Additive-assisted macroscopic self-assembly and control of the shape of assemblies based on host-guest interaction.

In these decades, considerable attention has focused on supramolecular polymers due to their unique structures and properties. More recently, macroscopic supramolecular polymers have attracted increasing interest from not only biologists but also materials scientists inspired by the sophisticated structures and functions of living organisms. Since the functions of supramolecular polymers are strongly dependent on their shape, control of the shape is an important issue in controlling the functions of supramolecular polymers. However, the control of shape in macroscopic supramolecular assemblies has not yet been sufficiently investigated. Previously, we studied the macroscopic self-assembly behavior of super absorbent polymer (SAP) microparticles modified with ß-cyclodextrin (ßCD) and adamantane (Ad) residues (ßCD(x)-SAP and Ad(y)-SAP microparticles, where x and y are the mol% contents of ßCD and Ad residues, respectively). More elongated assemblies were formed at higher y, indicating that the shape of assemblies can be controlled by varying the interaction strength. The noteworthy is that 1-adamantanamine hydrochloride (AdNH3Cl) assisted the formation of assemblies from ßCD(x)-SAP and Ad(y)-SAP microparticles, indicating that AdNH3Cl acts as a chemical stimulus for macroscopic assemblies of ßCD(x)-SAP and Ad(y)-SAP microparticles. In this study, we have thus studied the assembling behavior of ßCD(x)-SAP microparticles with Ad(y)-SAP microparticles and unmodified SAP microparticles assisted by AdNH3Cl, as well as the shape of the resulting macroscopic assemblies. AdNH3Cl assisted the formation of assemblies from ßCD(16.2)-SAP and Ad(15.1)-SAP microparticles, in which AdNH3Cl crosslinked the SAP microparticles through the formation of inclusion complexes of ßCD residues with the Ad residue and the electrostatic interaction of ammonium and carboxylate residues. Assemblies of ßCD(26.7)-SAP and unmodified SAP microparticles were formed at the concentrations of AdNH3Cl ([AdNH3Cl]0) higher than a certain level (ca. 0.05 mM). The aspect ratio (a/b) of assemblies showed a maximum at [AdNH3Cl]0 ~ 0.10 mM, indicating that the chemical stimulus, i.e., addition of AdNH3Cl, controls the shape of assemblies formed from ßCD(26.7)-SAP and unmodified SAP microparticles. This study suggests that other stimuli, e.g., heat, pH, light, redox, and force, can be utilized to control the shape of macroscopic assemblies based on supramolecular interactions.

[Cowden syndrome in a male patient with metachronous triple cancers and various clinical features:a case report].

A 66-year-old male patient with a thyroid and nasopharyngeal cancer history visited our hospital because of a positive fecal occult blood test. Total colonoscopy detected sessile or subpedunculated polyps in the ascending colon, sigmoid colon, and rectum. These polyps were endoscopically resected, and the rectal polyp was pathologically diagnosed as adenocarcinoma in adenoma and the others as adenomas. Additionally, multiple sessile lesions were revealed in the sigmoid colon and rectum. A complete gastrointestinal tract examination revealed multiple foci of glycogenic acanthosis in the esophagus, multiple sessile lesions in the stomach, multiple sessile lesions, clubbings (rod-shaped lesions), and venous malformations in the small bowel. Mucocutaneous examination indicated hemangiomas on the body trunk, patchy pigmentation on the glans penis, and keratotic papules in the inguinal region. The National Comprehensive Cancer Network diagnostic criteria for Cowden syndrome were used in this case. The patient met four major and two minor criteria;thus, Cowden syndrome was diagnosed. Moreover, the patient was had phosphatase and tensin homolog deleted on chromosome 10 gene mutation. This is the first reported case of metachronal triple cancers in a male patient with Cowden syndrome, and our results indicate the importance of cancer surveillance.

Physical mechanism of core-collapse supernovae that neutrinos drive.

The current understanding of the mechanism of core-collapse supernovae (CCSNe), one of the most energetic events in the universe associated with the death of massive stars and the main formation channel of compact objects such as neutron stars and black holes, is reviewed for broad readers from different disciplines of science who may not be familiar with the object. Therefore, we emphasize the physical aspects than the results of individual model simulations, although large-scale high-fidelity simulations have played the most important roles in the progress we have witnessed in the past few decades. It is now believed that neutrinos are the most important agent in producing the commonest type of CCSNe. The so-called neutrino-heating mechanism will be the focus of this review and its crucial ingredients in micro- and macrophysics and in numerics will be explained one by one. We will also try to elucidate the remaining issues.

Reversible Host-Guest Crosslinks in Supramolecular Hydrogels for On-Demand Mechanical Stimulation of Human Mesenchymal Stem Cells.

Stem cells are regulated not only by biochemical signals but also by biophysical properties of extracellular matrix (ECM). The ECM is constantly monitored and remodeled because the fate of stem cells can be misdirected when the mechanical interaction between cells and ECM is imbalanced. A well-defined ECM model for bone marrow-derived human mesenchymal stem cells (hMSCs) based on supramolecular hydrogels containing reversible host-guest crosslinks is fabricated. The stiffness (Young's modulus E) of the hydrogels can be switched reversibly by altering the concentration of non-cytotoxic, free guest molecules dissolved in the culture medium. Fine-adjustment of substrate stiffness enables the authors to determine the critical stiffness level E* at which hMSCs turn the mechano-sensory machinery on or off. Next, the substrate stiffness across E* is switched and the dynamic adaptation characteristics such as morphology, traction force, and YAP/TAZ signaling of hMSCs are monitored. These data demonstrate the instantaneous switching of traction force, which is followed by YAP/TAZ signaling and morphological adaptation. Periodical switching of the substrate stiffness across E* proves that frequent applications of mechanical stimuli drastically suppress hMSC proliferation. Mechanical stimulation across E* level using dynamic hydrogels is a promising strategy for the on-demand control of hMSC transcription and proliferation.

Highly Stretchable Stress-Strain Sensor from Elastomer Nanocomposites with Movable Cross-links and Ketjenblack.

Practical applications like very thin stress-strain sensors require high strength, stretchability, and conductivity, simultaneously. One of the approaches is improving the toughness of the stress-strain sensing materials. Polymeric materials with movable cross-links in which the polymer chain penetrates the cavity of cyclodextrin (CD) demonstrate enhanced strength and stretchability, simultaneously. We designed two approaches that utilize elastomer nanocomposites with movable cross-links and carbon filler (ketjenblack, KB). One approach is mixing SC (a single movable cross-network material), a linear polymer (poly(ethyl acrylate), PEA), and KB to obtain their composite. The electrical resistance increases proportionally with tensile strain, leading to the application of this composite as a stress-strain sensor. The responses of this material are stable for over 100 loading and unloading cycles. The other approach is a composite made with KB and a movable cross-network elastomer for knitting dissimilar polymers (KP), where movable cross-links connect the CD-modified polystyrene (PSCD) and PEA. The obtained composite acts as a highly sensitive stress-strain sensor that exhibits an exponential increase in resistance with increasing tensile strain due to the polymer dethreading from the CD rings. The designed preparations of highly repeatable or highly responsive stress-strain sensors with good mechanical properties can help broaden their application in electrical devices.

Efficient Synthesis of Cyclic Poly(ethylene glycol)s under High Concentration Conditions by the Assistance of Pseudopolyrotaxane with Cyclodextrin Derivatives.

An efficient synthesis of cyclic polymers (CPs) is in high demand due to their unique properties. However, polymer cyclization generally occurs at low concentrations (0.1 g/L), and the synthesis of CPs at high concentrations remains a challenge. Herein an efficient cyclization of poly(ethylene glycol) (Mn = 2000 g/mol, 4000 g/mol) (PEG-2k, PEG-4k) in high concentration (80 g/L) is realized by the assistance of pseudopolyrotaxane (pPRx). Water-soluble pPRx with a U-like-shape inclusion motif is prepared by mixing the 2-hydroxypropyl-γ-cyclodextrin (HPγCD) and PEG with (E)-3,4,5-trimethoxycinnamate (TCA-PEG-2k, TCA-PEG-4k). Subsequent irradiation of the pPRx solution (10-80 g/L) by UV light gives cyclic polymers through the intramolecular [2 + 2] photocycloaddition of the cinnamoyl moieties. The photoreaction of TCA-PEG-2k in the pPRx system gives cyclic monomers (C-1mer) as major products with a yield of 66% at 80 g/L. Additionally, the cyclization of TCA-PEG-4k also gives C-1mer as major products with a yield of 45% at a concentration of 80 g/L.

Usefulness of Serum Leucine-Rich Alpha-2 Glycoprotein as a Surrogate Marker of Small Bowel Mucosal Injury in Crohn's Disease.

Introduction: Although the importance of mucosal healing has been suggested in Crohn's disease, it is difficult to repeat endoscopy, especially for the entire small bowel. Recently, serum leucine-rich alpha-2 glycoprotein (LRG) has been used as a surrogate marker of endoscopy. However, few studies have investigated a correlation between LRG and mucosal injury of the entire small bowel. Methods: We retrospectively analyzed the clinical data of 30 patients with Crohn's disease from June 2020 to August 2022 at Yamaguchi Red Cross Hospital. All the patients were surveyed through the gastrointestinal tract by esophagogastroduodenoscopy, total colonoscopy, and capsule endoscopy (CE). Subjects with mucosal injury only in the small bowel were selected. Then, we assessed the relationship between serum biomarkers (LRG, C-reactive protein [CRP], hemoglobin, albumin) and small bowel mucosal injury scores (Lewis score [LS], Capsule Endoscopy Crohn's Disease Activity Index [CECDAI], and Crohn's Disease Activity in Capsule Endoscopy [CDACE]) calculated by CE. Results: LRG and CRP were significantly correlated with small bowel mucosal injury scores (LS, CECDAI, CDACE) (p < 0.05, Spearman's rank correlation coefficient). The degree of correlation was greater for LRG than for CRP. Conclusions: LRG is a useful surrogate marker that closely reflects small bowel mucosal injury in the entire small bowel.

Leaf-Inspired Host-Guest Complexation-Dictating Supramolecular Gas Sensors.

We report unique conductive leaf-inspired (in particular, stomata-inspired) supramolecular gas sensors in which acetylated cyclodextrin derivatives rule the electric output. The gas sensors consist of polymers bearing acetylated cyclodextrin, adamantane, and carbon black. Host-guest complexes between acetylated cyclodextrin and adamantane corresponding to the closed stomata realize a flexible polymeric matrix. Effective recombination of the cross-links contributes to the robustness. As gas sensors, the supramolecular materials detect ammonia as well as various other gases at 1 ppm in 10 min. The free acetylated cyclodextrin corresponding to open stomata recognized the guest gases to alter the electric resistivity. Interestingly, the conductive device failed to detect ammonia gases at all without acetylated cyclodextrin. The molecular recognition was studied by molecular dynamics simulations. The gas molecules existed stably in the cavity of free acetylated cyclodextrin. These findings show the potential for developing wearable gas sensors.

Multi-energy dissipation mechanisms in supramolecular hydrogels with fast and slow relaxation modes.

Reversible cross-links by non-covalent bonds have been widely used to produce supramolecular hydrogels that are both tough and functional. While various supramolecular hydrogels with several kinds of reversible cross-links have been designed for many years, a universal design that would allow control of mechanical and functional properties remains unavailable. The physical properties of reversible cross-links are usually quantified by thermodynamics, dynamics, and bond energies. Herein, we investigated the relationship between the molecular mobility and mechanical toughness of supramolecular hydrogels consisting of two kinetically distinct reversible cross-links via host-guest interactions. The molecular mobility was quantified as the second-order average relaxation time (〈τ〉w) of the reversible cross-links. We discovered that hydrogels combining fast (〈τ〉w = 1.8 or 18 s) and slowly (〈τ〉w = 6.6 × 103 or 9.5 × 103 s) reversible cross-links showed increased toughness compared to hydrogels with only one type of cross-link because relaxation processes in the former occurred with wide timescales.

[A case of chronic enteropathy associated with SLCO2A1 gene diagnosed by capsule endoscopy and successfully treated by ferric carboxymaltose].

Chronic non-specific multiple ulcers of the small intestine is a disease condition postulated in Japan. It is an uncommon gastrointestinal disease that causes chronic anemia and hypoalbuminemia by causing numerous ulcers without any histopathologically identifiable features. In recent years, it has been revealed that the mutations of SLCO2A1, which codes the prostaglandin transporter protein, are the cause of this disease;it is called the new name "chronic enteropathy associated with SLCO2A1 gene." The ileum, except the terminal ileum, is the most common place making it difficult to identify major lesions. Other than conservative treatments, such as nutrition therapy and iron supplements, no effective treatment has been identified so far. We present a case of chronic non-specific multiple ulcers of the small intestine diagnosed by capsule endoscopy and effectively treated by ferric carboxymaltose. A 48-year-old female had chronic iron deficiency anemia since around the age of 15. Because of severe anemia, the patient had upper and lower endoscopy at the age of 47 to find the source of the bleeding, but it was not detected. Except for the terminal ileum, the capsule endoscopy revealed ring-like ulcers, tape-like ulcers, and oblique ulcer scars in the ileum. Genetic analysis showed a homozygous mutation in intron 7, c.940+1G>A, indicating a definitive diagnosis of non-specific multiple ulcers of the small intestine. Anemia and anemia-related symptoms such as general malaise persisted despite continuous oral administration of iron drugs. Three intravenous injections of ferric carboxymaltose increased hemoglobin and enhanced the symptoms.

Time-strain inseparability in multiaxial stress relaxation of supramolecular gels formed via host-guest interactions.

Supramolecular hydrogels utilizing host-guest interactions (HG gels) exhibit large deformability and pronounced viscoelasticity. The inclusion complexes between ß-cyclodextrin (host) and adamantane (guest) units on the water-soluble polymers form transient bonds. The HG gels show significant stress relaxation with finite equilibrium stress following the step strain. The stress relaxation process reflects the detachment dynamics of the transient bonds which sustain the initial stress, while the finite equilibrium stress is preserved by the permanent topological cross-links with a rotaxane structure. Nonlinear stress relaxation experiments in biaxial stretching with various combinations of two orthogonal strains unambiguously reveal that time and strain effects on stress are not separable. The relaxation is accelerated for a short time frame (<102 s) with an increase in the magnitude of strain, whereas it is retarded for a longer time window with an increase in the anisotropy of the imposed biaxial strain. The time-strain inseparability in the HG gels is in contrast to the simple nonlinear viscoelasticity of a dual cross-link gel with covalent and transient cross-links in which the separability was previously validated by the same assessment. We currently interpret that the significant susceptibility of the detachment dynamics to the deformation type results from the structural characteristics of the HG gels, i.e., the host and guest moieties covalently connected to the network chains, the considerably low concentrations (<0.1 M) of these moieties, and the slidability of the permanent rotaxane cross-links.

Synergetic improvement in the mechanical properties of polyurethanes with movable crosslinking and hydrogen bonds.

Polyurethane (PU) materials with movable crosslinking were prepared by a typical two-step synthetic process using an acetylated γ-cyclodextrin (TAcγCD) diol compound. The soft segment of PU is polytetrahydrofuran (PTHF), and the hard segment consists of hexamethylene diisocyanate (HDI) and 1,3-propylene glycol (POD). The synthesized PU materials exhibited the typical mechanical characteristics of a movable crosslinking network, and the presence of hydrogen bonds from the urethane bonds resulted in a synergistic effect. Two kinds of noncovalent bond crosslinking increased the Young's modulus of the material without affecting its toughness. Fourier transform infrared spectroscopy and X-ray scattering measurements were performed to analyze the effect of introducing movable crosslinking on the internal hydrogen bond and the microphase separation structure of PU, and the results showed that the carbonyl groups on TAcγCD could form hydrogen bonds with the PU chains and that the introduction of movable crosslinking weakened the hydrogen bonds between the hard segments of PU. When stretched, the movable crosslinking of the PU materials suppressed the orientation of polymer chains (shish-kebab orientation) in the tensile direction. The mechanical properties of the movable crosslinked PU materials show promise for future application in the industrial field.

Control of Photoinduced Electron Transfer Using Complex Formation of Water-Soluble Porphyrin and Polyvinylpyrrolidone.

Inspired by the natural photosynthetic system in which proteins control the electron transfer from electron donors to acceptors, in this research, artificial polymers were tried to achieve this control effect. Polyvinylpyrrolidone (PVP) was found to form complex with pigments 5,10,15,20-tetrakis-(4-sulfonatophenyl) porphyrin (TPPS) and its zinc complex (ZnTPPS) quantitatively through different interactions (hydrogen bonds and coordination bonds, respectively). These complex formations hinder the interaction between ground-state TPPS or ZnTPPS and an electron acceptor (methyl viologen, MV2+) and could control the photoinduced electron transfer from TPPS or ZnTPPS to MV2+, giving more electron transfer products methyl viologen cationic radical (MV+•). Other polymers such as PEG did not show similar results, indicating that PVP plays an important role in controlling the photoinduced electron transfer.

Risk of Rebleeding in Patients with Small Bowel Vascular Lesions.

Objective With recent advances in endoscopic modalities, small bowel vascular lesions (SBVLs) are often now detected in patients with gastrointestinal bleeding. Given the high invasiveness of endoscopic treatment, it is important to select patients at high risk for bleeding. To assess the risk of rebleeding in patients with SBVLs as a systemic disease rather than a gastrointestinal disease in relation to their general health. Methods We retrospectively analyzed the clinical data of 55 patients with SBVLs among patients with obscure gastrointestinal bleeding. The possible association between the clinical findings and the updated Charlson comorbidity index with rebleeding was evaluated. Results Gastrointestinal rebleeding occurred in 20 patients (36.4%) during the follow-up period. The presence of multiple comorbidities as indicated by an updated Charlson comorbidity index of ≥4 was a risk factor for rebleeding (hazard ratio, 3.64; p=0.004). Other risk factors were arteriosclerosis of the superior mesenteric artery and multiple SBVLs. Endoscopic hemostasis and the discontinuation of antithrombotic medications were not significantly associated with rebleeding. Patients with a high updated Charlson comorbidity index had a high risk of death of causes other than gastrointestinal rebleeding. Conclusion Gastrointestinal rebleeding is not a rare condition among patients with SBVLs. Patients with poor general health may therefore have a higher risk of rebleeding.

The macroscopic shape of assemblies formed from microparticles based on host-guest interaction dependent on the guest content.

Biological macroscopic assemblies have inspired researchers to utilize molecular recognition to develop smart materials in these decades. Recently, macroscopic self-assemblies based on molecular recognition have been realized using millimeter-scale hydrogel pieces possessing molecular recognition moieties. During the study on macroscopic self-assembly based on molecular recognition, we noticed that the shape of assemblies might be dependent on the host-guest pair. In this study, we were thus motivated to study the macroscopic shape of assemblies formed through host-guest interaction. We modified crosslinked poly(sodium acrylate) microparticles, i.e., superabsorbent polymer (SAP) microparticles, with ß-cyclodextrin (ßCD) and adamantyl (Ad) residues (ßCD(x)-SAP and Ad(y)-SAP microparticles, respectively, where x and y denote the mol% contents of ßCD and Ad residues). Then, we studied the self-assembly behavior of ßCD(x)-SAP and Ad(y)-SAP microparticles through the complexation of ßCD with Ad residues. There was a threshold of the ßCD content in ßCD(x)-SAP microparticles for assembly formation between x = 22.3 and 26.7. On the other hand, the shape of assemblies was dependent on the Ad content, y; More elongated assemblies were formed at a higher y. This may be because, at a higher y, small clusters formed in an early stage can stick together even upon collisions at a single contact point to form elongated aggregates, whereas, at a smaller y, small clusters stick together only upon collisions at multiple contact points to give rather circular assemblies. On the basis of these observations, the shape of assembly formed from microparticles can be controlled by varying y.

Mechano-Responsive Hydrogels Driven by the Dissociation of a Host-Guest Complex.

We developed a mechano-responsive hydrogel that is driven by the dissociation of a host-guest complex. The hydrogel comprised a thermoresponsive linear polymer with adamantane as a guest molecule in its side chain and a nonthermoresponsive network structure with ß-cyclodextrin as a host molecule. Immobilization of the thermoresponsive polymer in the hydrogel via host-guest interaction resulted in a partial restriction of its phase transition, even above its lower critical solution temperature (LCST). The hydrogel demonstrated a decrease in transmittance when mechanical stress was applied at a temperature above its LCST, indicating that the phase transition of the thermoresponsive polymer was induced by the dissociation of the host-guest complex under mechanical stress. Moreover, this mechano-responsive behavior was repeatable by cooling the hydrogel to redissolve the thermoresponsive polymer. The strategy of the mechano-responsive phase transition will be useful for various applications that demand the control of desired functions by applied stress.

Palladium nanoparticle loaded ß-cyclodextrin monolith as a flow reactor for concentration enrichment and conversion of pollutants based on molecular recognition.

This study reports pollutant remediation by a catalyst-loaded, ß-cyclodextrin cross-linked polymer monolith. The monolith enabled removal of the pollutant to a residual concentration with no environmental effect and conversion of the adsorbed pollutant into useful compounds with enriched concentration, allowing for the adsorption capacity regeneration.