High-Resolution Single-Molecule Magnetic Tweezers.

Single-molecule magnetic tweezers deliver magnetic force and torque to single target molecules, permitting the study of dynamic changes in biomolecular structures and their interactions. Because the magnetic tweezer setups can generate magnetic fields that vary slowly over tens of millimeters-far larger than the nanometer scale of the single molecule events being observed-this technique can maintain essentially constant force levels during biochemical experiments while generating a biologically meaningful force on the order of 1-100 pN. When using bead-tether constructs to pull on single molecules, smaller magnetic beads and shorter submicrometer tethers improve dynamic response times and measurement precision. In addition, employing high-speed cameras, stronger light sources, and a graphics programming unit permits true high-resolution single-molecule magnetic tweezers that can track nanometer changes in target molecules on a millisecond or even submillisecond time scale. The unique force-clamping capacity of the magnetic tweezer technique provides a way to conduct measurements under near-equilibrium conditions and directly map the energy landscapes underlying various molecular phenomena. High-resolution single-molecule magnetic tweezerscan thus be used to monitor crucial conformational changes in single-protein molecules, including those involved in mechanotransduction and protein folding.

Evolutionary balance between foldability and functionality of a glucose transporter.

Despite advances in resolving the structures of multi-pass membrane proteins, little is known about the native folding pathways of these complex structures. Using single-molecule magnetic tweezers, we here report a folding pathway of purified human glucose transporter 3 (GLUT3) reconstituted within synthetic lipid bilayers. The N-terminal major facilitator superfamily (MFS) fold strictly forms first, serving as a structural template for its C-terminal counterpart. We found polar residues comprising the conduit for glucose molecules present major folding challenges. The endoplasmic reticulum membrane protein complex facilitates insertion of these hydrophilic transmembrane helices, thrusting GLUT3's microstate sampling toward folded structures. Final assembly between the N- and C-terminal MFS folds depends on specific lipids that ease desolvation of the lipid shells surrounding the domain interfaces. Sequence analysis suggests that this asymmetric folding propensity across the N- and C-terminal MFS folds prevails for metazoan sugar porters, revealing evolutionary conflicts between foldability and functionality faced by many multi-pass membrane proteins.

Distinct handedness of spin wave across the compensation temperatures of ferrimagnets.

Antiferromagnetic spin waves have been predicted to offer substantial functionalities for magnonic applications due to the existence of two distinct polarizations, the right-handed and left-handed modes, as well as their ultrafast dynamics. However, experimental investigations have been hampered by the field-immunity of antiferromagnets. Ferrimagnets have been shown to be an alternative platform to study antiferromagnetic spin dynamics. Here we investigate thermally excited spin waves in ferrimagnets across the magnetization compensation and angular momentum compensation temperatures using Brillouin light scattering. Our results show that right-handed and left-handed modes intersect at the angular momentum compensation temperature where pure antiferromagnetic spin waves are expected. A field-induced shift of the mode-crossing point from the angular momentum compensation temperature and the gyromagnetic reversal reveal hitherto unrecognized properties of ferrimagnetic dynamics. We also provide a theoretical understanding of our experimental results. Our work demonstrates important aspects of the physics of ferrimagnetic spin waves and opens up the attractive possibility of ferrimagnet-based magnonic devices.

Publisher Correction: Distinct handedness of spin wave across the compensation temperatures of ferrimagnets.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Fast-switching optically isotropic liquid crystal nano-droplets with improved depolarization and Kerr effect by doping high k nanoparticles.

We proposed and analyzed an optically isotropic nano-droplet liquid crystal (LC) doped with high k nanoparticles (NPs), exhibiting enhanced Kerr effects, which could be operated with reduced driving voltages. For enhancing the contrast ratio together with the light efficiencies, the LC droplet sizes were adjusted to be shorter than the wavelength of visible light to reduce depolarization effects by optical scattering of the LC droplets. Based on the optical analysis of the depolarization effects, the influence of the relationship between the LC droplet size and the NP doping ratio on the Kerr effect change was investigated.

HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr⁻/⁻ mice.

HL-217 is a new synthetic angiogenesis inhibitor. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. In this study, we examined the mechanism of action and efficacy of topical application of HL-217 on subretinal neovascularization in very low-density lipoprotein receptor knockout (Vldlr(-/-)) mice. In three-week-old male Vldlr(-/-) mice, HL-217 (1.5 or 3mg/ml) was administered twice per day for 4 weeks by topical eye drop instillation. Neovascular areas were then measured. We used a protein array to evaluate the expression levels of angiogenic factors. The inhibitory effect of HL-217 on the PDGF-BB/PDGFRß interaction was evaluated in vitro. The neovascular area in the Vldlr(-/-) mice was significantly reduced by HL-217. Additionally, HL-217 decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, HL-217 dose-dependently inhibited the PDGF-BB/PDGFRß interaction (IC50=38.9 ± 0.7 µM). These results suggest that HL-217 is a potent inhibitor of PDGF-BB. HL-217, when applied topically, is an effective inhibitor of subretinal neovascularization due to its ability to inhibit the pro-angiogenic effects of PDGF-BB.

Encapsulation of TiO2 nanoparticles with poly(4-vinylpyridine) using surface functionalized thiol-lactam initiated radical polymerization.

A nanocomposite of TiO2 nanoparticle with an electroactive poly(4-vinylpyridine) (PVP) was synthesized via a simple surface thiol-lactam initiated radical polymerization upon grafting from protocol. This can be achieved through the primary modification of the TiO2 surface with a silane coupling agent leading to thiol functionalized TiO2 (TiO2-SH). Subsequently, a controlled radical polymerization of 4-vinylpyridine in the presence of TiO2-SH and butyrolactam afforded PVP-g-TiO2 nanocomposites. The grafting of PVP on the surface of TiO2 was confirmed by FT-IR, TGA, XPS, EDX, TEM and SEM analyses. The UV-vis studies of the synthesized PVP-g-TiO2 nanocomposite demonstrated an exceptionally good dispersibility in organic solvents.

A facile route towards the synthesis of polystyrene/zinc oxide nanocomposites.

ZnO nanoparticles were covalently wrapped by polystyrene (PS) through surface thiol-lactam initiated radical polymerization using the grafting from approach. The surface of ZnO nanoparticles was initially modified by 3-mercapto propyltrimethoxysilane to afford thiol functionalized ZnO nanoparticles (ZnO-SH). The controlled radical polymerization of styrene (St) was subsequently accomplished by using an initiating system of ZnO-SH and butyrolactam. FT-IR, XPS, XRD, TGA, DSC, TEM and DLS were employed to investigate the chemical structure, morphology, thermal properties, the size and size distribution of nanocomposites. The dispersibility of ZnO nanoparticles was observed to be significantly improved upon functionalization by PS brushes. The controlled nature of the surface initiated thiol-lactam aided polymerization of St from the ZnO nanoparticles surface was confirmed by GPC analysis.

High-Speed Magnetic Tweezers for Nanomechanical Measurements on Force-Sensitive Elements.

Single-molecule magnetic tweezers (MTs) have served as powerful tools to forcefully interrogate biomolecules, such as nucleic acids and proteins, and are therefore poised to be useful in the field of mechanobiology. Since the method commonly relies on image-based tracking of magnetic beads, the speed limit in recording and analyzing images, as well as the thermal fluctuations of the beads, has long hampered its application in observing small and fast structural changes in target molecules. This article describes detailed methods for the construction and operation of a high-resolution MT setup that can resolve nanoscale, millisecond dynamics of biomolecules and their complexes. As application examples, experiments with DNA hairpins and SNARE complexes (membrane-fusion machinery) are demonstrated, focusing on how their transient states and transitions can be detected in the presence of piconewton-scale forces. We expect that high-speed MTs will continue to enable high-precision nanomechanical measurements on molecules that sense, transmit, and generate forces in cells, and thereby deepen our molecular-level understanding of mechanobiology.

Association of the etiology and peak level of markedly elevated aminotransferases with mortality: a multicenter study.

BACKGROUND: Markedly elevated aminotransferase levels are commonly encountered among hospitalized patients. However, data regarding the trajectory of enzyme elevation and disease-specific prognosis are limited. METHODS: This study included 3237 patients with at least one episode of aspartate aminotransferase or alanine aminotransferase level being higher than 400 U/L between January 2010 and December 2019 at 2 centers. Patients were classified into 5 groups comprising 13 diseases according to etiology. Factors associated with 30-day mortality were evaluated using a logistic regression analysis. RESULTS: The most common disease leading to markedly elevated aminotransferase level was ischemic hepatitis (33.7%), followed by pancreatobiliary disease (19.9%), DILI (12.0%), malignancy (10.8%), and viral hepatitis (7.0%). The 30-day all-cause mortality rate was 21.6%. The mortality rate for patients from the pancreatobiliary, hepatocellular, extrahepatic, malignancy, and ischemic hepatitis groups was 1.7%, 3.2%, 13.8%, 39.9%, and 44.2%, respectively. Age, etiology, and peak aminotransferase levels were independently associated with 30-day mortality. CONCLUSIONS: In patients with markedly elevated liver enzymes, the etiology and peak AST level are significantly associated with mortality.

Case report of laryngeal infection by Clinostomum complanatum 24 days after ingestion of raw fish.

RATIONALE: Clinostomum complanatum is a laryngeal fluke whose hosts include birds and mammals.[1] In humans, infection occurs accidentally during the consumption of raw freshwater fish.[1,2]. PATIENT CONCERNS: A 59-year-old female presented to our hospital with throat pain and globus sensation. The patient had been prescribed Proton Pump Inibitor for 3 weeks at another hospital. The patient continued the medication, but the discomfort persisted, and she was admitted to our hospital for further examination. The patient had eaten raw fish 24 days before, and the symptoms occurred after eating the raw fish. Endoscopy under sedation showed a fluke, with an approximate length of 8.0 mm and width of 3.2 mm, on the interaryepiglottic fold, with active motility on the mucosa. DIAGNOSIS INTERVENTIONS: It was extracted from the larynx using biopsy forceps and identified as C complanatum. OUTCOMES: After the fluke was removed, symptoms improved, and the patient was discharged. The globus symptoms completely resolved at the last follow-up visit. LESSONS: To the best of our knowledge, this is an endoscopically diagnosed and treated case of human infection by C complanatum in Korea after the longest period of infection. This suggests that C complanatum can survive for up to 3 weeks or more in the gastrointestinal tract. Endoscopy is a useful tool for the diagnosis and treatment of patients with atypical extraesophageal symptoms who do not respond to Proton Pump Inibitors.

Fabrication of gold nanoparticle/multi walled carbon nanotube hybrids by in situ reaction in water using poly(acryloyl beta-alanine).

Fabrication of a hybrid consists of gold nanoparticles and multi walled carbon nanotubes (MWCNTs) with the help of poly (amino acid) was investigated. Poly(acryloyl beta-alanine) was synthesized by precipitation polymerization in tetrahydrofuran. The polymers were used to form hybrids with MWCNTs in aqueous media. Subsequently, the polymer functionalized MWCNTs were fabricated by in situ formed gold nanoparticles. The fabrication by gold nanoparticles was confirmed by transmission electron microscopic analyses. The fabrication was attempted with different concentrations of lithium auric chloride solutions in the range of 0.1-1.2 mM in water. The lower concentration of the gold precursor solution resulted in the formation and attachment of gold nanoparticles without aggregation while the higher concentration above 1.0 mM led to the aggregation of gold nanoparticles. The gold nanoparticles were observed only on the surface of MWCNTs and none was in the bulk aqueous phase.

Polymer brushes on carbon nanotubes by thiol-lactam initiated radical polymerization of 2-hydroxyethyl methacrylate.

Water-soluble polymer brushes with multi-walled carbon nanotubes (MWNTs) as backbones were synthesized by grafting 2-hydroxyethyl methacrylate (HEMA) from surface functionalized MWNTs via in situ surface thiol-lactam initiated radical polymerization. MWNTs were functionalized with 2-mercaptoethanol and used as initiators in the polymerization of HEMA in the presence of butyrolactam. FT-IR, XPS, 1H NMR, GPC and TGA were used to determine chemical structure and the grafted polymer quantities of the resulting product. The covalent bonding of PHEMA to the MWNTs dramatically improved the water dispersibility of MWNTs. The average thicknesses of the polymer brushes in the functionalized MWNTs were detected with electron microscopy (SEM and TEM) and images indicated that the nanotubes were coated with polymer layer.

Healing Ion-Implanted Semiconductors by Hybrid Microwave Annealing: Activation of Nitrogen-Implanted TiO2.

In order to recover the damaged structure of a nitrogen-implanted TiO2 (N-I-TiO2) photoanode, hybrid microwave annealing (HMA) is proposed as an alternative postannealing process instead of conventional thermal annealing (CTA). Compared to CTA, HMA provides distinctive advantages: (i) facile transformation of the interstitial N-N states into substitutional N-Ti states, (ii) better preservation of the ion-implanted nitrogen in TiO2, and (iii) effective alleviation of lattice strain and reconstruction of the broken bonds. As a result, the HMA-activated photoanode improves the photocurrent density by a factor of ∼3.2 from 0.29 to 0.93 mA cm-2 at 1.23 VRHE and the incident photon-to-current conversion efficiency (IPCE) from ∼2.9% to ∼10.5% at 430 nm relative to those of the as-prepared N-I-TiO2 photoanode in photoelectrochemical water oxidation, which are much better than those of the CTA-activated photoanode (0.58 mA cm-2 at 1.23 VRHE and IPCE of 5.7% at 430 nm), especially in the visible light region (≥420 nm).

Markedly Elevated Aspartate Aminotransferase from Non-Hepatic Causes.

There have been no reports on mortality in patients with markedly elevated aspartate aminotransferase (AST) levels from non-hepatic causes to date. This study aimed to determine the etiologies of markedly elevated AST levels > 400 U/L due to non-hepatic causes and to investigate the factors associated with mortality in these cases. This retrospective study included 430 patients with AST levels > 400 U/L unrelated to liver disease at two centers between January 2010 and December 2021. Patients were classified into three groups according to etiology: skeletal muscle damage, cardiac muscle damage, and hematologic disorder. Binary logistic regression analysis was performed to evaluate the factors associated with 30-day mortality. The most common etiology for markedly elevated AST levels was skeletal muscle damage (54.2%), followed by cardiac muscle damage (39.1%) and hematologic disorder (6.7%). The 30-day mortality rates for the skeletal muscle damage, cardiac muscle damage, and hematologic disorder groups were 14.2%, 19.5%, and 65.5%, respectively. The magnitude of the peak AST level significantly correlated with 30-day mortality, with rates of 12.8%, 26.7%, and 50.0% for peak AST levels < 1000 U/L, <3000 U/L, and ≥3000 U/L, respectively. In the multivariate analysis, cardiac muscle damage (odds ratio [OR] = 2.76, 95% confidence interval [CI] = 1.31−5.80), hematologic disorder (OR = 9.47, 95% CI = 2.95−30.39), peak AST < 3000 U/L (OR = 2.94, 95% CI = 1.36−6.35), and peak AST ≥ 3000 U/L (OR = 9.61, 95% CI = 3.54−26.08) were associated with increased 30-day mortality. Our study revealed three etiologies of markedly elevated AST unrelated to liver disease and showed that etiology and peak AST level significantly affected the survival rate.

Clinical Features of Hepatitis C Virus-related Acute-on-chronic Liver Failure in a Korean Population.

Background/Aims: Acute-on-chronic liver failure (ACLF) is a widely recognized concept in which acute decompensation (AD) in patients with cirrhosis results in organ failure and high short-term mortality. On the other hand, few studies reflecting the various etiologies of cirrhosis are available. This study examined the clinical features of patients with hepatitis C virus (HCV)-related ACLF. Methods: Between January 2005 and December 2018, 109 HCV-related cirrhosis patients hospitalized for AD (ascites, hepatic encephalopathy, gastrointestinal hemorrhage, and bacterial infection) were enrolled for ACLF defined by the European Association for the Study of the Liver (EASL). Results: ACLF developed in 35 patients (32.1%) on admission. Eight, eight, and 19 patients had ACLF grades 1, 2, and 3, respectively. The 28-day and 90-day mortality rates were very low (2.7% and 5.4%, respectively) in patients without ACLF and very high (60.0% and 74.3%, respectively) in those with ACLF. In patients with HCV-related ACLF, compared to previous studies on hepatitis B virus-related ACLF and alcohol-related ACLF, the prevalence of liver failure was very low (17.1%), whereas that of kidney failure was very high (71.4%). Compared with all other prognostic scores, the Chronic liver failure Consortium Organ Failure score predicted the 90-day mortality most accurately, with an area under the receiver operator characteristic of 0.921. Conclusions: HCV-related ACLF has unique clinical characteristics distinct from hepatitis B virus-related and alcohol-related ACLF. ACLF defined by EASL can be useful for predicting the short-term mortality in HCV-related cirrhosis.

Synthesis and Electrochemical Performance of Microporous Hollow Carbon from Milkweed Pappus as Cathode Material of Lithium-Sulfur Batteries.

Microtube-like porous carbon (MPC) and tube-like porous carbon-sulfur (MPC-S) composites were synthesized by carbonizing milkweed pappus with sulfur, and they were used as cathodes for lithium-sulfur batteries. The morphology and uniformity of these materials were characterized using X-ray powder diffraction, Raman spectroscopy, scanning electron microscopy, transmission electron microscopy with an energy-dispersive X-ray analyzer, thermogravimetric analysis, and X-ray photoelectron spectrometry. The electrochemical performance of the MPC-S cathodes was measured using the charge/discharge cycling performance, C rate, and AC impedance. The composite cathodes with 93.8 wt.% sulfur exhibited a stable specific capacity of 743 mAh g-1 after 200 cycles at a 0.5 C.

In vitro and in vivo inhibition of glucocorticoid-induced osteoporosis by the hexane extract of Poncirus trifoliata.

This study was performed to discover a novel herbal therapeutic for effective glucocorticoid-induced osteoporosis (GIO) treatment and further to clarify its molecular mechanism of action. Ethanol or methanol extracts of 68 edible Korean native plants were screened to find effective natural plant sources for the treatment of GIO, and Poncirus trifoliata (L.) (Rutaceae, PT) was selected as a final candidate because of its high inhibitory activity plus its novelty. The hexane extract of PT (PT-H) inhibited apoptotic cell death in dexamethasone-induced osteoblastic cell lines, C3H10T1/2 and MC3T3-E1. In vivo mouse results indicated that PT-H not only had an inhibitory effect on the bone loss caused by glucocorticoid, but also promoted bone formation. The molecular mechanisms behind the effect of PT-H on GIO were further clarified by screening of differentially expressed genes (DEGs) between dexamethasone (Dex)-induced osteoblastic cells with or without PT-H treatment. Finally, it was found that the expression level of AnxA6 in Dex-induced osteoblastic cells and prednisolone (PD)-treated GIO-model mice was significantly decreased by PT-H treatment. These findings suggest that PT-H has a strong in vitro and in vivo inhibitory effect on GIO, and decreased expression of AnxA6 may play a key role in this inhibition.

Analyzing climate change impacts on health, energy, water resources, and biodiversity sectors for effective climate change policy in South Korea.

This study analyzes how climate change affects the economy, society, and environment in South Korea. Then, the study explores the ways to strengthen capabilities that can alleviate climate change impacts. To find them, the study employs a system dynamics simulation method and builds a model with several sectors including the urban, rural, population, and social-environmental sectors. The study compares the size of climate change damages in rural and urban areas. The results with representative concentration path (RCP) 8.5 show that the size of climate change damage will continue to increase by 2050. The projected damages from the reduced industrial outputs in urban areas will be larger than that in rural areas. The results also show that the service sector will face stronger impacts from climate change than the manufacturing and agricultural sectors. However, the total size of damage in the rural areas will be bigger than that of the urban areas. It is because the size of reduced industrial outputs per capita in the rural areas is twice bigger than that of the urban areas. The climate change damage in the social and environmental sectors (including a loss of biodiversity and an increase in health costs) account for the largest part of the total damage. The study finally provides suggestions and policies that can improve the capabilities to reduce the climate change damages. One of the major suggestions of this study is that the increase in the climate change budget corresponding to the GDP growth can minimize the size of climate change impacts.

Synthesis of poly(methyl methacrylate)/ montmorillonite nanocomposites using a 3-D surfactant as an organic modifier.

Poly(methyl methacrylate)/Montmorillonite clay nanocomposites were synthesized via the free radical polymerization of methyl methacrylate in the presence of alkyl ammonium substituted polysilsesquioxane surfactant-modified clay and AIBN initiator in ethanol and aqueous ethanol solvent. MMT clay was initially cation exchanged with the surfactant to enhance its hydrophobicity and to expand the interlamellar spaces of silicate platelets. The 3-D structured surfactant and water molecules reduce the surface energy of the clay dramatically, which promotes miscibility of polymer/ clay nanocomposites. The intercalation and dispersion of clay were quantified by both X-ray diffraction and transmission electron microscopy, and the morphologies of the nanocomposites were observed by scanning electron microscopy. Both the alkyl ammonium polysilsesquioxane surfactant and filler clay enhanced thermal and mechanical properties of the nanocomposites as investigated with thermo gravimetric analysis and differential scanning calorimetry.