Screening of Inhibitors Targeting Heat Shock Protein 47 Involved in the Development of Idiopathic Pulmonary Fibrosis

Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47-collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023 Compounds, 13 exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose-dependent manner. Epigallocatechin-3-O-gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A-ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product-derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis.     

An Engineered Biliverdin-Compatible Cyanobacteriochrome Enables a Unique Ultrafast Reversible Photoswitching Pathway

Cyanobacteriochromes (CBCRs) are promising optogenetic tools for their diverse absorption properties with a single compact cofactor-binding domain. We previously uncovered the ultrafast reversible photoswitching dynamics of a red/green photoreceptor AnPixJg2, which binds phycocyanobilin (PCB) that is unavailable in mammalian cells. Biliverdin (BV) is a mammalian cofactor with a similar structure to PCB but exhibits redder absorption. To improve the AnPixJg2 feasibility in mammalian applications, AnPixJg2_BV4 with only four mutations has been engineered to incorporate BV. Herein, we implemented femtosecond transient absorption (fs-TA) and ground state femtosecond stimulated Raman spectroscopy (GS-FSRS) to uncover transient electronic dynamics on molecular time scales and key structural motions responsible for the photoconversion of AnPixJg2_BV4 with PCB (Bpcb) and BV (Bbv) cofactors in comparison with the parent AnPixJg2 (Apcb). Bpcb adopts the same photoconversion scheme as Apcb, while BV4 mutations create a less bulky environment around the cofactor D ring that promotes a faster twist. The engineered Bbv employs a reversible clockwise/counterclockwise photoswitching that requires a two-step twist on ~5 and 35 picosecond (ps) time scales. The primary forward P_fr → P_o transition displays equal amplitude weights between the two processes before reaching a conical intersection. In contrast, the primary reverse P_o → P_fr transition shows a 2:1 weight ratio of the ~35 ps over 5 ps component, implying notable changes to the D-ring-twisting pathway. Moreover, we performed pre-resonance GS-FSRS and quantum calculations to identify the Bbv vibrational marker bands at ~659,797, and 1225 cm⁻¹. These modes reveal a stronger H-bonding network around the BV cofactor A ring with BV4 mutations, corroborating the D-ring-dominant reversible photoswitching pathway in the excited state. Implementation of BV4 mutations in other PCB-binding GAF domains like AnPixJg4, AM1_1870g3, and NpF2164g5 could promote similar efficient reversible photoswitching for more directional bioimaging and optogenetic applications, and inspire other bioengineering advances.     

Different feeding and gustatory responses to ecdysone and 20-hydroxyecdysone by larvae of the silkworm,Bombyx mori

The feeding and gustatory responses to ecdysone and 20-hydroxyecdysone were investigated in the silkworm,Bombyx mori. 20-Hydroxyecdysone reduced feeding response strongly in fourth- and fifth-instar larvae, whereas ecdysone had no effect on feeding response. 20-Hydroxyecdysone stimulated the R receptor, the receptor to feeding deterrents, to a great degree. By contrast, ecdysone was much less effective for stimulating the R receptor. These results indicate that ecdysone and 20-hydroxyecdysone have different effects on feeding response due to different interactions with mouthpart chemoreceptors.     

Band Gap Modification of Diamond Photonic Crystals by Changing the Volume Fraction of the Dielectric Lattice

Photonic crystals with a diamond structure of epoxy lattices in which TiO₂-based ceramic particles are dispersed were fabricated by stereolithography. The periodicity of the lattice was designed to reflect electromagnetic waves in the gigahertz range. The volume fraction (β) of the dielectric lattice medium was modified from 14% to 33% by changing the rod diameter of the lattice. The photonic band gap was observed along Γ-L 〈111〉, Γ-X 〈100〉, and Γ-K 〈110〉 directions and the complete photonic band gap was formed at over β= 20%. The width of the forbidden gap increased gradually when the β increased over 14%, and reached 2.4 GHz at β= 33%. These results agreed with the band calculation using the plane wave expansion method.     

Network formation and swelling behavior of photosensitive poly(vinyl alcohol) gels prepared by photogenerated crosslinking

Poly (vinyl alcohol) with pendent styrylpyridinium groups (SbQ) is insolubilized by photoirradiation. An association takes place in SbQ groups. The association of polymer chains becomes marked with increasing the number of SbQ groups. Mainly intermolecular crosslinks were formed. Transparent and homogeneous macrogels consisting of several intermolecular crosslinks are obtained. The proportion of the free water to the bound water in PVA-SbQ gels was 3.3?2.9 despite of the large change in conversion of photodimerization of SbQ groups, x=0.27?0.58. The water uptake after swelling of the gels in water increased 6–27 times compared to the original weight at pH=7. The higher the degree of photocrosslinking, the lower was the degree of swelling. The water diffusion coefficients, D, were (2.2?5.8) × 10^?5 cm² S^?1 for a 88% saponified PVA with 1 . 3 mol% SbQ groups. The volume of the gel increased discontinuously about 10-fold for the 99% saponified PVA with 0 . 096 mol% SbQ and 51% water (49% acetone). The acetone concentration at the transition decreased with increasing the degree of saponification of the PVA.     

Synthesis and properties of bismaleimide resins containing ether bonds

New bismaleimides containing ether bonds were prepared. The thermal properties of the bismaleimides were investigated by differential scanning calorimetry (DSC). The effects of structure of the bismaleimides and curing conditions on the thermal and mechanical properties of the cured resins such as initial decomposition temperature (T_d), glass transition temperature (T_g), and flexural strength were studied. The introduction of ether bonds to bismaleimide resins decreased the brittleness of the resins without reductions in their heat-resistant properties.     

Advanced Sn/C composite anodes for lithium ion batteries

Metallic tin was deposited in fine particulate form on the surface of carbonaceous mesophase spherules (CMS) and in the pores of porous carbon by the decomposition and reduction of tin(II) 2-ethylhexanoate at 450 °C. The Sn/C composite powders obtained were used as anode materials for lithium ion cells. Electrochemical cycling tests of coin cells show that the dispersion of tin into the carbonaceous materials enhances the reversible capacity of the electrodes. The capacity retention at the 50th cycle is 91 % for Sn/CMS composite containing 22% tin, against 428 mAh g^–1 at the first cycle. With further increase in tin content, the capacity fade upon cycling is more rapid.     

Dynamic compensation by fusing a high-speed actuator and high-speed visual feedback with its application to fast peg-and-hole alignment

This paper presents a dynamic compensation concept to grapple with the dynamic defects of a traditional robot arm, especially while performing high-speed endpoint regulations. The proposed high-speed dynamic compensation concept offers a new point of view for cooperating with a traditional manipulator to realize highly dexterous performance of manipulations. The concept is realized through adoption of a high-speed light-weight actuator as well as endpoint closed loop configured high-speed cameras. The dynamic compensation is analyzed experimentally with 1000 Hz visual feedback and a high-speed finger for a robot arm in the case of one degree of freedom. The advantage of the proposed approach is that the modeling for the robot system’s dynamics is not needed, whereas it is necessary and trivial in order to realize high-speed regulations by traditional approaches. Thus, the control issue becomes easier with the proposed approach. As an application for this concept, fast peg-and-hole alignment with large position and attitude uncertainty is studied. The alignment algorithm is based on a visual compliance strategy. Alignment experiments show that with the proposed concept of dynamic compensation as well as visual compliant motion control, robust and fast convergence was realized for most cases.