Machine-Learning-Aided Understanding of Protein Adsorption on Zwitterionic Polymer Brushes.

Constructing antifouling surfaces is a crucial technique for optimizing the performance of devices such as water treatment membranes and medical devices in practical environments. These surfaces are achieved by modification with hydrophilic polymers. Notably, zwitterionic (ZI) polymers have attracted considerable interest because of their ability to form a robust hydration layer and inhibit the adsorption of foulants. However, the importance of the molecular weight and density of the ZI polymer on the antifouling property is partially understood, and the surface design still retains an empirical flavor. Herein, we individually assessed the influence of the molecular weight and density of the ZI polymer on protein adsorption through machine learning. The results corroborated that protein adsorption is more strongly influenced by density than by molecular weight. Furthermore, the distribution of predicted protein adsorption against molecular weight and polymer density enabled us to determine conditions that enhanced (or weaken) antifouling. The relevance of this prediction method was also demonstrated by estimating the protein adsorption over a wide range of ionic strengths. Overall, this machine-learning-based approach is expected to contribute as a tool for the optimized functionalization of materials, extending beyond the applications of ZI polymer brushes.

Giant impurity effect on anomalous Hall effect of Mn3Sn.

Mn3Sn is an anomalous Hall effect (AHE) antiferromagnet that exhibits the hysteretic AHE in antiferromagnetic (AFM) phase at room temperature. We report that whisker Mn3Sn crystals grown by the flux method exhibit a non-hysteretic AHE at mid-to-low temperatures when the whisker Mn3Sn is surrounded by a thin layer of ferromagnetic Mn2-xSn. These crystals exhibit a hysteretic AHE above 275 K due to the spin alignment of the inverse triangular lattice, which is similar to other crystals. However, upon cooling the crystal, it exhibits a non-hysteretic AHE with a spiral AFM spin structure at 100-200 K. We concluded that the non-hysteretic AHE is induced at the interface of Mn2-xSn/Mn3Sn. We believe that the scalar-spin chirality in the spiral AFM phase of Mn3Sn, modulated by Mn2-xSn through the magnetic proximity effect, produces the AHE. This discovery opens a new avenue for tailoring the AHE by magnetic layers.

Design of a highly sensitive and versatile membrane-based immunosensor using a Cu-free click reaction.

A highly sensitive immunosensor is developed using membrane pores as the recognition interface. In this sensor, a Cu-free click reaction is used to efficiently immobilize antibodies, and the sensor inhibits the adsorption of nonspecific proteins that degrade sensitivity. Furthermore, the sensor demonstrates rapid interleukin-6 detection in the picogram per milliliter range.

Correlation between sphingomyelin and the membrane stability of mammalian erythrocytes.

Lipid compositions of mammalian erythrocyte membranes are different among species. Therefore, the information on hemolysis from mammalian erythrocytes is useful to understand membrane properties of human erythrocytes. In this work, pressure-induced hemolysis and hypotonic one were examined using erythrocytes of human, sheep, cow, cat, dog, pig, horse, rat, and mouse. Pressure-induced hemolysis was suppressed by membrane sphingomyelin, whereas hypotonic hemolysis decreased upon increment of cell diameter. Mass spectra of erythrocyte membrane lipids demonstrated that sphingomyelin with an acyl chain 24:1 was associated with the suppression of pressure-induced hemolysis. In cow erythrocytes, pressure-induced hemolysis was greatly suppressed and the detachment of cytoskeletal proteins from the membrane under hypotonic conditions was also inhibited. Taken together, these results suggest that sphingomyelin with 24:1 fatty acid plays an important role in the stability of the erythrocyte membrane, perhaps via cholesterol.

Development of a Potassium-Ion-Responsive Star Copolymer with Controlled Aggregation/Dispersion Transition.

Stimuli-responsive star polymers are promising functional materials whose aggregation, adhesion, and interaction with cells can be altered by applying suitable stimuli. Among several stimuli assessed, the potassium ion (K+), which is known to be captured by crown ethers, is of considerable interest because of the role it plays in the body. In this study, a K+-responsive star copolymer was developed using a polyglycerol (PG) core and grafted copolymer arms consisting of a thermo-responsive poly(N-isopropylacrylamide) unit, a metal ion-recognizing benzo-18-crown-6-acrylamide unit, and a photoluminescent fluorescein O-methacrylate unit. Via optimization of grafting density and copolymerization ratio of grafted arms, along with the use of hydrophilic hyperbranched core, microsized aggregates with a diameter of 5.5 µm were successfully formed in the absence of K+ ions without inducing severe sedimentation (the lower critical solution temperature (LCST) was 35.6 °C). In the presence of K+ ions, these aggregates dispersed due to the shift in LCST (47.2 °C at 160 mM K+), which further induced the activation of fluorescence that was quenched in the aggregated state. Furthermore, macrophage targeting based on the micron-sized aggregation state and subsequent fluorescence activation of the developed star copolymers in response to an increase in intracellular K+ concentration were performed as a potential K+ probe or K+-responsive drug delivery vehicle.

Suitable acid groups and density in electrolytes to facilitate proton conduction.

Proton conducting materials suffer from low proton conductivity under low-relative humidity (RH) conditions. Previously, it was reported that acid-acid interactions, where acids interact with each other at close distances, can facilitate proton conduction without water movement and are promising for overcoming this drawback [T. Ogawa, H. Ohashi, T. Tamaki and T. Yamaguchi, Chem. Phys. Lett., 2019, 731, 136627]. However, acid groups have not been compared to find a suitable acid group and density for the interaction, which is important to experimentally synthesize the material. Here, we performed ab initio calculations to identify acid groups and acid densities as a polymer design that effectively causes acid-acid interactions. The evaluation method employed parameters based on several different optimized coordination interactions of acids and water molecules. The results show that the order of the abilities of polymer electrolytes to readily induce acid-acid interactions is hydrocarbon-based phosphonated polymers > phosphonated aromatic hydrocarbon polymers > perfluorosulfonic acid polymers ≈ perfluorophosphonic acid polymers > sulfonated aromatic hydrocarbon polymers. The acid-acid interaction becomes stronger as the distance between acids decreases. The preferable distance between phosphonate moieties is within 13 Å.

A cobalt-manganese layered oxide/graphene composite as an outstanding oxygen evolution reaction electrocatalyst.

To enhance the oxygen evolution reaction mass activity of cobalt-manganese layered oxide (CMO), we develop a one-pot synthetic process to anchor CMO onto graphene sheets (CMO/G). Its mass activity is 66-fold higher than that of physically mixed bare CMO with graphene and even better than those of previously reported graphene-supported first-row transition metal oxide-based electrocatalysts. The remarkable mass activity is attributed to the excellent intrinsic activity of CMO, small and well-dispersed CMO nanosheets on graphene sheets and hydrophilized graphene due to the synthetic process. Furthermore, CMO/G exhibits excellent stability.

Importance of Cholesterol Side Chain in the Membrane Stability of Human Erythrocytes.

Cholesterol suppresses the hemolysis and the detachment of cytoskeletal proteins from bilayer in the human erythrocyte membrane under stress conditions. However, there is little information on how cholesterol functions. So, examining the role of a short side chain of cholesterol, we used the plant sterols such as ß-sitosterol and stigmasterol. Incorporation of sterols into the membrane using a sterol/methyl-ß-cyclodextrin complex was confirmed by the mass spectrometry. Hemolysis of human erythrocytes under high hydrostatic pressure (200 MPa) or hypotonic conditions was suppressed by cholesterol, but not by ß-sitosterol and stigmasterol. Moreover, the bilayer-cytoskeleton interaction was also strengthened by cholesterol, but not by ß-sitosterol and stigmasterol. Taken together, we suggest that the short side chain of cholesterol plays an important role in the membrane stability of human erythrocytes.

Numerical Modeling for Sensitive and Rapid Molecular Detection by Membrane-Based Immunosensors.

Rapid, simple, and sensitive point-of-care testing (POCT) has attracted attention in recent years due to its excellent potential for early disease diagnosis and health monitoring. The flow-through biosensor design is a candidate for POCT that utilizes the small-sized pores of a porous membrane as a recognition space where it emits a signal comparable to that of a conventional enzyme-linked immunosorbent assay within 35 min of detection time. In this paper, we present a numerical model for this immunosensing technology to systematically design an improved recognition system. The model considers mass transfer into the pore (convection and diffusion), the kinetics between the immobilized receptor and the target molecule, and the flow conditions, successfully leading to a bottleneck step (capture of secondary antibody) in sandwich-type detection. Our simulation results also show that this problem can be solved by adopting both appropriate receptors and analytical conditions. Eventually, the requirements to achieve the sensitivity required for POCT were fulfilled, which will allow for further development of immunosensing devices for disease detection.

Survey of actual conditions of erythema marginatum as a prodromal symptom in Japanese patients with hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is a rare but life-threatening condition. HAE types I and II (HAE-1/2) result from C1-inhibitor (C1-INH) deficiency. However, recent genetic analysis has established a new type of HAE with normal C1-INH (HAEnC1-INH). The mutations of factor XII, plasminogen, angiopoietin 1, and kininogen 1 genes may be the cause of HAEnC1-INH. Nevertheless, other causative molecules (HAE-unknown) may be involved. The Japanese therapeutic environment for HAE has been improving owing to the self-subcutaneous injection of icatibant, which was approved for the treatment of acute attack and enables early therapy. Erythema marginatum (EM) is a visible prodromal symptom which occasionally occurs prior to an angioedema attack; hence, recognizing the risk of an acute attack is important for early treatment. However, the detailed characteristics of EM remain unclear. In this study, we first investigated the clinical manifestations of EM in Japanese patients with HAE. METHODS: A 20-point survey was developed and distributed to 40 physicians to gather clinical data on EM from patients with HAE. RESULTS: Data on 68 patients with HAE (58 patients with HAE-1/2 and 10 patients with HAE-unknown) were collected. Of the patients with HAE-1/2, 53.4% experienced EM, whereas 43.1% did not. The forearm was the most frequent area of EM (64.5%), followed by the abdomen (29.0%) and upper arm and precordium (19.3%). Of the HAE-1/2 patients with EM, 41.9% always had angioedema following EM, while 29.0% always had colocalization of EM with angioedema. Moreover, 3.2% showed a correlation between the awareness of EM and severity of an angioedema attack. In 60.9% of HAE-1/2 patients with EM, the interval between the awareness of EM and appearance of angioedema was <3 h. Of the patients with HAE-unknown, 30.0% also experienced EM. CONCLUSION: We confirmed that more than one-half of Japanese patients with HAE-1/2 and one-third of those with HAE-unknown develop EM as the prodromal symptom of an angioedema attack. Physicians should communicate the significance of EM to patients with HAE to prepare them for possible imminent attacks.

Effect of Metal Coordination Fashion on Oxygen Electrocatalysis of Cobalt-Manganese Oxides.

The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are the most critical reactions that limit the efficiency of fuel cells, water electrolyzers, and metal-air batteries. Therefore, a need exists to develop cost-effective and highly active alternative electrocatalysts for ORR and OER. This study investigates the influence of metal coordination fashion on electrocatalytic ORR and OER activities among three types of Co-Mn bimetallic oxides (CMOs): tunnel-type (CMO_T), layer-type (CMO_L), and spinel-type (CMO_S) structures. An electrochemical evaluation for CMOs verifies that CMO_L has the highest ORR and OER specific activities, which is relatively better than the previously reported bifunctional metal oxides. Additionally, atomic configuration analysis for the oxides suggests that the excellent ORR and OER activities of CMO_L result from the difference in Co and Mn coordination states. This paper not only presents an excellent electrocatalyst for alkaline fuel cells and water electrolyzers but also provides an important guideline for the design of oxygen electrocatalysts.

Effects of Cholesterol on Membrane Stability of Human Erythrocytes.

Human erythrocytes contain abundant cholesterol as membrane lipids. Cholesterol contributes to the stability and function of the membrane. Membrane stability of the erythrocyte has been mainly examined under hypotonic conditions, but not under high hydrostatic pressure. So, the effect of cholesterol on the membrane stability of human erythrocyte was examined under a pressure of 200 MPa. As with hypotonic hemolysis, the pressure-induced hemolysis was enhanced by depletion of cholesterol from the intact erythrocyte membrane, whereas suppressed by cholesterol loading to the intact one. Enhancement of such hemolysis was associated with the suppression of fragmentation, whereas the hemolysis was suppressed by the facilitation of vesiculation. Cholesterol induced the tight linkage of the lipid bilayer with cytoskeleton. Taken together, these results suggest that the erythrocyte membrane stability is affected by such tight linkage by cholesterol.

Effect of weight change and lifestyle modifications on the development or remission of nonalcoholic fatty liver disease: sex-specific analysis.

The effects of changes in various lifestyle habits on nonalcoholic fatty liver disease (NAFLD) have not been well elucidated. We aimed to clarify how weight change and lifestyle modifications were associated with the development or remission of NAFLD. In this longitudinal cohort study, we reviewed the periodic health checkup data of 1,421 subjects with no causes of liver disease besides NAFLD who had received at least two health checkups between 2009 and 2018. The prevalence of NAFLD at baseline was 34.1% (484/1,421). During follow-up period (4.6 ± 2.8 years), 104 subjects developed NAFLD and 127 subjects demonstrated NAFLD remission. The frequency of NAFLD development or that of NAFLD remission significantly increased as the larger weight gain or weight loss was, respectively (both, p < 0.001). Approximately 40% of the subjects who maintained ≥ 1%/year weight loss achieved NAFLD remission. By multivariate analysis, quitting smoking were independently associated with NAFLD development (adjusted odds ratio [AOR], 2.86; 95% CI, 1.24-6.62). Subjects who quit smoking demonstrated large weight gain (≥1%/year) significantly more frequently than the other subjects (p < 0.001). In sex-specific analysis, starting to exercise was independently associated with NAFLD remission in men (AOR, 2.38; 95% CI, 1.25-4.53).

Connected iridium nanoparticle catalysts coated onto silica with high density for oxygen evolution in polymer electrolyte water electrolysis.

We propose connected Ir nanoparticle catalysts (Ir/SiO2) by coating 1.8 nm Ir particles with high density onto silica for the oxygen evolution reaction. Nanoparticles form electron-conducting networks, which can eliminate the need for an electron-conducting support. Ir/SiO2 showed a high electrochemical surface area, mass activity, and water electrolysis performance.

ATP effects on response of human erythrocyte membrane to high pressure.

Phosphorylation of membrane proteins in human erythrocytes is mediated by intracellular ATP levels. Such phosphorylation modulates the interactions of the bilayer with the cytoskeleton and affects the membrane stability under high pressure. In erythrocytes with high intracellular ATP levels, the bilayer-cytoskeleton interaction was weakened. Compression of such erythrocytes induced the release of large vesicles due to the suppression of fragmentation and resulted in the enhanced hemolysis. On the other hand, in ATP-depleted erythrocytes the interaction between the bilayer and the cytoskeleton was strengthened. Upon compression of these erythrocytes, the release of small vesicles due to the facilitation of vesiculation resulted in suppression of hemolysis. Taken together, these results suggest that the responses, i.e., vesiculation, fragmentation, and hemolysis, of the erythrocytes to high pressure are largely modulated by the bilayer-cytoskeleton interaction, which is mediated by intracellular ATP levels.

Flow-Based Immunosensing Using the Pore Channel of a Porous Membrane As a Reaction Space.

This Letter describes a new rapid and sensitive immunosensing device using the pore space of a porous membrane as the reaction space. A track-etched membrane with uniform cylindrical pores is used as the base substrate of this device. The capture antibodies are covalently and densely immobilized inside the membrane pores by the uniform introduction of poly(acrylic acid) (PAAc) via the plasma graft polymerization technique, followed by the active ester method. This membrane shows excellent antibody retention by covalent binding. The detection test was carried out via a sandwich-type assay, and all reaction steps from the antigen-antibody reaction to the enzyme reaction were conducted by permeating each solution into the pores. The detection test showed a signal comparable to that of the conventional enzyme-linked immunosorbent assay, although the detection time required in the test was shortened to 35 min. The reason for achieving both high sensitivity and short detection time is that the antibody accumulated pore space with high selectivity and promoted contact between the reactants by solution permeation. This report is expected to aid the design of systems for membrane-based devices, which currently have problems associated with sensitivity, rapidity, selectivity, or amount of sample. We further expect that this system could be applied to various diagnostic areas, including point-of-care testing.

Reduction of Thermotolerance by Heat Shock Protein 90 Inhibitors in Murine Erythroleukemia Cells.

Cells induce heat shock proteins (HSPs) against various stress. However, murine erythroleukemia (MEL) cells do not express HSP72, a heat-inducible member of HSP70 family. So, it is of interest to examine how MEL cells respond to heat stress (44°C, 30 min). Heat stress-induced apoptosis was suppressed by pretreatment of heat shock (44°C, 10 min). Such suppressive effects were maximal at 6 h after heat shock and remained up to 12 h. Interestingly, such effects of heat shock were abrogated by specific inhibitors of HSP90 such as 17-allylamino-17-demethoxygeldanamycin (17-AAG) and novobiocin. From flow cytometric analysis, it was found that MEL cells arrest in G2 phase at 6 h after heat shock, but restore original cell cycle at 12 h. High expression level of HSP90 was maintained before and after heat shock. Phosphorylation of HSP90α was observed in apoptotic cells induced by heat stress, but inhibited by pretreatment of heat shock. Such inhibition was abrogated by 17-AAG. Moreover, c-Jun NH2-terminal kinase (JNK) was activated in heat stress-induced apoptotic cells. Taken together, these results suggest that HSP90α in MEL cells plays an important role in the thermotolerance, i.e., suppression of heat stress-induced apoptosis by heat shock.

Development of a novel durable aromatic anion exchange membrane using a thermally convertible precursor.

We describe a new approach for obtaining high-performance anion exchange membranes by using a thermally convertible precursor. A new insoluble all-aromatic polymer containing anthracene units and benzyl trimethyl ammonium was successfully prepared from a highly soluble precursor polymer. The resulting polymer shows excellent chemical durability and conductivity.

Control of Target Molecular Recognition in a Small Pore Space with Biomolecule-Recognition Gating Membrane.

A biomolecule-recognition gating membrane, which introduces thermosensitive graft polymer including molecular recognition receptor into porous membrane substrate, can close its pores by recognizing target biomolecule. The present study reports strategies for improving both versatility and sensitivity of the gating membrane. First, the membrane is fabricated by introducing the receptor via a selectively reactive click reaction improving the versatility. Second, the sensitivity of the membrane is enhanced via an active delivering method of the target molecules into the pores. In the method, the tiny signal of the target biomolecule is amplified as obvious pressure change. Furthermore, this offers 15 times higher sensitivity compared to the previously reported passive delivering method (membrane immersion to sample solution) with significantly shorter recognition time. The improvement will aid in applying the gating membrane to membrane sensors in medical fields.