Research interest in boron nitride nanotubes (BNNTs) has increased after the recent success of large-scale BNNT syntheses using high-temperature-pressure laser ablation or high-temperature plasma ...methods. Nonetheless, there are limits to the application and commercialization of these materials because of the difficulties associated with their fine structural control. Herein, the growth kinetics of BNNTs were systemically studied for this purpose. The growth pressure of the nitrogen feed gas was varied while the growth temperature remained constant, which was confirmed by black body radiation measurements and calculations based on a heat loss model. Changing from the diffusion-limited regime to the supply-limited regime of growth kinetics based on the optimized BNNT synthesis condition afforded the control of the number of BNNT walls. The total amount of BNNTs possessing single and double walls was over 70%, and the BNNT surface area increased to 278.2 m
/g corresponding to small wall numbers and diameters. Taking advantage of the large surface area and high-temperature durability of the material, BNNTs utilized as a recyclable adsorbent for water purification. The efficiency of the BNNTs for capturing methylene blue particles in water was approximately 94%, even after three repetition cycles, showing the potential of the material for application in the filter industry.
Rgs2, a regulator of G proteins, lowers blood pressure by decreasing signaling through Gαq. Human patients expressing Met-Leu-Rgs2 (ML-Rgs2) or Met-Arg-Rgs2 (MR-Rgs2) are hypertensive relative to ...people expressing wild-type Met-Gln-Rgs2 (MQ-Rgs2). We found that wild-type MQ-Rgs2 and its mutant, MR-Rgs2, were destroyed by the Ac/N-end rule pathway, which recognizes Nα-terminally acetylated (Nt-acetylated) proteins. The shortest-lived mutant, ML-Rgs2, was targeted by both the Ac/N-end rule and Arg/N-end rule pathways. The latter pathway recognizes unacetylated N-terminal residues. Thus, the Nt-acetylated Ac-MX-Rgs2 (X = Arg, Gln, Leu) proteins are specific substrates of the mammalian Ac/N-end rule pathway. Furthermore, the Ac/N-degron of Ac-MQ-Rgs2 was conditional, and Teb4, an endoplasmic reticulum (ER) membrane-embedded ubiquitin ligase, was able to regulate G protein signaling by targeting Ac-MX-Rgs2 proteins for degradation through their Nα-terminal acetyl group.
Despite recent advances in commercially optimized identification systems, bacterial identification remains a challenging task in many routine microbiological laboratories, especially in situations ...where taxonomically novel isolates are involved. The 16S rRNA gene has been used extensively for this task when coupled with a well-curated database, such as EzTaxon, containing sequences of type strains of prokaryotic species with validly published names. Although the EzTaxon database has been widely used for routine identification of prokaryotic isolates, sequences from uncultured prokaryotes have not been considered. Here, the next generation database, named EzTaxon-e, is formally introduced. This new database covers not only species within the formal nomenclatural system but also phylotypes that may represent species in nature. In addition to an identification function based on Basic Local Alignment Search Tool (BLAST) searches and pairwise global sequence alignments, a new objective method of assessing the degree of completeness in sequencing is proposed. All sequences that are held in the EzTaxon-e database have been subjected to phylogenetic analysis and this has resulted in a complete hierarchical classification system. It is concluded that the EzTaxon-e database provides a useful taxonomic backbone for the identification of cultured and uncultured prokaryotes and offers a valuable means of communication among microbiologists who routinely encounter taxonomically novel isolates. The database and its analytical functions can be found at http://eztaxon-e.ezbiocloud.net/.
The Arg/N-end rule pathway targets for degradation proteins that bear specific unacetylated N-terminal residues while the Ac/N-end rule pathway targets proteins through their Nα-terminally acetylated ...(Nt-acetylated) residues. Here, we show that Ubr1, the ubiquitin ligase of the Arg/N-end rule pathway, recognizes unacetylated N-terminal methionine if it is followed by a hydrophobic residue. This capability of Ubr1 expands the range of substrates that can be targeted for degradation by the Arg/N-end rule pathway because virtually all nascent cellular proteins bear N-terminal methionine. We identified Msn4, Sry1, Arl3, and Pre5 as examples of normal or misfolded proteins that can be destroyed through the recognition of their unacetylated N-terminal methionine. Inasmuch as proteins bearing the Nt-acetylated N-terminal methionine residue are substrates of the Ac/N-end rule pathway, the resulting complementarity of the Arg/N-end rule and Ac/N-end rule pathways enables the elimination of protein substrates regardless of acetylation state of N-terminal methionine in these substrates.
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•N-terminal Met followed by a hydrophobic residue functions as an N-degron•Unacetylated Met-bearing proteins can be destroyed by the Arg/N-end rule pathway•The Arg/N-end rule and Ac/N-end rule pathways have complementary specificities•Both unacetylated and AcMet-proteins can be destroyed by these N-end rule pathways
The majority of cellular proteins initiate with methionine, and when followed by a hydrophobic residue, the protein becomes a substrate for N-end rule degradation pathways. These additional substrates significantly extend the capacity of Arg/- and Ac/N-end rule pathways for regulating the proteome.
Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial ...phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates and microsatellite stability, whereas EP subtype tumors show low genomic integrity. Clinically, the MP subtype is associated with markedly poor survival and resistance to standard chemotherapy, whereas the EP subtype is associated with better survival rates and sensitivity to chemotherapy. Integrative analysis shows that signaling pathways driving epithelial-to-mesenchymal transition and insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1R) pathway are highly activated in MP subtype tumors. Importantly, MP subtype cancer cells are more sensitive to inhibition of IGF1/IGF1R pathway than EP subtype. Detailed characterization of these two subtypes could identify novel therapeutic targets and useful biomarkers for prognosis and therapy response.
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•Unique three-dimensional graphene/mixed transition metal oxides modified activated carbon was prepared and characterized.•The nanocomposite electrode shows low charge transfer ...resistance and high specific capacitance.•Analysis of synchrotron-based hard X-ray absorption spectroscopy.•The fabricated nanocomposite exhibits a high electrosorption capacity of 9.34 mg g−1.
Over the last two decades, the capacitive deionization (CDI) technique has been developed into a high performance, low-cost, and environmental-friendly desalination technology. The development of novel advanced nanostructures via the hybridization of diverse carbon materials to improve the performance of CDI technology has attracted considerable attention. In this study, the combination of graphene hydrogel and ZrO2-doped TiO2 nanofibers as efficient dopants into activated carbon (AC), has been achieved through a simple electrospinning technique followed by a post annealing process. The strong interactions between the graphene hydrogel, nanofibers and AC were found to enhance the wettability as well as the electrical conductivity of the AC. The morphology and electrochemical performance of the as-synthesized composite were characterized by field-emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). What’s more, the X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and synchrotron X-ray absorption structures (XAS) are performed to investigate the atomic and electronic structure of titania and zirconia in order to understand their phase stability. We observed the appearance of anatase structure of titania and cubic structure of zirconia after doping the AC and graphene hydrogel with the nanofibers. The water contact angle of the composite was examined and found to be less than 3°. The introduced nanocomposite showed high electrosorption capacity of 9.34 mg g−1 at the initial solution conductivity of ∼100 μS cm−1, which is much higher compared to the other surveyed materials; these results should be attributed to its significant hydrophilicity, high specific capacitance, and reduced charge transfer resistance.
Genome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. ...As a continuous effort, we conducted GWAS in a large Korean RA case-control population.
We newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations.
We identified six new RA-risk loci (
,
,
,
,
and
) with p
<5×10
and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases.
This study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA.
Background
Current design strategies for small diameter vascular grafts (< 6 mm internal diameter; ID) are focused on mimicking native vascular tissue because the commercially available grafts still ...fail at small diameters, notably due to development of intimal hyperplasia and thrombosis. To overcome these challenges, various design approaches, material selection, and surface modification strategies have been employed to improve the patency of small-diameter grafts.
Review
The purpose of this review is to outline various considerations in the development of small-diameter vascular grafts, including material choice, surface modifications to enhance biocompatibility/endothelialization, and mechanical properties of the graft, that are currently being implanted. Additionally, we have taken into account the general vascular physiology, tissue engineering approaches, and collective achievements of the authors in this area. We reviewed both commercially available synthetic grafts (e-PTFE and PET), elastic polymers such as polyurethane and biodegradable and bioresorbable materials. We included naturally occurring materials by focusing on their potential application in the development of future vascular alternatives.
Conclusion
Until now, there are few comprehensive reviews regarding considerations in the design of small-diameter vascular grafts in the literature. Here-in, we have discussed in-depth the various strategies employed to generate engineered vascular graft due to their high demand for vascular surgeries. While some TEVG design strategies have shown greater potential in contrast to autologous or synthetic ePTFE conduits, many are still hindered by high production cost which prevents their widespread adoption. Nonetheless, as tissue engineers continue to develop on their strategies and procedures for improved TEVGs, soon, a reliable engineered graft will be available in the market. Hence, we anticipate a viable TEVG with resorbable property, fabricated
via
electrospinning approach to hold a greater potential that can overcome the challenges observed in both autologous and allogenic grafts. This is because they can be mechanically tuned, incorporated/surface-functionalized with bioactive molecules and mass-manufactured in a reproducible manner. It is also found that most of the success in engineered vascular graft approaching commercialization is for large vessels rather than small-diameter grafts used as cardiovascular bypass grafts. Consequently, the field of vascular engineering is still available for future innovators that can take up the challenge to create a functional arterial substitute.
Objective
Evidence for the utility of medications in settings lacking randomized trial data can come from studies of treatment persistence. The present study was undertaken to examine patterns of ...medication use in systemic lupus erythematosus (SLE) using data from a large multicenter longitudinal cohort.
Methods
Prospectively collected data from the Asia Pacific Lupus Collaboration cohort including disease activity (SLE Disease Activity Index 2000 SLEDAI‐2K) and medication details, captured at every visit from 2013–2018, were used. Medications were categorized as glucocorticoids (GCs), antimalarials (AM), and immunosuppressants (IS). Cox regression analyses were performed to determine the time‐to‐discontinuation of medications, stratified by SLE disease activity.
Results
Data from 19,804 visits of 2,860 patients were analyzed. Eight medication categories were observed: no treatment; GC, AM, or IS only; GC plus AM; GC plus IS; AM plus IS; and GC plus AM plus IS (triple therapy). Triple therapy was the most frequent pattern (31.4% of visits); single agents were used in 21% of visits, and biologics in only 3%. Time‐to‐discontinuation analysis indicated that medication persistence varied widely, with the highest treatment persistence for AM and lowest for IS. Patients with a time‐adjusted mean SLEDAI‐2K score of ≥10 had lower discontinuation of GCs and higher discontinuation of IS.
Conclusion
Most patients received combination treatment. GC persistence was high, while IS persistence was low. Patients with high disease activity received more medication combinations but had reduced IS persistence, consistent with limited utility. These data confirm unmet need for improved SLE treatments.
The objectives of this study are to identify the prevalence and incidence of rheumatoid arthritis (RA) and to investigate the patterns of medical care and drug utilization by RA patients in Korea. ...Korean National Health Insurance claims data were used for analysis. RA patients were defined as those having an RA code from 2009 to 2012 and using disease-modifying anti-rheumatic drugs (DMARDs) within 1 year after the code. RA patients identified in 2010 with a disease-free period for 12 months before the index date, and those who received continuous treatment in 2011–2013 were defined as incident cases. Patterns of medical care and drug utilization were compared among subgroups. The prevalence of RA increased yearly from 0.28% in 2009 to 0.32% in 2012. The incidence of RA in 2010 was 28.5 per 100,000 person-years. The use of biologic DMARDs (bDMARDs) increased from 2.31% in 2009 to 4.05% in 2012. Hydroxychloroquine (57.53–62.45%) was the most commonly used the conventional DMARDs, followed by methotrexate (49.99–51.87%). The use of bDMARDs (1.39 vs. 2.43%) was less frequent in EORA patients than YORA patients. Hydroxychloroquine (74.96 vs. 72.11%) was more frequently used, but methotrexate (55.24 vs. 59.25%) and sulfasalazine (27.96 vs. 32.72%) were used less frequently in EORA patients than in YORA patients. The prevalence of RA has increased in Korea. EORA patients used fewer bDMARDs, methotrexate, and sulfasalazine but more hydroxychloroquine than YORA patients.
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