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Umbilical venous (UV) catheters (UVCs) are commonly used in severely ill neonates. Complications associated with UVC often result from an inappropriate UVC position. Calcification of the UV, a rare complication, was observed in an extremely low-birth-weight infant born at 23 weeks of gestation. After birth, the infant experienced respiratory and circulatory dysfunction, followed by disseminated intravascular coagulation (DIC). A UVC was inserted, and circulatory agonists and blood transfusions were administered, as well as a calcium gluconate infusion for hypocalcemia and hyperkalemia. Ten days after birth, calcification was detected in the UV, likely due to a tunica intima injury caused by UVC, a hypercoagulable state due to DIC, and a high-dose calcium gluconate infusion. Additionally, proximal port malpositioning of the double-lumen catheter might have contributed to calcification within the UV. To prevent such complications, real-time ultrasound confirmation with agitated saline contrast during UVC placement is recommended; in the absence of the facility or skills for ultrasonography, X-rays should be performed in the lateral and anteroposterior views. Furthermore, when using multi-lumen catheters, physicians should not only verify the tip position but also ensure proper placement of proximal ports and carefully select medications administered through the ports. [ABSTRACT FROM AUTHOR]

To gain insight into how immunity develops against SARS-CoV-2 from 2020 to 2022, we analyzed the immune response of a small group of university staff and students who were either infected or vaccinated. We investigated the levels of receptor-binding domain (RBD)-specific and nucleocapsid (N)-specific IgG and IgA antibodies in serum and saliva samples taken early (around 10 days after infection or vaccination) and later (around 1 month later), as well as N-specific T-cell responses. One patient who had been infected in 2020 developed serum RBD and N-specific IgG antibodies, but declined eight months later, then mRNA vaccination in 2021 produced a higher level of anti-RBD IgG than natural infection. In the vaccination of naïve individuals, vaccines induced anti-RBD IgG, but it declined after six months. A third vaccination boosted the IgG level again, albeit to a lower level than after the second. In 2022, when the Omicron variant became dominant, familial transmission occurred among vaccinated people. In infected individuals, the levels of serum anti-RBD IgG antibodies increased later, while anti-N IgG peaked earlier. The N-specific activated T cells expressing IFN γ or CD107a were detected only early. Although SARS-CoV-2-specific salivary IgA was undetectable, two individuals showed a temporary peak in RBD- and N-specific IgA antibodies in their saliva on the second day after infection. Our study, despite having a small sample size, revealed that SARS-CoV-2 infection triggers the expected immune responses against acute viral infections. Moreover, our findings suggest that the temporary mucosal immune responses induced early during infection may provide better protection than the currently available intramuscular vaccines. [ABSTRACT FROM AUTHOR]

Aqueous solutions of conventional temperature-responsive amphiphilic polymers undergo a coil–globule conformational transition around the lower critical solution temperature (LCST) that causes the polymer surfaces to become hydrophobic and the polymers to aggregate together. Isocyanate polymers with alkylated oligo(ethylene oxide) side chains are expected to have rigid main chains and, thus, do not undergo the coil–globule structural transition, but they have recently been reported to exhibit temperature-responsive properties. In this study, molecular dynamics was used to calculate the agglomeration tendencies of two chains of poly(alkylated tri(ethylene oxide)isocyanate) (PRTEOIC, where R = methyl (Me) or ethyl (Et)) in aqueous solution to elucidate the LCST phenomenon in the absence of coil–globule conformational transition. Our MD simulations showed that aggregation also occurs in rod polymers. Furthermore, we found that both (PMeTEOIC)2 and (PEtTEOIC)2 showed parallel agglomeration of the two molecular chains with increasing temperature, but only (PMeTEOIC)2 showed a metastable T-shaped agglomeration in the middle temperature range. The crossing-point temperature (TCRP) at which the density of the first hydrophobic hydration shell around the sidechain alkyl group equals the bulk water density is a useful indicator for predicting the LCST of rod polymers with dense side chains terminated by alkyl groups. [ABSTRACT FROM AUTHOR]

Recently, experimental investigations of a class of temperature-responsive polymers tethered to oligooxyethylene side chains terminated with alkyl groups have been conducted. In this study, aqueous solutions of poly(glycidyl ether)s (PGE) with varying numbers of oxyethylene units, poly(methyl(oligooxyethylene)n glycidyl ether) (poly(Me(EO)nGE)), and poly(ethyl(oligooxyethylene)n glycidyl ether) (poly(Et(EO)nGE) (n = 0, 1, and 2) were investigated by all-atom molecular dynamics simulations, focusing on the thermal responses of their chain extensions, the recombination of intrapolymer and polymer–water hydrogen bonds, and water-solvation shells around the alkyl groups. No clear relationship was established between the phase-transition temperature and the polymer-chain extensions unlike the case for the coil–globule transition of poly(N-isopropylacrylamide). However, the temperature response of the first water-solvation shell around the alkyl group exhibited a notable correlation with the phase-transition temperature. In addition, the temperature at which the hydrophobic hydration shell strength around the terminal alkyl group equals the bulk water density ( T CRP ) was slightly lower than the cloud point temperature ( T CLP ) for the methyl-terminated poly(Me(EO)nGE) and slightly higher for the ethyl-terminated poly(Et(EO)nGE). It was concluded that the polymer-chain fluctuation affects the relationship between T CRP and T CLP . [ABSTRACT FROM AUTHOR]

The redox behaviors of macrocyclic molecules with an entirely π-conjugated system are of interest due to their unique optical, electronic, and magnetic properties. In this study, defect-free cyclic P3HT with a degree of polymerization (DPn) from 14 to 43 was synthesized based on our previously established method, and its unique redox behaviors arising from the cyclic topology were investigated. Cyclic voltammetry (CV) showed that the HOMO level of cyclic P3HT decreases from –4.86 eV (14 mer) to –4.89 eV (43 mer), in contrast to the linear counterparts increasing from –4.94 eV (14 mer) to –4.91 eV (43 mer). During the CV measurement, linear P3HT suffered from electro-oxidation at the chain ends, while cyclic P3HT was stable. ESR and UV–Vis–NIR spectroscopy suggested that cyclic P3HT has stronger dicationic properties due to the interactions between the polarons. On the other hand, linear P3HT showed characteristics of polaron pairs with multiple isolated polarons. Moreover, the dicationic properties of cyclic P3HT were more pronounced for the smaller macrocycles. [ABSTRACT FROM AUTHOR]

In our previous study, a novel method combining underwater high-voltage plasma discharge with acoustic cavitation (ACAP) was developed and implemented using rhodamine B (RhB) as a model organic pollutant. Results revealed that injecting argon gas into the ACAP reactor positively influences RhB decomposition efficiency, but there is still further potential for improvement. The aim of this study was therefore to further improve the efficiency of the ACAP process through Fenton reactions. Two options for ferrous ion supply were considered: the addition of FeCl2 or the dissolution of iron from ACAP reactor steel parts into the RhB-containing solution. The results revealed that the degradation efficiency is increased by 20% due to the Fenton reactions when the concentration of ferrous ions reaches an optimal value. Lower pH was found to be desirable for the effect of Fenton reactions. Based on measurements using high performance liquid chromatography, a plausible mechanism of RhB degradation by the ACAP process assisted by Fenton reactions is additionally proposed and discussed. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) are used in a wide range of applications, and the size control and stability of the nanoparticles are crucial aspects in their applications. In the present study, cyclized poly(ethylene glycol) (c-PEG) with various molecular weights, along with linear PEG with hydroxy chain ends (HO–PEG–OH) and methoxy chain ends (MeO–PEG–OMe) were applied for the Tollens' synthesis of AgNPs. The particle size was significantly affected by the topology and end groups of PEG. For example, the size determined by TEM was 40 ± 7 nm for HO–PEG5k–OH, 21 ± 4 nm for c-PEG5k, and 48 ± 9 nm for MeO–PEG5k–OMe when the molar ratio of PEG to AgNO3 (ω) was 44. The stability of AgNPs was also drastically improved by cyclization; the relative UV–Vis absorption intensity (A/A0 × 100%) at λmax to determine the proportion of persisting AgNPs in an aqueous NaCl solution (37.5 mM) was 58% for HO–PEG5k–OH, 80% for c-PEG5k, and 40% for MeO–PEG5k–OMe, despite the fact that AgNPs with c-PEG5k were much smaller than those with HO–PEG5k–OH and MeO–PEG5k–OMe. [ABSTRACT FROM AUTHOR]

Aluminum contaminations, particularly iron, present a serious challenge to aluminum recycling technology. This is why many studies have focused on the reduction of detrimental effects of iron-containing contaminations through addition of elements such as manganese and chromium. However, the desirable modifying effect is often difficult to achieve because it would require concentrations of added elements greater than the allowable limits for many aluminum alloys. Thus, an alternative way to obtain the modifying effect, by using a much smaller amount of the modifying elements which are added to the aluminum melt as solid particles, was proposed in this study. The main goal of the present study was to investigate the possibilities of fabricating an aluminum master alloy by adding CrSi2 particles onto the surface of the vortex formed during mechanical agitation of molten aluminum. Two kinds of CrSi2 powder were used: one was commercial powder, and the other was self-synthesized CrSi2 via mechanical alloying by planetary ball milling. The results revealed that CrSi2 particles with a larger size penetrate the melt better. Particles of three kinds were found to exist in the Al melt after the addition of CrSi2 powder: (1) inclusions of eutectic origin formed at the last stage of crystallization, (2) mixtures of Al-Cr compounds and original CrSi2 particles and (3) original CrSi2 particles. Low melt temperatures and short treatment times were found to favor the fabrication of master alloys because they impeded the dissolution of CrSi2 particles into the Al melt and, thus, allowed one to fabricate the master alloy containing the particles of the second and third types. [ABSTRACT FROM AUTHOR]

Simple Summary: Pituitary adenoma pathophysiology has been studied mainly using murine cell lines, animal models, and pituitary tumor samples. However, the lack of human pituitary cell line is a significant limiting factor in studying the molecular mechanisms of human pituitary tumors. Recently, pituitary induction methods from human-induced pluripotent stem cells (hiPSCs) have been established. These methods can induce human pituitary hormone-producing cells that retain physiological properties. hiPSCs in which tumor-causing gene mutations are introduced using genome-editing techniques, such as CRISPR/Cas9 systems, provide great opportunities to establish in vitro human pituitary adenoma disease models. The models will be a novel platform to discover novel drugs and investigate tumorigenesis and pathophysiology. The purpose of this review is to provide an overview of the applications of iPSCs for pituitary and neoplastic disorder research and genome-editing technologies to create strategies for developing pituitary adenoma models using iPSCs. Pituitary adenomas are characterized by abnormal growth in the pituitary gland. Surgical excision is the first-line treatment for functional (hormone-producing) pituitary adenomas, except for prolactin-producing adenomas; however, complete excision is technically challenging, and many patients require long-term medication after the treatment. In addition, the pathophysiology of pituitary adenomas, such as tumorigenesis, has not been fully understood. Pituitary adenoma pathophysiology has mainly been studied using animal models and animal tumor-derived cell lines. Nevertheless, experimental studies on human pituitary adenomas are difficult because of the significant differences among species and the lack of reliable cell lines. Recently, several methods have been established to differentiate pituitary cells from human pluripotent stem cells (hPSCs). The induced pituitary hormone-producing cells retain the physiological properties already lost in tumor-derived cell lines. Moreover, CRISPR/Cas9 systems have expedited the introduction of causative gene mutations in various malignant tumors into hPSCs. Therefore, hPSC-derived pituitary cells have great potential as a novel platform for studying the pathophysiology of human-specific pituitary adenomas and developing novel drugs. This review presents an overview of the recent progresses in hPSC applications for pituitary research, functional pituitary adenoma pathogenesis, and genome-editing techniques for introducing causative mutations. We also discuss future applications of hPSCs for studying pituitary adenomas. [ABSTRACT FROM AUTHOR]

Block copolymers (BCPs) have garnered considerable interest due to their ability to form microphase-separated structures suitable for nanofabrication. For these applications, it is critical to achieve both sufficient etch selectivity and a small domain size. To meet both requirements concurrently, we propose the use of oligosaccharide and oligodimethylsiloxane as hydrophilic and etch-resistant hydrophobic inorganic blocks, respectively, to build up a novel BCP system, i.e., carbohydrate-inorganic hybrid BCP. The carbohydrate-inorganic hybrid BCPs were synthesized via a click reaction between oligodimethylsiloxane with an azido group at each chain end and propargyl-functionalized maltooligosaccharide (consisting of one, two, and three glucose units). In the bulk state, small-angle X-ray scattering revealed that these BCPs microphase separated into gyroid, asymmetric lamellar, and symmetric lamellar structures with domain-spacing ranging from 5.0 to 5.9 nm depending on the volume fraction. Additionally, we investigated microphase-separated structures in the thin film state and discovered that the BCP with the most asymmetric composition formed an ultrafine and highly oriented gyroid structure as well as in the bulk state. After reactive ion etching, the gyroid thin film was transformed into a nanoporous-structured gyroid SiO2 material, demonstrating the material's promising potential as nanotemplates. [ABSTRACT FROM AUTHOR]

The topology effects of cyclization on thermal phase transition behaviors were investigated for a series of amphiphilic Pluronic copolymers of both hydrophilic–hydrophobic–hydrophilic and hydrophobic–hydrophilic–hydrophobic block sequences. The dye solubilization measurements revealed the lowered critical micelle temperatures (TCMT) along with the decreased micellization enthalpy (ΔHmic) and entropy (ΔSmic) for the cyclized species. Furthermore, the transmittance and dynamic light scattering (DLS) measurements indicated a block sequence-dependent effect on the clouding phenomena, where a profound decrease in cloud point (Tc) was only found for the copolymers with a hydrophilic–hydrophobic–hydrophilic block sequence. Thus, the effect of cyclization on these critical temperatures was manifested differently depending on its block sequence. Finally, a comparison of the linear hydroxy-terminated, methoxy-terminated, and cyclized species indicated the effect of cyclization to be unique from a simple elimination of the terminal hydrophilic moieties. [ABSTRACT FROM AUTHOR]

Tele-guidance systems for the remote monitoring and maintenance of equipment have been extensively investigated. Such systems enable a remote helper to provide guidance to a local worker while perceiving local conditions. In this study, we propose a tele-guidance system that supports the anticipation of an interlocutor's actions during communication. Our proposed system enables a helper and worker to anticipate each other's actions by allowing them to move around in the workspace freely and observe each other's non-verbal cues (e.g., body motions and other gestures) through a head-mounted display. We conducted an experiment to compare the effectiveness of our proposed method with that of existing methods (a simple tele-pointer) that support anticipation during communication. [ABSTRACT FROM AUTHOR]

The proliferation and differentiation of skeletal muscle cells are usually controlled by serum components. Myogenic differentiation is induced by a reduction of serum components in vitro. It has been recently reported that serum contains not only various growth factors with specific actions on the proliferation and differentiation of myogenic cells, but also exogenous exosomes, the function of which is poorly understood in myogenesis. We have found that exosomes in fetal bovine serum are capable of exerting an inhibitive effect on the differentiation of C2C12 myogenic cells in vitro. In this process of inhibition, the downregulation of Tceal5 and Tceal7 genes was observed. Expression of these genes is specifically increased in direct proportion to myogenic differentiation. Loss- or gain- of function studies with Tceal5 and Tceal7 indicated that they have the potential to regulate myogenic differentiation via exosomes in fetal bovine serum. [ABSTRACT FROM AUTHOR]

Herein, we report the Suzuki–Miyaura catalyst-transfer polycondensation (SCTP) of triolborate-type carbazole monomers, i.e., potassium 3-(6-bromo-9-(2-octyldodecyl)-9H-carbazole-2-yl)triolborate (M1) and potassium 2-(7-bromo-9-(2-octyldodecyl)-9H-carbazole-2-yl) triolborate (M2), as an efficient and versatile approach for precisely synthesizing poly[9-(2-octyldodecyl)-3,6-carbazole] (3,6-PCz) and poly[9-(2-octyldodecyl)-2,7-carbazole] (2,7-PCz), respectively. The SCTP of triolborate-type carbazole monomers was performed in a mixture of THF/H2O using an initiating system consisted of 4-iodobenzyl alcohol, Pd2(dba)3•CHCl3, and t-Bu3P. In the SCTP of M1, cyclic by-product formation was confirmed, as reported for the corresponding pinacolboronate-type monomer. By optimizing the reaction temperature and reaction time, we successfully synthesized linear end-functionalized 3,6-PCz for the first time. The SCTP of M2 proceeded with almost no side reaction, yielding 2,7-PCz with a functional initiator residue at the α-chain end. Kinetic and block copolymerization experiments demonstrated that the SCTP of M2 proceeded in a chain-growth and controlled/living polymerization manner. This is a novel study on the synthesis of 2,7-PCz via SCTP. By taking advantage of the well-controlled nature of this polymerization system, we demonstrated the synthesis of high-molecular-weight 2,7-PCzs (Mn = 5–38 kg mol−1) with a relatively narrow ÐM (1.35–1.48). Furthermore, we successfully synthesized fluorene/carbazole copolymers as well as 2,7-PCz-containing diblock copolymers, demonstrating the versatility of the present polymerization system as a novel synthetic strategy for well-defined polycarbazole-based materials. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cells (hPSCs) are grouped into two cell types; embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs). hESCs have provided multiple powerful platforms to study human biology, including human development and diseases; however, there were difficulties in the establishment of hESCs from human embryo and concerns over its ethical issues. The discovery of hiPSCs has expanded to various applications in no time because hiPSCs had already overcome these problems. Many hPSC-based studies have been performed using two-dimensional monocellular culture methods at the cellular level. However, in many physiological and pathophysiological conditions, intra- and inter-organ interactions play an essential role, which has hampered the establishment of an appropriate study model. Therefore, the application of recently developed technologies, such as three-dimensional organoids, bioengineering, and organ-on-a-chip technology, has great potential for constructing multicellular tissues, generating the functional organs from hPSCs, and recapitulating complex tissue functions for better biological research and disease modeling. Moreover, emerging techniques, such as single-cell transcriptomics, spatial transcriptomics, and artificial intelligence (AI) allowed for a denser and more precise analysis of such heterogeneous and complex tissues. Here, we review the applications of hPSCs to construct complex organs and discuss further prospects of disease modeling and drug discovery based on these PSC-derived organs. [ABSTRACT FROM AUTHOR]

Amber—the fossilized resin of trees—is rich in terpenoids and rosin acids. The physiological effects, such as antipyretic, sedative, and anti-inflammatory, were used in traditional medicine. This study aims to clarify the physiological effects of amber extract on lipid metabolism in mouse 3T3-L1 cells. Mature adipocytes are used to evaluate the effect of amber extract on lipolysis by measuring the triglyceride content, glucose uptake, glycerol release, and lipolysis-related gene expression. Our results show that the amount of triacylglycerol, which is stored in lipid droplets in mature adipocytes, decreases following 96 h of treatment with different concentrations of amber extract. Amber extract treatment also decreases glucose uptake and increases the release of glycerol from the cells. Moreover, amber extract increases the expression of lipolysis-related genes encoding perilipin and hormone-sensitive lipase (HSL) and promotes the activity of HSL (by increasing HSL phosphorylation). Amber extract treatment also regulates the expression of other adipocytokines in mature adipocytes, such as adiponectin and leptin. Overall, our results indicate that amber extract increases the expression of lipolysis-related genes to induce lipolysis in 3T3-L1 cells, highlighting its potential for treating various obesity-related diseases. [ABSTRACT FROM AUTHOR]

The present study addresses the incorporation of fine particles into liquids via the creation of a large-scale swirling vortex on the liquid free surface using a rotary impeller positioned along the axis of a cylindrical vessel. Four types of particles are used in the experiments to investigate the incorporation efficiency of the particles into a water bath under different impeller rotation speeds. Additionally, the vortex characteristics are investigated numerically. The results reveal that two factors, namely the particle wettability and turbulent oscillations at the bottom part of vortex surface, play dominant roles in determining the particle incorporation behavior. Hydrophobic particles are incapable of being incorporated into the water bath under any of the conditions examined in the present study. Partly wettable particles are entrained into the water bath, with the efficiency increasing with the impeller rotation speed and particle size. This is because an increase in the impeller rotation speed causes vortex deformation, whereby its bottom part approaches the impeller blades where the turbulent surface oscillations reach maximum amplitudes. Another possible mechanism of particle incorporation is the effect of capillary increases of liquid into the spaces between particles, which accumulate on the bottom surface of the vortex. [ABSTRACT FROM AUTHOR]

Nuclear factor-κB (NF-κB) is an important transcription factor involved in various biological functions, including tumorigenesis. Hence, NF-κB has attracted attention as a target factor for cancer treatment, leading to the development of several inhibitors. However, existing NF-κB inhibitors do not discriminate between its subunits, namely, RelA, RelB, cRel, p50, and p52. Conventional methods used to evaluate interactions between transcription factors and DNA, such as electrophoretic mobility shift assay and luciferase assays, are unsuitable for high-throughput screening (HTS) and cannot distinguish NF-κB subunits. We developed a HTS method named DNA strand exchange fluorescence resonance energy transfer (DSE-FRET). This assay is suitable for HTS and can discriminate a NF-κB subunit. Using DSE-FRET, we searched for RelA-specific inhibitors and verified RelA inhibition for 32,955 compounds. The compound A55 (2-(3-carbamoyl-6-hydroxy-4-methyl-2-oxopyridin-1(2H)-yl) acetic acid) selectively inhibited RelA–DNA binding. We propose that A55 is a seed compound for RelA-specific inhibition and could be used in clinical applications. [ABSTRACT FROM AUTHOR]

The activation and proliferation of microglia is characteristic of the early stages of brain pathologies. In this study, we aimed to identify a factor that promotes microglial activation and proliferation and examined the in vitro effects on these processes. We cultured microglial cell lines, EOC 2 and SIM-A9, with various growth factors and evaluated cell proliferation, death, and viability. The results showed that only transforming growth factor beta (TGF-β) caused an increase in the in vitro proliferation of both microglial cell lines. It has been reported that colony-stimulating factor 1 promotes the proliferation of microglia, while TGF-β promotes both proliferation and inhibition of cell death of microglia. However, upon comparing the most effective doses of both (assessed from the proliferation assay), we identified no statistically significant difference between the two factors in terms of cell death; thus, both have a proliferative effect on microglial cells. In addition, a TGF-β receptor 1 inhibitor, galunisertib, caused marked inhibition of proliferation in a dose-dependent manner, indicating that inhibition of TGF-β signalling reduces the proliferation of microglia. Therefore, galunisertib may represent a promising therapeutic agent for the treatment of neurodegenerative diseases via inhibition of nerve injury-induced microglial proliferation, which may result in reduced inflammatory and neuropathic and cancer pain. [ABSTRACT FROM AUTHOR]

The present work investigated melt flow pattern and temperature distribution in the sump of aluminum billets produced in a hot-top equipped direct chilling (DC) caster conventionally and with ultrasonic irradiation. The main emphasis was placed on clarifying the effects of acoustic streaming and hot-top unit type. Acoustic streaming characteristics were investigated first by using the earlier developed numerical model and water model experiments. Then, the acoustic streaming model was applied to develop a numerical code capable of simulating unsteady flow phenomena in the sump during the DC casting process. The results revealed that the introduction of ultrasonic vibrations into the melt in the hot-top unit had little or no effect on the temperature distribution and sump profile, but had a considerable effect on the melt flow pattern in the sump. Our results showed that ultrasound irradiation makes the flow velocity faster and produces a lot of relatively small eddies in the sump bulk and near the mushy zone. The latter causes frequently repeated thinning of the mushy zone layer. The numerical predictions were verified against measurements performed on a pilot DC caster producing 203 mm billets of Al-17%Si alloy. The verification revealed approximately the same sump depth and shape as those in the numerical simulations, and confirms the frequent and large fluctuations of the melt temperature during ultrasound irradiation. However, the measured temperature distribution in the sump significantly differed from that predicted numerically. This suggests that the present mathematical model should be further improved, particularly in terms of more accurate descriptions of boundary conditions and mushy zone characteristics. [ABSTRACT FROM AUTHOR]

In this study, we investigate structures and stabilities of the micelles of a cyclic amphiphile (c-PBA-b-PEO) composed of poly(n-butyl acrylate) (PBA) and poly(ethylene oxide) (PEO) blocks and its linear diblock and triblock analogues (l-PBA-b-PEO and l-PBA-b-PEO-b-PBA) by using synchrotron X-ray scattering and quantitative data analysis. The comprehensive scattering analysis gives details and insights to the micellar architecture through structural parameters. Furthermore, this analysis provides direct clues for structural stabilities in micelles, which can be used as a good guideline to design highly stable micelles. Interestingly, in water, all topological polymers are found to form ellipsoidal micelles rather than spherical micelles; more interestingly, the cyclic polymer and its linear triblock analog make oblate-ellipsoidal micelles while the linear diblock analog makes a prolate-ellipsoidal micelle. The analysis results collectively inform that the cyclic topology enables more compact micelle formation as well as provides a positive impact on the micellar structural integrity. [ABSTRACT FROM AUTHOR]

Cyclic polymers exhibit unique physical and chemical properties because of the restricted chain mobility and absence of chain ends. Although many types of homopolymers and diblock copolymers possessing cyclic architectures have been synthesized to date, there are relatively few reports of cyclic triblock terpolymers because of their synthetic difficulties. In this study, a novel synthetic approach for μ-ABC tricyclic miktoarm star polymers involving t-Bu-P4-catalyzed ring-opening polymerization (ROP) of glycidyl ethers and intramolecular copper-catalyzed azido-alkyne cycloaddition (CuAAC) was developed. First, the t-Bu-P4-catalyzed ROP of decyl glycidyl ether, dec-9-enyl glycidyl ether, and 2-(2-(2-methoxyethoxy) ethoxy) ethyl glycidyl ether with the aid of functional initiators and terminators was employed for the preparation of a clickable linear triblock terpolymer precursor possessing three azido and three ethynyl groups at the selected positions. Next, the intramolecular CuAAC of the linear precursor successfully produced the well-defined tricyclic triblock terpolymer with narrow dispersity in a reasonable yield. The present strategy is useful for synthesizing model polymers for studying the topological effects on the triblock terpolymer self-assembly. [ABSTRACT FROM AUTHOR]

Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α) is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase domain-containing protein have been developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1) has also been shown to have the potential to activate HIF-α. However, few small-molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a series of furan- and thiophene-2-carbonyl amino acid derivatives having the potential to inhibit FIH-1. The inhibitory activities of these compounds were evaluated in SK-N-BE(2)c cells by measuring HIF response element (HRE) promoter activity. Several furan- and thiophene-2-carbonyl amino acid derivatives inhibited FIH-1 based on correlations among the docking score of the FIH-1 active site, the chemical structure of the compounds, and biological HIF-α/HRE transcriptional activity. [ABSTRACT FROM AUTHOR]

The activation and proliferation of microglia is characteristic of the early stages of brain pathologies. In this study, we aimed to identify a factor that promotes microglial activation and proliferation and examined the in vitro effects on these processes. We cultured microglial cell lines, EOC 2 and SIM-A9, with various growth factors and evaluated cell proliferation, death, and viability. The results showed that only transforming growth factor beta (TGF-β) caused an increase in the in vitro proliferation of both microglial cell lines. It has been reported that colony-stimulating factor 1 promotes the proliferation of microglia, while TGF-β promotes both proliferation and inhibition of cell death of microglia. However, upon comparing the most effective doses of both (assessed from the proliferation assay), we identified no statistically significant difference between the two factors in terms of cell death; thus, both have a proliferative effect on microglial cells. In addition, a TGF-β receptor 1 inhibitor, galunisertib, caused marked inhibition of proliferation in a dose-dependent manner, indicating that inhibition of TGF-β signalling reduces the proliferation of microglia. Therefore, galunisertib may represent a promising therapeutic agent for the treatment of neurodegenerative diseases via inhibition of nerve injury-induced microglial proliferation, which may result in reduced inflammatory and neuropathic and cancer pain.