Chloride binding properties of a macrocyclic receptor equipped with an acetylide gold(I) complex: synthesis, characterization, reactivity, and cytotoxicity studies

In this work, we report the synthesis and characterization of a mono-nuclear “two wall” aryl-extended calix4]pyrrole receptor (2Au) decorated with an acetylide-gold(I)-PTA complex at its upper rim. We describe the1 H NMR titration experiments of 2Au and its “two wall” aryl-extended calix4]pyrrole synthetic precursors: the non-symmetric mono-iodo-mono-ethynyl 2 and the symmetric bis-iodo 3 with TBACl in dichloromethane and acetone solution. In acetone solution, we use isothermal titration calorimetry (ITC) experiments to thermodynamically characterize the formed 1:1 chloride complexes and perform pair-wise competitive binding experiments. In both solvents, we measured a decrease in the binding constant of the mono-nuclear 2Au complex for chloride compared to the parent mono-iodo-mono-ethynyl 2. In turn, receptor 2 also shows a reduction in binding affinity for chloride compared to its precursor bis-iodo calix4]pyrrole 3. The free energy differences (¿G) of the 1:1 chloride complexes cannot be exclusively attributed to their dissimilar electrostatic surface potential values either at the center of the meso-phenyl wall or its para-substituent. We conclude that solvation/desolvation processes play an important role in the stabilization of the chloride complexes. In acetone solution and in the presence of TBACl, 6Au, a reference compound for the acetylide Au(I)•PTA unit, produces a bis(alkynyl)gold(I) anionic complex 7Au]-. Thus, the observation of two separate sets of signals for the bound aromatic calix4]pyrrole protons, when more than 1 equiv. of the salt is added, is assigned to the formation of the chloride complexes of 2Au and of the “in situ” formed calix4]pyrrole anionic dimer 8Au]-. Finally, preliminary data obtained in cell viability assays of 2Au and 6Au with human cancer cells lines assign them with moderate activities showing that the calix4]pyrrole unit is not relevant. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Lenalidomide Maintenance with or without Prednisone in Newly Diagnosed Myeloma Patients: A Pooled Analysis

We conducted a pooled analysis of two phase III trials, RV-MM-EMN-441 and EMN01, to compare maintenance with lenalidomide-prednisone vs. lenalidomide in newly diagnosed transplant-eligible and -ineligible myeloma patients. Primary endpoints were progression-free survival, progression-free survival 2 and overall survival with both regimens. A secondary aim was to evaluate the impact of duration of maintenance on overall survival and on outcome after relapse. A total of 625 patients (lenalidomide-prednisone arm, n = 315; lenalidomide arm, n = 310) were analyzed. The median follow-up was 58 months. Median progression-free survival (25 vs. 19 months; p = 0.08), progression-free survival 2 (56 vs. 49 months; p = 0.9) and overall survival (73 months vs. NR; p = 0.08) were not significantly different between the two arms. Toxicity profiles of lenalidomide-prednisone and lenalidomide were similar, with the exception of neutropenia that was higher in the lenalidomide arm (grade ≥ 3: 9% vs. 19%, p < 0.001), without an increase in the rate of infections. Overall survival (median NR vs. 49 months, p < 0.001), progression-free survival from relapse (median 35 vs. 24 months, p = 0.004) and overall survival from relapse (median not reached vs. 41 months, p = 0.002) were significantly longer in patients continuing maintenance for ≥2 years. We showed that the addition of prednisone at 25 or 50 mg every other day (eod) to lenalidomide maintenance did not induce any significant advantage

Investigating fairness in global supply chains: applying an extension of the living wage to the Western European clothing supply chain.

YesThis paper explores the issue of fairness in global supply chains. Taking the Western European clothing supply chain as a case study, we demonstrate how applying a normative indicator in Social Life Cycle Assessment (SLCA) can contribute academic and practical insights into debates on fairness. To do so, we develop a new indicator that addresses some of the limitations of the living wage for SLCA. We extend the standard form of living wage available for developing countries to include income tax and social security contributions. We call this extension 'living labour compensation'. Using publically available data, we estimate net living wages, gross living wages, and living labour compensation rates for Brazil, Russia, India, and China (BRIC) in 2005. We then integrate living labour compensation rates into an input-output framework, which we use to compare living labour compensation and actual labour compensation in the BRIC countries in the Western European clothing supply chain in 2005. We find that in 2005, actual labour compensation in the Western European clothing supply chain was around half of the living labour compensation level, with the greatest difference being in the Agricultural sector. Therefore, we argue that BRIC pay in the Western European clothing supply chain was unfair. Furthermore, our living labour compensation estimates for BRIC in 2005 are ~ 35% higher than standard living wage estimates. Indeed, adding income taxes and employee social security contributions alone increases the living wage by ~ 10%. Consequently, we argue there is a risk that investigations based on living wages are not using a representative measure of fairness from the employee's perspective and are substantially underestimating the cost of living wages from an employer's perspective. Finally, we discuss implications for retailers and living wage advocacy groups. Living labour compensation extends the living wage, maintaining its strengths and addressing key weaknesses. It can be estimated for multiple countries from publically available data and can be applied in an input-output framework. Therefore, it is able to provide a normative assessment of fairness in complex global supply chains. Applying it to the Western European clothing supply chain, we were able to show that pay for workers in Brazil, Russia, India, and China is unfair, and draw substantive conclusions for practice