Improving the Accuracy of the Evaluation Method for the Interfacial Shear Strength of Fiber-Reinforced Thermoplastic Polymers through the Short Beam Shear Test.

Short fiber-reinforced thermoplastic polymers (SFRTPs) are commonly used in various molding methods due to their high specific elasticity and strength. To evaluate the interfacial strength, several determination methods have been proposed, including the interfacial shear strength (IFSS). In previous research, an IFSS evaluation method based on the short beam shear method was proposed. However, this method is only applicable to micrometer-sized fibers with high stiffness levels that are not easily bent. When utilizing cellulose fiber, the interfacial shear strength (IFSS) results frequently exhibit significant deviations. To tackle this issue, we suggest an enhanced experimental technique that employs beam-shaped specimens with welding points based on the short beam shear test. Furthermore, we conducted a three-dimensional analysis of the original method to determine the fiber orientation angle and IFSS. The outcomes were compared with previously reported determinations. The IFSS achieved through the novel method proposed in this paper exhibits high precision and reliability, rendering it suitable for use with soft and flexible fibers.

Effect of Carbon Nanofiber Distribution on Mechanical Properties of Injection-Molded Aramid-Fiber-Reinforced Polypropylene.

The mechanical recycling of discarded plastic products as resources for environmental preservation has recently gained research attention. In this context, it is necessary to use waste materials for fiber-reinforced thermoplastics (FRTP). Glass and carbon fibers are often damaged by shear and compression during melt-forming processes. To achieve a sustainable society, it is necessary for thermal recycling to produce minimal to no residue and for mechanical recycling to maintain the length of fibers used in FRTP to preserve their performance as a reinforcing agent. Aramid fibers (AFs) do not shorten during the melt-molding process, and their composites have excellent impact strength. On the other hand, plastics reinforced with glass or carbon fibers are reported to have a superior strength and modulus of elasticity compared to aramid fibers. This study investigates the dispersion of a carbon nanofiber (CNF), a whisker, as the third component in aramid-fiber-reinforced polypropylene (PP/AF). The results and discussion sections demonstrate how the dispersion of CNF in PP/AF can enhance the mechanical properties of injection-molded products without compromising their impact resistance. The proposed composition will have excellent material recyclability and initial mechanical properties compared to glass-fiber-reinforced thermoplastics.

Impact Energy Dissipation and Quantitative Models of Injection Molded Short Fiber-Reinforced Thermoplastics.

Glass short fiber-reinforced thermoplastics (SGFRTP) are used to reduce carbon dioxide emissions from transportation equipment, especially household vehicles. The mechanical properties required for SGFRTP include flexural strength, impact resistance, etc. In particular, impact resistance is an important indicator of the use of SGFRTP. For this study, a mechanical model was developed to explain the notched impact strength of SGFRTP injection molded products in terms of their interfacial shear strength. The values obtained from the model show good agreement with the experimentally obtained results (R2 > 0.95). Results also suggest that the model applies to different fiber orientation angle and a range of fiber lengths in the molded product that are sufficiently shorter than the critical fiber length.

Mechanical Anisotropy of Injection-Molded PP/PS Polymer Blends and Correlation with Morphology.

The molecular orientation formed by melt-forming processes depends strongly on the flow direction. Quantifying this anisotropy, which is more pronounced in polymer blends, is important for assessing the mechanical properties of thermoplastic molded products. For injection-molded polymer blends, this study used short-beam shear testing to evaluate the mechanical anisotropy as a stress concentration factor, and clarified the correlation between the evaluation results and the phase structure. Furthermore, because only shear yielding occurs with short-beam shear testing, the yielding conditions related to uniaxial tensile loading were identified by comparing the results with those of three-point bending tests. For continuous-phase PP, the phase structure formed a sea-island structure. The yield condition under uniaxial tensile loading was interface debonding. For continuous-phase PS, the phase structure was dispersed and elongated in the flow direction. The addition of styrene-ethylene-butadiene-styrene (SEBS) altered this structure. The yielding condition under uniaxial tensile loading was shear yielding. The aspect ratio of the dispersed phase was found to correlate with the stress concentration factor. When the PP forming the sea-island structure was of continuous phase, the log-complex law was sufficient to explain the shear yield initiation stress without consideration of the interfacial interaction stress.

Correction: Takayama, T. Inorganic Particles Contribute to the Compatibility of Polycarbonate/Polystyrene Polymer Blends. Materials 2023, 16, 1536.

There was an error in the original publication [...].

Inorganic Particles Contribute to the Compatibility of Polycarbonate/Polystyrene Polymer Blends.

Polycarbonate (PC), an engineering plastic, has excellent mechanical strength and toughness. Moreover, this transparent polymer material can be used in fields where materials require mechanical properties and transparency. Nevertheless, PC is known to have a high melt viscosity. Moreover, blending with polystyrene (PS), an inherently brittle material, has been used to adjust its melt viscosity. As a result, the PS makes PC/PS polymer blends more brittle than PC alone. As described herein, after attempting to achieve compatibility with inorganic particles, the results show that the dispersion of small amounts of inorganic clay and silica particles in PC/PS polymer blends maintained transparency while improving the impact strength to a level comparable to that of polycarbonate. Apparently, the inorganic particles promote the fine dispersion of PS. Moreover, the spherical morphology of the inorganic particles is more effective at compatibilizing the polymer blend because the inorganic particles can apply isotropic interaction forces.

Discovery of novel 2-[(4-hydroxy-6-oxo-2,3-dihydro-1H-pyridine-5-carbonyl)amino]acetic acid derivatives as HIF prolyl hydroxylase inhibitors for treatment of renal anemia.

Prolyl hydroxylase domain-containing protein (PHD) inhibitors are useful as orally administered agents for the treatment of renal anemia. Based on the common structures of known PHD inhibitors, we found novel PHD inhibitor 1 with a 2-[(4-hydroxy-6-oxo-2,3-dihydro-1H-pyridine-5-carbonyl)amino]acetic acid motif. The PHD2-inhibitory activity, lipophilicity (CLogP), and PK profiles (hepatocyte metabolism, protein binding, and/or elimination half-life) of this inhibitor were used as the evaluation index to optimize the structure and eventually discovered clinical candidate 42 as the suitable compound. Compound 42 was demonstrated to promote the production of erythropoietin (EPO) following oral administration in mice and rats. The predicted half-life of this compound in humans was 1.3-5.6 h, therefore, this drug may be expected to administer once daily with few adverse effects caused by excessive EPO production.

Mechanical characterization and modelling of the temperature-dependent impact behaviour of a biocompatible poly(L-lactide)/poly(ε-caprolactone) polymer blend.

Poly(ε-caprolactone) (PCL) is a ductile, bioabsorbable polymer that has been employed as a blend partner for poly(L-lactic acid) (PLLA). An improvement of the material strength and impact resistance of PLLA/PCL polymer blends compared to pure PLLA has been shown previously. To use numerical simulations in the design process of new components composed of the PLLA/PCL blend, a constitutive model for the material has to be established. In this work, a constitutive model for a PLLA/PCL polymer blend is established from the results of compressive tests at high and low strain rates at three different temperatures, including the body temperature. Finite element simulations of the split Hopkinson pressure bar test using the established constitutive model are carried out under the same condition as the experiments. During the experiments, the changes in the diameter and thickness of the specimens are captured by a high-speed video camera. The accuracy of the numerical model is tested by comparing the simulation results, such as the stress, strain, thickness and diameter histories of the specimens, with those measured in the experiments. The numerical model is also validated against an impact test of non-homogenous strains and strain rates. The results of this study provide a validated numerical model for a PLLA/PCL polymer blend at strain rates of up to 1800 s(-1) in the temperature range between 22°C and 50°C.

Isoquinoline derivatives as potent, selective, and orally active CRTH2 antagonists.

Synthesis and structure-activity relationship of a novel series of isoquinoline CRTH2 antagonists bearing a methylene linker between the isoquinoline and benzamide moieties were described. Optimization focusing on the substituents of the benzamide portion in the right hand part of the molecule led to the identification of TASP0412098 (9l), which is a potent, selective CRTH2 antagonist (binding affinity: IC50=2.1 nM, functional activity: IC50=12 nM). Compound 9l, which was orally bioavailable in mice and guinea pigs, showed in vivo efficacy after oral administration in a bronchial asthma model of guinea pigs.

Isoquinoline derivatives as potent CRTH2 antagonists: design, synthesis and SAR.

In this study, we describe the synthesis and structure-activity relationship (SAR) of a series of isoquinoline chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists. TASP0376377 (15-20), one of the most potent compounds, showed a potent binding affinity (IC50=19 nM) in addition to the excellent functional antagonist activity (IC50=13 nM). Moreover, the efficacy of this compound in a chemotaxis assay (IC50=23 nM) was in good agreement with its potency as a CRTH2 antagonist. In addition, 15-20 exhibited greater selectivity in binding to CRTH2 than to the DP1 prostanoid receptor (IC50 >1 µM) or the enzymes COX-1 and COX-2 (IC50 >10 µM).

The daily response for proton pump inhibitor treatment in Japanese reflux esophagitis and non-erosive reflux disease.

We investigated comparison according to reflux esophagitis and non-erosive reflux disease about "daily" symptom improvement for proton pump inhibitor treatment. We enrolled 57 reflux esophagitis and 90 non-erosive reflux disease patients. They took rabeprazole 10 mg/day for 28 days and completed "daily" in the Frequency Scale for the Symptoms of GERD from baseline until day 14, and after 28 days of treatment. The efficacy endpoint was the improvement rates in Frequency Scale for the Symptoms of GERD, based on baseline. Frequency Scale for the Symptoms of GERD was decreased in reflux esophagitis and non-erosive reflux disease (p<0.001) and was significantly lower in reflux esophagitis than in non-erosive reflux disease from the first day of treatment (p<0.05). Symptomatic improvement rates were also significantly higher in reflux esophagitis (50.3 ± 44.9%) than in non-erosive reflux disease (31.7 ± 43.2%) from the first day of treatment (p<0.0001). The symptomatic improvement rates in reflux esophagitis were significant increased from the second day of treatment until after 28 days of treatment (p = 0.0006), however, these in non-erosive reflux disease were significant increased from third days until after 28 days of treatment (p = 0.0002). In non-erosive reflux disease, the improvement of dysmotility symptom was particularly gradual as well as of reflux symptom, too. As for results of prediction of proton pump inhibitor response (completed symptom resolution) form early symptom improvement within 1 week, it was able to predict proton pump inhibitor response from the symptom improvement rate on 3 days in reflux esophagitis and on day 7 in non-erosive reflux disease. In conclusion, the prediction of the proton pump inhibitor response in non-erosive reflux disease was slow in comparison with reflux esophagitis. The cause was gradual improvement of dysmotility symptom.

5-(1,3-Benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazole derivatives as potent and selective transforming growth factor-ß type I receptor inhibitors.

A series of 5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazole derivatives was synthesized as transforming growth factor-ß (TGF-ß) type I receptor (also known as activin-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and for their TGF-ß-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. As a representative compound, 16i was a potent and selective ALK5 inhibitor, exhibiting a good enzyme inhibitory activity (IC(50) = 5.5 nM) as well as inhibitory activity against TGF-ß-induced Smad2/3 phosphorylation at a cellular level (IC(50) = 36 nM). Furthermore, the topical application of 3% 16i lotion significantly inhibited Smad2 phosphorylation in Mouse skin (90% inhibition compared with vehicle-treated animals).

Isoquinoline derivatives as potent CRTH2 receptor antagonists: synthesis and SAR.

Synthesis and structure-activity relationship of a novel series of isoquinoline CRTH2 receptor antagonists are described. One of the most potent compounds, TASP0376377 (6m), showed not only potent binding affinity (IC(50)=19 nM) but also excellent functional antagonist activity (IC(50)=13 nM). TASP0376377 was tested for its ability of a chemotaxis assay to show the effectiveness (IC(50)=23 nM), which was in good agreement with the CRTH2 antagonist potency. Furthermore, TASP0376377 showed sufficient selectivity for binding to CRTH2 over the DP1 prostanoid receptor (IC(50)>1 µM) and COX-1 and COX-2 enzymes (IC(50)>10 µM).

Blocking S1P interaction with S1P1 receptor by a novel competitive S1P1-selective antagonist inhibits angiogenesis.

Sphingosine 1-phosphate receptor type 1 (S1P(1)) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P(1) and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P(1)-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P(1) antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P(1) is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

Lymphopenia induced by a novel selective S1P(1) antagonist structurally unrelated to S1P.

Sphingosine 1-phosphate (S1P) regulates lymphocyte trafficking via type-1 S1P receptor (S1P(1)) and participates in many pathological conditions. We developed a novel type S1P(1)-selective antagonist, TASP0251078, which is structurally unrelated to S1P. This competitive antagonist inhibited binding of S1P to S1P(1) resulting in reduced signaling downstream of S1P(1), including GTPγS-binding and cAMP formation. TASP0251078 also inhibited S1P-induced cellular responses such as chemotaxis and receptor-internalization. Furthermore, when administered in vivo, TASP0251078 induced lymphopenia in blood, which is different from previously reported effects of other S1P(1)-antagonists. In a mouse contact hypersensitivity model, TASP0251078 effectively suppressed ear swelling, leukocyte infiltration, and hyperplasia. These findings provide the chemical evidence that S1P(1) antagonism is responsible for lymphocyte sequestration from the blood, and suggest that the effect of S1P(1) agonists on lymphocyte sequestration results from their functional antagonism.

Amelioration of collagen-induced arthritis by a novel S1P1 antagonist with immunomodulatory activities.

Sphingosine 1-phosphate (S1P) regulates lymphocyte trafficking through the type 1 sphingosine 1-phosphate receptor (S1P(1)) and participates in many pathological conditions, including autoimmune diseases. We developed a novel S1P(1)-selective antagonist, TASP0277308, which is structurally unrelated to S1P. This antagonist competitively inhibited S1P-induced cellular responses, such as chemotaxis and receptor internalization. Furthermore, differing from previously reported S1P(1) antagonists, TASP0277308 demonstrated in vivo activities to induce lymphopenia, a block in T cell egress from the thymus, displacement of marginal zone B cells, and upregulation of CD69 expression on both T and B cells, all of which recapitulate phenotypes of S1P(1)-deficient lymphocytes. In a mouse collagen-induced arthritis model, TASP0277308 significantly suppressed the development of arthritis, even after the onset of disease. These findings provide the first chemical evidence to our knowledge that S1P(1) antagonism is responsible for immunosuppression in the treatment of autoimmune diseases and also resolve the discrepancies between genetic and chemical studies on the functions of S1P(1) in lymphocytes.

Effect of annealing on the mechanical properties of PLA/PCL and PLA/PCL/LTI polymer blends.

The effects of annealing on the mechanical properties of polymer blends of poly(lactic acid) (PLA) and poly(ε-caprolactone) (PCL) were investigated. The bending strength and modulus of PLA/PCL tend to increase due to crystallization of the PLA phase by annealing. The mode I fracture energy, J(in), of PLA/PCL decreases dramatically due to the suppression of the ductile deformation of the spherical PCL phase by annealing. The immiscibility of PLA and PCL can be improved by adding lysine triisocyanate (LTI) as a result of additional polymerization. The phase transformation due to LTI addition reduces the size of the spherical PCL phase, resulting in higher fracture energy. An annealing process applied to PLA/PCL/LTI further strengthens the microstructure, resulting in effective improvement of the fracture energy.

Effects of the novel and potent lymphocyte-specific protein tyrosine kinase inhibitor TKM0150 on mixed lymphocyte reaction and contact hypersensitivity in mice.

Lymphocyte-specific protein tyrosine kinase (Lck) plays a critical role in T cell activation. In the present study, the effect of a newly synthesized small molecule compound, 7-[2-(dimethylamino)ethoxy]-2-(4-phenoxyphenyl)-9,10-dihydro-4H- pyrazolo[5,1-b] [1,3]benzodiazepine-3-carboxamide (TKM0150) on Lck activity was investigated. TKM0150 inhibited Lck with an 1C50 value of 0.7 nM. To evaluate if TKM0150 is a specific inhibitor of Lck, the activity against several Src (Proto-oncogene tyrosine-protein kinase Src) and non-Src family kinases were assayed. TKM150 inhibited Src family kinases, Src and Csk (c-Src kinase) (with IC50 values of 0.6 nM and 1.7 nM, respectively) as well as Fyn (p59-Fyn) and Lyn (tyrosine-protein kinase Lyn) at a dose of 1 microM; however, it did not inhibit kinase which is a non-Src family kinase in the tyrosine kinase (TK) group, nor kinases in other groups. Then, the anti-inflammtory potential of TKM0150 was evaluated by known experimental models. TKM0150 inhibited the murine mixed lymphocyte reaction (MLR) in vitro with an IC50 value of 0.7 nM, and 2,4,6-trinitro-1-chlorobenzene-induced contact hypersensitivity in vivo at a dose of 0.3 and 1% w/v administered topically. These results indicate that TKM0150 is a specific inhibitor of Lck/Src kinase and can block T cell-mediated responses in vitro and in vivo. Accordingly, TKM0150 would be expected as a drug candidate for treating T cell-mediated disorders including atopic dermatitis.

Ring-fused pyrazole derivatives as potent inhibitors of lymphocyte-specific kinase (Lck): Structure, synthesis, and SAR.

We have identified a novel series of ring-fused pyrazole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s <1nM) as well as excellent cellular activity against mixed lymphocyte reaction (MLR) (IC(50)s <1nM).

Pyrrole derivatives as potent inhibitors of lymphocyte-specific kinase: Structure, synthesis, and SAR.

We have described the synthesis, enzyme inhibitory activity, structure-activity relationships, and proposed binding mode of a novel series of pyrrole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s <10nM) for Lck kinase inhibition.