Cardiovascular Safety of Atomoxetine and Methylphenidate in Patients With Attention-Deficit/Hyperactivity Disorder in Japan: A Self-Controlled Case Series Study.

OBJECTIVE: To investigate the association between atomoxetine or methylphenidate use and arrhythmia, heart failure (HF), stroke, and myocardial infarction (MI) in attention-deficit/hyperactivity disorder (ADHD) patients mainly focused on the people of working age. METHODS: In a self-controlled case series study using a Japanese claims database, we identified events of arrhythmia, HF, stroke, and MI among 15,472 atomoxetine new users and 12,059 methylphenidate new users. Adjusted incidence rate ratios (aIRRs) of outcome events were estimated using multivariable conditional Poisson regression. RESULTS: An increased risk of arrhythmia was observed during the first 7 days after the initial atomoxetine exposure (aIRR 6.22, 95% CI [1.90, 20.35]) and in the subsequent exposure (3.23, [1.58, 6.64]). No association was found between methylphenidate exposure and arrhythmia, nor between atomoxetine or methylphenidate exposure and HF. The limited number of stroke and MI cases prevented thorough analysis. CONCLUSIONS: Clinicians should consider monitoring for arrhythmia after patients initiating or re-initiating atomoxetine.

Enzyme immobilization on covalent organic framework supports.

Enzymes are natural catalysts with high catalytic activity, substrate specificity and selectivity. Their widespread utilization in industrial applications is limited by their sensitivity to harsh reaction conditions and difficulties relating to their removal and re-use after the reaction is complete. These limitations can be addressed by immobilizing the enzymes in solid porous supports. Covalent organic frameworks (COFs) are ideal candidate carriers because of their good biocompatibility, long-term water stability and large surface area. In post-synthetic immobilization, the enzyme is added to an existing COF; this has had limited success because of enzyme leaching and pore blockage by enzymes that are too large. Direct-immobilization methods-building the COF around the enzyme-allow tailored incorporation of proteins of any size and result in materials with lower levels of leaching and better mass transport of reactants and products. This protocol describes direct-immobilization methods that can be used to fabricate enzyme@COF (@ = engulfing) biocomposites with rationally programmed structures and functions. If COF construction requires harsh reaction conditions, the enzyme can be protected by using a removable metal-organic framework. Alternatively, a direct in situ approach, in which the enzyme and the COF monomers assemble under very mild conditions, can be used. Examples of both approaches are described: enzyme@COF-42-B/43-B capsules (enzymes including catalase, glucose oxidase, etc.) with ZIF-90 or ZPF-2 as protectors, and lipase@NKCOF-98/99 via in situ direct-immobilization methods (synthesis timing: 30-100 min). Example assays for physical and functional characterization of the COF and enzyme@COF materials are also described.

Association of dietary inflammatory potential and non-alcoholic fatty liver disease in US adults.

OBJECTIVES: Long-term inflammatory effects of diet may elevate the risk of non-alcoholic fatty liver disease (NAFLD). The present study aims to investigate dietary patterns associated with inflammation and whether such diets were associated with the risk of NAFLD. METHODS: Data were collected from the 2017-2018 National Health and Nutrition Examination Survey. Dietary intake was obtained through two 24-hour dietary recall interviews, and levels of inflammatory biomarkers were assessed in blood samples. NAFLD was defined as a controlled attenuation parameter (CAP) ≥ 274 dB/m. Reduced-rank regression (RRR) analysis was used to derive sex-specific inflammatory dietary patterns (IDPs). Logistic regression analysis was used to examine the association between IDPs and NAFLD. RESULTS: A total of 3570 participants were included in this study. We identified the IDP characterized by higher intake of added sugars, and lower intake of fruits, vegetables, whole grains, seafood high in n -3 fatty acids, soybean products, nuts, seeds, yogurt, and oils. After multivariate adjustment, the highest tertile of the IDP scores had a significantly higher risk of NAFLD than the lowest tertile [odds ratio (OR) = 1.884, 95% confidence interval (CI) = 1.003-3.539, P for trend = 0.044 for males; OR = 1.597, 95% CI = 1.129-2.257, P for trend = 0.010 for females]. CONCLUSION: Overall, the IDP was positively associated with the prevalence of NAFLD. The findings may provide dietary prevention strategies for controlling chronic inflammation and further preventing NAFLD.

Performance Investigation of Micromixer with Spiral Pattern on the Cylindrical Chamber Side Wall.

In this paper, a sequence of passive micromixers with spiral patterns on the side wall of cylindrical chambers are designed, optimized, prepared and tested. The simulation studies show that the vortex magnitude and continuity in the mixing chamber are the most important factors to determine mixing performance, while the inlet position and structural parameters are secondary influences on their performance. According to the above principles, the performance of a micromixer with a continuous sidewall spiral finally wins out. The total mixing length is only 14 mm, but when Re = 5, the mixing index can reach 99.81%. The multi-view visual tests of these mixer chips prepared by 3D printing are consistent with the simulation results. This paper provides a new idea for optimizing the micromixer with spiral patterns on the side wall and the problems of floor area and pressure loss are significantly improved compared to the conventional spiral structure.

Uncovering Dislocation- and Precipitate-Induced Viscoplastic Damage in Al-Zn-Mg Alloy.

The existing phenomenological theories of plastic forming of sheet metal lack the predictability of the influences of dislocations and precipitates on viscoplastic damage in Al-Zn-Mg alloys. This study examines the evolution of grain size that occurs when the Al-Zn-Mg alloy undergoes a hot deformation process, specifically concentrating on dynamic recrystallization (DRX). The uniaxial tensile tests are conducted at deformation temperatures ranging from 350 to 450 °C and strain rates of 0.01-1 s-1. The intragranular and intergranular dislocation configurations and their interactions with dynamic precipitates are revealed by transmission electron microscopy (TEM). In addition, the MgZn2 phase induces microvoid formation. Subsequently, an improved multiscale viscoplastic constitutive model is established that emphasizes the effect of precipitates and dislocations on the evolution of microvoid-based damage. Using a calibrated and validated micromechanical model, the simulation of hot-formed U-shaped parts is conducted through finite element (FE) analysis. During the hot U-forming process, the formation of defects is expected to have an impact on both the distribution of thickness and the level of damage. In particular, the damage accumulation rate is influenced by temperature and strain rate, and local thinning is caused by the damage evolution of U-shaped parts.

A Dynamic Defect Generation Strategy for Efficient Enzyme Immobilization in Robust Metal-Organic Frameworks for Catalytic Hydrolysis and Chiral Resolution.

Enzyme immobilization has been demonstrated to be a favorable protocol for promoting the industrialization of bioactive molecules, but still with formidable challenge. Addressing this challenge, we create a dynamic defect generation strategy for enzyme immobilization by using the dissociation equilibrium of metal-organic frameworks (MOFs) mediated by enzymes. Enzymes can act as "macro ligands" to generate competitive coordination against original ligands, along with the release of metal clusters of MOFs to generate defects, hence promoting the gradual transport of enzymes from the surface to inside. Various enzymes can be efficiently immobilized in MOFs to afford composites with good enzymatic activities, protective performances and exceptional reusabilities. Moreover, multienzyme bioreactors capable of efficient cascade reactions can also be generated. This study provides new opportunities to construct highly efficient biocatalysts incorporating different types of enzymes.

Bottom-Up Synthesis of Covalent Organic Frameworks with Quasi-Three-Dimensional Integrated Architecture via Interlayer Cross-Linking.

Developing strategies to enhance the structural robustness of covalent organic frameworks (COFs) is of great importance. Here, we rationally design and synthesize a class of cross-linked COFs (CCOFs), in which the two-dimensional (2D) COF layers are anchored and connected by polyethylene glycol (PEG) or alkyl chains through covalent bonds. The bottom-up fabrication of these CCOFs is achieved by the condensation of cross-linked aldehyde monomers and tritopic amino monomers. All the synthesized CCOFs possess high crystallinity and porosity, and enhanced structural robustness surpassing the typical 2D COFs, which means that they cannot be exfoliated under ultrasonication and grinding due to the cross-linking effect. Furthermore, the cross-linked patterns of PEG units are uncovered by experimental results and Monte Carlo molecular dynamics simulations. It is found that all CCOFs are dominated by vertical cross-layer (interlayer) connections (clearly observed in high-resolution transmission electron microscopy images), allowing them to form quasi-three-dimensional (quasi-3D) structures. This work bridges the gap between 2D COFs and 3D COFs and provides an efficient way to improve the interlayered stability of COFs.

Redox and spectroscopic properties of mammalian nitrite reductase-like hemoproteins.

Besides the canonical pathway of L-arginine oxidation to produce nitric oxide (NO) in vivo, the nitrate-nitrite-NO pathway has been widely accepted as another source for circulating NO in mammals, especially under hypoxia. To date, there have been at least ten heme-containing nitrite reductase-like proteins discovered in mammals with activities mainly identified in vitro, including four globins (hemoglobin, myoglobin, neuroglobin (Ngb), cytoglobin (Cygb)), three mitochondrial respiratory chain enzymes (cytochrome c oxidase, cytochrome bc1, cytochrome c), and three other heme proteins (endothelial nitric oxide synthase, cytochrome P450 and indoleamine 2,3-dioxygenase 1 (IDO1)). The pathophysiological functions of these proteins are closely related to their redox and spectroscopic properties, as well as their protein structure, although the physiological roles of Ngb, Cygb and IDO1 remain unclear. So far, comprehensive summaries of the redox and spectroscopic properties of these nitrite reductase-like hemoproteins are still lacking. In this review, we have mainly summarized the published data on the application of ultraviolet-visible, electron paramagnetic resonance, circular dichroism and resonance Raman spectroscopies, and X-ray crystallography in studying nitrite reductase-like activity of these 10 proteins, in order to sort out the relationships among enzymatic function, structure and spectroscopic characterization, which might help in understanding their roles in redox biology and medicine.

Green and Scalable Fabrication of High-Performance Biocatalysts Using Covalent Organic Frameworks as Enzyme Carriers.

Enzyme immobilization is essential to the commercial viability of various critical large-scale biocatalytic processes. However, challenges remain for the immobilization systems, such as difficulties in loading large enzymes, enzyme leaching, and limitations for large-scale fabrication. Herein, we describe a green and scalable strategy to prepare high-performance biocatalysts through in situ assembly of enzymes with covalent organic frameworks (COFs) under ambient conditions (aqueous solution and room temperature). The obtained biocatalysts have exceptional reusability and stability and serve as efficient biocatalysts for important industrial reactions that cannot be efficiently catalyzed by free enzymes or traditional enzyme immobilization systems. Notably, this versatile enzyme immobilization platform is applicable to various COFs and enzymes. The reactions in an aqueous solution occurred within a short timeframe (ca. 10-30 min) and could be scaled up readily (ca. 2.3 g per reaction).

Bipolar Metal Flexible Electrospun Fibrous Membrane Based on Metal-Organic Framework for Gradient Healing of Tendon-to-Bone Interface Regeneration.

Metal ions play a significant role in tissue repair, with widely application in clinical treatment. However, the therapeutic effect of metal ions is always limited due to metabolization and narrow repair capability. Here, a bipolar metal flexible electrospun fibrous membrane based on a metal-organic framework (MOF), which is bioinspired by the gradient structure of the tendon-to-bone interface, with a combination of regulating osteoblasts differentiation and angiogenesis properties, is constructed successfully by a continuous electrospinning technique and matching the longitudinal space morphology for synchronous regeneration. Furthermore, the MOF, acting as carriers, can not only achieve the sustainable release of metal ions, but promote the osteogenesis and tenogenesis on the scaffold. The in vitro data show that this novel hierarchical structure can accelerate the tenogenesis, the biomineralization, and angiogenesis. Moreover, in the in vivo experiment, the flexible fibrous membrane can promote tendon and bone tissue repair, and fibrocartilage reconstruction, to realize the multiple tissue synchronous regeneration at the damaged tendon-to-bone interface. Altogether, this newly developed bipolar metal flexible electrospun fibrous membrane based on a MOF, as a new biomimetic flexible scaffold, has great potential in reconstruct the tissue damage, especially gradient tissue damage.

Fabrication of Biomolecule-Covalent-Organic-Framework Composites as Responsive Platforms for Smart Regulation of Fermentation Application.

Exploration of novel material platforms to protect biological preservatives and realize intelligent regulation during fermentation is of great significance in industry. Herein, we established an intelligent responsive platform by introducing antimicrobial biomolecules (nisin) into rationally designed covalent organic frameworks (COFs), resulting in a new type of "smart formulation", which could responsively inhibit microbial contamination and ensure the orderly progression of the fermentation process. The encapsulated biomolecules retained their activity while exhibiting enhanced stability and pH-responsive releasing process (100% bacteriostatic efficiency at a pH of 3), which can ingeniously adapt to the environmental variation during the fermentation process and smartly fulfill the regulation needs. Moreover, the nisin@COF composites would not affect the fermentation strains. This study will pave a new avenue for the preparation of highly efficient and intelligent antimicrobial agents for the regulation of the fermentation process and play valuable roles in the drive toward green and sustainable biomanufacturing.

One-pot method based on deep eutectic solvent for extraction and conversion of polydatin to resveratrol from Polygonum cuspidatum.

The acquisition of resveratrol from Polygonum cuspidatum is complicated and costs organic solvents due to extraction and hydrolysis of its corresponding glycoside (polydatin). In this work, a novel one-pot method based on deep eutectic solvent (DES) was developed for simultaneous extraction and conversion of polydatin to resveratrol from Polygonum cuspidatum for the first time. The extraction yield of resveratrol by DES-based one-pot method were significantly higher than that of water, methanol and ethanol. After optimization by One-Variable-at-a-Time and response surface methodology, the extraction yield of resveratrol reached 12.26 ± 0.14 mg/g within 80 min. The conversation efficiency of polydatin to resveratrol in Polygonum cuspidatum from five different origins was more than 96.3%. Scanning electron microscope results indicated the selected DES disrupted plant cell walls to enhance the yield of resveratrol. The results indicated that one green method was successfully established for efficient extraction and conversion of polydatin to resveratrol from Polygonum cuspidatum.

Fabricating Covalent Organic Framework Capsules with Commodious Microenvironment for Enzymes.

Enzyme immobilization has been demonstrated to be a favorable protocol to promote industrialization of biomacromolecules. Despite tremendous efforts to develop new strategies and materials to realize this process, maintaining enzyme activity is still a formidable challenge. Herein we created a sacrificial templating method, using metal-organic frameworks (MOFs) as sacrificial templates to construct hollow covalent organic framework (COF) capsules for enzyme encapsulation. This strategy can provide a capacious microenvironment to unleash enzyme molecules. The improved conformational freedom of enzymes, enhanced mass transfer, and protective effect against the external environment ultimately boosted the enzymatic activities. We also found that this strategy possesses high versatility that is suitable for diverse biomacromolecules, MOF templates, and COF capsules. Moreover, the dimensions, pore sizes, and shell thickness of COF capsules can be conveniently tuned, allowing for customizing bioreactors for specific functions. For example, coencapsulation of different enzymes with synergistic functions were successfully demonstrated using this bioreactor platform. This study not only opens up a new avenue to overcome the present limitations of enzymatic immobilization in porous matrixes but also provides new opportunities for construction of biomicrodevices or artificial organelles based on crystalline porous materials.

Covalent Organic Frameworks with Chirality Enriched by Biomolecules for Efficient Chiral Separation.

The separation of racemic compounds is important in many fields, such as pharmacology and biology. Taking advantage of the intrinsically strong chiral environment and specific interactions featured by biomolecules, here we contribute a general strategy is developed to enrich chirality into covalent organic frameworks (COFs) by covalently immobilizing a series of biomolecules (amino acids, peptides, enzymes) into achiral COFs. Inheriting the strong chirality and specific interactions from the immobilized biomolecules, the afforded biomolecules⊂COFs serve as versatile and highly efficient chiral stationary phases towards various racemates in both normal and reverse phase of high-performance liquid chromatography (HPLC). The different interactions between enzyme secondary structure and racemates were revealed by surface-enhanced Raman scattering studies, accounting for the observed chiral separation capacity of enzymes⊂COFs.

A Green Route to Hexagonal and Monoclinic BiPO4:Ln3+ (Ln = Sm, Eu, Tb, Dy) Nanocrystallites for Tailoring Luminescent Performance.

Selective synthesis of specific phased nanomaterials via a green route is a promising yet challeng- ing task. In the present work, the hexagonal and monoclinic phases of BiPO4:Ln3+ (Ln = Sm, Eu, Tb, Dy) were prepared via room temperature co-precipitation method. For adjusting the phase of the products, the prepared mediums selected were the most common solvents, i.e., water and ethanol. It was very important that the prepared mediums could be easily recycled and reused by evapo- rating the filtrate. The formation mechanisms of hexagonal in water and monoclinic in ethanol were investigated. Interestingly, the growth behaviors of these phases were quite distinct and thus gave rise to distinct morphology and particle size. The hexagonal phase possesses a rod-like morphol- ogy with diameters of 50-160 nm and lengths of 65-400 nm while the monoclinic phase consists of almost entirely irregular nanoparticles. Also, it was found that the bending and stretching vibrations of O-H and PO4 tetrahedra were quite different for the products prepared in water and ethanol. Moreover, it was found that the luminescence properties, including emission intensity, lifetime, quan- tum efficiency, and color, could be readily tailored through controlling the phase structures and microstructures. The results showed that the monoclinic phase exhibited superior luminescent per- formance to the hexagonal phase. The methodologies reported in this work were fundamentally important, which could be easily extended to large-scale synthesis of other phased nanomaterials for potential applications as electroluminescent devices, optical integrated circuits, or biomarkers.

Land use changes and its driving forces in hilly ecological restoration area based on gis and RS of northern China.

Land use change is one of the important aspects of the regional ecological restoration research. With remote sensing (RS) image in 2003, 2007 and 2012, using geographic information system (GIS) technologies, the land use pattern changes in Yimeng Mountain ecological restoration area in China and its driving force factors were studied. Results showed that: (1) Cultivated land constituted the largest area during 10 years, and followed by forest land and grass land; cultivated land and unused land were reduced by 28.43% and 44.32%, whereas forest land, water area and land for water facilities and others were increased. (2) During 2003-2007, forest land change showed the largest, followed by unused land and grass land; however, during 2008-2012, water area and land for water facilities change showed the largest, followed by grass land and unused land. (3) Land use degree was above the average level, it was in the developing period during 2003-2007 and in the degenerating period during 2008-2012. (4) Ecological Restoration Projects can greatly change the micro topography, increase vegetation coverage, and then induce significant changes in the land use distribution, which were the main driving force factors of the land use pattern change in the ecological restoration area.

[Study on the FTIR spectra of OH in olivines from mengyin kimberlite].

The results of FTIR spectra study of OH in olivines from Mengyin kimberlite show that there are more than 60 OH absorption peaks in the range of 3800-3000 cm(-1). We identified four major spectral features in the OH absorption bands of kimberlitic olivines. One is with nuOH in the range of 3800-3700 cm(-1), which is caused by the vapour of the room circumstance, and can not be regarded as intrinsic or non-intrinsic nuOH of the olivines. Another one is with nuOH in the range of 3710-3620 cm(-1), which belongs to three "water"-bearing minerals including serpentine, talc and Mg-bearing amphiboles, which is the non-intrinsic nuOH of the olivines. There is the possibility that H in hydrous minerals mainly entered into olivines during post-emplacement processes of the kimberlite magma. The third one is with nuOH in the range of 3620-3425 cm(-1), which originated from H occupying the Si-defect in the olivine structure, forming humite-like defects, and/or the defects that H occupies (Mg,Fe)-depletion, which is certainly attributed to the intrinsic nuOH of the olivines. In this case, H possibly entered into olivines following its immersion in the high temperature and rich fluid kimberlite magma in the mantle circumstance. The last one is with nuOH in the range of 3425-3000 cm(-1). In this area, nuOH is assigned to fluid inclusions of the olivines, and is the non-intrinsic nuOH of olivines. Fluid inclusions can enter into the olivines either during post-emplacement processes of the kimberlite magma or during the periods that olivines were formed in the mantle.

[Study on the micro-FTIR and Raman spectra of the alluvial diamonds from yangtze craton and their geological significances].

The FTIR and Raman spectra of 10 diamonds from Yuanshui, Hunan province show that the alluvial diamonds from this area are mostly IaAB type, with a significant character that the A-center is enriched relatively; the nitrogen concentration in the diamonds is between 38.20 and 840.67 microg x g(-1), which has a tremendous distinction in different crystal. The residence time of the diamonds in the mantle are between 0.043 and 3.315 Ga, which is also has a great difference in different diamond grains. The remotest residence time (3.315 Ga) of one diamond is older than the most aged rock (3.285 Ga) in Xiang-E-Qian-Gui contiguous zone. A remarkable environment change had took place during the process of diamonds formation. The formation depth of dodecahedral diamonds is deeper than that of the octahedral ones.

[Study on the micro-infrared spectra and origin of polycrystalline diamonds from Mengyin kimberlite pipes].

The natural polycrystalline diamonds from the Mengyin kimberlite pipes can be classified as the euhedral faceted polycrystalline diamonds and anhedral rounded polycrystalline diamonds. The results of micro-FTIR spectra characterization of the polycrystalline diamonds show that the concentration of nitrogen is low, varying from 16.69 to 72.81 microgram per gram and is different among different diamond grains or position in polycrystalline diamonds. The euhedral faceted polycrystalline diamonds are Ia AB type and have higher concentration of A-center defects than B-center defects. Most of the anhedral rounded polycrystalline diamonds are Ia AB type and have higher content of B-center defects. A minority of the anhedral rounded polycrystalline diamonds have C-center, A-center and B-center defects simultaneously. The polycrystalline diamonds probably originated from the relatively deeper mantle and were not formed in diamond nucleation stage, but in the diamond growth period or some special conditions after the diamond grains were formed already. Furthermore, the euhedral faceted polycrystalline diamonds were formed slightly later and the anhedral rounded polycrystalline diamonds were formed obviously earlier than the diamond single crystals from the Mengyin kimberlite pipes.

Development of bone-targeted catalase derivatives for inhibition of bone metastasis of tumor cells in mice.

Removal of hydrogen peroxide by delivering catalase to the vicinity of metastasizing tumor cells is a promising approach for inhibiting tumor metastasis. To inhibit bone metastasis, catalase was conjugated with 3,5-di(ethylamino-2,2-bisphosphono)benzoic acid (Bip), a derivative of bone-seeking bisphosphonates, polyethylene glycol (PEG), or both. Bip-conjugated catalase derivatives, that is, catalase-Bip and PEG-catalase-Bip, exhibited a higher affinity for bone matrix as compared with their counterparts without Bip. The tissue distribution of (111) In-labeled catalase derivatives indicated that the accumulation of radioactivity in bones was increased by conjugation of either Bip or PEG with catalase. An experimental bone metastasis model was developed by injecting male C57BL/6 mice with murine melanoma B16-BL6/Luc cells, which stably express firefly luciferase into left ventricle. Repeated injections of catalase to tumor-bearing mice had no significant effect on the number of melanoma cells in tibiae and femurs, whereas injections of catalase-Bip, PEG-catalase, or PEG-catalase-Bip significantly reduced the number. These results indicate that targeted delivery of catalase to the bones can be achieved by conjugating the enzyme with either Bip or PEG, and this delivery is effective in inhibiting the bone metastasis of tumor cells.