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Understanding core level shifts in aromatic compounds is crucial for the correct interpretation of x-ray photoelectron spectroscopy (XPS) of polycyclic aromatic hydrocarbons (PAHs), including acenes, as well as of styrenic polymers, which are increasingly relevant for the microelectronic industry, among other applications. The effect of delocalization through π aromatic systems on the stabilization of valence molecular orbitals has been widely investigated in the past. However, little has been reported on the impact on the deeper C1s core energy levels. In this work, we use first-principles calculations at the level of many body perturbation theory to compute the C1s binding energies of several aromatic systems. We report a C1s red shift in PAHs and acenes of increasing size, both in the gas phase and in the molecular crystal. C1s red shifts are also calculated for stacked benzene and naphthalene pairs at decreasing intermolecular distances. A C1s red shift is in addition found between oligomers of poly(p-hydroxystyrene) and polystyrene of increasing length, which we attribute to ring–ring interactions between the side-chains. The predicted shifts are larger than common instrumental errors and could, therefore, be detected in XPS experiments. [ABSTRACT FROM AUTHOR]

The folding of RNA and DNA strands plays crucial roles in biological systems and bionanotechnology. However, studying these processes with high-resolution numerical models is beyond current computational capabilities due to the timescales and system sizes involved. In this article, we present a new coarse-grained model for investigating the folding dynamics of nucleic acids. Our model represents three nucleotides with a patchy particle and is parameterized using well-established nearest-neighbor models. Thanks to the reduction of degrees of freedom and to a bond-swapping mechanism, our model allows for simulations at timescales and length scales that are currently inaccessible to more detailed models. To validate the performance of our model, we conducted extensive simulations of various systems: We examined the thermodynamics of DNA hairpins, capturing their stability and structural transitions, the folding of an MMTV pseudoknot, which is a complex RNA structure involved in viral replication, and also explored the folding of an RNA tile containing a k-type pseudoknot. Finally, we evaluated the performance of the new model in reproducing the melting temperatures of oligomers and the dependence on the toehold length of the displacement rate in toehold-mediated displacement processes, a key reaction used in molecular computing. All in all, the successful reproduction of experimental data and favorable comparisons with existing coarse-grained models validate the effectiveness of the new model. [ABSTRACT FROM AUTHOR]

Aβ aggregation leads to the formation of both insoluble amyloid fibrils and soluble oligomers. Understanding the structures of Aβ oligomers is important for delineating the mechanism of Aβ aggregation and developing effective therapeutics. Here, we use site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy to study Aβ42 oligomers prepared by using the protocol of Aβ-derived diffusible ligands. We obtained the EPR spectra of 37 Aβ42 oligomer samples, each spin-labeled at a unique residue position of the Aβ42 sequence. Analysis of the disordered EPR components shows that the N-terminal region has a lower local structural stability. Spin label mobility analysis reveals three structured segments at residues 9-11, 15-22, and 30-40. Intermolecular spin-spin interactions indicate a parallel in-register β-sheet structure, with residues 34-38 forming the structural core. Residues 16-21 also adopt the parallel in-register β-structure, albeit with weaker intermolecular packing. Our results suggest that there is a structural class of Aβ oligomers that adopt fibril-like conformations.

In tetracene, the energies of the lowest singlet excited state and twice that of the lowest triplet excited state are similar, allowing both down‐conversion (i.e., singlet fission, SF) and up‐conversion (i.e., triplet‐triplet annihilation up‐conversion, TTA‐UC) processes. Through‐space and through‐bond contributions to the inter‐tetracene coupling in purposefully designed oligomers play a crucial role in determining which of the two processes dominates. In this work, the focus is exclusively on SF in newly synthesized oligo‐tetracenes linked by conjugated [2.2]paracyclophane (PCP) building blocks. By choosing different PCP substitution patterns and by varying the degree of substitution the inter‐tetracene couplings are addressed. An independent variable is connecting the tetracences to the PCP at different positions to alter the through‐bond and through‐space coupling of the resulting oligo‐tetracenes. The novel oligo‐tetracenes are investigated by means of steady‐state and time‐resolved absorption and fluorescence spectroscopies with respect to the initial events of SF, that is, the transformation of a singlet excited state into a correlated triplet pair state. Briefly, through‐space couplings are profoundly weaker than through‐bond couplings that enable the correlated triplet pair state formation. If interactions are through‐space, correlated triplet pair state formation is turned off, while it is turned on if through‐bond interactions are operative. [ABSTRACT FROM AUTHOR]

Polycondensation and ring‐formation reactions are the main factors that cause instability in the molecular structure of commercial polyamide 6 (PA6) during melting. In this study, the mechanisms and interactions of the ring‐formation and polycondensation reactions induced by various factors were thoroughly investigated. The findings suggest that the average molecular weight of PA6 increased by 20.4% during melting. The total monomer and oligomer content increased by 79.2%, and the ring‐forming reaction was promoted with an increase in temperature. Moreover, a high concentration of the end‐amino in PA6 promoted the ring‐forming reaction, whereas similar concentrations of the end‐amino and end‐carboxyl groups were more conducive to the polycondensation reaction. In short, the nitrogen atoms in the end‐amino group on the PA6 molecular chain attack the carbonyl carbon at different sites, including the carbonyl carbon in the amide bond and the carbonyl carbon in the end‐carboxyl group, which is the key to the strength of the ring‐formation and polycondensation reactions. [ABSTRACT FROM AUTHOR]

NRCs are essential helper NLR (nucleotide-binding domain and leucine-rich repeat) proteins that execute immune responses triggered by sensor NLRs. The resting state of NbNRC2 was recently shown to be a homodimer, but the sensor-activated state remains unclear. Using cryo-EM, we determined the structure of sensor-activated NbNRC2, which forms a hexameric inflammasome-like resistosome. Mutagenesis of the oligomerization interface abolished immune signaling, confirming the functional significance of the NbNRC2 resistosome. Comparative structural analyses between the resting state homodimer and sensor-activated homohexamer revealed substantial rearrangements, providing insights into NLR activation mechanisms. Furthermore, structural comparisons between NbNRC2 hexamer and previously reported CC-NLR pentameric assemblies revealed features allowing an additional protomer integration. Using the NbNRC2 hexamer structure, we assessed the recently released AlphaFold 3 for predicting activated CC-NLR oligomers, revealing high-confidence modeling of NbNRC2 and other CC-NLR amino-terminal a1 helices, a region proven difficult to resolve structurally. Overall, our work sheds light on NLR activation mechanisms and expands understanding of NLR structural diversity. [ABSTRACT FROM AUTHOR]

The use of the laccase enzyme from the fungus Trametes versicolor, coupled with the mediator 1-hydroxybenzotriazole (1-HBT) has been shown to be effective for the biocatalytic conversion of a hexameric lignin model compound containing three of the most common linkages found in native lignin. Cleavage of the model takes place over a 24 hours period predominantly at the β-O-4 ether linkage to give a previously known β-5 dimer intermediate which in turn was rapidly consumed to further degradation products. There is also mass spectrometric evidence of repolymerisation of the β-5 dimer and other degradation intermediates to form higher oligomers. Mechanistic pathways to account for the major catalytic processes are proposed. [ABSTRACT FROM AUTHOR]

Synthetic duplexes with high stabilities have promising potential for mimicking biomolecular functions and developing supramolecular smart materials. Herein, we describe the synthesis and stimuli‐responsive properties of molecular duplexes derived from indolocarbazole–pyridine (I−P) oligomers. These duplexes adopt nonclassical helical structures, stabilized by I−P hydrogen‐bonding pairs in anhydrous chlorinated solvents. Notably, the longest duplex 62 (11‐mer)2 displays remarkable stability, forming twenty hydrogen bonds; its exchange energy barrier was determined to be ΔG≠=22.0 kcal ⋅ mol−1 at 75 °C in anhydrous (CDCl2)2. Upon the addition of water, a hydrated duplex 62 (11‐mer)2⊃10H2O was formed, with one water molecule inserted between each I−P hydrogen‐bonding pair. The Hill coefficient (n) for this process is 6.1, demonstrating extremely positive cooperativity. Conversely, the hydrated duplex 62 (11‐mer)2⊃10H2O was completely converted into the original anhydrous duplex 62 (11‐mer)2 when the temperature was increased. Interconversion between these two distinct duplexes can be repeatedly carried out by varying the temperature. Furthermore, reversible switching between hetero‐duplexes and homo‐duplexes was also demonstrated by controlling the temperature, with concomitant changes in the characteristic emission signals. [ABSTRACT FROM AUTHOR]

Discrete oligomers can be used to precisely evaluate the structure–property relationship and enable unique chiroptical activities, however, the role of stereochemical sequences on chirality transfer is still unclear. Herein, we report the successful synthesis of a series of sequence‐defined chiral azobenzene (Azo) oligomers via iterative stepwise chain growth strategy. Sequence‐defined stereoisomers with one single chiral (L or D) stereocenter at the α‐position, ω‐position and middle‐ (m−) position have completely different self‐assembly dynamics. ω‐positional stereocenter can effectively command all Azo building blocks to adopt a tilted π–π stacking along the helical superbundles, exhibiting the activation of chirality transfer. However, discrete oligomers with the stereocenter at other positions can only self‐assemble into non‐helical nanowires, accompanied by the deactivation of chirality transfer.Cooperative supramolecular interactions, including the π–π interaction between Azo units, the intermolecular hydrogen bonding and steric hindrance, are intrinsic driving forces for these differentiations. [ABSTRACT FROM AUTHOR]

Carbonized polymer dots (CPDs) have shown exceptional potential across a wide range of applications. However, their practical utilization is significantly greatly impeded by the lack of precise control over their structures and functionalities. Consequently, the development of controlled synthesis strategies for CPDs with well‐defined structures and tailored functionalities remains a critical challenge in the field. Here, the controlled synthesis of functional CPDs with reversible assembly properties via airflow‐assisted melt polymerization, followed by a one‐step post‐synthetic doping strategy, is reported. This synthetic approach achieves high product yield, uniform and tunable structures, as well as customized functionalities including solid‐state emission, enhanced catalytic performance (3.5–45 times higher than conventional methods), and selective gas storage in the resulting CPDs. The ability to tailor the properties of CPDs through controlled synthesis opens up new opportunities for their practical application in photocatalysis and gas storage. [ABSTRACT FROM AUTHOR]

A comprehensive molecular understanding of carbohydrate aggregation is key to optimize carbohydrate utilization and to engineer bioinspired analogues with tailored shapes and properties. However, the lack of well‐defined synthetic standards has substantially hampered advances in this field. Herein, we employ a phosphorylation‐assisted strategy to synthesize previously inaccessible long oligomers of cellulose, chitin, and xylan. These oligomers were subjected to enzyme‐triggered assembly (ETA) for the on‐demand formation of well‐defined carbohydrate nanomaterials, including elongated platelets, helical bundles, and hexagonal particles. Cryo‐electron microscopy and electron diffraction analysis provided molecular insights into the aggregation behavior of these oligosaccharides, establishing a direct connection between the resulting morphologies and the oligosaccharide primary sequence. Our findings demonstrate that ETA is a powerful approach to elucidate the intrinsic aggregation behavior of carbohydrates in nature. Moreover, the ability to access a diverse array of morphologies, expanded with a non‐natural sequence, underscores the potential of ETA, coupled with sequence design, as a robust tool for accessing programmable glycan architectures. [ABSTRACT FROM AUTHOR]

Molecular phosphorescence in the second near‐infrared window (NIR‐II, 1000–1700 nm) holds promise for deep‐tissue optical imaging with high contrast by overcoming background fluorescence interference. However, achieving bright and stable NIR‐II molecular phosphorescence suitable for biological applications remains a formidable challenge. Herein, we report a new series of symmetric isocyanorhodium(I) complexes that could form oligomers and exhibit bright, long‐lived (7–8 μs) phosphorescence in aqueous solution via metallophilic interaction. Ligand substituents with enhanced dispersion attraction and electron‐donating properties were explored to extend excitation/emission wavelengths and enhanced stability. Further binding the oligomers with fetal bovine serum (FBS) resulted in NIR‐II molecular phosphorescence with high quantum yields (up to 3.93 %) and long‐term stability in biological environments, enabling in vivo tracking of single‐macrophage dynamics and high‐contrast time‐resolved imaging. These results pave the way for the development of highly‐efficient NIR‐II molecular phosphorescence for biomedical applications. [ABSTRACT FROM AUTHOR]

The network structure and reactivity of suitable restoration agent consisting of silane coupling agents (SCAs) of the brittle walls of a cultural heritage site located underground in a desert area in Egypt were investigated using 1H pulsed nuclear magnetic resonance (pulse NMR). It should possess both high coagulation strength and ductility to ensure that it can withstand an earthquake; it should also contain ethoxy rather than methoxy groups, which generate toxic methanol. The solidification rate for the SCA or oligomer with ethoxy groups was lower than those with methoxy groups; however, the final polycondensates showed the same relaxation time (hardness). The difference spectrum was developed newly to analyze the network structure combined higher strength and ductility. The distribution of crosslinking degree of such polycondensates was narrow, and the amount of lower crosslinking degree was small. On the other hand, the distribution was wide in the polycondensates with ductility but lower strength. From the compression tests of model sand solidified with the restoration agent for both methoxy and ethoxy types showed the superior properties combined higher strength and ductility. The pulse NMR experiment was useful for estimating the solidification rate and the network structure. [ABSTRACT FROM AUTHOR]

Optoelectronic properties of linear π‐conjugated polymers/oligomers are of great importance for the fabrication of organic photonic and electronic devices. To this end, the π‐conjugated polymers/oligomers need to meet both optoelectronic and key structural properties in order to fulfill their implementation as active components. In particular, they need to possess low bandgap and high thermal, conformational, and photochemical stabilities. So far, several strategies have been developed to attain such requirements including the covalent and non‐covalent rigidification concepts of the π‐conjugated systems. On the basis of these findings, we describe herein the theoretical studies of novel series of covalently bridged derivatives demonstrating the benefits of the strategy. Comparison of these derivatives with compounds previously described in the literature highlights enhanced optoelectronic properties and behaviors that would be beneficial for the construction and development of new linear π‐conjugated polymers. [ABSTRACT FROM AUTHOR]

The understanding of the optical characteristics and the influence of thermally induced crystallization is vital to evaluate newly synthesized organic semiconductors for their potential applications. Variable‐angle spectroscopic ellipsometry (VASE) is employed to determine the complex dielectric function of two recently developed discrete oligomers based on naphthalene diimide (NDI) and bithiophene (T2), applying an anisotropic optical model. It is shown that the as‐cast films are optically near‐isotropic, while the annealed films exhibit pronounced anisotropies with respect to the orientation of the π−π* transition. Differences between the two distinct molecules are observed and discussed. The degree of optical anisotropy is quantified using the average molecular orientation angle φ, associated with the orientation of the π−π* transition dipole, and the related orientation order parameter S. The molecules are shown to form crystallites of several microns in size upon annealing. Imaging ellipsometry is thus additionally employed to study their optical anisotropy on a microscopic scale, and the agreement with results from macroscopic measurements is evaluated. [ABSTRACT FROM AUTHOR]

Synaptotagmin-1 (Syt1) is a calcium sensor that regulates synaptic vesicle fusion in synchronous neurotransmitter release. Syt1 interacts with negatively charged lipids and the SNARE complex to control the fusion event. However, it remains incompletely understood how Syt1 mediates Ca2+-trigged synaptic vesicle fusion. Here, we discovered that Syt1 undergoes liquid–liquid phase separation (LLPS) to form condensates both in vitro and in living cells. Syt1 condensates play a role in vesicle attachment to the PM and efficiently recruit SNAREs and complexin, which may facilitate the downstream synaptic vesicle fusion. We observed that Syt1 condensates undergo a liquid-to-gel-like phase transition, reflecting the formation of Syt1 oligomers. The phase transition can be blocked or reversed by Ca2+, confirming the essential role of Ca2+ in Syt1 oligomer disassembly. Finally, we showed that the Syt1 mutations causing Syt1-associated neurodevelopmental disorder impair the Ca2+- driven phase transition. These findings reveal that Syt1 undergoes LLPS and a Ca2+-sensitive phase transition, providing new insights into Syt1-mediated vesicle fusion. [ABSTRACT FROM AUTHOR]

Switchable adhesives are materials of utmost importance due to their capability of having their adhesion/cohesion properties reversibly triggered upon stimuli, allowing on‐demand surface attaching/detaching. Still, several challenges mainly associated with complex uncontrolled chemical processes hinders their production. In this study, it is found that unexpectedly vinyl ethers are able to react with thiols in the presence of a catalytic concentration of base, which allows the preparation of well‐defined phase‐separated switchable adhesives. Indeed, these findings show that base‐catalyzed thiol‐acrylate and thiol‐vinyl ether are highly orthogonal, making the acrylate reaction faster. This is explored to react in the first stage thiols with acrylates in the presence of vinyl ethers to end‐cap all the oligomers with stable vinyl ethers and suppress undesirable disulfide formation. In a second stage the UV‐triggered thiol‐ene “click reaction” is carried out, forming the network. It is shown that the network prepared by this approach presents superior adhesion due to greater backbone length, a controlled crosslinking motif, and better‐defined microphase separation. Additionally, the adhesives made by this strategy are thermo‐switchable due to the temperature‐triggered base‐catalyzed thioether dynamic covalent character at 200 °C. Despite providing superior adhesive properties, the proposed technology endows scalable, thermo‐switchable, and O2‐resistant adhesives with huge industrialization potential. [ABSTRACT FROM AUTHOR]

Misfolding and aggregation of TAR DNA‐binding protein, TDP‐43, is linked to devastating proteinopathies such as ALS. Therefore, targeting TDP‐43's aggregation is significant for therapeutics. Recently, green tea polyphenol, EGCG, was observed to promote non‐toxic TDP‐43 oligomer formation disallowing TDP‐43 aggregation. Here, we investigated if the anti‐aggregation effect of EGCG is mediated via EGCG's binding to TDP‐43. In silico molecular docking and molecular dynamics (MD) simulation suggest a strong binding of EGCG with TDP‐43's aggregation‐prone C‐terminal domain (CTD). Three replicas, each having 800 ns MD simulation of the EGCG‐TDP‐43‐CTD complex, yielded a high negative binding free energy (ΔG) inferring a stable complex formation. Simulation snapshots show that EGCG forms close and long‐lasting contacts with TDP‐43's Phe‐313 and Ala‐341 residues, which were previously identified for monomer recruitment in CTD's aggregation. Notably, stable physical interactions between TDP‐43 and EGCG were also detected in vitro using TTC staining and isothermal titration calorimetry which revealed a high‐affinity binding site of EGCG on TDP‐43 (Kd, 7.8 μM; ΔG, −6.9 kcal/mol). Additionally, TDP‐43 co‐incubated with EGCG was non‐cytotoxic when added to HEK293 cells. In summary, EGCG's binding to TDP‐43 and blocking of residues important for aggregation can be a possible mechanism of its anti‐aggregation effects on TDP‐43. [ABSTRACT FROM AUTHOR]

Linear chlorinated phosphazene acid is prepared using PCl5 and NH4Cl as raw materials. Using hexaethylcyclotrisiloxane as the monomer, 1,1,3,3-tetramethyldisiloxane or 1,3-divinyl-1,1,3,3-tetramethyldisiloxane as the end-capping agent, and linear chlorinated phosphazene acid as the catalyst, polydiethylsiloxane oligomers terminated with active Si-H or Si-CH=CH2 groups have been prepared. Using hexaethylcyclotrisiloxane and 1,3,5,7-octamethylcyclotetrasiloxane as comonomers, 1,1,3,3-tetramethyldisiloxane or hexamethyldisiloxane as the end-capping agent, or using hexaethylcyclotrisiloxane and octamethylcyclotetrasiloxane as comonomers, 1,1,3,3-tetramethyldisiloxane as the end-capping agent, copolymers containing active Si-H bonds and dimethylsiloxane segments have been prepared under the catalysis of linear chlorinated phosphazene acid. The effects of catalyst dosage, reaction temperature, reaction time, end-capping agent, and polymerization monomer dosage on polymer yield and structure were investigated. Using 300 ppm of linear chlorinated phosphazene acid, oligomers and copolymers containing an active Si-H bond and diethylsiloxane segment were prepared under mild conditions. The molecular weight of the obtained polymers was close to their designed values, but their PDI values were small. The highest yield of α, ω-bisdimethylsiloxyl-terminated PDES oligomers reached 93%. Using oligomers and copolymers containing Si-H bonds and diethylsiloxane segments as crosslinkers, a silicone gel containing diethylsiloxane segments was prepared by hydrosilylation reaction. With the introduction of a diethylsiloxane segment, the glass transition temperature of the silicone gel decreased relative to that of the PDMS oligomer, but the temperature at 5% weight loss in nitrogen atmosphere decreased from 347 °C to 312 °C. The mechanism of the ring-opening polymerization of hexaethylcyclotrisiloxane catalyzed by linear chlorinated phosphazene acid is also discussed. [ABSTRACT FROM AUTHOR]

Chemical degradation of PET with natural rubber was carried out. The product obtained was characterized by FTIR, and it was found that the intensity of the vibration signal of the carbonyl group (1719 cm−1) depends on the mass of rubber used in the reaction and not on the PET degradation products, reaching an adequate mass ratio of Rubber/PET = 4. The chemical structure of the product obtained was rubber chains with end groups of ethylene terephthalate oligomers. The pasting properties of the banana starch were modified with the resulting product, affecting its gelatinization process and the maximum viscosity value of 5.78 Pa.s to 1.50 Pa.s at a temperature of 25 °C. Starch degraded PET-rubber films have better mechanical properties than starch-only films. Additionally, these films degrade at lower temperatures (491 to 469 °C) than starch-only films. The ability of these films to conduct electrical current increases up to 25.52% with respect to that of the native starch film. SEM morphology of the starch degraded PET-rubber films shows the formation of clusters, which causes the films to present adhesive characteristics, indicating that these films have a high potential for application in the adhesive and paint industry as biodegradable materials. [ABSTRACT FROM AUTHOR]

[Display omitted] • We developed an aggressive multiple system atrophy-cerebellar variant mouse model. • In mice, human α-synuclein was expressed in oligodendrocytes via Tet-Off regulation. • We observed age-dependent phosphorylated α-synuclein deposition in glia and neurons. • Marked microglial and astrocytic reaction with inflammation in demyelinated lesions. • α-Synuclein oligomers spread from oligodendrocytes to astrocytes and neurons. Multiple system atrophy (MSA) is a severe α-synucleinopathy facilitated by glial reactions; the cerebellar variant (MSA-C) preferentially involves olivopontocerebellar fibres with conspicuous demyelination. A lack of aggressive models that preferentially involve olivopontocerebellar tracts in adulthood has hindered our understanding of the mechanisms of demyelination and neuroaxonal loss, and thus the development of effective treatments for MSA. We therefore aimed to develop a rapidly progressive mouse model that recaptures MSA-C pathology. We crossed Plp1 -tTA and tetO- SNCA*A53T mice to generate Plp1 -tTA::tetO- SNCA*A53T bi-transgenic mice, in which human A53T α-synuclein—a mutant protein with enhanced aggregability—was specifically produced in the oligodendrocytes of adult mice using Tet-Off regulation. These bi-transgenic mice expressed mutant α-synuclein from 8 weeks of age, when doxycycline was removed from the diet. All bi-transgenic mice presented rapidly progressive motor deterioration, with wide-based ataxic gait around 22 weeks of age and death around 30 weeks of age. They also had prominent demyelination in the brainstem/cerebellum. Double immunostaining demonstrated that myelin basic protein was markedly decreased in areas in which SM132, an axonal marker, was relatively preserved. Demyelinating lesions exhibited marked ionised calcium-binding adaptor molecule 1-, arginase-1-, and toll-like receptor 2-positive microglial reactivity and glial fibrillary acidic protein-positive astrocytic reactivity. Microarray analysis revealed a strong inflammatory response and cytokine/chemokine production in bi-transgenic mice. Neuronal nuclei-positive neuronal loss and patchy microtubule-associated protein 2-positive dendritic loss became prominent at 30 weeks of age. However, a perceived decrease in tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta in bi-transgenic mice compared with wild-type mice was not significant, even at 30 weeks of age. Wild-type, Plp1 -tTA, and tetO- SNCA*A53T mice developed neither motor deficits nor demyelination. In bi-transgenic mice, double immunostaining revealed human α-synuclein accumulation in neurite outgrowth inhibitor A (Nogo-A)-positive oligodendrocytes beginning at 9 weeks of age; its expression was further increased at 10 to 12 weeks, and these increased levels were maintained at 12, 24, and 30 weeks. In an α-synuclein-proximity ligation assay, α-synuclein oligomers first appeared in brainstem oligodendrocytes as early as 9 weeks of age; they then spread to astrocytes, neuropil, and neurons at 12 and 16 weeks of age. α-Synuclein oligomers in the brainstem neuropil were most abundant at 16 weeks of age and decreased thereafter; however, those in Purkinje cells successively increased until 30 weeks of age. Double immunostaining revealed the presence of phosphorylated α-synuclein in Nogo-A-positive oligodendrocytes in the brainstem/cerebellum as early as 9 weeks of age. In quantitative assessments, phosphorylated α-synuclein gradually and successively accumulated at 12, 24, and 30 weeks in bi-transgenic mice. By contrast, no phosphorylated α-synuclein was detected in wild-type, tetO- SNCA*A53T , or Plp1 -tTA mice at any age examined. Pronounced demyelination and tubulin polymerisation, promoting protein-positive oligodendrocytic loss, was closely associated with phosphorylated α-synuclein aggregates at 24 and 30 weeks of age. Early inhibition of mutant α-synuclein expression by doxycycline diet at 23 weeks led to fully recovered demyelination; inhibition at 27 weeks led to persistent demyelination with glial reactions, despite resolving phosphorylated α-synuclein aggregates. In conclusion, our bi-transgenic mice exhibited progressively increasing demyelination and neuroaxonal loss in the brainstem/cerebellum, with rapidly progressive motor deterioration in adulthood. These mice showed marked microglial and astrocytic reactions with inflammation that was closely associated with phosphorylated α-synuclein aggregates. These features closely mimic human MSA-C pathology. Notably, our model is the first to suggest that α-synuclein oligomers may spread from oligodendrocytes to neurons in transgenic mice with human α-synuclein expression in oligodendrocytes. This model of MSA is therefore particularly useful for elucidating the in vivo mechanisms of α-synuclein spreading from glia to neurons, and for developing therapies that target glial reactions and/or α-synuclein oligomer spreading and aggregate formation in MSA. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) increases the long-term risk of neurodegenerative diseases, including Alzheimer's disease (AD). Here, we demonstrate that protein variant pathology generated in brain tissue of an experimental TBI mouse model is similar to protein variant pathology observed during early stages of AD, and that subacute accumulation of AD associated variants of amyloid beta (Aβ) and tau in the TBI mouse model correlated with behavioral deficits. Male C57BL/6 mice were subjected to midline fluid percussion injury or to sham injury, after which sensorimotor function (rotarod, neurological severity score), cognitive deficit (novel object recognition), and affective deficits (elevated plus maze, forced swim task) were assessed post-injury (DPI). Protein pathology at 7, 14, and 28 DPI was measured in multiple brain regions using an immunostain panel of reagents selectively targeting different neurodegenerative disease-related variants of Aβ, tau, TDP-43, and alpha-synuclein. Overall, TBI resulted in sensorimotor deficits and accumulation of AD-related protein variant pathology near the impact site, both of which returned to sham levels by 14 DPI. Individual mice, however, showed persistent behavioral deficits and/or accumulation of toxic protein variants at 28 DPI. Behavioral outcomes of each mouse were correlated with levels of seven different protein variants in ten brain regions at specific DPI. Out of 21 significant correlations between protein variant levels and behavioral deficits, 18 were with variants of Aβ or tau. Correlations at 28 DPI were all between a single Aβ or tau variant, both of which are strongly associated with human AD cases. These data provide a direct mechanistic link between protein pathology resulting from TBI and the hallmarks of AD. [ABSTRACT FROM AUTHOR]

The self-assembly of highly functionalized phenanthrene–DNA conjugates into supramolecular nanostructures is presented. DNA oligomers modified with phenanthrene residues at the 3′-end and internal positions self-assemble into spherical nanostructures. The nanospheres exhibit light-harvesting properties. Upon irradiation of phenanthrene, the excitation energy is transferred along phenanthrene units, resulting in phenanthrene–pyrene exciplex formation. [ABSTRACT FROM AUTHOR]

Polyether ether ketone (PEEK) oligomers were synthesized through a solution reaction using sulfolane as a solvent, the resultant oligomers were employed to synthesize high melt viscosity PEEK through solid-state polymerization in a twin-roller mixer. The effects of polymerization time on the crystallization properties, thermal properties and flowability of PEEK were investigated. The results indicated that both the degree of crystallinity and crystallization completeness of PEEK decreased with an increase in polymerization time. The degree of crystallinity of PEEK after polymerization for 5 h decreased by about 31. 4 % as compared to that of the oligomers. All samples possessed residual weights greater than 50 % at 900 °C, indicating outstanding thermal stability. In addition, the melt viscosities of PEEKs increased significantly with an increase in the polymerization time, and it reached approximately 13-360 times as high as that of oligomers. [ABSTRACT FROM AUTHOR]

Electroorganic synthesis has become an exciting tool for the asymmetric conversion of pro-chiral compounds. Herein, we introduced a wireless methodology based on bipolar electrochemistry in synergy with the enantioselective capabilities of inherently chiral oligomers to induce an umpolung chirality transfer. This was exemplified by the electro-conversion of a racemic mixture of lansoprazole to an enantio-enriched solution of a single antipode. [ABSTRACT FROM AUTHOR]

Background: The insoluble tangles of alpha-synuclein (α-syn) protein in the nigrostriatal circuit, characteristic of synucleinopathy, originate from low molecular weight oligomers, whose appearance and dissemination are related to neuroinflammation. These oligomeric forms of α-syn are considered highly cytotoxic but transient, so knowing the timing in which they appear remains challenging. Therefore, this study aimed to analyze the abundance of oligomeric forms of α-syn and tyrosine hydroxylase (TH) between 3 and 7 days after inducing neuroinflammation with lipopolysaccharide (LPS). Methods and results: LPS (2.5 µg/2.5 µL) was stereotaxically injected in the substantia nigra (SN) of adult male Wistar rats, which were sacrificed 3, 5 and 7 days after this intervention. The brains were processed for semi quantitative Western blot, along with brains from control and sham animals. Our results show an increased expression of α-syn monomer (15 kDa) only 3 days after LPS infusion, and the formation of 50 KDa and 60 kDa α-syn oligomers in the SN and striatum (STR) between 3 and 7 days after LPS infusion. Furthermore, the presence of these oligomers was accompanied by a decrease in the expression of nigral TH. Conclusion: These findings highlight the rapidity with which potentially toxic forms of α-syn appear in the nigrostriatal circuit after a neuroinflammatory challenge, in addition to allowing us to identify specific oligomers and a temporal relation with neurodegeneration of TH-positive cells. Knowledge of the timing and location in which these small oligomers appear is essential to developing therapeutic strategies to prevent its formation. [ABSTRACT FROM AUTHOR]

Superhydrophobic strain sensors are highly promising for human motion and health monitoring in wet environments. However, the introduction of superhydrophobicity inevitably alters the mechanical and conductive properties of these sensors, affecting sensing performance and limiting behavior monitoring. Here, we developed an alkylated MXene–carbon nanotube/microfiber composite material (AMNCM) that is simultaneously flexible, superhydrophobic, and senses properties. Comprising a commercially available fabric substrate that is coated with a functional network of alkylated MXene/multi-walled carbon nanotubes and epoxy–silicone oligomers, the AMNCM offers high mechanical and chemical robustness, maintaining high conductivity and strain sensing properties. Furthermore, the AMNCM strain sensor achieves a gauge factor of up to 51.68 within a strain range of 80–100%, and exhibits rapid response times (125 ms) and long-term stability under cyclic stretching, while also displaying superior direct/indirect anti-fouling capabilities. These properties position the AMNCM as a promising candidate for next-generation wearable devices designed for advanced environmental interactions and human activity monitoring. [ABSTRACT FROM AUTHOR]

Escherichia coli small heat‐shock protein IbpB (MW: 16 KDa) has holding chaperone activity and is present in cells at 30 °C as two large oligomers of MW 2.0–3.0 MDa and 600–700 KDa. We report here about the presence of two additional oligomers of MW around 400 and 130 KDa in cells under heat‐stress at 50 °C. These two smaller oligomers possess the most chaperone activity, as observed from the extent of inhibition of inactivation and aggregation separately, of L‐Lactate dehydrogenase in the presence of the individual oligomers at 52 and 60 °C, respectively. It is suggested here that the two larger oligomers act as poorly active storage forms, which under heat stress dissociate partially into smaller oligomers with high holdase activity. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Side‐chain engineering has emerged as a highly effective strategy for tailoring the aggregation behavior and charge transport properties of non‐fullerene small molecule acceptors (SMAs). In this study, we designed and synthesized two SMAs, namely BTPSi‐Bu and BTPSi‐Pr, respectively incorporating tributylsilyloxy and triisopropylsilyloxy groups in their outer positions. Notably, BTPSi‐Bu exhibited better planarity, crystallization, and favorable phase separation when paired with PM6 donor polymer compared to its counterpart, BTPSi‐Pr. The resulting organic solar cells, utilizing the PM6:BTPSi‐Bu blend, demonstrated a remarkable power conversion efficiency of 17.41% and a high open‐circuit voltage of 0.859 V. These findings underscore the significance of integrating trialkylsilyloxy side chains into SMAs as a rational design approach for enhancing the performance of photovoltaic systems. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Side‐chain engineering has emerged as a highly effective strategy for tailoring the aggregation behavior and charge transport properties of non‐fullerene small molecule acceptors (SMAs). In this study, we designed and synthesized two SMAs, namely BTPSi‐Bu and BTPSi‐Pr, respectively incorporating tributylsilyloxy and triisopropylsilyloxy groups in their outer positions. Notably, BTPSi‐Bu exhibited better planarity, crystallization, and favorable phase separation when paired with PM6 donor polymer compared to its counterpart, BTPSi‐Pr. The resulting organic solar cells, utilizing the PM6:BTPSi‐Bu blend, demonstrated a remarkable power conversion efficiency of 17.41% and a high open‐circuit voltage of 0.859 V. These findings underscore the significance of integrating trialkylsilyloxy side chains into SMAs as a rational design approach for enhancing the performance of photovoltaic systems. [ABSTRACT FROM AUTHOR]

Organic donor‐acceptor (D‐A) conjugated macrocycles, which are regarded as terminal‐less counterparts of linear π‐systems, have emerged as a promising class material for organic optoelectronics. Nevertheless, circular symmetry generally makes the lowest electronic transition symmetry forbidden, which is a huge obstacle to developing bright near‐infrared macrocyclic dyes. Here, a series of cyclic D‐A oligomers (e.g., cyclic D‐A dimer ([2]C16TT‐TPA), trimer ([3]C16TT‐TPA), and tetramer ([4]C16TT‐TPA)) are synthesized in which triphenylamine and 4,6‐bisthienylthieno[3,4‐c]thiadiazole are alternately coupled. The ring size‐dependent photophysical properties of D‐A cyclic oligomers, such as photoluminescence quantum yield and radiative decay rate, are revealed through both experiments and theoretical calculations. Owing to conformational flexibility and dominant twisted conformation, [3]C16TT‐TPA shows increasing S0→S1 transition and thereby produces a champion photoluminescence quantum yield of 6.35  % in solution with emission beyond 900 nm, much higher than that of acyclic oligomer (1.56%). Furthermore, the [3]C16TT‐TPA‐based organic light‐emitting diode achieves a relatively high external quantum efficiency of 0.15% with a maximum radiance of 2897 mW sr−1 m−2. The study not only provides insights into the mechanism of ring size‐dependent photophysical properties but also demonstrates the potential of D–A cyclic oligomers for bright near‐infrared emitters. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cetuximab, formulated in Erbitux® (5 mg/mL), is a therapeutic monoclonal antibody (mAb) widely used in several cancer treatments. Currently, there is insufficient knowledge about the behavior of cetuximab with regard to the risk associated with its routine handling or unintentional mishandling in hospitals. Forced degradation studies can simulate these conditions and provide insights into the biophysical and biochemical properties of mAbs. Methods: In this study, we conducted a deep physicochemical and functional characterization of the critical quality attributes of cetuximab in control samples and under controlled degraded conditions, including freeze–thaw cycles, heat, agitation, and light exposure. To achieve this purpose, we used a set of proper analytical techniques, including CD, IT-FS, DLS, SE/UHPLC-UV, UHPLC-MS/MS, and ELISA, to check functionality based on antigen–antibody binding. Results: The results revealed that light exposure was the stress stimuli with the greatest impact on the drug product, leading to the formation of non-natural oligomers, fragmentation, and oxidation of methionine residues. Additionally, cetuximab (Erbitux®, 5 mg/mL) showed a tendency to aggregate when submitted to 60 °C for 1 h. In terms of functionality, cetuximab (Erbitux®, 5 mg/mL) samples were found to be affected when subjected to freeze–thaw cycles, 60 °C (1 h), and when exposed to light (daylight with room temperature excursion and accelerated light exposure). Conclusions: Thus, we suggest that Erbitux® (5 mg/mL) should be shielded from these environmental conditions, as they compromise both the safety and efficacy of the drug product. [ABSTRACT FROM AUTHOR]

During the hydrolysis process of caprolactam to produce polyamide 6, a considerable number of cyclic oligomers are inevitably formed. Among these, the cyclic dimer, with its propensity for aggregation, poses significant challenges to both process safety and product quality. Thus, understanding the characteristics of cyclic oligomers is crucial for ensuring process safety and enhancing product quality. This paper employs a personification approach to vividly describe the properties of cyclic oligomers, elucidating the formation mechanism of cyclic dimers, delineating the behavior of crystal phase transitions, and highlighting the detrimental effects of cyclic dimers on industrial production. Moreover, it proposes methods for process optimization. [ABSTRACT FROM AUTHOR]

[Display omitted] Hypothesis : Understanding the rules that control the assembly of nanostructured soft materials at interfaces is central to many applications. We hypothesize that electrolytes can be used to alter the hydration shell of amphiphilic oligomers at the air-aqueous interface of Langmuir films, thereby providing a means to control the formation of emergent nanostructures. Experiments : Three representative salts – (NaF, NaCl, NaSCN) were studied for mediating the self-assembly of oligodimethylsiloxane methylimidazolium (ODMS-MIM+) amphiphiles in Langmuir films. The effects of the different salts on the nanostructure assembly of these films were probed using vibrational sum frequency generation (SFG) spectroscopy and Langmuir trough techniques. Experimental data were supported by atomistic molecular dynamic simulations. Findings : Langmuir trough surface pressure – area isotherms suggested a surprising effect on oligomer assembly, whereby the presence of anions affects the stability of the interfacial layer irrespective of their surface propensities. In contrast, SFG results implied a strong anion effect that parallels the surface activity of anions. These seemingly contradictory trends are explained by anion driven tail dehydration resulting in increasingly heterogeneous systems with entangled ODMS tails and appreciable anion penetration into the complex interfacial layer comprised of headgroups, tails, and interfacial water molecules. These findings provide physical and chemical insight for tuning a wide range of interfacial assemblies. [ABSTRACT FROM AUTHOR]

Nano-plastics have been found in snow and evidence shows that they can act as nuclei. The aerosol water-uptake ability is an important property that will determine wet deposition, a potential main route for nano-plastics to fall to the ground. In this work, we measure the hygroscopicity of three nano-plastics: low-density polyethylene (LDPE), polyethylene terephthalate (PET) and polyvinyl chloride (PVC), and a fourth compound, cellulose, with in-situ aerosol techniques via a cloud condensation nuclei counter. Cellulose is a high-molecular weight compound and a main component of commonly used paper products. Ultrafine nano-plastic particles in the range of 20 to 200 nm are explored. Nano-plastic materials LDPE, PET, and PVC form droplets more readily than cellulose nanoparticles. The high hygroscopicity of nano-plastics indicates that the nano-plastics are either oligomers or a polymer with properties for water adsorption. Furthermore, a single parameter hygroscopicity, κ, derived from different droplet activation models (Flory Huggins Köhler and Frenkel-Halsey-Hill adsorption theory) are reported. Moreover, the molecular weights of the leached oligomers are predicted by Flory Huggins Köhler theory assuming ideal polymer mixing. The observed intrinsic hygroscopicity is size-dependent, hence the adsorption-based hygroscopicity model could be applied. Nano-plastics can be incorporated into clouds, transported globally, and may also be removed from the atmosphere via wet deposition processes. The analysis of hygroscopicity help estimating the lifetime and transport of nano-plastic particles in the atmosphere. [ABSTRACT FROM AUTHOR]

In the last few years, there have been notable developments in organic solar cells using both small molecule donor and acceptor. It has been noted that adding halogens to the end groups of small molecules could enhance the film structure and, consequently, the performance of the devices. In this study, three novel small molecule donors are created. The molecules include a vinyl‐CPDT oligomer with three units, with end‐caps made up of indanedione groups and containing four H, four Cl, and four F substituents. The purpose of the study is to investigate how the halogen substituent affects the photovoltaic characteristics of binary devices made with the non‐fullerene acceptor (NFA) TOCR2 as the acceptor. Having the halogen in the device enhances its effectiveness, and FG5, which has 4‐Cl substituents in the end groups, shows the highest efficiency among all devices with a PCE of 14.39%. Incredibly, the ternary device that is created in normal atmospheric conditions with chloro‐substituted FG5 as the donor, TOCR2 as the acceptor, and the wide band gap NFA DICTF as the third element shows significantly improved efficiency, achieving PCE values of up to 16.35%. [ABSTRACT FROM AUTHOR]

The microtubule associated protein, tau, is implicated in a multitude of neurodegenerative disorders that are collectively termed as tauopathies. These disorders are characterized by the presence of tau aggregates within the brain of afflicted individuals. Mutations within the MAPT gene that encodes the tau protein form the genetic backdrop for familial forms of tauopathies, such as frontotemporal dementia (FTD), but the molecular consequences of such alterations and their pathological effects are unclear. We sought to investigate the conformational properties of the aggregates of three tau mutants: A152T, P301L, and R406W, all implicated within FTD, and compare them to those of the native form (WT‐Tau 2N4R). Our immunochemical analysis reveals that mutants and WT tau oligomers exhibit similar affinity for conformation‐specific antibodies but have distinct morphology and secondary structure. Additionally, these oligomers possess different dye‐binding properties and varying sensitivity to proteolytic processing. These results point to conformational variety among them. We then tested the ability of the mutant oligomers to cross‐seed the aggregation of WT tau monomer. Using similar array of experiments, we found that cross‐seeding with mutant aggregates leads to the formation of conformationally unique WT oligomers. The results discussed in this paper provide a novel perspective on the structural properties of oligomeric forms of WT tau 2N4R and its mutant, along with shedding some light on their cross‐seeding behavior. [ABSTRACT FROM AUTHOR]

N-Alkylated oligo- and poly(p-benzamide)s exist as dynamic helical structures with all-cis amide conformation. Imidazole N-alkylated amides also show cis conformational preference, but their major conformer is changed from cis to trans by addition of acid. Here, based on those findings, we designed and synthesized aromatic triamides 3 and hexaamides 4 containing an imidazole ring as candidate foldamers anticipated to exhibit acidinduced conformational change. X-ray structure analysis of oligomer 3c showed that it takes all-cis conformation in the crystal. In solution, all the oligoamides examined existed as an equilibrium mixture of 4 conformers, among which the major conformer was the folded all-cis structure as judged from the low-temperature ¹H NMR spectra. When trifluoroacetic acid-d was added to a solution of the oligoamides in methylene chlorided2, only 2 conformers were observed in the low-temperature ¹H NMR spectra, and the major conformer was the (trans, cis) form with respect to the amide bonds of the imidazole at the 4 and 2 positions. Experimental and theoretical analysis of the CD spectra indicated that the conformation of hexaamides 4 changes upon the addition of acid. Our results suggest that N-alkylated imidazole amide can serve as a key structural motif for the construction of foldamers with acid-switchable conformation. [ABSTRACT FROM AUTHOR]

We synthesized a "cyborg protein," wherein a synthetic molecule partially substitutes the main peptide chain by linking 2 protein domains with a synthetic oligomer. Green fluorescent protein (GFP) served as the model for constructing the cyborg proteins. We prepared circularly permuted GFP (cpGFP) with new termini between β10 and β11, where the original N- and C-termini were linked by a cleavable peptide loop. The cyborg GFP was constructed from cpGFP by linking the β10 and β11 with oligo(ethylene glycol) (OEG) using maleimide-cysteine couplings, followed by the enzymatic cleavage of the N- and C-termini linking loop by thrombin. With the help of machine learning, we were able to obtain the cpGFP mutants that significantly alter the fluorescence intensity (53% increase) by thrombin treatment, which splits cpGFP into 2 fragments (fragmented GFP), and by heat shock. When the cyborg GFP was constructed using this mutant, the fluorescence intensity increased by 13% after heat treatment, similar to cpGFP (33% increase), and the behavior was significantly different from that of the fragmented GFP. This result suggests the possibility that the OEG chain in the cyborg protein plays a similar role to the peptide in the main chain of the protein. [ABSTRACT FROM AUTHOR]

Time-resolved spectroscopy is commonly used to study diverse phenomena in chemistry, biology, and physics. Pump–probe experiments and coherent two-dimensional (2D) spectroscopy have resolved site-to-site energy transfer, visualized electronic couplings, and much more. In both techniques, the lowest-order signal, in a perturbative expansion of the polarization, is of third order in the electric field, which we call a one-quantum (1Q) signal because in 2D spectroscopy it oscillates in the coherence time with the excitation frequency. There is also a two-quantum (2Q) signal that oscillates in the coherence time at twice the fundamental frequency and is fifth order in the electric field. We demonstrate that the appearance of the 2Q signal guarantees that the 1Q signal is contaminated by non-negligible fifth-order interactions. We derive an analytical connection between an nQ signal and (2n + 1)th-order contaminations of an rQ (with r < n) signal by studying Feynman diagrams of all contributions. We demonstrate that by performing partial integrations along the excitation axis in 2D spectra, we can obtain clean rQ signals free of higher-order artifacts. We exemplify the technique using optical 2D spectroscopy on squaraine oligomers, showing clean extraction of the third-order signal. We further demonstrate the analytical connection with higher-order pump–probe spectroscopy and compare both techniques experimentally. Our approach demonstrates the full power of higher-order pump–probe and 2D spectroscopy to investigate multi-particle interactions in coupled systems. [ABSTRACT FROM AUTHOR]

Ambient hydrocarbons adsorbed on the contact surface of nanoelectromechanical (NEM) switches would impact its performance. In this study, we utilized reactive molecular dynamics simulations to investigate the cyclic contact/separation process of Pt(111)/C2H2/Pt(111) systems. Our results demonstrate that substrate damage decreases as acetylene coverage increases from sub-monolayer to multilayer. This suppression occurs due to the presence of acetylene molecules, which can suppress direct (Pt–Pt connection) and indirect (Pt–(Cx)–Pt-like connection) interfacial bonding between the two substrates, depending on their coverage. Moreover, we observed the formation of chain-like oligomers after multiple contact/separation simulations in the monolayer model, much more significantly compared with the sub-monolayer and multilayer models. These oligomers arise from polymerization reactions among fragmented acetylene molecules, primarily formed through acetylene dehydrogenation. In the sub-monolayer model, numerous transferred Pt atoms at the interface hinder bonding between acetylene fragments, whereas in the multilayer model, only a few acetylene fragments form during the contact process, due to the well-organized and dense acetylene layer adsorbed on the substrate surfaces. These insights shed light on the atomic-scale mechanisms underlying substrate damage and chain-like oligomers formation in metal NEM switches. [ABSTRACT FROM AUTHOR]

Synucleinopathies are neurodegenerative diseases characterized by the accumulation of α-synuclein protein aggregates in the neurons and glial cells. Both ex vivo and in vitro α-synuclein fibrils tend to show polymorphism. Polymorphism results in structure variations among fibrils originating from a single polypeptide/protein. The polymorphs usually have different biophysical, biochemical and pathogenic properties. The various pathologies of a single disease might be associated with distinct polymorphs. Similarly, in the case of different synucleinopathies, each condition might be associated with a different polymorph. Fibril formation is a nucleation-dependent process involving the formation of transient and heterogeneous intermediates from monomers. Polymorphs are believed to arise from heterogeneous oligomer populations because of distinct selection mechanisms in different conditions. To test this hypothesis, we isolated and incubated different intermediates during in vitro fibrillization of α-synuclein to form different polymorphs. Here, we report 13C and 15N chemical shifts and the secondary structure of fibrils prepared from the helical intermediate using solid-state nuclear magnetic spectroscopy. [ABSTRACT FROM AUTHOR]

Poly(vinyl alcohol) (PVA) has ice binding and ice nucleating properties. Here, we explore the dependence of the molecular size of PVA on its ice nucleation activity. For this purpose, we studied ice nucleation in aqueous solutions of PVA samples with molar masses ranging from 370 to 145 000 g mol−1, with a particular focus on oligomer samples with low molar mass. The experiments employed a novel microfluidic setup that is a follow-up on the previous WeIzmann Supercooled Droplets Observation on a Microarray (WISDOM) design by Reicher et al. The modified setup introduced and characterized here, termed nanoliter Bielefeld Ice Nucleation ARraY (nanoBINARY), uses droplet microfluidics with droplets (96 ± 4) µm in diameter and a fluorinated continuous oil phase and surfactant. A comparison of homogeneous and heterogeneous ice nucleation data obtained with nanoBINARY to those obtained with WISDOM shows very good agreement, underpinning its ability to study low-temperature ice nucleators as well as homogeneous ice nucleation due to the low background of impurities. The experiments on aqueous PVA solutions revealed that the ice nucleation activity of shorter PVA chains strongly decreases with a decrease in molar mass. While the cumulative number of ice nucleating sites per mass nm of polymers with different molar masses is the same, it becomes smaller for oligomers and completely vanishes for dimer and monomer representatives such as 1,3-butanediol, propan-2-ol, and ethanol, most likely because these molecules become too small to effectively stabilize the critical ice embryo. Overall, our results are consistent with PVA polymers and oligomers acting as heterogeneous ice nucleators. [ABSTRACT FROM AUTHOR]

Abstract Islet amyloid polypeptide (IAPP) is co-secreted with insulin from pancreatic ß-cells. Its oligomerisation is regarded as disease driving force in type 2 diabetes (T2D) pathology. Up to now, IAPP oligomers have been detected in affected tissues. IAPP oligomer concentrations in blood have not been analysed so far. Using the IAPP single-oligomer-sensitive and monomer-insensitive surface-based fluorescence intensity distribution analysis (sFIDA) technology, levels of IAPP oligomers in blood plasma from healthy controls and people with T2D in different disease stages where determined. Subsequently, the level of IAPP oligomerisation was introduced as the ratio between the IAPP oligomers determined with sFIDA and the total IAPP concentration determined with ELISA. Highest oligomerisation levels were detected in plasma of people with T2D without late complication and without insulin therapy. Their levels stand out significantly from the control group. Healthy controls presented with the lowest oligomerisation levels in plasma. In people with T2D without complications, IAPP oligomerisation levels correlated with disease duration. The results clearly demonstrate that IAPP oligomerisation in insulin-naïve patients correlates with duration of T2D. Although a correlation per se does not identify, which is cause and what is consequence, this result supports the hypothesis that IAPP aggregation is the driving factor of T2D development and progression. The alternative and conventional hypothesis explains development of T2D with increasing insulin resistance causing exhaustion of pancreatic ß-cells due to over-secretion of insulin, and thus IAPP, too, resulting in subsequent IAPP aggregation and fibril deposition in the pancreas. Further experiments and comparative analyses with primary tissues are warranted.

Digital information encoded in polymers has been exclusively decoded by mass spectrometry. However, the size limit of analytes in mass spectrometry restricts the storage capacity per chain. In addition, sequential decoding hinders random access to the bits of interest without full‐chain sequencing. Here we report the shotgun sequencing of a 512‐mer sequence‐defined polymer whose molecular weight (57.3 kDa) far exceeds the analytical limit of mass spectrometry. A 4‐bit fragmentation code was implemented at aperiodic positions during the synthetic encoding of 512‐bit information without affecting storage capacity per chain. Upon activating the fragmentation code, the polymer chain splits into 18 oligomers, which could be individually decoded by tandem‐mass sequencing. These sequences were computationally reconstructed into a full sequence using an error‐detection method. The proposed sequencing method eliminates the storage limit of a single polymer chain and allows random access to the bits of interest without full‐chain sequencing. [ABSTRACT FROM AUTHOR]

The synthetic methodology for the preparation of photoresponsive dioxazaborocanes‐containing oligomers is developed. It relies on the transformation of the (diisopropylamino)boryl group (−BH(NiPr2)) into a dioxazaborocane unit in the presence of β‐aminodiols and involves a bis‐borylated dithienylethene photochromic unit. The photophysical properties of the obtained oligomers are evaluated as well as their processability for the preparation of spin‐coated films. The photomechanical behavior of the resulting films is assessed via displacement tracking profile. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common age-associated neurodegenerative disorder, characterized by progressive cognitive decline, memory impairment, and structural brain changes, primarily involving Aβ plaques and neurofibrillary tangles of hyperphosphorylated tau protein. Recent research highlights the significance of smaller Aβ and Tau oligomeric aggregates (AβO and TauO, respectively) in synaptic dysfunction and disease progression. Calcineurin (CaN), a key calcium/calmodulin-dependent player in regulating synaptic function in the central nervous system (CNS) is implicated in mediating detrimental effects of AβO on synapses and memory function in AD. This study aims to investigate the specific impact of CaN on both exogenous and endogenous TauO through the acute and chronic inhibition of CaN. We previously demonstrated the protective effect against AD of the immunosuppressant CaN inhibitor, FK506, but its influence on TauO remains unclear. In this study, we explored the short-term effects of acute CaN inhibition on TauO phosphorylation and TauO-induced memory deficits and synaptic dysfunction. Mice received FK506 post-TauO intracerebroventricular injection and TauO levels and phosphorylation were assessed, examining their impact on CaN and GSK-3β. The study investigated FK506 preventive/reversal effects on TauO-induced clustering of CaN and GSK-3β. Memory and synaptic function in TauO-injected mice were evaluated with/without FK506. Chronic FK506 treatment in 3xTgAD mice explored its influence on CaN, Aβ, and Tau levels. This study underscores the significant influence of CaN inhibition on TauO and associated AD pathology, suggesting therapeutic potential in targeting CaN for addressing various aspects of AD onset and progression. These findings provide valuable insights for potential interventions in AD, emphasizing the need for further exploration of CaN-targeted strategies. [ABSTRACT FROM AUTHOR]

Amyloid β peptide (Aβ) aggregation and deposition are considered the main causes of Alzheimer's disease. In a previous study, we demonstrated that anionic Zn-phthalocyanine (ZnPc) can interact with the Aβ peptide and inhibit the fibril-formation process. However, due to the inability of anionic ZnPc to cross the intact blood–brain barrier, we decided to explore the interaction of cationic methylated Zn-phthalocyanine (cZnPc) with the peptide. Using a ThT fluorescence assay, we observed that cZnPc dose-dependently and time-dependently inhibited Aβ1-42 fibril levels under in vitro fibril-formation conditions. Electron microscopy revealed that it caused Aβ1-42 peptides to form small aggregates. Western blotting and dot immunoblot oligomer experiments demonstrated that cZnPc increased rather than decreased the levels of oligomers from the very early stages of incubation. A binding assay confirmed that cZnPc could bind with the peptide. Docking simulations indicated that the oligomer species of Aβ1-42 had a higher ability to interact with cZnPc. ANS fluorescence assay results indicated that cZnPc did not affect the hydrophobicity of the peptide. However, cZnPc significantly increased intrinsic tyrosine fluorescence of the peptide after 8 h of incubation in fibril-formation conditions. Importantly, cell culture experiments demonstrated that cZnPc did not exhibit any toxicity up to a concentration of 10 µM. Instead, it protected a neuronal cell line from Aβ1-42-induced toxicity. Thus, our results suggest that cZnPc can affect the aggregation process of Aβ1-42, rendering it non-toxic, which could be crucial for the therapy of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Intra- or extracellular aggregates of proteins are central pathogenic features in most neurodegenerative disorders. The accumulation of such proteins in diseased brains is believed to be the end-stage of a stepwise aggregation of misfolded monomers to insoluble cross-ß fibrils via a series of differently sized soluble oligomers/protofibrils. Several studies have shown how a-synuclein, amyloid-ß, tau and other amyloidogenic proteins can act as nucleating particles and thereby share properties with misfolded forms, or strains, of the prion protein. Although the roles of different protein assemblies in the respective aggregation cascades remain unclear, oligomers/protofibrils are considered key pathogenic species. Numerous observations have demonstrated their neurotoxic effects and a growing number of studies have indicated that they also possess seeding properties, enabling their propagation within cellular networks in the nervous system. The seeding behavior of oligomers differs between the proteins and is also affected by various factors, such as size, shape and epitope presentation. Here, we are providing an overview of the current state of knowledge with respect to the "prion-like" behavior of soluble oligomers for several of the amyloidogenic proteins involved in neurodegenerative diseases. In addition to providing new insight into pathogenic mechanisms, research in this field is leading to novel diagnostic and therapeutic opportunities for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

This concept article explores the emerging role of atropisomerism in foldamer chemistry, a field focussed on oligomers that adopt well‐defined conformations through non‐covalent interactions. Atropisomerism introduces a novel dimension to foldamer design by restricting rotational freedom around single bonds to dictate molecular shape with precision. Despite the prevalence of atropisomeric bonds in organic synthesis, their application within foldamers remains underexplored. Here, we discuss key developments in both backbone and sidechain atropisomerism, and suggest future directions for atropisomeric foldamers in the context of a recent surge in atropselective synthetic methods. We propose that judicious use of atropisomerism may serve as a transformative tool in the construction of shape‐defined macromolecules. [ABSTRACT FROM AUTHOR]