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The number of methylene groups between strongly interacting functional groups within polymer repeating units induces even-odd effects on thermal and mechanical properties. However, detailed studies correlating the even-odd effect with structural changes are still lacking. In this work, we establish correlations between the structure and thermal properties of poly(ester amide)s containing long alkyl chain lengths. The even-odd effect impacts the thermal properties, including the melting temperature and crystallinity degree. It influences the spherulitic morphology of poly(ester amide)s, controlling the appearance of banding. We demonstrate that even-odd effects in poly(ester amides)s persist even with 27 CH 2 groups within the repeating unit, an effect due to strong hydrogen bonds caused by the amide groups. Our X-ray studies reveal that the even-odd effect originates from changes in the crystalline structure of the materials. This work helps elucidate the role of strong intermolecular interactions (i.e., hydrogen bonding) on the even-odd effect in long-chain poly(ester amides).

We synthesize four series of novel biodegradable poly(alkylene succinate- ran -caprolactone) random copolyesters using a two-step ring-opening/transesterification and polycondensation process with ε-caprolactone (PCL) as a common comonomer. The second comonomers are succinic acid derivatives, with variations in the number of methylene groups ( n CH2 ) in the glycol segment, n CH2 = 2, 4, 8, and 12. The obtained copolyesters were poly(ethylene succinate- ran -PCL) (ES x CL y ), poly(butylene succinate- ran -PCL) (BS x CL y ), poly(octamethylene succinate- ran -PCL) (OS x CL y ), and poly(dodecylene succinate- ran -PCL) (DS x CL y ). We discovered a new mixed isodimorphic/comonomer exclusion crystallization in ES x CL y copolymers. The BS x CL y , OS x CL y , and DS x CL y copolymers display isodimorphic behavior. Our findings revealed a significant variation in the pseudoeutectic point position, from mixed isodimorphism/comonomer exclusion crystallization to isodimorphism with pseudoeutectic point variation from 54% to up to 90%. Moreover, we established a link between the melting temperature depression slope variation and the comonomer inclusion/exclusion balance, providing valuable insights into the complex topic of isodimorphic random copolymers.

The generation of long-chain branches (LCB) in biobased and biodegradable polylactide (PLA) by adding different amounts of a chain extender is studied. The rheological and calorimetric behavior have been used to determine the effect of LCB presence and their topology on PLA melt strength and crystallization behavior. Rheological modeling of linear and non-linear viscoelastic shear and extensional properties identified several possible branched structures. Moreover, remarkable differences were observed for the different topologies regarding the intrinsic non-linear parameters and the intra-cycle elastic and viscous non-linearities. Differential scanning calorimetry and polarized light optical microscopy measurements revealed a significant increase in the nucleation density and rate of PLA with increasing the amount of LCB, albeit they provoke a decrease in the growth rate due to a reduction in chain diffusion. Nevertheless, overall crystallization rate values revealed a predominant effect of nucleation over crystal growth. The introduction of LCB within the chains is highly beneficial as they increase nucleation, crystallinity, and elongational viscosity, thus improving the properties of biodegradable PLA., Competing Interests: Declaration of competing interest We are confirming that there are no known conflicts of interest associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Simultaneously attaining high strength and toughness has been a significant challenge in designing thermoplastic elastomers, especially biodegradable ones. In this context, we present a class of biodegradable elastomers based on multiblock copolyesters that afford extraordinary strength, toughness, and low-strain resilience despite expedient chemical synthesis and sample processing. With the incorporation of the semi-crystalline soft block and the judicious selection of block periodicity, the thermoplastic materials feature low quiescent crystallinity ("reserve") albeit with vast potential for strain-induced crystallization ("release"), resulting in their significantly enhanced ultimate strength and energy-dissipating capabilities. Moreover, a breadth of mechanical responses of the materials - from reinforced elastomers to shape-memory materials to toughened thermoplastics - can be achieved by orthogonal variation of segment lengths and ratios. This work and the "reserve-release" crystallization strategy herein highlight the double crystalline multiblock chain architecture as a potential avenue towards reconciling the strength-toughness trade-off in thermoplastic elastomers and can possibly be extended to other biodegradable building blocks to deliver functional materials with diverse mechanical performances., (© 2024 Wiley-VCH GmbH.)

Asthma is one of the most common chronic respiratory diseases and is characterized by airway inflammation, increased mucus production, and structural changes in the airways. Recently, there is increasing evidence that the disease is much more heterogeneous than expected, with several distinct asthma endotypes. Based on the specificity of T cells as the best-known driving force in airway inflammation, bronchial asthma is categorized into T helper cell 2 (Th2) and non-Th2 asthma. The most studied effector cells in Th2 asthma include T cells and eosinophils. In contrast to Th2 asthma, much less is known about the pathophysiology of non-Th2 asthma, which is often associated with treatment resistance. Besides T cells, the interaction of myeloid cells such as monocytes/macrophages and mast cells with the airway epithelium significantly contributes to the pathogenesis of asthma. However, the underlying molecular regulation and particularly the specific relevance of this cellular network in certain asthma endotypes remain to be understood. In this review, we summarize recent findings on the regulation of and complex interplay between epithelial cells and the "nonclassical" innate effector cells mast cells and monocytes/macrophages in Th2 and non-Th2 asthma with the ultimate goal of providing the rationale for future research into targeted therapy regimens.

Over the past decade, the preparation of novel materials by enzyme-embedding into biopolyesters has been proposed as a straightforward method to produce self-degrading polymers. This paper reports the preparation and enzymatic degradation of extruded self-degradable films of three different biopolyesters: poly(lactic acid) (PLA), poly(butylene adipate- co -terephthalate) (PBAT), and poly(butylene succinate) (PBS), as well as three binary/ternary blends. Candida antarctica lipase B (CalB) has been employed for the enzyme-embedding procedure, and to the best of our knowledge, the use of this approach in biopolyester blends has not been reported before. The three homopolymers exhibited differentiated degradation and suggested a preferential attack of CalB on PBS films over PBAT and PLA. Moreover, the self-degradable films obtained from the blends showed slow degradation, probably due to the higher content in PLA and PBAT. These observations pave the way for exploring enzymes capable of degrading all blend components or an enzymatic mixture for blend degradation.

FEZF2 encodes a transcription factor critical to neurodevelopment that regulates other neurodevelopment genes. Rare variants in FEZF2 have previously been suggested to play a role in autism, and cases of 3p14 microdeletions that include FEZF2 share a neurodevelopmental phenotype including mild dysmorphic features and intellectual disability. We identified seven heterozygous predicted deleterious variants in FEZF2 (three frameshifts, one recurrent missense in two independent cases, one nonsense, and one complete gene deletion) in unrelated individuals with neurodevelopmental disorders including developmental delay/intellectual disability, autism, and/or attention-deficit/hyperactivity. Variants were confirmed to be de novo in five of seven cases and paternally inherited from an affected father in one. Predicted deleterious variants in FEZF2 may affect the expression of genes that are involved in fate choice pathways in developing neurons, and thus contribute to the neurodevelopmental phenotype. Future studies are needed to clarify the mechanism by which FEZF2 leads to this neurodevelopmental disorder., (© 2024 Wiley Periodicals LLC.)

Although sulfurated polymers promise unique properties, their controlled synthesis, particularly when it comes to complex and functional architectures, remains challenging. Here, we show that the copolymerization of oxetane and phenyl isothiocyanate selectively yields polythioimidocarbonates as a new class of sulfur containing polymers, with narrow molecular weight distributions (M n =5-80 kg/mol with Đ≤1.2; M n,max =124 kg/mol) and high melting points of up to 181 °C. The method tolerates different substituent patterns on both the oxetane and the isothiocyanate. Self-nucleation experiments reveal that π-stacking of phenyl substituents, the presence of unsubstituted polymer backbones, and the kinetically controlled linkage selectivity are key factors in maximising melting points. The increased tolerance to macro-chain transfer agents and the controlled propagation allows the synthesis of double crystalline and amphiphilic diblock copolymers, which can be assembled into micellar- and worm-like structures with amorphous cores in water. In contrast, crystallization driven self-assembly in ethanol gives cylindrical micelles or platelets., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Neutrophils play a crucial role in inflammation and in the increased thrombotic risk in myeloproliferative neoplasms (MPNs). We have investigated how neutrophil-specific expression of JAK2-V617F or CALRdel re-programs the functions of neutrophils., Methods: Ly6G-Cre JAK2-V617F and Ly6G-Cre CALRdel mice were generated. MPN parameters as blood counts, splenomegaly and bone marrow histology were compared to wild-type mice. Megakaryocyte differentiation was investigated using lineage-negative bone marrow cells upon in vitro incubation with TPO/IL-1β. Cytokine concentrations in serum of mice were determined by Mouse Cytokine Array. IL-1α expression in various hematopoietic cell populations was determined by intracellular FACS analysis. RNA-seq to analyse gene expression of inflammatory cytokines was performed in isolated neutrophils from JAK2-V617F and CALR-mutated mice and patients. Bioenergetics of neutrophils were recorded on a Seahorse extracellular flux analyzer. Cell motility of neutrophils was monitored in vitro (time lapse microscopy), and in vivo (two-photon microscopy) upon creating an inflammatory environment. Cell adhesion to integrins, E-selectin and P-selection was investigated in-vitro. Statistical analysis was carried out using GraphPad Prism. Data are shown as mean ± SEM. Unpaired, two-tailed t-tests were applied., Results: Strikingly, neutrophil-specific expression of JAK2-V617F, but not CALRdel, was sufficient to induce pro-inflammatory cytokines including IL-1 in serum of mice. RNA-seq analysis in neutrophils from JAK2-V617F mice and patients revealed a distinct inflammatory chemokine signature which was not expressed in CALR-mutant neutrophils. In addition, IL-1 response genes were significantly enriched in neutrophils of JAK2-V617F patients as compared to CALR-mutant patients. Thus, JAK2-V617F positive neutrophils, but not CALR-mutant neutrophils, are pathogenic drivers of inflammation in MPN. In line with this, expression of JAK2-V617F or CALRdel elicited a significant difference in the metabolic phenotype of neutrophils, suggesting a stronger inflammatory activity of JAK2-V617F cells. Furthermore, JAK2-V617F, but not CALRdel, induced a VLA4 integrin-mediated adhesive phenotype in neutrophils. This resulted in reduced neutrophil migration in vitro and in an inflamed vessel. This mechanism may contribute to the increased thrombotic risk of JAK2-V617F patients compared to CALR-mutant individuals., Conclusions: Taken together, our findings highlight genotype-specific differences in MPN-neutrophils that have implications for the differential pathophysiology of JAK2-V617F versus CALR-mutant disease., (© 2024. The Author(s).)

The melt memory effect on crystallization is an intriguing phenomenon displayed by semicrystalline polymers, as opposed to low molar mass molecules. It concerns the effect of melt temperature on nucleation upon recrystallization. Typically, polymer crystals must be considerably superheated to erase the effect of previous morphology on the subsequent crystallization, avoiding an acceleration of the process. Despite being known for decades, its origin is still not fully understood. Investigating model poly(ethylene oxide) covering a wide range of molar mass, it is demonstrated that melt memory originates from topological constraints among the chains, i.e., entanglements, for PEO in which weak intermolecular interactions are present due to the ether groups. In fact, no memory is observed for samples below the critical molar mass for the formation of entanglements (about 1 kg mol -1 ). The increase in molar mass raises the number of entanglements and induces the formation of folded chains crystals, both factors leading to a topologically complex amorphous phase, enhancing the melt memory effect. The molecular origin of the melt memory effect in polymers with weak intermolecular interactions is thus ascribed to a slower isotropization in the melt of the chain segments originally contained in the crystals, due to the presence of entanglements among the chains. This study defines the distinction between small molecules and polymers from the point of view of melt memory., (© 2024 Wiley‐VCH GmbH.)

Gut-draining mesenteric and celiac lymph nodes (mLNs and celLNs) critically contribute to peripheral tolerance toward food and microbial antigens by supporting the de novo induction of regulatory T cells (Tregs). These tolerogenic properties of mLNs and celLNs are stably imprinted within stromal cells (SCs) by microbial signals and vitamin A (VA), respectively. Here, we report that a single, transient gastrointestinal infection in the neonatal, but not adult, period durably abrogates the efficient Treg-inducing capacity of celLNs by altering the subset composition and gene expression profile of celLNSCs. These cells carry information about the early-life pathogen encounter until adulthood and durably instruct migratory dendritic cells entering the celLN with reduced tolerogenic properties. Mechanistically, transiently reduced VA levels cause long-lasting celLN functional impairment, which can be rescued by early-life treatment with VA. Together, our data highlight the therapeutic potential of VA to prevent sequelae post gastrointestinal infections in infants., Competing Interests: Declaration of interests L.P. is affiliated with BioDecipher GmbH, Magdeburg, Germany., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Delving into the mechanism behind the molecular interactions at the atomic level of short-sequence peptides plays a key role in the development of nanomaterials with specific structure-property-function relationships from a bottom-up perspective. Due to their poor water solubility, the self-assembly of Fmoc-bearing peptides is usually induced by dissolution in an organic solvent, followed by a dilution step in water, pH changes, and/or a heating-cooling process. Herein, we report a straightforward methodology for the gelation of Fmoc-FFpY (F: phenylalanine; Y: tyrosine; and p: PO 4 2- ), a negatively charged tripeptide, in NaCl solution. The electrostatic interactions between Fmoc-FFpY and Na + ions give rise to different nanofibrillar hydrogels with rheological properties and nanofiber sizes modulated by the NaCl concentration in pure aqueous media. Initiated by the electrostatic interactions between the peptide phosphate groups and the Na + ions, the peptide self-assembly is stabilized thanks to hydrogen bonds between the peptide backbones and the π-π stacking of aromatic Fmoc and phenyl units. The hydrogels showed self-healing and thermo-responsive properties for potential biomedical applications. Molecular dynamics simulations from systems devoid of prior training not only confirm the aggregation of peptides at a critical salt concentration and the different interactions involved, but also corroborate the secondary structure of the hydrogels at the microsecond timescale. It is worth highlighting the remarkable achievement of reproducing the morphological behavior of the hydrogels using atomistic simulations. To our knowledge, this study is the first to report such a correspondence.

The chain architecture and topology of macromolecules impact their physical properties and final performance, including their crystallization process. In this work, comb polymers constituted by poly(ethylene glycol), PEG, side chains, and a dithiol-yne-based ring polymer backbone have been studied, focusing on the micro- and nanostructures of the system, thermal behavior, and crystallization kinetics. The designed comb system allows us to investigate the role of a ring backbone, the impact of varying the distance between two neighboring side chains, and the effect of the molecular weight of the side chain. The results reflect that the governing factor in the crystalline properties is the molar mass of the side chains and that the tethering of PEG chains to the ring backbone brings important constraints to the crystallization process, reducing the crystallinity degree and slowing down the crystallization kinetics in comparison to analogue PEG homopolymers. We demonstrate that the effect of spatial hindrance in the comb-like PEG polymers drives the morphology toward highly ordered, self-assembled, semicrystalline superstructures with either extended interdigitated chain crystals or novel (for comb polymers) interdigitated folded chain lamellar crystals. These structures depend on PEG molecular weight, the distance between neighboring tethered PEG chains, and the crystallization conditions (nonisothermal versus isothermal). This work sheds light on the role of chain architecture and topology in the structure of comb-like semicrystalline polymers., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Leishmania is the causative agent of the tropical neglected disease leishmaniasis and infects macrophages as its definitive host cell. In order to sustain and propagate infections, Leishmania parasites have to complete cycles of exit and re-infection. Yet, the mechanism driving the parasite spread to other cells remains unclear. Recent studies reported pro-inflammatory monocytes as replicative niche of Leishmania major and showed prolonged expression of IL-1β at the site of infection, indicating an activation of the NLRP3 inflammasome and pointing toward pyroptosis as a possible mechanism of parasite spread. To address the species-specific inflammasome activation of human cells, we characterized the BLaER1 monocytes as a model for L. major infection. We found that BLaER1 monocytes support infection and activation by Leishmania parasites to the same extent as primary human macrophages. Harnessing the possibilities of this infection model, we first showed that BLaER1 GSDMD -/- cells, which carry a deletion of the pore-forming protein gasdermin D, are more resistant to pyroptotic cell death and, concomitantly, display a strongly delayed release of intracellular parasite. Using that knockout in a co-incubation assay in comparison with wild-type BLaER1 cells, we demonstrate that impairment of the pyroptosis pathway leads to lower rates of parasite spread to new host cells, thus, implicating pyroptotic cell death as a possible exit mechanism of L. major in pro-inflammatory microenvironments., (© 2023 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

Cyclic block copolymers ( c BCP) are fundamentally intriguing materials, but their synthetic challenges that demand precision in controlling both the monomer sequence and polymer topology limit access to AB and ABC block architectures. Here, we show that cyclic ABAB tetra-BCPs ( c ABAB) and their linear counterpart ( l ABAB) can be readily obtained at a speed and scale from one-pot (meth)acrylic monomer mixtures, through coupling the Lewis pair polymerization's unique compounded-sequence control with its precision in topology control. This approach achieves fast (<15 min) and quantitative (>99%) conversion to tetra-BCPs of predesignated linear or cyclic topology at scale (40 g) in a one-pot procedure, precluding the needs for repeated chain extensions, stoichiometric addition steps, dilute conditions, and postsynthetic modifications, and/or postsynthetic ring-closure steps. The resulting l ABAB and c ABAB have essentially identical molecular weights ( M n = 165-168 kg mol -1 ) and block degrees/symmetry, allowing for direct behavioral comparisons in solution (hydrodynamic volume, intrinsic viscosity, elution time, and refractive indices), bulk (thermal transitions), and film (thermomechanical and rheometric properties and X-ray scattering patterns) states. To further the morphological characterizations, allylic side-chain functionality is exploited via the thiol-ene click chemistry to install crystalline octadecane side chains and promote phase separation between the A and B blocks, allowing visualization of microdomain formation.

Mobile fitness applications provide the opportunity to show users real-time feedback on their current fitness activity. For such applications, it is essential to accurately track the user's current fitness activity using available mobile sensors, such as inertial measurement units (IMUs). Convolutional neural networks (CNNs) have been shown to produce strong results in different time series classification tasks, including the recognition of daily living activities. However, fitness activities can present unique challenges to the human activity recognition task (HAR), including greater similarity between individual activities and fewer available data for model training. In this paper, we evaluate the applicability of CNNs to the fitness activity recognition task (FAR) using IMU data and determine the impact of input data size and sensor count on performance. For this purpose, we adapted three existing CNN architectures to the FAR task and designed a fourth CNN variant, which we call the scaling fully convolutional network (Scaling-FCN). We designed a preprocessing pipeline and recorded a running exercise data set with 20 participants, in which we evaluated the respective recognition performances of the four networks, comparing them with three traditional machine learning (ML) methods commonly used in HAR. Although CNN architectures achieve at least 94% test accuracy in all scenarios, two traditional ML architectures surpass them in the default scenario, with support vector machines (SVMs) achieving 99.00 ± 0.34% test accuracy. The removal of all sensors except one foot sensor reduced the performance of traditional ML architectures but improved the performance of CNN architectures on our data set, with our Scaling-FCN reaching the highest accuracy of 99.86 ± 0.11% on the test set. Our results suggest that CNNs are generally well suited for fitness activity recognition, and noticeable performance improvements can be achieved if sensors are dropped selectively, although traditional ML architectures can still compete with or even surpass CNNs when favorable input data are utilized.

Solid polymer electrolytes that combine both a high lithium-ion transference number and mechanical properties at high temperatures are searched for improving the performance of batteries. Here, we show a salt-free all-polymer nanocomposite solid electrolyte for lithium metal batteries that improves the mechanical properties and shows a high lithium-ion transference number. For this purpose, lithium sulfonamide-functionalized poly(methyl methacrylate) nanoparticles (LiNPs) of very small size (20-30 nm) were mixed with poly(ethylene oxide) (PEO). The morphology of all-polymer nanocomposites was first investigated by transmission electron microscopy (TEM), showing a good distribution of nanoparticles (NPs) even at high contents (50 LiNP wt %). The crystallinity of PEO was investigated in detail and decreased with the increasing concentration of LiNPs. The highest ionic conductivity value for the PEO 50 wt % LiNP nanocomposite at 80 °C is 1.1 × 10 -5 S cm -1 , showing a lithium-ion transference number of 0.68. Using dynamic mechanic thermal analysis (DMTA), it was shown that LiNPs strengthen PEO, and a modulus of ≈10 8 Pa was obtained at 80 °C for the polymer nanocomposite. The nanocomposite solid electrolyte was stable with respect to lithium in a Li||Li symmetrical cell for 1000 h. In addition, in a full solid-state battery using LiFePO 4 as the cathode and lithium metal as the anode, a specific capacity of 150 mAhg -1 with a current density of 0.05 mA cm -2 was achieved., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Poly(3-hydroxybutyrate) (P3HB), a biologically produced, biodegradable natural polyester, exhibits excellent thermal and barrier properties but suffers from mechanical brittleness, largely limiting its applications. Here we report a mono-material product design strategy to toughen stereoperfect, brittle bio or synthetic P3HB by blending it with stereomicrostructurally engineered P3HB. Through tacticity ([mm] from 0 to 100 %) and molecular weight (M n to 788 kDa) tuning, high-performance synthetic P3HB materials with tensile strength to ≈30 MPa, fracture strain to ≈800 %, and toughness to 126 MJ m -3 (>110× tougher than bio-P3HB) have been produced. Physical blending of the brittle P3HB with such P3HB in 10 to 90 wt % dramatically enhances its ductility from ≈5 % to 95-450 % and optical clarity from 19 % to 85 % visible light transmittance while maintaining desirably high elastic modulus (>1 GPa), tensile strength (>35 MPa), and melting temperature (160-170 °C). This P3HB-toughening-P3HB methodology departs from the traditional approach of incorporating chemically distinct components to toughen P3HB, which hinders chemical or mechanical recycling, highlighting the potential of the mono-material product design solely based on biodegradable P3HB to deliver P3HB materials with diverse performance properties., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Well-defined multicrystalline multiblock polymers are essential model polymers for advancing crystallization physics, phase separation, self-assembly, and improving the mechanical properties of materials. However, due to different chain properties and incompatible synthetic methodologies, multicrystalline multiblock polymers with more than two crystallites are rarely reported. Herein, by combining polyhomologation, ring-opening polymerization, and catalyst switch strategy, we synthesized a pentacrystalline pentablock quintopolymer, polyethylene-b-poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(L-lactide)-b-polyglycolide (PE-b-PEO-b-PCL-b-PLLA-b-PGA). The fluoroalcohol-assisted catalyst switch enables the successful incorporation of a high melting point polyglycolide block into the complex multiblock structure. Solid-state nuclear magnetic resonance spectroscopy, X-ray diffraction, and differential scanning calorimetry revealed the existence of five different crystalline phases., (© 2023. The Author(s).)

In the polyester family, the biopolymer with the greatest industrial potential could be poly(3-hydroxybutyrate) (PHB), which can be produced nowadays biologically or chemically. The scarce commercial use of PHB derives from its poor mechanical properties, which can be improved by incorporating a flexible aliphatic polyester with good mechanical performance, such as poly(ε-caprolactone) (PCL), while retaining its biodegradability. This work studies the structural, thermal, and morphological properties of block and random copolymers of PHB and PCL. The presence of a comonomer influences the thermal parameters following nonisothermal crystallization and the kinetics of isothermal crystallization. Specifically, the copolymers exhibit lower melting and crystallization temperatures and present lower overall crystallization kinetics than neat homopolymers. The nucleation rates of the PHB components are greatly enhanced in the copolymers, reducing spherulitic sizes and promoting transparency with respect to neat PHB. However, their spherulitic growth rates are depressed so much that superstructural growth becomes the dominating factor that reduces the overall crystallization kinetics of the PHB component in the copolymers. The block and random copolymers analyzed here also display important differences in the structure, morphology, and crystallization that were examined in detail. Our results show that copolymerization can tailor the thermal properties, morphology (spherulitic size), and crystallization kinetics of PHB, potentially improving the processing, optical, and mechanical properties of PHB.

The synthesis of waterborne thiol-ene polymer dispersions is challenging due to the high reactivity of thiol monomers and the premature thiol-ene polymerization that leads to high irreproducibility. By turning this challenge into an advantage, a synthesis approach of high solid content film-forming waterborne poly(thioether) prepolymers is reported based on initiator-free step growth sonopolymerization. Copolymerization of bifunctional thiol and ene monomers diallyl terephthalate, glycol dimercaptoacetate, glycol dimercaptopropionate, and 2,2-(ethylenedioxy)diethanethiol gave rise to linear poly(thioether) functional chains with molar mass ranging between 7 and 23 kDa when synthesized at 30% solid content and between 1 and 9 kDa at increased solid content of 50%. To further increase the polymers' molar mass, an additional photopolymerization step was performed in the presence of a water-soluble photoinitiator, i.e., lithium phenyl-2,4,6-trimethylbenzoylphosphinate, leading to high molar mass chains of up to 200 kDa, the highest reported so far for step grown poly(thioethers). The polymer dispersions presented good film-forming ability at room temperature, yielding semicrystalline films with a high potential for barrier coating applications. Nevertheless, affected by the polymer chemical repeating structure, which includes an aromatic ring, these thiol-ene chains can only crystallize very slowly from the molten state. Herein, for the first time, we present the successful implementation of a self-nucleation (SN) procedure for these types of poly(thioethers), which effectively accelerates their crystallization kinetics., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

In this work, poly(hexamethylene- ran -octamethylene carbonate) copolycarbonates were synthesized by melt polycondensation in a wide range of compositions. The copolymers displayed some of the characteristic isodimorphic thermal behavior, such as crystallization for all the compositions and a pseudoeutectic behavior of the melting temperature ( T m ) versus composition. The pseudoeutectic point was located at 33 mol % poly(octamethylene carbonate) (POC) content (i.e., corresponding to the PH 67 O 33 C copolymer). Surprisingly, the crystallinities ( X c ) for a wide range of copolymer compositions were higher than those of the parent components, a phenomenon that has not been observed before in isodimorphic random copolymers. The structural characterization, performed by wide-angle X-ray scattering (WAXS) and small-angle X-ray scattering experiments, revealed unexpected results depending on composition. On the one hand, the poly(hexamethylene carbonate) (PHC)- and POC-rich copolymers crystallize in PHC- and POC-type crystals, as expected. Moreover, upon cooling and heating, in situ WAXS experiments evidenced that these materials undergo reversible solid-solid transitions [δ-α (PHC) and δ-α-β (POC)] present in the parent components but at lower temperatures. On the other hand, a novel behavior was found for copolymers with 33-73 mol % POC (including the pseudoeutectic point), which are those with higher crystallinities than the parent components. For these copolymers, a new crystalline phase that is different from that of both homopolymers was observed. The in situ WAXS results for these copolymers confirmed that this novel phase is stable upon cooling and heating and does not show any crystallographic feature of the parent components or their solid-solid transitions. FTIR experiments confirmed this behavior, revealing that the new phase adopts a polyethylene-like chain conformation that differs from the trans -dominant ones exhibited by the parent components. This finding challenges the established concepts of isodimorphism and questions whether a combination of crystallization modes (isodimorphism and isomorphism) is possible in the same family of random copolymers just by changing the composition., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Over the last decade, significant progress has been made in developing hydrogels as medical devices. By physically cross-linking pharmaceutically approved polymers into three-dimensional matrices, we can ensure their biocompatibility and facilitate their seamless transition from the laboratory to clinical applications. Moreover, the reversible nature of their physical cross-links allows hydrogels to dissolve in the presence of external stimuli. Particularly, their high degree of hydration, high molecular weight, and superior flexibility of the polymer chains facilitate their interaction with complex biological barriers ( e.g. , mucus layer), making them ideal candidates for mucosal drug delivery. However, fine-tuning the composition of the hydrogel formulations is of great importance to optimize the performance of the medical device and its therapeutic cargo. Herein, we investigated the influence of different Eudragits® on the properties of hydrogels based on polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and polyethylene glycol (PEG), which were originally proposed as ocular inserts in previous reports. Our research aims to determine the effects that including different Eudragits® have on the structure and protein ocular delivery ability of various hydrogel formulations. Properties such as matrix stability, protein encapsulation, release kinetics, mucoadhesion, and biocompatibility have been analyzed in detail. Our study represents a guideline of the features that Eudragits® have to exhibit to endow hydrogels with good adhesion to the eye's conjunctiva, biocompatibility, and structural strength to cope with the ocular biointerface and allow sustained protein release. This work has important implications for the design of new hydrogel materials containing Eudragits® in their composition, particularly in mucosal drug delivery.

Melt memory effects in polymer crystallization have attracted much attention in the past few years. Although progress has been made in understanding how the chemical structure of polymers can affect melt memory, there are still some knowledge gaps. In this work, we study how incorporating a second comonomer unit that is partially included in the crystalline unit cell affects the melt memory effect of the major component in a random isodimorphic copolymer for the first time. This second comonomer unit depresses the melting temperature of the homopolymer, reduces the crystallinity, and distorts the crystalline unit cell. However, its effect on the stability of self-nuclei and the production of melt memory has not been studied so far. To this aim, we have selected poly[(butylene succinate)- ran -(ε-caprolactone)] random copolyesters PBS- ran -PCL that are isodimorphic, i.e., they exhibit a pseudoeutectic point. This point separates the formation of BS-rich crystals from CL-rich crystals as a function of composition. The results reveal that the melt memory effect of these isodimorphic copolymers is strongly reduced with the incorporation of even very small amounts of comonomer unit (i.e., 1 molar %). This indicates that the incorporation of a second comonomer unit in the polymer chain disrupts the intermolecular interactions present between the chain segments in the crystal lattice of the major component and reduces the capacity of the material to produce self-nuclei. This reduction is more drastic for copolymers in which the second comonomer unit is mostly rejected from the crystalline phase. Contrary to olefin-based copolymers, for copolyesters, the second comonomer unit eases the process to reach an isotropic melt state upon melting. This work reveals the impact of introducing comonomer units on the melt memory effect in isodimorphic random copolyesters., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The performance of sustainable polymers can be modified and enhanced by incorporating functional groups in the backbone of the polymer chain that increases intermolecular interactions, thus impacting the thermal properties of the material. However, in-depth studies on the role of intermolecular interactions on the crystallization of these polymers are still needed. This work aims to ascertain whether incorporating functional groups able to induce intermolecular interactions can be used as a suitable systematic strategy to modify the polymer thermal properties and crystallization kinetics. Thus, amide and additional ester groups have been incorporated into aliphatic polyesters (PEs). The impact of intermolecular interactions on the melting and crystallization behavior, crystallization kinetics, and crystalline structure has been determined. Functional groups that form strong intermolecular interactions increase both melting and crystallization temperatures but retard the crystallization kinetics. Selecting appropriate functional groups allows tuning the crystallinity degree, which can potentially improve the mechanical properties and degradability in semicrystalline materials. The results demonstrate that it is possible to tune the thermal transitions and the crystallization kinetics of PEs independently by varying their chemical structure., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

The virulence of intracellular pathogens relies largely on the ability to survive and replicate within phagocytes but also on release and transfer into new host cells. Such cell-to-cell transfer could represent a target for counteracting microbial pathogenesis. However, our understanding of the underlying cellular and molecular processes remains woefully insufficient. Using intravital 2-photon microscopy of caspase-3 activation in the Leishmania major-infected (L. major-infected) live skin, we showed increased apoptosis in cells infected by the parasite. Also, transfer of the parasite to new host cells occurred directly without a detectable extracellular state and was associated with concomitant uptake of cellular material from the original host cell. These in vivo findings were fully recapitulated in infections of isolated human phagocytes. Furthermore, we observed that high pathogen proliferation increased cell death in infected cells, and long-term residency within an infected host cell was only possible for slowly proliferating parasites. Our results therefore suggest that L. major drives its own dissemination to new phagocytes by inducing host cell death in a proliferation-dependent manner.

Aliphatic polyesters are widely studied due to their excellent properties and low-cost production and also because, in many cases, they are biodegradable and/or recyclable. Therefore, expanding the range of available aliphatic polyesters is highly desirable. This paper reports the synthesis, morphology, and crystallization kinetics of a scarcely studied polyester, polyheptalactone (PHL). First, we synthesized the η-heptalactone monomer by the Baeyer-Villiger oxidation of cycloheptanone before several polyheptalactones of different molecular weights (in the range between 2 and 12 kDa), and low dispersities were prepared by ring-opening polymerization (ROP). The influence of molecular weight on primary nucleation rate, spherulitic growth rate, and overall crystallization rate was studied for the first time. All of these rates increased with PHL molecular weight, and they approached a plateau for the highest molecular weight samples employed here. Single crystals of PHLs were prepared for the first time, and hexagonal-shaped flat single crystals were obtained. The study of the crystallization and morphology of PHL revealed strong similarities with PCL, making PHLs very promising materials, considering their potential biodegradable character.

A complex crystallization behavior was observed for the alternating copolymer DMDS- alt -DVE synthesized via thiol-ene step-growth polymerization. Understanding the underlying complex crystallization processes of such innovative polythioethers is critical for their application, for example, in polymer coating technologies. These alternating copolymers have polymorphic traits, resulting in different phases that may display distinct crystalline structures. The copolymer DMDS- alt -DVE was studied in an earlier work, where only two crystalline phases were reported: a low melting, L - T m , and high melting, H - T m phase. Remarkably, the H - T m form was only achieved by the previous formation and melting of the L - T m form. We applied calorimetric techniques encompassing seven orders of magnitude in scanning rates to further explore this complex polymorphic behavior. Most importantly, by rapidly quenching the sample to temperatures well below room temperature, we detected an additional polymorphic form (characterized by a very low melting phase, denoted VL - T m ). Moreover, through tailored thermal protocols, we successfully produced samples containing only one, two, or all three polymorphs, providing insights into their interrelationships. Understanding polymorphism, crystallization, and the resulting morphological differences can have significant implications and potential impact on mechanical resistance and barrier properties., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Most clinically applied cancer immunotherapies rely on the ability of CD8 + cytolytic T cells to directly recognize and kill tumour cells 1-3 . These strategies are limited by the emergence of major histocompatibility complex (MHC)-deficient tumour cells and the formation of an immunosuppressive tumour microenvironment 4-6 . The ability of CD4 + effector cells to contribute to antitumour immunity independently of CD8 + T cells is increasingly recognized, but strategies to unleash their full potential remain to be identified 7-10 . Here, we describe a mechanism whereby a small number of CD4 + T cells is sufficient to eradicate MHC-deficient tumours that escape direct CD8 + T cell targeting. The CD4 + effector T cells preferentially cluster at tumour invasive margins where they interact with MHC-II + CD11c + antigen-presenting cells. We show that T helper type 1 cell-directed CD4 + T cells and innate immune stimulation reprogramme the tumour-associated myeloid cell network towards interferon-activated antigen-presenting and iNOS-expressing tumouricidal effector phenotypes. Together, CD4 + T cells and tumouricidal myeloid cells orchestrate the induction of remote inflammatory cell death that indirectly eradicates interferon-unresponsive and MHC-deficient tumours. These results warrant the clinical exploitation of this ability of CD4 + T cells and innate immune stimulators in a strategy to complement the direct cytolytic activity of CD8 + T cells and natural killer cells and advance cancer immunotherapies., (© 2023. The Author(s).)

Polyhydroxyalkanoates are natural polyesters synthesized by microorganisms and bacteria. Due to their properties, they have been proposed as substitutes for petroleum derivatives. This work studies how the printing conditions employed in fuse filament fabrication (FFF) affect the properties of poly(hydroxybutyrate-co-hydroxy hexanoate) or PHBH. Firstly, rheological results predicted the printability of PHBH, which was successfully realized. Unlike what usually happens in FFF manufacturing or several semi-crystalline polymers, it was observed that the crystallization of PHBH occurs isothermally after deposition on the bed and not during the non-isothermal cooling stage, according to calorimetric measurements. A computational simulation of the temperature profile during the printing process was conducted to confirm this behavior, and the results support this hypothesis. Through the analysis of mechanical properties, it was shown that the nozzle and bed temperature increase improved the mechanical properties, reducing the void formation and improving interlayer adhesion, as shown by SEM. Intermediate printing velocities produced the best mechanical properties.

Stereo-defects present in stereo-regular polymers often diminish thermal and mechanical properties, and hence suppressing or eliminating them is a major aspirational goal for achieving polymers with optimal or enhanced properties. Here, we accomplish the opposite by introducing controlled stereo-defects to semicrystalline biodegradable poly(3-hydroxybutyrate) (P3HB), which offers an attractive biodegradable alternative to semicrystalline isotactic polypropylene but is brittle and opaque. We enhance the specific properties and mechanical performance of P3HB by drastically toughening it and also rendering it with the desired optical clarity while maintaining its biodegradability and crystallinity. This toughening strategy of stereo-microstructural engineering without changing the chemical compositions also departs from the conventional approach of toughening P3HB through copolymerization that increases chemical complexity, suppresses crystallization in the resulting copolymers, and is thus undesirable in the context of polymer recycling and performance. More specifically, syndio-rich P3HB ( sr -P3HB), readily synthesized from the eight-membered meso -dimethyl diolide, has a unique set of stereo-microstructures comprising enriched syndiotactic [ rr ] and no isotactic [ mm ] triads but abundant stereo-defects randomly distributed along the chain. This sr -P3HB material is characterized by high toughness ( U T = 96 MJ/m 3 ) as a result of its high elongation at break (>400%) and tensile strength (34 MPa), crystallinity ( T m = 114 °C), optical clarity (due to its submicron spherulites), and good barrier properties, while it still biodegrades in freshwater and soil.

Background: Fetal akinesia (FA) results in variable clinical presentations and has been associated with more than 166 different disease loci. However, the underlying molecular cause remains unclear in many individuals. We aimed to further define the set of genes involved., Methods: We performed in-depth clinical characterisation and exome sequencing on a cohort of 23 FA index cases sharing arthrogryposis as a common feature., Results: We identified likely pathogenic or pathogenic variants in 12 different established disease genes explaining the disease phenotype in 13 index cases and report 12 novel variants. In the unsolved families, a search for recessive-type variants affecting the same gene was performed; and in five affected fetuses of two unrelated families, a homozygous loss-of-function variant in the kinesin family member 21A gene ( KIF21A ) was found., Conclusion: Our study underlines the broad locus heterogeneity of FA with well-established and atypical genotype-phenotype associations. We describe KIF21A as a new factor implicated in the pathogenesis of severe neurogenic FA sequence with arthrogryposis of multiple joints, pulmonary hypoplasia and facial dysmorphisms. This hypothesis is further corroborated by a recent report on overlapping phenotypes observed in Kif21a null piglets., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder., Methods: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature., Results: The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss., Conclusion: This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities., Competing Interests: Conflict of Interest Megan Li is an employee of Invitae. Erin Torti, Amber Begtrup, and Rhonda E Schnur are employees of GeneDx, Inc. All other authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Understanding the complex crystallization process of semiconducting polymers is key for the advance of organic electronic technologies as the optoelectronic properties of these materials are intimately connected to their solid-state microstructure. These polymers often have semirigid backbones and flexible side chains, which results in a strong tendency to organize/order in the liquid state. Therefore, crystallization of these materials frequently occurs from liquid states that exhibit-at least partial-molecular order. However, the impact of the preexisting molecular order on the crystallization process of semiconducting polymers- indeed, of any polymer-remained hitherto unknown. This study uses fast scanning calorimetry (FSC) to probe the crystallization kinetics of poly(9,9-di- n -octylfluorenyl-2,7-diyl (PFO) from both an isotropic disordered melt state ( ISO state ) and a liquid-crystalline ordered state ( NEM state ). Our results demonstrate that the preexisting molecular order has a profound impact on the crystallization of PFO. More specifically, it favors the formation of effective crystal nucleation centers, speeding up the crystallization kinetics at the early stages of phase transformation. However, samples crystallized from the NEM state require longer times to reach full crystallization (during the secondary crystallization stage) compared to those crystallized from the ISO state , likely suggesting that the preexisting molecular order slows down the advance in the latest stages of the crystallization, that is, those governed by molecular diffusion. The fitting of the data with the Avrami model reveals different crystallization mechanisms, which ultimately result in a distinct semicrystalline morphology and photoluminescence properties. Therefore, this work highlights the importance of understanding the interrelationships between processing, structure, and properties of polymer semiconductors and opens the door for performing fundamental investigations via newly developed FSC methodologies of such materials that otherwise are not possible with conventional techniques., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society.)

Our knowledge about respiratory virus spreading is mostly based on monolayer cultures that hardly reflect the complex organization of the airway epithelium. Thus, there is a strong demand for biologically relevant models. One possibility to study virus spreading at the cellular level is real-time imaging. In an attempt to visualize virus spreading under somewhat more physiological conditions, Calu-3 cells and human primary fibroblasts were co-cultured submerged or as air-liquid interface (ALI). An influenza A virus (IAV) replicating well in cell culture, and carrying a red fluorescent protein (RFP) reporter gene was used for real-time imaging. Our three-dimensional (3D) models exhibited important characteristics of native airway epithelium including a basement membrane, tight junctions and, in ALI models, strong mucus production. In submerged models, first fluorescence signals appeared between 9 and 12 h post infection (hpi) with a low multiplicity of infection of 0.01. Virus spreading further proceeded in the immediate vicinity of infected cells. In ALI models, RFP was found at 22 hpi and later. Consequently, the progression of infection was delayed, in contrast to the submerged model. With these features, we believe that our 3D airway models can deliver new insights in the spreading of IAV and other respiratory viruses.

Staphylococcus aureus is a leading cause of difficult-to-treat infections. The capacity of S. aureus to survive and persist within phagocytic cells is an important factor contributing to therapy failures and infection recurrence. Therefore, interfering with S. aureus intracellular persistence is key to treatment success. In this study, we used a S. aureus strain carrying the reporter mKikumeGR that enables the monitoring of the metabolic status of intracellular bacteria to achieve a better understanding of the molecular mechanisms facilitating S. aureus survival and persistence within macrophages. We found that shortly after bacteria internalization, a large fraction of macrophages harbored mainly S. aureus with high metabolic activity. This population decreased gradually over time with the concomitant increase of a macrophage subpopulation harboring S. aureus with low metabolic activity, which prevailed at later times. A dual RNA-seq analysis performed in each macrophage subpopulation showed that the host transcriptional response was similar between both subpopulations. However, intracellular S. aureus exhibited disparate gene expression profiles depending on its metabolic state. Whereas S. aureus with high metabolic activity exhibited a greater expression of genes involved in protein synthesis and proliferation, bacteria with low metabolic activity displayed a higher expression of oxidative stress response-related genes, silenced genes involved in energy-consuming processes, and exhibited a dormant-like state. Consequently, we propose that reducing metabolic activity and entering into a dormant-like state constitute a survival strategy used by S. aureus to overcome the adverse environment encountered within macrophages and to persist in the intracellular niche. IMPORTANCE The capacity of Staphylococcus aureus to survive and persist within phagocytic cells has been associated with antibiotic treatment failure and recurrent infections. Here, we investigated the molecular mechanisms leading to S. aureus persistence within macrophages using a reporter system that enables to distinguish between intracellular bacteria with high and low metabolic activity in combinstion with a dual RNA-seq approach. We found that with the progression of infection, intracellular S. aureus transitions from a high metabolic state to a low metabolic dormant-like state by turning off major energy-consuming processes while remaining viable. This process seems to be driven by the level of stress encountered in the intracellular niche. Our study indicates that effective therapies by which to treat S. aureus infections should be able to target not only high metabolic bacteria but also intracellular dormant-like S. aureus.

T cells orchestrate adaptive and innate immune responses against pathogens and transformed cells. However, T cells are also the main adaptive effector cells that mediate allergic and autoimmune reactions. Within the last few years, it has become abundantly clear that activation, differentiation, effector function, and environmental adaptation of T cells is closely linked to their energy metabolism. Beyond the provision of energy equivalents, metabolic pathways in T cells generate building blocks required for clonal expansion. Furthermore, metabolic intermediates directly serve as a source for epigenetic gene regulation by histone and DNA modification mechanisms. To date, several antibiotics were demonstrated to modulate the metabolism of T cells especially by altering mitochondrial function. Here, we set out to systematically review current evidence about how beta-lactam antibiotics, macrolides, fluoroquinolones, tetracyclines, oxazolidinones, nitroimidazoles, and amphenicols alter the metabolism and effector functions of CD4 + T helper cell populations and CD8 + T cells in vitro and in vivo . Based on this evidence, we have developed an overview on how the use of these antibiotics may be beneficial or detrimental in T cell-mediated physiological and pathogenic immune responses, such as allergic and autoimmune diseases, by altering the metabolism of different T cell populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Franz, Negele, Bruno, Böttcher, Mitchell-Flack, Reemts, Krone, Mougiakakos, Müller, Zautner and Kahlfuss.)

In this work, hybrid hydrogels were synthesized with the inclusion of two types of clay materials that are considered industrial waste: red mud (RM) and ferrosilicomanganese fines (FeSiMn). These solid waste materials were characterized by studying their particle size and chemical composition, which are two key variables for their application in the synthesis of hybrid hydrogels. The morphology imaged by transmission electron microscopy (TEM) and scanning electron microscopy (SEM), showed, in the case of RM, heterogeneous size and shape particles, with 73% of the particles having lengths of less than 5 μm. On the other hand, FeSiMn had particles with a circular morphology of nanometric sizes. Regarding the synthesis of the hybrid hydrogels, it was determined that the incorporation of small percentages (0.1%) of the inorganic phases improved the capacity of the materials to absorb water (swelling indices of 1678% and 1597% for the RM and FeSiMn hydrogels, respectively) compared to the conventional polyacrylamide hydrogel (1119%). An improvement in Vickers microhardness and storage modulus (G') was also observed: the hybrid with 10% RM presented a G', 50 times higher than conventional hydrogel. The results show the merit of RM and FeSiMn in improving the properties of hydrogels.

Poly(3-hydroxybutyrate) (PHB) is naturally accumulated by bacteria but can also be synthesized chemically. Its processability is limited, as it tends to degrade at temperatures above its melting temperature; hence, investigation into crystallization kinetics and morphology of PHB materials of both natural and synthetic origins is of great need and interest to get a better understanding of structure-property relationship. Accordingly, this contribution reports a first study of the crystallization and morphology of synthetic PHB materials of different molecular weights. These synthetic PHBs are racemic mixtures (50/50 mol %) of R and S chain configurations and are compared with an enantiopure bacterial R -PHB. Nonisothermal and isothermal crystallization studies show that R and S chains of PHB can cocrystallize in the same unit cell as the R -PHB. Most significantly, the results show that the presence of S chains decreases the overall crystallization rate, which could enhance the processability and industrialization of PHB-based materials.

In this contribution, we study the effect of trifluoro ethylene (TrFE) comonomer content (samples with 80/20, 75/25, and 70/30 VDF/TrFE molar ratios were used) on the crystallization in P(VDF- co -TrFE) in comparison with a PVDF (Poly(vinylidene fluoride)) homopolymer. Employing Polarized Light Optical Microscopy (PLOM), the growth rates of spherulites or axialites were determined. Differential Scanning Calorimetry (DSC) was used to determine overall crystallization rates, self-nucleation, and Successive Self-nucleation and Annealing (SSA) thermal fractionation. The ferroelectric character of the samples was explored by polarization measurements. The results indicate that TrFE inclusion can limit the overall crystallization of the copolymer samples, especially for the ones with 20 and 25% TrFE. Self-nucleation measurements in PVDF indicate that the homopolymer can be self-nucleated, exhibiting the classic three Domains . However, the increased nucleation capacity in the copolymers provokes the absence of the self-nucleation Domain II . The PVDF displays a monomodal distribution of thermal fractions after SSA, but the P(VDF- co -TrFE) copolymers do not experience thermal fractionation, apparently due to TrFE incorporation in the PVDF crystals. Finally, the maximum and remnant polarization increases with increasing TrFE content up to a maximum of 25% TrFE content, after which it starts to decrease due to the lower dipole moment of the TrFE defect inclusion within the PVDF crystals.

Biallelic variants of the gene encoding for the zinc-finger protein 142 (ZNF142) have recently been associated with intellectual disability (ID), speech impairment, seizures, and movement disorders in nine individuals from five families. In this study, we obtained phenotype and genotype information of 26 further individuals from 16 families. Among the 27 different ZNF142 variants identified in the total of 35 individuals only four were missense. Missense variants may give a milder phenotype by changing the local structure of ZF motifs as suggested by protein modeling; but this correlation should be validated in larger cohorts and pathogenicity of the missense variants should be investigated with functional studies. Clinical features of the 35 individuals suggest that biallelic ZNF142 variants lead to a syndromic neurodevelopmental disorder with mild to moderate ID, varying degrees of delay in language and gross motor development, early onset seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism. The differences in symptom frequencies observed in the unpublished individuals compared to those of published, and recognition of previously underemphasized facial features are likely to be due to the small sizes of the previous cohorts, which underlines the importance of larger cohorts for the phenotype descriptions of rare genetic disorders., (© 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

This work presents, for the first time, a detailed report on how the nucleation and crystallization of polylactide (PLLA) are affected by biobased aliphatic polyesters plasticizers. Three biobased polyesters were synthesized via solvent-free two-stage melt polycondensation of adipic acid (AdA) with three different biobased aliphatic diols and used as plasticizers for poly (L-lactic acid) (PLLA). The molecular structure of the synthesized polyesters was proved using 1 H NMR, 13 C NMR and Fourier transform infrared (FTIR) spectroscopy. PLLA/AdA-based blends containing 10 wt% of the polyester plasticizers were studied by tensile tests, dynamic mechanical analysis (DMA), wide-angle x-ray scattering (WAXS), differential scanning calorimetry (DSC) and polarized light optical microscopy (PLOM). Adding the plasticizers to PLLA decreased T g by up to 11 °C and significantly increased the elongation at break by about 8 times compared with neat PLLA. The addition of 10 wt% of any AdA-based plasticizer to PLLA increases the nucleation rate from the glassy state by around 50-110 % depending on the plasticizer. The overall crystallization rate from the glassy state was 2-3 times faster for the plasticized PLLAs than neat PLLA. These results are a consequence of the lower energy barrier for both nucleation and growth processes. The incorporation of AdA-based linear polyesters had an incremental impact on the crystal growth rate (or secondary nucleation) of PLLA spherulites from the melt and glassy states. In conclusion, the AdA-based aliphatic polyesters allowed to enhance PLLA crystallization rates and showed interesting potential for the formulation of fully biobased PLLA blends., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

We have previously shown that semicrystalline polymers can be reinforced by adding nanoparticles (NPs) and then ordering them into specific motifs using the crystallization process. A key result we have found is that when the spherulite growth rate is slowed below a critical value, then, NPs can order into the amorphous interlamellar regions of the semicrystalline structure. The effects of spherulite growth rate in this context have previously been examined, and here we focus on the role of NP diffusivity. We achieve this goal by changing the poly(ethylene oxide) (PEO) molecular weight as a route to altering the matrix viscosity. In particular, four molecular weights of PEO were employed ranging from 5.4-46 kDa. Each sample was loaded with 10 vol % of bare 14 nm diameter silica NPs. After initially studying spherulite growth rates, experiments were designed to fix the spherulite growth rate across sample molecular weights to study particle ordering, induced by polymer crystallization. We find that, at the fastest growth rate studied (12 μm/s), the lowest molecular weight sample showed the highest order, presumably due to enhanced particle mobility. However, as the spherulite growth rate is slowed, the maximum ordering behavior is observed at intermediate molecular weights. The trend observed at slow growth rates is explained by the large-scale segregation of NPs (presumably into the grain boundaries, i.e., the interspherulitic regions); evidence for this is the observed transition of spherulite growth to diffusion-control at slow growth rates in the lowest molecular weight PEO sample studied.

Natural deep eutectics solvents (NADES), owing to their high solvation capacity and nontoxicity, are actively being sought for many technological applications. Herein, we report a series of novel NADES based on choline chloride and plant-derived polyphenols. Most of the obtained phenolic NADES have a wide liquid range and high thermal stability above 150 °C. Among them, small-sized polyphenols, like pyrogallol, vanillyl alcohol, or gentisic acid, lead to low-viscosity liquids with ionic conductivities in the order of 10 -3 S cm -1 at room temperature. Interestingly, polyphenols possess valuable properties as therapeutic agents, antioxidants, adhesives, or redox-active compounds, among others. Thus, we evaluated the potential of these novel NADES for two applications: bioadhesives and corrosion protection. The mixture of choline chloride-vanillyl alcohol (2:3 mol ratio) and gelatin resulted in a highly adhesive viscoelastic liquid (adhesive stress ≈ 135 kPa), affording shear thinning behavior. Furthermore, choline chloride-tannic acid (20:1) showed an extraordinary ability to coordinate iron ions, reaching excellent corrosion inhibitive efficiencies in mild steel protection., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

We present in situ tracking of silica nanoparticle (NP) migration from a poly(ethylene oxide) (PEO) melt into interlamellar region using in situ atomic force microscopy (AFM). Our results confirm the previous hypothesis that NPs migrate into the interlamellar regions at crystallization growth rates smaller than a critical value under isothermal conditions. Under these slow crystallization conditions, bare silica NPs are rejected as defects by the growing crystal of PEO, and the in situ imaging on the large (50 nm) NPs helps track the migration into the amorphous zones. We extend this AFM technique to estimate lamellar growth rates that correlate with spherulite growth rates determined by polarized light optical microscopy (PLOM) but at smaller undercoolings than are typical for PLOM.

Poly(hydroxy urethane)s (PHUs) based on 5-membered cyclic carbonates have emerged as sustainable alternatives to conventional isocyanate-based polyurethanes. However, while from the point of view of sustainability they represent an improvement, their properties are still not competitive with conventional polyurethanes. In this work, the potential of PHUs as reversible hot-melt adhesives is discussed. We found that with a judicious choice of reagents (i.e., the dicyclic carbonate and diamine), the detrimental hydrogen bonding between the soft segment of the chains and the pendant hydroxyl groups was partially avoided, thus imparting PHUs with hot-melt adhesion properties (i.e., adhesion at elevated temperatures and cohesiveness at a temperature lower than T g / T m ). The importance of a balanced hard to soft segment ratio, along with the relevance of the chain extender in the final properties, is highlighted. Addition of aliphatic diamines (HMDA, 1,12-DAD) resulted in rubbery materials, while the employment of cycloaliphatic (CBMA) or aromatic ones (MXDA, PXDA) led to materials with hot-melt adhesive properties. The thermoreversibility of all compositions was assessed by rebonding specimens after lap-shear tests. Lap-shear strength values that were comparable to the virgin adhesives were observed. The breaking and reformation of hydrogen bonding interactions was demonstrated by FTIR measurements at different temperatures, as well as by rheological frequency sweep experiments. In order to mitigate the negative impact of the low molar mass PHUs and to enhance the service temperature of the adhesives, a hybrid PHU was prepared by adding a small amount of an epoxy resin, which acts as a cross-linker. These hybrid PHUs maintain the thermoreversibility displayed by thermoplastic PHUs while providing better adhesion at elevated temperatures. We believe that this work provides some important insights into the design of PHU-based hot-melt adhesives., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Objectives: To examine the diagnostic yield of trio exome sequencing in fetuses with multiple structural defects with no pathogenic findings in cytogenetic and microarray analyses., Methods: We recruited 51 fetuses with two or more defects, non-immune fetal hydrops or fetal akinesia deformation syndrome|or fetal akinesia deformation sequence (FADS). Trio exome sequencing was performed on DNA from chorionic villi samples and parental blood. Detection of genomic variation and prioritization of clinically relevant variants was performed according to in-house standard operating procedures., Results: Median maternal and gestational age was 32.0 years and 21.0 weeks, respectively. Forty-three (84.3%) fetuses had two or more affected organ systems. The remaining fetuses had isolated fetal hydrops or FADS. In total, the exome analysis established the genetic cause for the clinical abnormalities in 22 (43.1%, 95% CI 29.4%-57.8%) pregnancies., Conclusions: In fetuses with multiple defects, hydrops or FADS and normal standard genetic results, trio exome sequencing has the potential to identify genetic anomalies in more than 40% of cases., (© 2022 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)