Polyhydroxybutyrate (PHB)-based triblock copolymers: synthesis of hydrophobic PHB/poly(benzyl beta-malolactonate) and amphiphilic PHB/poly(malic acid) analogues by ring-opening polymerization

International audiencePolyhydroxyalkanoates (PHAs) are biocompatible and biodegradable polyesters widely used for biomedical applications. Amphiphilic triblock copolymers with a PHB hydrophobic segment recently demonstrated attractive advantages such as high colloidal stability and low critical micellar concentration (CMC) values for the elaboration of drug delivery systems. Our approach aims at associating PHB with a fully biodegradable hydrophilic block to access new self-assembled systems with unique potential. Well-defined alpha,omega-dihydroxy telechelic PHA-based hydrophobic triblock copolymers with tunable segments length were synthesized by the controlled ring-opening polymerization (ROP) of benzyl beta-malolactonate, using polyhydroxybutyrate (PHB) diol/Nd(OTf)(3) as the catalytic system. Remarkably, the reaction proceeds with the selective oxygen-acyl bond cleavage of the beta-lactone. The corresponding amphiphilic copolymers were then obtained by hydrogenolysis. These copolymers are the only examples of fully biodegradable PHA-PHB-PHA triblock copolymers. The hydrophilic weight fraction of the copolymers was tuned from 7 to 83% upon modulating the monomer loading thus affording the ability to next access different self-assembling architectures

Linear and three-arm star hydroxytelechelic poly(benzyl β-malolactonate)s: a straightforward one-step synthesis through ring-opening polymerization

International audienceRing-opening polymn. (ROP) of racemic-benzyl β-malolactonate (MLABe) initiated by an alc. such as 1,3-propanediol (PPD) or 2-hydroxymethyl-1,3-propanediol (TMM), and catalyzed by a metal triflate M(OTf)3 with M = Nd, Bi, proceeded under mild operating conditions (in bulk at 60 °C). The functionality of the alc. dictates the topol. of the resulting hydroxy telechelic PMLABe. The ROP promoted by the neodymium-based catalytic system afforded a satisfactory activity and control in terms of molar mass and dispersity values (Mn,NMR up to 7000 g mol-1, DM \textless 1.35). Mechanistic insights revealed that ring-opening of MLABe took place through the selective oxygen-acyl bond cleavage without undesirable side reactions such as transesterification or crotonisation, as evidenced by NMR and mass spectrometry analyses of the recovered polyesters. The structure of the corresponding α,ω-hydroxy telechelic PMLABes was ascertained by 1H and 13C\1H\ NMR, SEC, and MALDI-ToF mass spectrometry analyses. In comparison, methane and trifluoromethane sulfonic acids did not allow the formation of well-defined PMLABe diols. Differences in the behavior of MLABe and the related β-butyrolactone are highlighted. The present Nd(OTf)3/PPD or TMM catalytic ROP of MLABe thus represents a valuable direct synthesis of PMLABe diols and triols, resp., without requiring chem. modification of a preformed PMLABe precursor

What do international ethics guidelines say in terms of the scope of medical research ethics?

BACKGROUND: In research ethics, the most basic question would always be, "which is an ethical issue, which is not?" Interestingly, depending on which ethics guideline we consult, we may have various answers to this question. Though we already have several international ethics guidelines for biomedical research involving human participants, ironically, we do not have a harmonized document which tells us what these various guidelines say and shows us the areas of consensus (or lack thereof). In this manuscript, we attempted to do just that. METHODS: We extracted the imperatives from five internationally-known ethics guidelines and took note where the imperatives came from. In doing so, we gathered data on how many guidelines support a specific imperative. RESULTS: We found that there is no consensus on the majority of the imperatives and that in only 8.2% of the imperatives were there at least moderate consensus (i.e., consensus of at least 3 of the 5 ethics guidelines). Of the 12 clusters (Basic Principles; Research Collaboration; Social Value; Scientific Validity; Participant Selection; Favorable Benefit/Risk Ratio; Independent Review; Informed Consent; Respect for Participants; Publication and Registration; Regulatory Sanctions; and Justified Research on the Vulnerable Population), Informed Consent has the highest level of consensus and Research Collaboration and Regulatory Sanctions have the least. CONCLUSION: There was a lack of consensus in the majority of imperatives from the five internationally-known ethics guidelines. This may be partly explained by the differences among the guidelines in terms of their levels of specification as well as conceptual/ideological differences

Aminoacids and flavonoids profiling in tempranillo berries can be modulated by the arbuscular mychorrhizal fungi

(1) Background: Vitis vinifera L. cv. Tempranillo is cultivated over the world for its wine of high quality. The association of Tempranillo with arbuscular mycorrhizal fungi (AMF) induced the accumulation of phenolics and carotenoids in leaves, affected the metabolism of abscisic acid (ABA) during berry ripening, and modulated some characteristics and quality aspects of grapes. The objective of this study was to elucidate if AMF influenced the profiles and the content of primary and secondary metabolites determinants for berry quality in Tempranillo. (2) Methods: Fruit-bearing cuttings inoculated with AMF or uninoculated were cultivated under controlled conditions. (3) Results: Mycorrhizal symbiosis modified the profile of metabolites in Tempranillo berries, especially those of the primary compounds. The levels of glucose and amino acids clearly increased in berries of mycorrhized Tempranillo grapevines, including those of the aromatic precursor amino acids. However, mycorrhizal inoculation barely influenced the total amount and the profiles of anthocyanins and flavonols in berries. (4) Conclusions: Mycorrhizal inoculation of Tempranillo grapevines may be an alternative to the exogenous application of nitrogen compounds in order to enhance the contents of amino acids in grapes, which may affect the aromatic characteristics of wines

Controlling the length of porphyrin supramolecular polymers via coupled equilibria and dilution-induced supramolecular polymerization

Multi-component systems often display convoluted behavior, pathway complexity and coupled equilibria. In recent years, several ways to control complex systems by manipulating the subtle balances of interaction energies between the individual components have been explored and thereby shifting the equilibrium between different aggregate states. Here we show the enantioselective chain-capping and dilution-induced supramolecular polymerization with a Zn(2+)-porphyrin-based supramolecular system when going from long, highly cooperative supramolecular polymers to short, disordered aggregates by adding a monotopic Mn(3+)-porphyrin monomer. When mixing the zinc and manganese centered monomers, the Mn(3+)-porphyrins act as chain-cappers for Zn(2+)-porphyrin supramolecular polymers, effectively hindering growth of the copolymer and reducing the length. Upon dilution, the interaction between chain-capper and monomers weakens as the equilibria shift and long supramolecular polymers form again. This dynamic modulation of aggregate morphology and length is achieved through enantioselectivity in the aggregation pathways and concentration-sensitive equilibria. All-atom and coarse-grained molecular simulations provide further insights into the mixing of the species and their exchange dynamics. Our combined experimental and theoretical approach allows for precise control of molecular self-assembly and chiral discrimination in complex systems

Factors associated with anaemia among pregnant women in Rwanda: an analysis of the Rwanda demographic and health survey of 2020

Background: Anaemia in pregnancy is associated with several adverse outcomes for mothers and newborns, as well as their families. In this study, we assessed the prevalence of anaemia and the associated factors among pregnant women in Rwanda. Methods: Secondary data from the 2020 Rwanda Demographic and Health Survey (RDHS) was used. Multistage stratified sampling was used to select 435 pregnant women included in the study. Anaemia among pregnant women was defined as a haemoglobin value/dL. Multivariable logistic regression was used to assess the associated factors with anaemia in pregnancy, using SPSS (version 26). Results: Of the 435 pregnant women, 24.6% (95%CI: 21.1–29.3) were anaemic (1 in 4 pregnant women). Not working (AOR=2.45; 95%CI: 1.14–5.26), being unmarried (AOR=1.23; 95%CI: 1.24–3.57), low wealth index (AOR=9.19; 95%CI:1.64–51.56), having difficulty accessing a nearby health facility (AOR=5.40; 95%CI: 2.21–13.23), and normal body mass index (AOR=3.33; 95%CI: 1.46–7.59) were associated with higher odds of being anaemic. However, not taking iron supplements (AOR=0.16; 95% CI: 0.04–0.67), having no exposure to television (AOR=0.35; 95%CI: 0.14–0.91), being from the southern region (AOR=0.14; 95% CI: 0.03–0.66), and low husband/partner’s education (AOR=0.08; 95% CI:0.01–0.59) were associated with lower odds of being anaemic. Conclusions: The study findings indicate a high prevalence of anaemia in pregnancy, which was associated with several socio-demographics. There is a need for setting up mobile clinics and health facilities in hard-to-reach areas for easy accessibility to early anaemia screening services. Conducting mass screening for anaemia targeting pregnant women who are not working, the unmarried, and those with a low wealth index would also be beneficial. The intake of locally available iron-rich foods and/ or bio-fortified foods is also recommended. Keywords: Anaemia, Pregnancy, Women, Iron deficiency, Rwand