Synergistic Effects of Polybenzimidazole and Aramide on Enhancing Flame-Retardancy and Solubility

Aromatic and functional polymers with processibility derived from biobased starting materials are prerequisite considering sustainable society. Poly(2,5-benzimidazole)s are rigid-rod polymers to show ultrahigh thermal stability such as flame retardance, while usually suffer from poor solubility. Here, poly(benzimidazole-co-amide)s are synthesized from two biobased monomers, 3,4-diaminobenzoic acid and a semirigid comonomer, 4-aminohydrocinnamic acid. The copolymers with an amide composition of 80 mol% and higher are soluble in widely used polar solvents to fabricate the films keeping high flame retardance, which is comparable with popular high-performance polymers such as aromatic polyimides, polyetheretherketone, polyphenylene sulfide, etc.     

Thermal desorption and pyrolysis direct analysis in real time mass spectrometry of Nafion membrane

Perfluorosulfonic acid ionomer membranes have been widely used as proton conducting membranes in various electrochemical processes such as polymer electrolyte fuel cells and water electrolysis. While their thermal stability has been studied by thermogravimetry and analysis of low molecular weight products, their decomposition mechanism is little understood. In this study a newly developed methodology of thermal desorption and pyrolysis in combination with direct analysis in real time mass spectrometry is applied for Nafion membrane. An ambient ionization source and a high-resolution time-of-flight mass spectrometer enabled unambiguous assignment of gaseous products. Thermal decomposition is initiated by side chain detachment above 350°C, which leaves carbonyls on the main chain at the locations of the side chains. Perfluoroalkanes are released above 400°C by main chain scission and their further decomposition products dominate above 500 °C. DFT calculation of reaction energies and barrier heights of model compounds support proposed decomposition reactions.     

Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.     

Reduced Claudin-12 Expression Predicts Poor Prognosis in Cervical Cancer

Background: Within the claudin (CLDN) family, CLDN12 mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications. Methods: We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer. Results: Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, p = 0.002 and HR 2.615, p = 0.029, respectively). Conclusions: It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases.     

Numerical Simulation of Sterilization Processes for Shear‐Thinning Food in Taylor‐Couette Flow Systems

The performance of the Taylor‐Couette flow apparatus as a heat sterilizer is numerically investigated. The destruction of Clostridium botulinum and thiamine (vitamin B1) was selected as model reaction. When Taylor vortices were formed in the annular space, the heat transfer significantly enhanced as compared to the case without vortex flow. As a result, the equivalent lethality calculated from the temperature field increased, which is regarded as a quantum leap. Conversely, the improvement of heat transfer induced destruction of thiamine. These results suggest that there is a trade‐off relationship between the enhancement of heat transfer and the avoidance of thermal destruction of nutritional components. In conclusion, the Taylor‐Couette flow sterilizer has the potential for process intensification in heat sterilization processes.     

Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model

We evaluated the abscopal effect of re-implantation of liquid nitrogen-treated tumor-bearing bone grafts and the synergistic effect of anti-PD-1 (programmed death-1) therapy using a bone metastasis model, created by injecting MMT-060562 cells into the bilateral tibiae of 6–8-week-old female C3H mice. After 2 weeks, the lateral tumors were treated by excision, cryotreatment using liquid nitrogen, excision with anti-PD-1 treatment, and cryotreatment with anti-PD-1 treatment. Anti-mouse PD-1 4H2 was injected on days 1, 6, 12, and 18 post-treatment. The mice were euthanized after 3 weeks; the abscopal effect was evaluated by focusing on growth inhibition of the abscopal tumor. The re-implantation of frozen autografts significantly inhibited the growth of the remaining abscopal tumors. However, a more potent abscopal effect was observed in the anti-PD-1 antibody group. The number of CD8+ T cells infiltrating the abscopal tumor and tumor-specific interferon-γ (IFN-γ)-producing spleen cells increased in the liquid nitrogen-treated group compared with those in the excision group, with no significant difference. The number was significantly higher in the anti-PD-1 antibody-treated group than in the non-treated group. Overall, re-implantation of tumor-bearing frozen autograft has an abscopal effect on abscopal tumor growth, although re-implantation of liquid nitrogen-treated bone grafts did not induce a strong T-cell response or tumor-suppressive effect.     

Urothelium-Specific Deletion of Connexin43 in the Mouse Urinary Bladder Alters Distension-Induced ATP Release and Voiding Behavior

Connexin43 (Cx43), the main gap junction and hemichannel forming protein in the urinary bladder, participates in the regulation of bladder motor and sensory functions and has been reported as an important modulator of day–night variations in functional bladder capacity. However, because Cx43 is expressed throughout the bladder, the actual role played by the detrusor and the urothelial Cx43 is still unknown. For this purpose, we generated urothelium-specific Cx43 knockout (uCx43KO) mice using Cre-LoxP system. We evaluated the day–night micturition pattern and the urothelial Cx43 hemichannel function of the uCx43KO mice by measuring luminal ATP release after bladder distention. In wild-type (WT) mice, distention-induced ATP release was elevated, and functional bladder capacity was decreased in the animals’ active phase (nighttime) when Cx43 expression was also high compared to levels measured in the sleep phase (daytime). These day–night differences in urothelial ATP release and functional bladder capacity were attenuated in uCx43KO mice that, in the active phase, displayed lower ATP release and higher functional bladder capacity than WT mice. These findings indicate that urothelial Cx43 mediated ATP signaling and coordination of urothelial activity are essential for proper perception and regulation of responses to bladder distension in the animals’ awake, active phase.     

Design,Synthesis, and Biological Evaluation of Lysine Demethylase 5 C Degraders

Lysine demethylase 5 C (KDM5C) controls epigenetic gene expression and is attracting great interest in the field of chemical epigenetics. KDM5C has emerged as a therapeutic target for anti-prostate cancer agents, and recently we identified triazole 1 as an inhibitor of KDM5C. Compound 1 exhibited highly potent KDM5C-inhibitory activity in in vitro enzyme assays, but did not show strong anticancer effects. Therefore, a different approach is needed for the development of anticancer agents targeting KDM5C. Here, we attempted to identify KDM5C degraders by focusing on a protein-knockdown strategy. Compound 3 b , which was designed based on compound 1 , degraded KDM5C and inhibited the growth of prostate cancer PC-3 cells more strongly than compound 1 . These findings suggest that KDM5C degraders are more effective as anticancer agents than compounds that only inhibit the catalytic activity of KDM5C.     

Full Eulerian deformable solid-fluid interaction scheme based on building-cube method for large-scale parallel computing

We propose a full Eulerian incompressible solid-fluid interaction scheme capable of achieving high parallel efficiency and easily generating meshes for complex solid geometries. While good scalability of a full Eulerian solid-fluid interaction formulation has been reported by Sugiyama et al, their analysis was carried out using uniform Cartesian mesh and an artificial compressibility method. Typically, it is more challenging to achieve good scalability for hierarchical Cartesian meshes and a fully incompressible formulation. In addition, the conventional full Eulerian methods require a large computational cost to resolve complex solid geometries due to the usage of uniform Cartesian meshes. In an attempt to overcome the aforementioned issues, we employ the building-cube method, where the computational domain is divided into cubic regions called cubes. Each cube is divided at equal intervals, the same number of cubes is assigned to each core, and the spatial loop processing is executed for each cube. The numerical method is verified by computing five numerical examples. In the weak scaling test, the parallel efficiency at 32768 cores with 32 cores as a reference is 93.6%. In the strong scaling test, the parallel efficiency at 32768 cores with 128 cores as a reference is 70.2%.     

Flexible and Conductive 3D Printable Polyvinylidene Fluoride and Poly(N,N‐dimethylacrylamide) Based Gel Polymer Electrolytes

In this work, 3D printable gel polymer electrolytes (GPEs) based on N,N‐dimethylacrylamide (DMAAm) and polyvinylidene fluoride (PVDF) in lithium chloride containing ethylene glycol solution are synthesized and their physicochemical properties are investigated. 3D printing is carried out with a customized stereolithography type 3D gel printer named “Soft and Wet Intelligent Matter‐Easy Realizer” and free forming GPE samples having variable shapes and sizes are obtained. Printed PVDF/PDMAAm‐based GPEs exhibit tunable mechanical properties and favorable thermal stability. Electrochemical proprieties of the printed GPEs are carried out via impedance spectroscopy in the temperature range of 25–90 °C by varying PVDF content. Ionic conductivity as high as 6.5 × 10^?4 S cm^?1 is achieved at room temperature for GPE containing low PVDF content (5 wt%) and conductivity of the GPEs is increased as temperature rises.