Significance of myocardial tenascin-C expression in left ventricular remodelling and long-term outcome in patients with dilated cardiomyopathy

Aim Dilated cardiomyopathy (DCM) has a variety of causes, and no useful approach to predict left ventricular (LV) remodelling and long-term outcome has yet been established. Myocardial tenascin-C (TNC) is known to appear under pathological conditions, possibly to regulate cardiac remodelling. The aim of this study was to clarify the significance of myocardial TNC expression in LV remodelling and the long-term outcome in DCM. Methods and results One hundred and twenty-three consecutive DCM patients who underwent endomyocardial biopsy for initial diagnosis were studied. Expression of TNC in biopsy sections was analysed immunohistochemically to quantify the ratio of the TNC-positive area to the whole myocardial tissue area (TNC area). Clinical parameters associated with TNC area were investigated. The patients were divided into two groups based on receiver operating characteristic analysis of TNC area to predict death: high TNC group with TNC area ≥2.3% (22 patients) and low TNC group with TNC area <2.3% (101 patients). High TNC was associated with diabetes mellitus. Comparing echocardiographic findings between before and 9 months after endomyocardial biopsy, the low TNC group was associated with decreased LV end-diastolic diameter and increased LV ejection fraction, whereas the high TNC group was not. Survival analysis revealed a worse outcome in the high TNC group than in the low TNC group (P < 0.001). Multivariable Cox regression analysis revealed that TNC area was independently associated with poor outcome (HR = 1.347, P = 0.032). Conclusions Increased myocardial TNC expression was associated with worse LV remodeling and long-term outcome in DCM

Drug review process advancement and required manufacturer and contract research oraganization responses

\ua9 2024 The Japanese Society of Toxicologic Pathology.The United States Senate passed the “FDA Modernization Act 2.0.” on September 29, 2022. Although the effectiveness of this Bill, which aims to eliminate the mandatory use of laboratory animals in new drug development, is limited, it represents a significant trend that will change the shape of drug applications in the United States and other countries. However, pharmaceutical companies have not taken major steps towards the complete elimination of animal testing from the standpoint of product safety, where they prioritize patient safety. Nonetheless, society is becoming increasingly opposed to animal testing, and efforts will be made to use fewer animals and conduct fewer animal tests as a natural and reasonable response. These changes eventually alter the shape of new drug applications. Based on the assumption that fewer animal tests will be conducted or fewer animals will be used in testing, this study explored bioinformatics and new technologies as alternatives to compensate for reduced information and provide a picture of how future new drug applications may look. The authors also discuss the directions that pharmaceutical companies and nonclinical contract research organizations should adopt to promote the replacement, reduction, and refinement of animals used in research, teaching, testing, and exhibitions

Important Roles of Te 5p and Ir 5d Spin-orbit Interactions on the Multi-band Electronic Structure of Triangular Lattice Superconductor Ir1-xPtxTe2

We report an angle-resolved photoemission spectroscopy (ARPES) study on a triangular lattice superconductor Ir$_{1-x}$Pt$_{x}$Te$_2$ in which the Ir-Ir or Te-Te bond formation, the band Jahn-Teller effect, and the spin-orbit interaction are cooperating and competing with one another. The Fermi surfaces of the substituted system are qualitatively similar to the band structure calculations for the undistorted IrTe$_2$ with an upward chemical potential shift due to electron doping. A combination of the ARPES and the band structure calculations indicates that the Te $5p$ spin-orbit interaction removes the $p_x/p_y$ orbital degeneracy and induces $p_x \pm ip_y$ type spin-orbit coupling near the A point. The inner and outer Fermi surfaces are entangled by the Te $5p$ and Ir $5d$ spin-orbit interactions which may provide exotic superconductivity with singlet-triplet mixing.Comment: 10 pages, 4 figure

An energy scale directly related to superconductivity in the high-TcT_c cuprate superconductors: Universality from the Fermi arc picture

We have performed a temperature dependent angle-resolved photoemission spectroscopy (ARPES) study of the tri-layer high-$T_c$ cuprate superconductor (HTSC) Bi$_2$Sr$_2$Ca$_2$Cu$_3$O$_{10+\delta}$ (Bi2223), and have shown that the \textquotedblleft effective\textquotedblright superconducting (SC) gap $\Delta_{\rm{sc}}$ defined at the end point of the Fermi arc and the $T_c$ (= 110 K) approximately satisfies the weak-coupling BCS-relationship 2$\Delta_{\rm{sc}}$ = 4.3$k_{\rm{B}}T_c$. Combining this result with previous ARPES results on single- and double-layer cuprates, we show that the relationship between 2$\Delta_{\rm{sc}}$ = 4.3$k_{\rm{B}}T_c$ holds for various HTSCs. Furthermore, at $T$ $\sim$ $T_c$, the quasi-patricle width at the end point of the Fermi arc is found to coincide with $\Delta_{\rm{sc}}$, consistent with the context of Planckian dissipation.Comment: 5 pages, 4 figure

Electronic structure reconstruction by orbital symmetry breaking in IrTe2

We report an angle-resolved photoemission spectroscopy (ARPES) study on IrTe2 which exhibits an interesting lattice distortion below 270 K and becomes triangular lattice superconductors by suppressing the distortion via chemical substitution or intercalation. ARPES results at 300 K show multi-band Fermi surfaces with six-fold symmetry which are basically consistent with band structure calculations. At 20 K in the distorted phase, whereas the flower shape of the outermost Fermi surface does not change from that at 300 K, topology of the inner Fermi surfaces is strongly modified by the lattice distortion. The Fermi surface reconstruction by the distortion depends on the orbital character of the Fermi surfaces, suggesting importance of Ir 5d and/or Te 5p orbital symmetry breaking.Comment: 4pages, 4figure

Orbital Degeneracy and Peierls Instability in Triangular Lattice Superconductor Ir1−x_{1-x}Ptx_xTe2_2

We have studied electronic structure of triangular lattice Ir$_{1-x}$Pt$_x$Te$_2$ superconductor using photoemission spectroscopy and model calculations. Ir $4f$ core-level photoemission spectra show that Ir $5d$ $t_{2g}$ charge modulation established in the low temperature phase of IrTe$_2$ is suppressed by Pt doping. This observation indicates that the suppression of charge modulation is related to the emergence of superconductivity. Valence-band photoemission spectra of IrTe$_2$ suggest that the Ir $5d$ charge modulation is accompanied by Ir $5d$ orbital reconstruction. Based on the photoemission results and model calculations, we argue that the orbitally-induced Peierls effect governs the charge and orbital instability in the Ir$_{1-x}$Pt$_x$Te$_2$.Comment: 5 pages,4 figure

Effect of electron-phonon coupling in the ARPES spectra of the tri-layer cuprate Bi2_2Sr2_2Ca2_2Cu3_3O10+δ_{10+\delta}

Angle-resolved photoemission spectroscopy using tunable low energy photons allows us to study the quasi-particle (QP) dispersions of the inner and outer CuO2 planes (IP and OP) separately in the tri-layer cuprate Bi$_2$Sr$_2$Ca$_2$Cu$_3$O$_{10+\delta}$ (Bi2223). The kink energy of the OP band is $\sim$ 70 meV, as observed in various high-$T_c$ cuprates, while that of the IP band is as large as 100 meV in the superconducting (SC) state. This large kink energy is attributed to the $\sim$ 35 meV buckling mode plus the large ($\sim$ 60 meV) SC gap of IP. The IP band also shows a weak kink feature at 70 meV in the SC state. The latter feature can be explained either by the 70 meV half-breathing mode or by the $\sim$ 35 meV buckling-phonon mode plus the $\sim$ 40 meV SC gap of OP if interlayer scattering of QP is involved.Comment: 5 pages, 2 figure