A Fluorescent Probe for Rapid,High‐Contrast Visualization of Folate‐Receptor‐Expressing Tumors In Vivo

Folate receptors (FRs) are membrane proteins involved in folic acid uptake, and the alpha isoform (FR‐α) is overexpressed in ovarian and endometrial cancer cells. For fluorescence imaging of FRs in vivo, the near‐infrared (NIR) region (650–900 nm), in which tissue penetration is high and autofluorescence is low, is optimal, but existing NIR fluorescent probes targeting FR‐α show high non‐specific tissue adsorption, and require prolonged washout to visualize tumors. We have designed and synthesized a new NIR fluorescent probe, FolateSiR‐1 , utilizing a Si‐rhodamine fluorophore having a carboxy group at the benzene moiety, coupled to a folate ligand moiety through a negatively charged tripeptide linker. This probe exhibits very low background fluorescence and afforded a tumor‐to‐background ratio (TBR) of up to 83 in FR‐expressing tumor‐bearing mice within 30 min. Thus, FolateSiR‐1 has the potential to contribute to the research in the field of biology and the clinical medicine.     

A Fluorescent Probe for Rapid,High-Contrast Visualization of Folate-Receptor-Expressing Tumors In Vivo

Folate receptors (FRs) are membrane proteins involved in folic acid uptake, and the alpha isoform (FR-α) is overexpressed in ovarian and endometrial cancer cells. For fluorescence imaging of FRs in vivo, the near-infrared (NIR) region (650–900 nm), in which tissue penetration is high and autofluorescence is low, is optimal, but existing NIR fluorescent probes targeting FR-α show high non-specific tissue adsorption, and require prolonged washout to visualize tumors. We have designed and synthesized a new NIR fluorescent probe, FolateSiR-1 , utilizing a Si-rhodamine fluorophore having a carboxy group at the benzene moiety, coupled to a folate ligand moiety through a negatively charged tripeptide linker. This probe exhibits very low background fluorescence and afforded a tumor-to-background ratio (TBR) of up to 83 in FR-expressing tumor-bearing mice within 30 min. Thus, FolateSiR-1 has the potential to contribute to the research in the field of biology and the clinical medicine.     

Stability of periodic travelling wave solutions with large spatial periods in reaction-diffusion systems

We consider a spatially homogeneous system of reaction-diffusion equation defined on the interval (?∞, ∞) of the one-dimensional spatial variable x. It is known that this equation has a one-parameter family of periodic travelling wave solutions Ψ(x + ct; c) if this equation has a spatially homogeneous periodic solution φ(t). The spatial period L(c) of the travelling wave solution satisfies $\text{L(c)}\text{c}\text{→ T}\text{if}\text{c → +∞}$, where c is the propagation speed and T is the period of φ(t). We prove that, in the case c > 0 is sufficiently large, Ψ(x + ct; c) is unstable if φ(t) is “strongly unstable” and Ψ(x + ct; c) is “marginally stable” if φ(t) is “strongly stable.” If the equation is defined on a finite interval [0, l] of the variable x with the periodic boundary conditions, we can obtain a more precise result regarding the stability of $\text{Ψ(x +}\text{c}\text{?}\text{t;}\text{c}\text{?}\text{)}$, where $\text{c}\text{?}\text{> 0}$ is a speed which satisfies $\text{l = mL(}\text{c}\text{?}\text{)}$ for some positive integer m. We prove that this solution is asymptotically stable in the sense of waveform stability if $\text{c}\text{?}\text{> 0}$ is sufficiently large and if φ(t) is “strongly stable.”     

Trace inequalities for products of matrices

In this short paper, we study some trace inequalities of the products of the matrices and the power of matrices by the use of elementary calculations.     

Highly activatable and environment-insensitive optical highlighters for selective spatiotemporal imaging of target proteins

Optical highlighters are photoactivatable fluorescent molecules that exhibit pronounced changes in their spectral properties in response to irradiation with light of a specific wavelength and intensity. Here, we present a novel design strategy for a new class of caged BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) fluorophores, based on the use of photoremovable protecting groups (PRPGs) with high reduction potentials that serve as both a photosensitive unit and a fluorescence quencher via photoinduced electron transfer (PeT). 2,6-Dinitrobenzyl (DNB)-caged BODIPY was efficiently photoactivated, with activation ratios exceeding 600-fold in aqueous solutions. We then combined this photoactivatable fluorophore with a SNAP (mutant of O(6)-alkylguanine DNA alkyltransferase) ligand to obtain a small-molecule-based optical highlighter for visualization of protein dynamics, using the well-established SNAP tag technology. As proof of concept, we demonstrate spatiotemporal imaging of the fusion protein of epidermal growth factor receptor (EGFR) with SNAP tag in living cells. We also demonstrate highlighting of cells of interest in live zebrafish embryos, using the fusion protein of histone 2A with SNAP tag.     

Polar antiferromagnets produced with orbital order

Polar states are realized in pseudocubic manganite films fabricated on high-index substrates, in which a Jahn-Teller (JT) distortion remains an active variable. Several types of orbital orders (OOs) were found to develop large optical second harmonics, signaling broken-inversion symmetry distinct from their bulk forms and films on (100) substrates. The observed symmetry lifting and first-principles calculation both indicate that the modified JT q2 mode drives Mn-site off centering, which can be controlled by a magnetic-field-induced phase transition via a coupling of OO and spin orders.     

Design and synthesis of an enzyme activity-based labeling molecule with fluorescence spectral change

Methods of covalent labeling of a specific tag protein with small-molecular dyes play an important role in studying dynamic behaviors of proteins in living cells. On the basis of quinone methide chemistry, we designed and synthesized a beta-galactosidase labeling probe, CMFbeta-gal, which shows a fluorescence wavelength change accompanying the labeling reaction, owing to fluorescence resonance energy transfer (FRET). Since the FRET efficiency changes accompanying the labeling reaction, fluorescence of labeled protein can be observed separately from that of the unreacted probe, so immediate detection of the target protein is possible. This is the first report of a protein labeling probe which features a change of fluorescence wavelength upon reaction, allowing the labeled protein to be detected even in the presence of unreacted probe.     

Multiscale evaluation method of the drag effect on shallow water flow through coastal forests based on 3D numerical simulations

This study presents a method for determining the drag parameter in the 2D shallow water (SW) equation for flows through a coastal forest by conducting a series of 3D numerical simulations (3D NSs). Following the theory of multiscale modeling, an evaluation method procedure is proposed. We first prepare a local test domain that contains a sufficient number of trees to constitute part of a coastal forest. Then, 3D NSs are conducted in this test domain with various inflow conditions. Based on the corresponding results, the momentum losses over the test domain are converted into the drag parameter of the global SW equation. A response surface of the drag parameter is constructed as a function of the flow conditions. The stabilized finite element method is employed for both the local and the global NSs, and the phase-field method is utilized to represent 3D free surfaces. Comparisons between the 2D SW calculation results and the 3D NS results are also performed to verify the validity of the proposed method.     

1,17‐Hepta­decane­diol

In the title compound, C₁₇H₃₆O₂, one of the hydroxyl groups has a gauche conformation with respect to the hydro­carbon skeleton, which is all‐trans, whereas the other has a trans conformation. The molecular shape is rod‐like and the compound has a rotator phase in which mol­ecules are assured greater motional freedom, as in liquid crystals. In addition, the mol­ecules arranged along the longest axis, b, form layers which are very similar to those of the smectic A liquid crystals.