Diol or Hydrogen Peroxide-responsive Micellar Systems and Their Rheological Properties.

External stimuli-responsive worm-like micelles (WLMs) have the potential for a wide range of applications. In particular, sugar (a polyol compound)-responsive WLMs have the potential for use in smartdrug release systems. Phenylboronic acid (PBA) functions as a cis-diol sensor in a similar manner it does as a glucose sensor. Thus, WLMs, primarily composed of surfactants and PBA, are expected to function as cis-diol-responsive viscoelastic systems. PBA also reacts irreversibly with hydrogen peroxide (H2O2 ) and is converted into phenol and boric acid. H2O2 is one of reactive oxygen species crucial for several physiological processes. Therefore, H2O2 -responsive WLMs have the potential for various applications. In this review, we describe cis-diol- and H2O2 -responsive micellar systems composed of cetyltrimethylammonium bromide and PBA moieties that shift their viscosities in response to stimuli.

Phenylboronate-salicylate ester cross-linked self-healing hydrogel composed of modified hyaluronan at physiological pH.

Several hydrogels with boronate/diol ester cross-linking have been reported. However, multiple synthetic steps or expensive reagents are required to modify some diol moieties into polymers. Therefore, diol-modified polymers, which are easily and inexpensively prepared via a single-step process, are required for the formation of boronate esters. This study reports a novel hydrogel composed of phenylboronic acid-modified hyaluronic acid and salicylic acid-modified hyaluronic acid. This hydrogel is injectable, can self-heal at physiological pH, and can be easily and inexpensively prepared. The polymer system behaved as a sol at pH 12.0 and a weak gel at pH 9.4 and 11.2, whereas it behaved as a gel over a wide pH range of 4.0-8.2. The viscoelasticity of the system decreased in response to sugar at pH 7.3. Thus, salicylic acid can be considered a promising diol moiety for hydrogel formation via boronate ester cross-linking.

Draft genome sequence of the basidiomycetous yeast Mrakia hoshinonis JCM 32575T isolated from Ellesmere Island, Canadian High Arctic.

Mrakia hoshinonis JCM 32575 was isolated from glacial sediments on Ellesmere Island in the Canadian High Arctic and described as a new basidiomycetous yeast. This species does not require amino acids and vitamins for growth and can grow at sub-zero temperatures. Here, we report a draft genome sequence of this strain.

Long-term Consequences on Soil Fungal Community Structure: Monoculture Planting and Natural Regeneration.

Understanding the regeneration and succession of belowground communities, particularly in forests, is vital for maintaining ecosystem health. Despite its importance, there is limited knowledge regarding how fungal communities change over time during ecosystem development, especially under different forest restoration strategies. In this study, we focused on two restoration methods used in northern Japan: monoculture planting and natural regeneration. We examined the responses of the fungal community to monoculture plantations (active tree planting) and naturally regenerated (passive regeneration) forests over a 50-year chronosequence, using natural forests as a reference. Based on DNA metabarcoding, we assessed the richness of fungal Operational Taxonomic Units (OTUs) and their dissimilarity. Our findings revealed that soil fungal richness remained stable after natural regeneration but declined in monoculture plantations, from 354 to 247 OTUs. While the compositional dissimilarity of fungal assemblages between monoculture plantations and natural forests remained consistent regardless of the time since tree planting, it significantly decreased after natural regeneration, suggesting recovery to a state close to the reference level. Notably, the composition of key functional fungal groups-saprotrophic and ectomycorrhizal- has increasingly mirrored that of natural forests over time following passive natural regeneration. In summary, our study suggests that monoculture plantations may not be effective for long-term ecosystem function and service recovery because of their limited support for soil fungal diversity. These results underscore the importance of natural regeneration in forest restoration and management strategies.

Synergistic effects of succession and microtopography of moraine on the fungal spatial diversity in a glacier forefield.

Primary succession and microtopography result in environmental changes and are important processes influencing the community assembly of soil fungi in the Arctic region. In glacier forefields that contain a series of moraine ridges, both processes contribute synchronously to fungal spatial diversity. To reveal the synergistic effects of succession and microtopography, we investigated the fungal community structure and environmental variables in the moraines of the Arklio Glacier, Ellesmere Island. The study sites were established at four locations from the top to the bottom of the ridge slope within each of the three moraine ridges of different post-glacial ages. The location-dependent community composition was equally diverse in both the initial and later stages of succession, suggesting that successional time could alter the effects of microtopography on the fungal community. Moreover, our results suggest that fungal communities at different locations follow different successional trajectories, even if they have passed through the same time lapse. Such a synergistic effect of succession and microtopography of moraines does not allow for parallel changes in fungal communities among moraines or among locations, suggesting that the moraine series contributes substantially to fungal spatial diversity in the glacier forefield.

Higher-Order VLP-Based Protein Macromolecular Framework Structures Assembled via Coiled-Coil Interactions.

Hierarchical organization is one of the fundamental features observed in biological systems that allows for efficient and effective functioning. Virus-like particles (VLPs) are elegant examples of a hierarchically organized supramolecular structure, where many subunits are self-assembled to generate the functional cage-like architecture. Utilizing VLPs as building blocks to construct two- and three-dimensional (3D) higher-order structures is an emerging research area in developing functional biomimetic materials. VLPs derived from P22 bacteriophages can be repurposed as nanoreactors by encapsulating enzymes and modular units to build higher-order catalytic materials via several techniques. In this study, we have used coiled-coil peptide interactions to mediate the P22 interparticle assembly into a highly stable, amorphous protein macromolecular framework (PMF) material, where the assembly does not depend on the VLP morphology, a limitation observed in previously reported P22 PMF assemblies. Many encapsulated enzymes lose their optimum functionalities under the harsh conditions that are required for the P22 VLP morphology transitions. Therefore, the coiled-coil-based PMF provides a fitting and versatile platform for constructing functional higher-order catalytic materials compatible with sensitive enzymes. We have characterized the material properties of the PMF and utilized the disordered PMF to construct a biocatalytic 3D material performing single- and multistep catalysis.

Fabrication of Protein Macromolecular Frameworks (PMFs) and Their Application in Catalytic Materials.

The construction of three-dimensional (3D) array materials from nanoscale building blocks has drawn significant interest because of their potential to exhibit collective properties and functions arising from the interactions between individual building blocks. Protein cages such as virus-like particles (VLPs) have distinct advantages as building blocks for higher-order assemblies because they are extremely homogeneous in size and can be engineered with new functionalities by chemical and/or genetic modification. In this chapter, we describe a protocol for constructing a new class of protein-based superlattices, called protein macromolecular frameworks (PMFs). We also describe an exemplary method to evaluate the catalytic activity of enzyme-enclosed PMFs, which exhibit enhanced catalytic activity due to the preferential partitioning of charged substrates into the PMF.

Vegetation as a key driver of the distribution of microbial generalists that in turn shapes the overall microbial community structure in the low Arctic tundra.

Understanding the variability of microbial niches and their interaction with abiotic and biotic factors in the Arctic can provide valuable insights into microbial adaptations to extreme environments. This study investigates the structure and diversity of soil bacterial communities obtained from sites with varying vegetation coverage and soil biogeochemical properties in the low Arctic tundra and explores how bacteria interact under different environmental parameters. Our findings reveal differences in bacterial composition and abundance among three bacterial niche breadths (specialists, common taxa, and generalists). Co-occurrence network analysis revealed Rhizobiales and Ktedonobacterales as keystone taxa that connect and support other microbes in the habitat. Low-elevation indicators, such as vascular plants and moisture content, were correlated with two out of three generalist modular hubs and were linked to a large proportion of generalists' distribution (18%). Structural equation modeling revealed that generalists' distribution, which influenced the remaining microbial communities, was mainly regulated by vegetation coverage as well as other abiotic and biotic factors. These results suggest that elevation-dependent environmental factors directly influence microbial community structure and module formation through the regulation of generalists' distribution. Furthermore, the distribution of generalists was mainly affected by macroenvironment filtering, whereas the distribution of specialists was mainly affected by microenvironment filtering (species-engineered microbial niche construction). In summary, our findings highlight the strong top-down control exerted by vegetation on generalists' distribution, which in turn shapes the overall microbial community structure in the low Arctic tundra.

Anomalous glucose-responsive rheological changes in a boronic acid-modified hyaluronan.

Herein, we report anomalous glucose (Glc)-responsive gelation/solation in 3-aminophenylboronic acid-modified hyaluronic acid. With 5-20 mM Glc, gelation occurred, resulting in the formation of crosslinks via Glc, which could reversibly bind to the two boronic acid sites. Solation was induced at Glc concentrations of >80 mM.

Comparison of the efficacy and safety of standard- and high-dose daptomycin: A systematic review and meta-analysis.

AIMS: Standard doses of daptomycin at 4 and 6 mg/kg were used for the treatment of skin and soft tissue for infections and bacteraemia, respectively. However, increased doses of daptomycin are recommended for complicated infections by Gram-positive organisms. METHODS: A systematic review was conducted using 4 databases. We compared treatment success between standard-dose (SD, 4-6 mg/kg) and high-dose (HD, >6 mg/kg) daptomycin in patients with all-cause bacteraemia, complicated bacteraemia, infective endocarditis, osteomyelitis and foreign body/prosthetic infection as the primary outcome. We also compared the success between SD and HD2 (≥8 mg/kg) daptomycin treatments in patients with these diseases as the secondary outcome. The incidence of creatine phosphokinase (CPK) elevation was evaluated as safety. RESULTS: In patients with complicated bacteraemia and infective endocarditis, the treatment success was significantly lower in the SD group than in the HD group (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30-0.76 and OR 0.50, 95% CI 0.30-0.82) and HD2 group (OR 0.38, 95% CI 0.21-0.69 and OR 0.30, 95% CI 0.15-0.60), respectively. A significant difference was demonstrated only in the HD2 group in patients with bacteraemia, including simple infection. SD did not decrease the success rate for the treatment of osteomyelitis and foreign body/prosthetic infection. The incidence of elevated CPK was significantly lower in SD group than in HD group. CONCLUSION: SD daptomycin was associated with significantly lower treatment success than HD in patients with complicated bacteraemia/infective endocarditis. The CPK elevation should be considered in patients treated with high daptomycin doses.

Discrepancies of fungi and plants in the pattern of beta-diversity with environmental gradient imply a comprehensive community assembly rule.

Beta-diversity partitioning has shown that the nestedness component is developed with environmental stress in a variety of taxa. However, soil fungal community may maintain its turnover components in contrast to the development of plants' nestedness component, and the potential causes remain unclear. To investigate the process of species turnover of soil fungi along a stress gradient in the Arctic, we divided species turnover component into sub-components: ßsim_hete and ßsim_homo representing species turnover with and without a change in the guilds, respectively. The results indicate that fungal communities maintain their turnover components, unlike plant communities; however, their ßsim_hete increased under stressful conditions. Additionally, GDM analysis showed that ßsim_hete was mainly explained by stress gradient and plant nestedness, suggesting that the functionality of soil fungi was ecologically filtered by environmental stress and plant community structure. The discordant trend of beta-diversity values between plant and fungi (i.e. development of plant nestedness and maintenance of fungal turnover) is possibly not caused by different assembly rules working in parallel on the two taxa, but according to an ecological rule that reflects plant-fungal interaction.

A Case of Exacerbation of Haloperidol-Induced Rhabdomyolysis Following the Onset of COVID-19.

BACKGROUND Rhabdomyolysis is a condition in which intracellular components are released into the blood and urine. Rhabdomyolysis can be caused by drug-related complications and COVID-19; however, the underlying mechanism is not clear. In this study, we report a case of rhabdomyolysis complicated by COVID-19, in which we presumed that the cause of rhabdomyolysis was related to prior administration of haloperidol by assessment of the drug history and progression of myopathy. CASE REPORT A 52-year-old man with schizophrenia experienced worsening insomnia 10 days before admission. Thus, haloperidol was increased from 1.5 mg to 3 mg once daily, and 2 to 3 days later, he developed hand tremors and weakness. One day prior to admission, the patient suddenly developed severe back pain. Based on the examination, the patient was diagnosed with COVID-19 complicated with rhabdomyolysis. Laboratory findings on admission were as follows: creatine phosphokinase: 41 539 IU/L; urinary myoglobin, 190×10³ ng/mL; and hematuria scale, grade 4. On day 1, he was started on saline infusion; therefore, haloperidol was discontinued. On day 2, the hematuria resolved. On day 5, the tremor, weakness, and back pain had resolved. On day 7, his creatine kinase level was 242 IU/L, and saline was administered. CONCLUSIONS It has been suggested that the onset of COVID-19 can exacerbate haloperidol-induced rhabdomyolysis. Therefore, if there is a complication of rhabdomyolysis and COVID-19, it is important to review the drug history, specifically that of haloperidol. We recommend hydration and discontinuation of haloperidol to avoid acute kidney injury, in addition to treating COVID-19.

Multilayered Ordered Protein Arrays Self-Assembled from a Mixed Population of Virus-like Particles.

Biology shows many examples of spatially controlled assembly of cells and biomacromolecules into hierarchically organized structures, to which many of the complex biological functions are attributed. While such biological structures have inspired the design of synthetic materials, it is still a great challenge to control the spatial arrangement of individual building blocks when assembling multiple types of components into bulk materials. Here, we report self-assembly of multilayered, ordered protein arrays from mixed populations of virus-like particles (VLPs). We systematically tuned the magnitude of the surface charge of the VLPs via mutagenesis to prepare four different types of VLPs for mixing. A mixture of up to four types of VLPs selectively assembled into higher-order structures in the presence of oppositely charged dendrimers during a gradual lowering of the ionic strength of the solution. The assembly resulted in the formation of three-dimensional ordered VLP arrays with up to four distinct layers including a central core, with each layer comprising a single type of VLP. A coarse-grained computational model was developed and simulated using molecular dynamics to probe the formation of the multilayered, core-shell structure. Our findings establish a simple and versatile bottom-up strategy to synthesize multilayered, ordered materials by controlling the spatial arrangement of multiple types of nanoscale building blocks in a one-pot fabrication.

The Efficacy of Expiratory Muscle Training during Inspiratory Load in Healthy Adult Males: A Randomized Controlled Trial.

This study aimed to evaluate the effects of expiratory muscle training (EMT) on respiratory muscle strength and respiratory distress during inspiratory load. Thirty-one healthy adult males were randomly divided into an EMT group who underwent EMT (n = 15) and a control group who did not undergo EMT (n = 16). The EMT group underwent EMT with a 50% load of maximum expiratory mouth pressure (PEmax) for 15 min, twice a day, every day, for 4 weeks. The parameter of respiratory muscle fatigue was a decrease in maximum inspiratory mouth pressure (PImax) and PEmax during 20 min of inspiratory load; thus, PImax and PEmax during inspiratory load were measured. Respiratory distress during inspiratory load was assessed using the Borg scale. These assessments were performed on the same subjects in each group before and after the 4 week study. In the EMT group, the PEmax values after the study were significantly higher than those before the study (p < 0.01). Furthermore, before the study, the PImax and PEmax values for the EMT group during inspiratory load were significantly lower than those before inspiratory load (p < 0.01). However, after the study, there was no difference in these values between during and before inspiratory load. In the EMT group, the Borg scale value during inspiratory load from 6 to 20 min was significantly lower after the study than before the study (p < 0.05). EMT increases expiratory muscle strength, thereby attenuating decreased respiratory muscle strength (PImax and PEmax) and respiratory distress during inspiratory load in healthy subjects.

Diol responsive viscosity increase in a cetyltrimethylammonium bromide/sodium salicylate/3-fluorophenylboronic acid micelle system.

We report a novel smart micellar system utilising a phenylboronic acid (PBA) derivative whose viscosity increases on adding diol compounds such as sugar or sugar alcohol. We prepared a typical worm-like micelle (WLM) system in 100 mM cetyltrimethylammonium bromide (CTAB)/70 mM sodium salicylate (NaSal), which showed high zero-shear viscosity (η 0). Upon the addition of 20 mM 3-fluorophenylboronic acid (3FPBA) to the WLM system, η 0 decreased by 1/300 that of the system without 3FPBA. Furthermore, upon the addition of 1.12 M fructose (Fru) and 1.12 M sorbitol (Sor) to the CTAB/NaSal/3FPBA system, η 0 increased by 50-fold and 30-fold, respectively. 19F NMR spectral results of the systems using 4-fluorosalicylic acid (FSal) instead of NaSal demonstrated that the FSal/3FPBA-complex interacts with CTAB. Moreover, the addition of sugar or sugar alcohol to the micellar system leads to a decrease in the amount of FSal/3FPBA-complex interacting with CTA+ and an increase in the amount of 3FPBA/Fru or Sor-complex, which does not interact with CTA+. These changes in molecular interactions induce the elongation of the WLMs and increase the viscosity of the system. This system utilises the competitive cyclic ester bond between the NaSal/3FPBA and 3FPBA/sugar or sugar alcohol to induce viscosity changes.

Harnessing physicochemical properties of virus capsids for designing enzyme confined nanocompartments.

Viruses have drawn significant scientific interest from a wide variety of disciplines beyond virology because of their elegant architectures and delicately balanced activities. A virus-like particle (VLP), a noninfectious protein cage derived from viruses or other cage-forming proteins, has been exploited as a nano-scale platform for bioinspired engineering and synthetic manipulation with a range of applications. Encapsulation of functional proteins, especially enzymes, is an emerging use of VLPs that is promising not only for developing efficient and robust catalytic materials, but also for providing fundamental insights into the effects of enzyme compartmentalization commonly observed in cells. This review highlights recent advances in employing VLPs as a container for confining enzymes. To accomplish larger and more controlled enzyme loading, various different enzyme encapsulation strategies have been developed; many of these strategies are inspired from assembly and genome loading mechanisms of viral capsids. Characterization of VLPs' physicochemical properties, such as porosity, could lead to rational manipulation and a better understanding of the catalytic behavior of the materials.

Incidence of elevated creatine phosphokinase between daptomycin alone and concomitant daptomycin and statins: A systematic review and meta-analysis.

AIMS: The present systematic review and meta-analysis evaluated the incidence of elevated creatine phosphokinase (CPK) levels between daptomycin alone and concomitant daptomycin and statin use. METHODS: We searched the PubMed, Web of Sciences, Cochrane Library and ClinicalTrials.gov databases. We analysed the incidence of elevated CPK between daptomycin alone and concomitant daptomycin and statins among studies defining CPK elevation as levels ≥ the upper limit of normal (ULN) or ≥5× ULN. We also analysed the incidence of rhabdomyolysis between the groups. We then calculated the odds ratios (ORs) and 95% confidence intervals (CIs) based on the included studies. RESULTS: Comparing CPK elevation defined as CPK levels ≥ULN, a significantly higher incidence of CPK elevation was observed with concomitant daptomycin and statin use than with daptomycin alone (OR = 2.55, 95% CI 1.78-3.64, P < .00001, I2  = 0%). Likewise, when CPK elevation was defined as CPK levels ≥5× ULN, a significantly higher incidence of CPK elevation was detected with concomitant daptomycin and statin use than with daptomycin alone (OR = 1.89, 95% CI 1.06-3.35, P = .03, I2  = 48%). The incidence of rhabdomyolysis was significantly higher following concomitant daptomycin and statin use than with daptomycin alone (OR = 11.60, 95% CI 1.81-74.37, P = .01, I2  = 0%). CONCLUSION: The combined use of daptomycin and statins were significant risk factors for the incidence of CPK elevation defined as levels ≥ULN or ≥5× ULN and rhabdomyolysis.

Identification of Risk Factors for Daptomycin-Associated Creatine Phosphokinase Elevation and Development of a Risk Prediction Model for Incidence Probability.

BACKGROUND: In this study, we investigated the risk factors for daptomycin-associated creatine phosphokinase (CPK) elevation and established a risk score for CPK elevation. METHODS: Patients who received daptomycin at our hospital were classified into the non-elevated or elevated CPK group based on their peak CPK levels during daptomycin therapy. Univariable and multivariable analyses were performed, and a risk score and prediction model for the incidence probability of CPK elevation were calculated based on logistic regression analysis. RESULTS: The non-elevated and elevated CPK groups included 181 and 17 patients, respectively. Logistic regression analysis revealed that concomitant statin use (odds ratio [OR], 4.45 [95% confidence interval {CI}, 1.40-14.47]; risk score 4), concomitant antihistamine use (OR, 5.66 [95% CI, 1.58-20.75]; risk score 4), and trough concentration (Cmin) between 20 and <30 µg/mL (OR, 14.48 [95% CI, 2.90-87.13]; risk score 5) and ≥30.0 µg/mL (OR, 24.64 [95% CI, 3.21-204.53]; risk score 5) were risk factors for daptomycin-associated CPK elevation. The predicted incidence probabilities of CPK elevation were <10% (low risk), 10%-<25% (moderate risk), and ≥25% (high risk) with total risk scores of ≤4, 5-6, and ≥8, respectively. The risk prediction model exhibited a good fit (area under the receiver operating characteristic curve, 0.85 [95% CI, .74-.95]). CONCLUSIONS: These results suggested that concomitant use of statins with antihistamines and Cmin ≥20 µg/mL were risk factors for daptomycin-associated CPK elevation. Our prediction model might aid in reducing the incidence of daptomycin-associated CPK elevation.

Above-ordering-temperature large anomalous Hall effect in a triangular-lattice magnetic semiconductor.

While anomalous Hall effect (AHE) has been extensively studied in the past, efforts for realizing large Hall response have been mainly limited within intrinsic mechanism. Lately, however, a theory of extrinsic mechanism has predicted that magnetic scattering by spin cluster can induce large AHE even above magnetic ordering temperature, particularly in magnetic semiconductors with low carrier density, strong exchange coupling, and finite spin chirality. Here, we find out a new magnetic semiconductor EuAs, where Eu2+ ions with large magnetic moments form distorted triangular lattice. In addition to colossal magnetoresistance, EuAs exhibits large AHE with an anomalous Hall angle of 0.13 at temperatures far above antiferromagnetic ordering. As also demonstrated by model calculations, observed AHE can be explained by the spin cluster scattering in a hopping regime. Our findings shed light on magnetic semiconductors hosting topological spin textures, developing a field targeting diluted carriers strongly coupled to noncoplanar spin structures.

Functionally explicit partitioning of plant ß-diversity reveal soil fungal assembly in the subarctic tundra.

Metabarcoding technologies for soil fungal DNA pools have enabled to capture the diversity of fungal community and the agreement of their ß-diversity with plant ß-diversity. However, processes underlying the synchrony of the aboveground-belowground biodiversity is still unclear. By using partitioning methods for plant ß-diversity, this study explored the process driving synchrony in tundra ecosystems, in which drastic vegetation shifts are observed with climate warming. Our methods based on Baselga's partitioning enabled the division of plant ß-diversity into two phenomena and three functional components. Correlation of fungal ß-diversity with the components of plant ß-diversity showed that the spatial replacement of fungi was promoted by plant species turnover, in particular, plant species turnover with functional exchange. In addition, spatial variety of graminoid or forbs species, rather than shrubs, enhanced fungal ß-diversity. These results suggest the importance of small-scale factors such as plant-fungal interactions or local environments modified by plants for the fungal community assemblage. The process-based understanding of community dynamics of plants and fungi allows us to predict the ongoing shrub encroachment in the Arctic region, which could weaken the aboveground-belowground synchrony.