases belong to a wide array of intracellular signaling networks that mediate multiple cellular processes including proliferation. As a result, Hsp90 and Cdc37 represent innovative therapeutic targets in various cancers (such as leukemia, multiple myeloma, and hepatocellular carcinoma (HCC)) in which their expression levels are elevated. Conventional small molecule Hsp90 inhibitors act by blocking the conserved adenosine triphosphate (ATP) binding site. However, by targeting less conserved sites in a more specific manner, peptides and peptidomimetics (modified peptides) hold potential as more efficacious and less toxic alternatives to the conventional small molecule inhibitors. Using a rational approach, we herein developed bioactive peptides targeting Hsp90/Cdc37 interaction. A six amino acid linear peptide derived from Cdc37, KTGDEK, was designed to target Hsp90. We used in silico computational docking to first define its mode of interaction, and binding orientation, and then conjugated the peptide with a cell penetrating peptide, TAT, and a fluorescent dye to confirm its ability to colocalize with Hsp90 in HCC cells. Based on the parent linear sequence, we developed a peptidomimetics library of pre-cyclic and cyclic derivatives. These peptidomimetics were evaluated for their binding affinity to Hsp90, and bioactivity in HCC cell lines. Among them, a pre-cyclic peptidomimetic demonstrates high binding affinity and bioactivity in HCC cells, causing reduced cell proliferation that is associated with induction of cell apoptosis, and down-regulation of phosphorylated MEK1/2. Overall, this generalized approach of rational design, structural optimization, and cellular validation of 'drug-like' peptidomimetics against Hsp90/Cdc37 offers a feasible and promising way to design novel therapeutic agents for malignancies and other diseases that are dependent on this molecular chaperone complex.

Effect of Silicon Content on Microstructures and Properties of Directionally Solidified Fe-B Alloy.

In order to investigate the effect of Si content on the microstructures and properties of directionally solidified (DS) Fe-B alloy, a scanning electron microscope (SEM) with an energy dispersive spectrum (EDS), and X-ray diffraction have been employed to investigate the as-cast microstructures of DS Fe-B alloy. The results show that Si can strongly refine the columnar microstructures of the DS Fe-B alloy, and the columnar grain thickness of the oriented Fe2B is reduced with the increase of Si addition. In addition, Si is mainly distributed in the ferrite matrix, almost does not dissolve in boride, and seems to segregate in the center of the columnar ferrite to cause a strong solid solution strengthening and refinement effect on the matrix, thus raising the microhardness of the matrix and bulk hardness of the DS Fe-B alloy.

Effect of Mo Content on In-Situ Anisometric Grains Growth and Mechanical Properties of Mo2FeB2-Based Cermets.

Mo2FeB2-based cermets have wide applications in fields of wear resistance, corrosion resistance and heat resistance due to their simple preparation process, low-cost raw materials, and prominent mechanical properties. Herein, Mo2FeB2-based cermets with xMo (x = 43.5, 45.5, 47.5, 49.5, wt.%) were prepared by means of the vacuum liquid phase sintering technique. Investigations on the microstructure and mechanical properties of Mo2FeB2-based cermets with Mo addition were performed. Experimental results show that, with Mo content increasing, the average particle size decreases gradually, revealing that the grain coarsening of Mo2FeB2-based cermets is controlled by interface reaction. In addition, Mo2FeB2 grains gradually transform from an elongated shape to a nearly equiaxed shape. The improvement of Mo2FeB2 hard phase on the morphology is mainly due to the inhibition of solution-precipitation reaction by increasing Mo. Furthermore, the relative density of cermets decreases due to the reduced Fe content. When Mo content is 47.5 wt.%, a relatively small grain size of Mo2FeB2 is obtained (about 2.03 µm). Moreover, with the increase in Mo content, hardness and transverse rupture strength (TRS) of Mo2FeB2-based cermets increase firstly and then decrease. Whereas, with increasing Mo content, the fracture toughness deteriorates gradually. When Mo content is 47.5 wt.%, the comprehensive mechanical properties of cermets are the best. The optimal raw material ratio for the preparation of Mo2FeB2-based cermets in this study is determined to be 47.5 wt.% Mo-6.0 wt.% B-Fe.

Effect of TiC on Microstructure and Properties of Wear-Resistant Mo2FeB2 Claddings.

Alloy blocks with different TiC content were designed, and Mo2FeB2 cermets were prepared by carbon arc surfacing process. The interaction law of TiC content and the microstructure, phase, composition, hardness and wear resistance of the cladding were studied in detail by the combination of experiment and theoretical analysis. On the other hand, the phase transition process of the weldpool is theoretically analyzed by thermodynamic calculation method. XRD test results show that in addition to Mo2FeB2 synthesized in situ, the cladding also forms phases such as TiC, CrB, MoB and Fe-Cr. The number of Mo2FeB2 hard phases gradually increases when TiC content varies from 0% to 15%. The average microhardness of the cladding with 0%, 5%, 10%, and 15% TiC was 992 HV0.5, 1035 HV0.5, 1018 HV0.5 and 689 HV0.5, respectively, with 5% TiC being the largest. Moreover, the cladding with 5% TiC content has excellent wear resistance, which is 14.6 times that of the substrate.

Investigation of the Tribological Behavior and Microstructure of Plasma-Cladded Fe-Cr-Mo-Ni-B Coating.

In this study, an Fe-Cr-Mo-Ni-B coating was prepared using plasma cladding on Cr5 steel substrate. The microstructure, phase evolution and tribological performance of the Fe-Cr-Mo-Ni-B coating were investigated. The microstructure is mainly composed of Mo2FeB2, Fe2B, α-Fe, γ-Fe and MoB. The process of phase evolution in the coating was observed in situ by HT-CLSM. The Mo2FeB2 phase with good thermodynamic stability can exist in the high-temperature liquid phase. It also has a phenomenon of connection and merging and turns into different morphology during the plasma cladding process. The hardness value of coating was much higher than the base metal, and the hardness value of Mo2FeB2 (785.5 HV) was higher than the eutectic matrix (693.2 HV). The wear mechanisms of the cladding under dry sliding were primarily caused by adhesive wear, accompanying slight oxidation wear. The Mo2FeB2 phase has an important effect on the wear resistance property.

Effects of Boride Orientation and Si Content on High-Temperature Oxidation Resistance of Directionally Solidified Fe-B Alloys.

In this work, the as-cast directionally solidified (DS) Fe-B alloys with various Si contents and different boride orientation were designed and fabricated, and the as-cast microstructures and static oxidation behaviors of the DS Fe-B alloys were investigated extensively. The as-cast microstructure of the DS Fe-B alloys consists of the well-oriented Fe2B columnar grains and α-Fe, which are strongly refined by Si addition. The oxidation interface of the scales in the DS Fe-B alloy with 3.50 wt.% Si demonstrates an obvious saw-tooth shaped structure and is embedded into the alternating distributed columnar layer structures of the DS Fe-B alloy with oriented Fe2B and α-Fe matrix, which is beneficial to improve the anti-peeling performance of the oxide film compared with lower amounts of Si addition in DS Fe-B alloys with oriented Fe2B [002] orientation parallel to the oxidation direction (i.e., oxidation diffusion direction, labeled as Fe2B// sample). In the DS Fe-B alloys with oriented Fe2B [002] orientation vertical to the oxidation direction (i.e., labeled as Fe2B⟂ sample), due to the blocking and barrier effect of laminated-structure boride, Si is mainly enriched in the lower part of the oxide film to form a dense SiO2 thin layer adhered to layered boride. As a result, the internal SiO2 thin layer plays an obstructed and shielded role in oxidation of the substrate, which hinders the further internal diffusion of oxygen ions and improves the anti-oxidation performance of the Fe2B⟂ sample, making the average anti-oxidation performance better than that of the Fe2B// sample.

Use of PtC Nanotips for Low-Voltage Quantum Tunneling Applications.

The use of focused ion and focused electron beam (FIB/FEB) technology permits the fabrication of micro- and nanometer scale geometries. Therefore, FIB/FEB technology is a favorable technique for preparing TEM lamellae, nanocontacts, or nanowires and repairing electronic circuits. This work investigates FIB/FEB technology as a tool for nanotip fabrication and quantum mechanical tunneling applications at a low tunneling voltage. Using a gas injection system (GIS), the Ga-FIB and FEB technology allows both additive and subtractive fabrication of arbitrary structures. Using energy dispersive X-ray spectroscopy (EDX), resistance measurement (RM), and scanning tunneling microscope (STM)/spectroscopy (STS) methods, the tunneling suitability of the utilized metal-organic material-platinum carbon (PtC) is investigated. Thus, to create electrode tips with radii down to 15 nm, a stable and reproducible process has to be developed. The metal-organic microstructure analysis shows suitable FIB parameters for the tunneling effect at high aperture currents (260 pA, 30 kV). These are required to ensure the suitability of the electrodes for the tunneling effect by an increased platinum content (EDX), a low resistivity (RM), and a small band gap (STM). The STM application allows the imaging of highly oriented pyrolytic graphite (HOPG) layers and demonstrates the tunneling suitability of PtC electrodes based on high FIB aperture currents and a low tunneling voltage.