SOPRANO: Macitentan in patients with pulmonary hypertension following left ventricular assist device implantation.

Macitentan is a dual endothelin receptor antagonist (ERA) approved for treating pulmonary arterial hypertension (PAH). SOPRANO evaluated the efficacy and safety of macitentan versus placebo in pulmonary hypertension (PH) patients after left ventricular assist device (LVAD) implantation. SOPRANO was a phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group study.

Positional effects of electron-donating and withdrawing groups on the photophysical properties of single benzene fluorophores.

We investigated how the positional arrangement of electron-donating (amino) and electron-withdrawing (ester) groups in single benzene-based fluorophores influences their emission properties. By synthesizing 26 regioisomeric fluorophores, we achieved wavelength modulation from 322 to 539 nm, revealing key correlations between functional group positioning and photophysical behavior.

Highly emissive 4-carbazole-appended salen-indium complex: the effect of strong donor-acceptor interaction.

Herein, we report our findings on 4-carbazole (CBZ)-appended salen-based indium complexes, CBZIn1 and CBZIn2, which feature diimine bridges exhibiting different electron-accepting properties. Notably, CBZIn2 exhibited a significantly higher photoluminescence quantum efficiency (PLQY, ) in toluene than CBZIn1, with a value over 15 times greater ( = 57.7% for CBZIn2; = 3.

Deoxyhypusine synthase mutations alter the post-translational modification of eukaryotic initiation factor 5A resulting in impaired human and mouse neural homeostasis.

DHPS deficiency is a rare genetic disease caused by biallelic hypomorphic variants in the () gene. The DHPS enzyme functions in mRNA translation by catalyzing the post-translational modification, and therefore activation, of eukaryotic initiation factor 5A (eIF5A). The observed clinical outcomes associated with human mutations in include developmental delay, intellectual disability, and seizures.

Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder.

Deoxyhypusine hydroxylase (DOHH) is the enzyme catalyzing the second step in the post-translational synthesis of hypusine [N-(4-amino-2-hydroxybutyl)lysine] in the eukaryotic initiation factor 5A (eIF5A). Hypusine is formed exclusively in eIF5A by two sequential enzymatic steps catalyzed by deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Hypusinated eIF5A is essential for translation and cell proliferation in eukaryotes, and all three genes encoding eIF5A, DHPS, and DOHH are highly conserved throughout eukaryotes.

Neuron-specific ablation of eIF5A or deoxyhypusine synthase leads to impairments in growth, viability, neurodevelopment, and cognitive functions in mice.

Eukaryotic initiation factor 5A (eIF5A) is an essential protein that requires a unique amino acid, hypusine, for its activity. Hypusine is formed exclusively in eIF5A post-translationally via two enzymes, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase. Each of the genes encoding these proteins, Eif5a, Dhps, and Dohh, is required for mouse embryonic development.

Post-translational formation of hypusine in eIF5A: implications in human neurodevelopment.

Hypusine [N-(4-amino-2-hydroxybutyl)lysine] is a derivative of lysine that is formed post-translationally in the eukaryotic initiation factor 5A (eIF5A). Its occurrence at a single site in one cellular protein defines hypusine synthesis as one of the most specific post-translational modifications. Synthesis of hypusine involves two enzymatic steps: first, deoxyhypusine synthase (DHPS) cleaves the 4-aminobutyl moiety of spermidine and transfers it to the ε-amino group of a specific lysine residue of the eIF5A precursor protein to form an intermediate, deoxyhypusine [N-(4-aminobutyl)lysine].

Inhibition of topoisomerase I shapes antitumor immunity through the induction of monocyte-derived dendritic cells.

Understanding the rationale of combining immunotherapy and other anticancer treatment modalities is of great interest because of interpatient variability in single-agent immunotherapy. Here, we demonstrated that topoisomerase I inhibitors, a class of chemotherapeutic drugs, can alter the tumor immune landscape, corroborating their antitumor effects combined with immunotherapy. We observed that topotecan-conditioned TC-1 tumors were occupied by a vast number of monocytic cells that highly express CD11c, CD64, and costimulatory molecules responsible for the favorable changes in the tumor microenvironment.

The United States Chronic Thromboembolic Pulmonary Hypertension Registry: Protocol for a Prospective, Longitudinal Study.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare sequela of acute pulmonary embolism that is treatable when recognized. Awareness of this disease has increased with recent advancements in therapeutic options, but delays in diagnosis remain common, and diagnostic and treatment guidelines are often not followed. Data gathered from international registries have improved our understanding of CTEPH, but these data may not be applicable to the US population owing to differences in demographics and medical practice patterns.

Synthesis and Photophysical Properties of a Series of Dimeric Indium Quinolinates.

A novel class of quinolinol-based dimeric indium complexes (-) was synthesized and characterized using H and C(H) NMR spectroscopy and elemental analysis. Compounds - exhibited typical low-energy absorption bands assignable to quinolinol-centered π-π* charge transfer (CT) transition. The emission spectra of - exhibited slight bathochromic shifts with increasing solvent polarity (-xylene < tetrahydrofuran (THF) < dichloromethane (DCM)).

Ranolazine Improves Right Ventricular Function in Patients With Precapillary Pulmonary Hypertension: Results From a Double-Blind, Randomized, Placebo-Controlled Trial.

Introduction: A major outcome determinant in patients with precapillary pulmonary hypertension (PH) is right ventricular (RV) function. We studied the effect of ranolazine on RV function over 6 months using cardiovascular magnetic resonance (CMR) imaging in patients with precapillary PH (groups I, III, and IV).

Methods And Results: We enrolled patients with PH and RV dysfunction (CMR imaging ejection fraction [EF] of <45%) in a longitudinal, randomized, double-blinded, placebo controlled, multicenter study of ranolazine treatment.

Clinical Practice Guideline for Care in the Last Days of Life.

A clinical practice guideline for patients in the dying process in general wards and their families, developed through an evidence-based process, is presented herein. The purpose of this guideline is to enable a peaceful death based on an understanding of suitable management of patients' physical and mental symptoms, psychological support, appropriate decision-making, family care, and clearly-defined team roles. Although there are limits to the available evidence regarding medical issues in patients facing death, the final recommendations were determined from expert advice and feedback, considering values and preferences related to medical treatment, benefits and harms, and applicability in the real world.

Enhanced Immunogenicity of Engineered HER2 Antigens Potentiates Antitumor Immune Responses.

For cancer vaccines, the selection of optimal tumor-associated antigens (TAAs) that can maximize the immunogenicity of the vaccine without causing unwanted adverse effects is challenging. In this study, we developed two engineered Human epidermal growth factor receptor 2 (HER2) antigens, K965 and K1117, and compared their immunogenicity to a previously reported truncated HER2 antigen, K684, within a B cell and monocyte-based vaccine (BVAC). We found that BVAC-K965 and BVAC-K1117 induced comparable antigen-specific antibody responses and antigen-specific T cell responses to BVAC-K684.

Ir-Catalyzed C-H Amidation Using Carbamoyl Azides for the Syntheses of Unsymmetrical Ureas.

An iridium-catalyzed C-H amidation for the syntheses of unsymmetrical urea was developed using carbamoyl azides (R(R')N-C(O)-N) as the nitrogen source. A combination of iridium and silver gave an active catalyst for C-N bond formation. A variety of urea derivatives were synthesized using carbamoyl azides with only dinitrogen byproducts.

Photophysical Properties of Spirobifluorene-Based -Carboranyl Compounds Altered by Structurally Rotating the Carborane Cages.

9,9'-Spirobifluorene-based -carboranyl compounds and were prepared and fully characterized by multinuclear nuclear magnetic resonance (NMR) spectroscopy and elemental analysis. The solid-state structure of was also determined by single-crystal X-ray diffractometry. The two carboranyl compounds display major absorption bands that are assigned to -* transitions involving their spirobifluorene groups, as well as weak intramolecular charge-transfer (ICT) transitions between the -carboranes and their spirobifluorene groups.

Spirobifluorene-Based o-Carboranyl Compounds: Insights into the Rotational Effect of Carborane Cages on Photoluminescence.

9,9'-Spirobifluorene-based closo-o-carboranyl (SFC1 and SFC2) compounds and their nido-derivatives (nido-SFC1 and nido-SFC2) were prepared and characterized. The two closo-compounds displayed major absorption bands assignable to π-π* transitions involving the spirobifluorene group, as well as weak intramolecular charge-transfer (ICT) transitions between the o-carboranes and their spirobifluorene moieties. The nido-compounds exhibited slightly blueshifted absorption bands resulting from the absence of the ICT transitions corresponding to the o-carborane moieties due to the anionic character of the nido-o-carboranes.

Elevation of cellular Mg levels by the Mg transporter, Alr1, supports growth of polyamine-deficient cells.

The polyamines putrescine, spermidine, and spermine are required for normal eukaryotic cellular functions. However, the minimum requirement for polyamines varies widely, ranging from very high concentrations (mm) in mammalian cells to extremely low in the yeast Yeast strains deficient in polyamine biosynthesis (Δ, lacking ornithine decarboxylase, and Δ, lacking SAM decarboxylase) require externally supplied polyamines, but supplementation with as little as 10 m spermidine restores their growth. Here, we report that culturing a Δ mutant or a Δ mutant in a standard polyamine-free minimal medium (SDC) leads to marked increases in cellular Mg content.

Synthesis of o-carborane-functionalized metal-organic frameworks through ligand exchanges for aggregation-induced emission in the solid state.

The carborane (CB)-functionalized ligand was installed in a variety of MOFs through postsynthetic ligand exchange processes. This methodology is a general method for preparing o-CB-functionalized MOFs with known frameworks. Furthermore, the photoluminescence (PL) spectra revealed intriguing aggregation-induced emission (AIE) features following the systematic incorporation of o-CB functionalities into framework-type materials.

Carbazole-Appended Salen-Indium Conjugate Systems: Synthesis and Enhanced Luminescence Efficiency.

Novel carbazole-conjugated salen-In complexes ( and ) were prepared and fully characterized by H and C NMR spectroscopy, elemental analysis, and high-resolution mass spectrometry. The major low-energy absorption bands at λ = 342 nm for and 391 nm for , respectively, are assigned to typical intramolecular charge transfer (ICT) transitions between the carbazole unit and the salen-In center. The solvatochromism effects in various organic solvents and their large Stokes shift distinctly supported the ICT nature.

Effect of the Metal within Regioisomeric Paddle-Wheel-Type Metal-Organic Frameworks.

The effect of metal on the degree of flexibility upon evacuation of metal-organic frameworks (MOFs) has been revealed with positional control of the organic functionalities. Although Co-, Cu-, and Zn-based DMOFs (DMOF = DABCO MOF, DABCO = 1,4-diazabicyclo[2.2.

Efficient Aluminum Catalysts for the Chemical Conversion of CO into Cyclic Carbonates at Room Temperature and Atmospheric CO Pressure.

A series of dimeric aluminum compounds [Al(OCMe CH N(R)CH X)] [X=pyridin-2-yl, R=H (Pyr ); X= pyridin-2-yl, R=Me (Pyr ); X=furan-2-yl, R=H (Fur ); X= furan-2-yl, R=Me (Fur ); X=thiophen-2-yl, R=H (Thio ); X= thiophen-2-yl, R=Me (Thio )] containing heterocyclic pendant group attached to the nitrogen catalyze the coupling of CO with epoxides under ambient conditions. In a comparison of their catalytic activities with those of aluminum complexes without pendant groups at N [X=H, R=H (H ); X=H, R=Me (H )] or with non-heterocyclic pendant groups [X=CH CH OMe, R=H (OMe ); X=CH CH NMe , R=H (NMe2 ); X=CH CH NMe , R=Me (NMe2 )], complexes containing heterocycles, in conjunction with (nBu) NBr as a cocatalyst, show higher catalytic activities for the synthesis of cyclic carbonates under the same ambient conditions. The best catalyst system for this reaction is Pyr /(nBu) NBr system, which gives a turnover number of 99 and a turnover frequency of 4.

Delayed autologous stem cell transplantation following cardiac transplantation experience in patients with cardiac amyloidosis.

This study sought to retrospectively investigate the outcomes of patients with light-chain amyloidosis (AL) with advanced cardiac involvement who were treated with a strategy of heart transplantation (HT) followed by delayed autologous stem cell transplantation (ASCT) at 1-year posttransplant. Patients with AL amyloidosis with substantial cardiac involvement have traditionally had very poor survival (eg, several months). A few select centers have reported their outcomes for HT followed by a strategy of early ASCT (ie, 6 months) for CA.

A Series of Quinolinol-Based Indium Luminophores: A Rational Design Approach for Manipulating Photophysical Properties.

An approach to the design of a series of quinolinol-based indium complexes that can exhibit different optical properties is proposed. Mono-incorporated (Inq and InMeq), bis-incorporated (InMeq), and tris-incorporated (Inq and InMeq) indium quinolinate complexes have been prepared. These complexes have also been characterized by X-ray crystallography.