Structural basis for ligand reception by anaplastic lymphoma kinase.

The proto-oncogene ALK encodes anaplastic lymphoma kinase, a receptor tyrosine kinase that is expressed primarily in the developing nervous system. After development, ALK activity is associated with learning and memory1 and controls energy expenditure, and inhibition of ALK can prevent diet-induced obesity2. Aberrant ALK signalling causes numerous cancers3. In particular, full-length ALK is an important driver in paediatric neuroblastoma4,5, in which it is either mutated6 or activated by ligand7. Here we report crystal structures of the extracellular glycine-rich domain (GRD) of ALK, which regulates receptor activity by binding to activating peptides8,9. Fusing the ALK GRD to its ligand enabled us to capture a dimeric receptor complex that reveals how ALK responds to its regulatory ligands. We show that repetitive glycines in the GRD form rigid helices that separate the major ligand-binding site from a distal polyglycine extension loop (PXL) that mediates ALK dimerization. The PXL of one receptor acts as a sensor for the complex by interacting with a ligand-bound second receptor. ALK activation can be abolished through PXL mutation or with PXL-targeting antibodies. Together, these results explain how ALK uses its atypical architecture for its regulation, and suggest new therapeutic opportunities for ALK-expressing cancers such as paediatric neuroblastoma.

Core planar cell polarity genes VANGL1 and VANGL2 in predisposition to congenital vertebral malformations.

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Transcriptome-based molecular subtypes and differentiation hierarchies improve the classification framework of acute myeloid leukemia.

The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. Robust identification of clinically and biologically relevant molecular subtypes from nongenomic high-throughput sequencing data remains challenging. We established the largest multicenter AML cohort (n = 655) in China, with all patients subjected to RNA sequencing (RNA-Seq) and 619 (94.5%) to targeted or whole-exome sequencing (TES/WES). Based on an enhanced consensus clustering, eight stable gene expression subgroups (G1-G8) with unique clinical and biological significance were identified, including two unreported (G5 and G8) and three redefined ones (G4, G6, and G7). Apart from four well-known low-risk subgroups including PML::RARA (G1), CBFB::MYH11 (G2), RUNX1::RUNX1T1 (G3), biallelic CEBPA mutations or -like (G4), four meta-subgroups with poor outcomes were recognized. The G5 (myelodysplasia-related/-like) subgroup enriched clinical, cytogenetic and genetic features mimicking secondary AML, and hotspot mutations of IKZF1 (p.N159S) (n = 7). In contrast, most NPM1 mutations and KMT2A and NUP98 fusions clustered into G6-G8, showing high expression of HOXA/B genes and diverse differentiation stages, from hematopoietic stem/progenitor cell down to monocyte, namely HOX-primitive (G7), HOX-mixed (G8), and HOX-committed (G6). Through constructing prediction models, the eight gene expression subgroups could be reproduced in the Cancer Genome Atlas (TCGA) and Beat AML cohorts. Each subgroup was associated with distinct prognosis and drug sensitivities, supporting the clinical applicability of this transcriptome-based classification of AML. These molecular subgroups illuminate the complex molecular network of AML, which may promote systematic studies of disease pathogenesis and foster the screening of targeted agents based on omics.

TRIM21/USP15 balances ACSL4 stability and the imatinib resistance of gastrointestinal stromal tumors.

BACKGROUND: Imatinib has become an exceptionally effective targeted drug for treating gastrointestinal stromal tumors (GISTs). Despite its efficacy, the resistance to imatinib is common in GIST patients, posing a significant challenge to the effective treatment. METHODS: The expression profiling of TRIM21, USP15, and ACSL4 in GIST patients was evaluated using Western blot and immunohistochemistry. To silence gene expression, shRNA was utilized. Biological function of TRIM21, USP15, and ACSL4 was examined through various methods, including resistance index calculation, colony formation, shRNA interference, and xenograft mouse model. The molecular mechanism of TRIM21 and USP15 in GIST was determined by conducting Western blot, co-immunoprecipitation, and quantitative real-time PCR (qPCR) analyses. RESULTS: Here we demonstrated that downregulation of ACSL4 is associated with imatinib (IM) resistance in GIST. Moreover, clinical data showed that higher levels of ACSL4 expression are positively correlated with favorable clinical outcomes. Mechanistic investigations further indicated that the reduced expression of ACSL4 in GIST is attributed to excessive protein degradation mediated by the E3 ligase TRIM21 and the deubiquitinase USP15. CONCLUSION: These findings demonstrate that the TRIM21 and USP15 control ACSL4 stability to maintain the IM sensitive/resistant status of GIST.

iFLAS: positive-unlabeled learning facilitates full-length transcriptome-based identification and functional exploration of alternatively spliced isoforms in maize.

The advent of full-length transcriptome sequencing technologies has accelerated the discovery of novel splicing isoforms. However, existing alternative splicing (AS) tools are either tailored for short-read RNA-Seq data or designed for human and animal studies. The disparities in AS patterns between plants and animals still pose a challenge to the reliable identification and functional exploration of novel isoforms in plants. Here, we developed integrated full-length alternative splicing analysis (iFLAS), a plant-optimized AS toolkit that introduced a semi-supervised machine learning method known as positive-unlabeled (PU) learning to accurately identify novel isoforms. iFLAS also enables the investigation of AS functions from various perspectives, such as differential AS, poly(A) tail length, and allele-specific AS (ASAS) analyses. By applying iFLAS to three full-length transcriptome sequencing datasets, we systematically identified and functionally characterized maize (Zea mays) AS patterns. We found intron retention not only introduces premature termination codons, resulting in lower expression levels of isoforms, but may also regulate the length of 3'UTR and poly(A) tail, thereby affecting the functional differentiation of isoforms. Moreover, we observed distinct ASAS patterns in two genes within heterosis offspring, highlighting their potential value in breeding. These results underscore the broad applicability of iFLAS in plant full-length transcriptome-based AS research.

High-Q metasurface signal isolator for 1.5T surface coil magnetic resonance imaging on the go.

The combination of surface coils and metamaterials remarkably enhance magnetic resonance imaging (MRI) performance for significant local staging flexibility. However, due to the coupling in between, impeded signal-to-noise ratio (SNR) and low-contrast resolution, further hamper the future growth in clinical MRI. In this paper, we propose a high-Q metasurface decoupling isolator fueled by topological LC loops for 1.5T surface coil MRI system, increasing the magnetic field up to fivefold at 63.8 MHz. We have employed a polarization conversion mechanism to effectively eliminate the coupling between the MRI metamaterial and the radio frequency (RF) surface transmitter-receiver coils. Furthermore, a high-Q metasurface isolator was achieved by taking advantage of bound states in the continuum (BIC) for extremely high-resolution MRI and spectroscopy. An equivalent physical model of the miniaturized metasurface design was put forward through LC circuit analysis. This study opens up a promising route for the easy-to-use and portable surface coil MRI scanners.

CYP eicosanoid pathway mediates colon cancer-promoting effects of dietary linoleic acid.

Human and animal studies support that consuming a high level of linoleic acid (LA, 18:2ω-6), an essential fatty acid and key component of the human diet, increases the risk of colon cancer. However, results from human studies have been inconsistent, making it challenging to establish dietary recommendations for optimal LA intake. Given the importance of LA in the human diet, it is crucial to better understand the molecular mechanisms underlying its potential colon cancer-promoting effects. Using LC-MS/MS-based targeted lipidomics, we find that the cytochrome P450 (CYP) monooxygenase pathway is a major pathway for LA metabolism in vivo. Furthermore, CYP monooxygenase is required for the colon cancer-promoting effects of LA, since the LA-rich diet fails to exacerbate colon cancer in CYP monooxygenase-deficient mice. Finally, CYP monooxygenase mediates the pro-cancer effects of LA by converting LA to epoxy octadecenoic acids (EpOMEs), which have potent effects on promoting colon tumorigenesis via gut microbiota-dependent mechanisms. Overall, these results support that CYP monooxygenase-mediated conversion of LA to EpOMEs plays a crucial role in the health effects of LA, establishing a unique mechanistic link between dietary fatty acid intake and cancer risk. These results could help in developing more effective dietary guidelines for optimal LA intake and identifying subpopulations that may be especially vulnerable to LA's negative effects.

Mutation breeding of high-stress resistant strains for succinic acid production from corn straw.

The production of succinic acid from corn stover is a promising and sustainable route; however, during the pretreatment stage, byproducts such as organic acids, furan-based compounds, and phenolic compounds generated from corn stover inhibit the microbial fermentation process. Selecting strains that are resistant to stress and utilizing nondetoxified corn stover hydrolysate as a feedstock for succinic acid production could be effective. In this study, A. succinogenes CICC11014 was selected as the original strain, and the stress-resistant strain A. succinogenes M4 was obtained by atmospheric and room temperature plasma (ARTP) mutagenesis and further screening. Compared to the original strain, A. succinogenes M4 exhibited a twofold increase in stress resistance and a 113% increase in succinic acid production when hydrolysate was used as the substrate. By conducting whole-genome resequencing of A. succinogenes M4 and comparing it with the original strain, four nonsynonymous gene mutations and two upstream regions with base losses were identified. KEY POINTS: • A high-stress-resistant strain A. succinogenes M4 was obtained by ARTP mutation •  The production of succinic acid increased by 113% • The mutated genes of A. succinogenes M4 were detected and analyzed.

Exploring the association between congenital vertebral malformations and neural tube defects.

Congenital vertebral malformations (CVMs) and neural tube defects (NTDs) are common birth defects affecting the spine and nervous system, respectively, due to defects in somitogenesis and neurulation. Somitogenesis and neurulation rely on factors secreted from neighbouring tissues and the integrity of the axial structure. Crucial signalling pathways like Wnt, Notch and planar cell polarity regulate somitogenesis and neurulation with significant crosstalk. While previous studies suggest an association between CVMs and NTDs, the exact mechanism underlying this relationship remains unclear. In this review, we explore embryonic development, signalling pathways and clinical phenotypes involved in the association between CVMs and NTDs. Moreover, we provide a summary of syndromes that exhibit occurrences of both CVMs and NTDs. We aim to provide insights into the potential mechanisms underlying the association between CVMs and NTDs, thereby facilitating clinical diagnosis and management of these anomalies.

Enhanced Electron Delocalization Induced by Ferromagnetic Sulfur doped C3N4 Triggers Selective H2O2 Production.

For the 2D metal-free carbon catalysts, the atomic coplanar architecture enables a large number of pz orbitals to overlap laterally, thus forming π-electron delocalization, and the delocalization degree of the central atom dominates the catalytic activity. Herein, designing sulfur-doped defect-rich graphitic carbon nitride (S-Nv-C3N4) materials as a model, we propose a strategy to promote localized electron polarization by enhancing the ferromagnetism of ultra-thin 2D carbon nitride nanosheets. The introduction of sulfur (S) further promotes localized ferromagnetic coupling, thereby inducing long-range ferromagnetic ordering and accelerating the electron interface transport. Meanwhile, the hybridization of sulfur atoms breaks the symmetry and integrity of the unit structure, promotes electron enrichment and stimulating electron delocalization at the active site. This optimization enhances the *OOH desorption, providing a favorable kinetic pathway for the production of hydrogen peroxide (H2O2). Consequently, S-Nv-C3N4 exhibits high selectivity (>95 %) and achieves a superb H2O2 production rate, approaching 4374.8 ppm during continuous electrolysis over 300 hour. According to theoretical calculation and in situ spectroscopy, the ortho-S configuration can provide ferromagnetic perturbation in carbon active centers, leading to the electron delocalization, which optimizes the OOH* adsorption during the catalytic process.

Unconventional Bilateral Compressive Strained Ni-Ir Interface Synergistically Accelerates Alkaline Hydrogen Oxidation.

The alkaline hydrogen oxidation reaction (HOR) involves the coupling of adsorbed hydrogen (Had) and hydroxyl (OHad) species and is thus orders of magnitude slower than that in acid media. According to the Sabatier principle, developing electrocatalysts with appropriate binding energy for both intermediates is vital to accelerating the HOR though it is still challenging. Herein, we propose an unconventional bilateral compressive strained Ni-Ir interface (Ni-Ir(BCS)) as efficient synergistic HOR sites. Density functional theory (DFT) simulations reveal that the bilateral compressive strain effect leads to the appropriate adsorption for both Had and OHad, enabling their coupling thermodynamically spontaneous and kinetically preferential. Such Ni-Ir(BCS) is experimentally achieved by embedding sub-nanometer Ir clusters in graphene-loaded high-density Ni nanocrystals (Ni-Ir(BCS)/G). As predicted, it exhibits a HOR mass activity of 7.95 and 2.88 times those of commercial Ir/C and Pt/C together with much enhanced CO tolerance, respectively, ranking among the most active state-of-the-art HOR catalysts. These results provide new insights into the rational design of advanced electrocatalysts involving coordinated adsorption and activation of multiple reactants.

Altering Ligand Microenvironment of Atomically Dispersed CrN4 by Axial Ligand Sulfur for Enhanced Oxygen Reduction Reaction in Alkaline and Acidic Medium.

Because of the instability and Fenton reactivity of non-precious metal nitrogen-carbon based catalyst when processing the oxygen reduction reaction (ORR), seeking for electrocatalysts with highly efficient performance becomes very highly desired to speed up the commercialization of fuel cell. Herein, chromium (Cr)-N4  electrocatalyst containing extraterrestrial S formed axial S1 -Cr1 N4  bonds (S1 Cr1 N4 C) is achieved via an assembly polymerization and confined pyrolysis strategy. Benefiting from the adjusting  coordination configuration and electronic structure of the metal center through axial coordination, S1 Cr1 N4 C exhibits enhanced the intrinsic activity (half-wave potential (E1/2 ) is 0.90 V versus reversable hydrogen electrode, RHE) compared with that of CrN4 C and Pt/C catalysts. More notably, the catalyst is almost inert in catalyzing the Fenton reaction, and thus shows the high stability. Density functional theory (DFT) results further reveal that the existence of axial S atoms in S1 Cr1 N4 C moiety has the better ORR activity than Cr1 N4 C moieties. The axial S ligand in S1 Cr1 N4 C moiety can break the electron localization around the planar Cr1 N4  active center, which facilitated the rate-limiting reductive release of OH* and accelerated overall ORR process. The present work opens up a new avenue to modulate the axial ligand type of the single-atoms (SAs) active center to enhance intrinsic SAs performances.

Fe-Regulated Amorphous-Crystal Ni(Fe)P2 Nanosheets Coupled with Ru Powerfully Drive Seawater Splitting at Large Current Density.

Water electrolysis is an ideal method for industrial green hydrogen production. However, due to increasing scarcity of freshwater, it is inevitable to develop advanced catalysts for electrolyzing seawater especially at large current density. This work reports a unique Ru nanocrystal coupled amorphous-crystal Ni(Fe)P2 nanosheet bifunctional catalyst (Ru-Ni(Fe)P2 /NF), caused by partial substitution of Fe to Ni atoms in Ni(Fe)P2 , and explores its electrocatalytic mechanism by density functional theory (DFT) calculations. Owing to high electrical conductivity of crystalline phases, unsaturated coordination of amorphous phases, and couple of Ru species, Ru-Ni(Fe)P2 /NF only requires overpotentials of 375/295 and 520/361 mV to drive a large current density of 1 A cm-2 for oxygen/hydrogen evolution reaction (OER/HER) in alkaline water/seawater, respectively, significantly outperforming commercial Pt/C/NF and RuO2 /NF catalysts. In addition, it maintains stable performance at large current density of 1 A cm-2 and 600 mA cm-2 for 50 h in alkaline water and seawater, respectively. This work provides a new way for design of catalysts toward industrial-level seawater splitting.

Characterizing Rosai-Dorfman disease with [18F]FDG PET/CT: a retrospective analysis of a single-center study.

OBJECTIVES: Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferative disorder. We performed a retrospective study to characterize the clinical and [18F]FDG PET/CT features of RDD. METHODS: We retrospectively recruited 38 RDD patients with [18F]FDG PET/CT scan in our center. [18F]FDG PET/CT features were assessed, and clinical and follow-up data were recorded. RESULTS: In the recruited patients, 20/38 (52.6%) patients had single-system disease, while others (18/38, 47.4%) had disease affecting multiple system. RDD most commonly involved the upper respiratory tract (47.4%), followed by cutaneous/subcutaneous lesion (39.5%), lymph node (36.8%), bone (31.6%), central nervous system (28.9%), and cardiovascular system (13.2%) in the recruited patients. In PET/CT, the RDD lesions were FDG-avid, and the SUVmax of the hottest lesion in an individual patient was positively correlated with C-reactive protein levels (r = 0.418, p = 0.014), and negatively correlated with hemoglobin levels (r = -0.359, p = 0.036). The overall response rate of the first-line treatment was 80.8% in newly diagnosed RDD patients, and for patients with relapsed/progressive RDD, the overall response rate was 72.7%. CONCLUSION: [18F]FDG PET/CT could be a useful tool for evaluating RDD. KEY POINTS: • About half of the patients with Rosai-Dorfman disease had single-system disease, while others had disease affecting multiple system. Rosai-Dorfman disease most commonly involved the upper respiratory tract, followed by cutaneous/subcutaneous lesion, lymph node, bone, central nervous system, and cardiovascular system. • In [18F]FDG PET/CT, Rosai-Dorfman disease was usually hypermetabolic, and the SUVmax of the hottest lesion in an individual patient was positively correlated with C-reactive protein levels. • Rosai-Dorfman disease usually has a high overall response rate after treatment.

Development of SNP marker panels for genotyping by target sequencing (GBTS) and its application in soybean.

A high-throughput genotyping platform with customized flexibility, high genotyping accuracy, and low cost is critical for marker-assisted selection and genetic mapping in soybean. Three assay panels were selected from the SoySNP50K, 40K, 20K, and 10K arrays, containing 41,541, 20,748, and 9670 SNP markers, respectively, for genotyping by target sequencing (GBTS). Fifteen representative accessions were used to assess the accuracy and consistency of the SNP alleles identified by the SNP panels and sequencing platform. The SNP alleles were 99.87% identical between technical replicates and 98.86% identical between the 40K SNP GBTS panel and 10× resequencing analysis. The GBTS method was also accurate in the sense that the genotypic dataset of the 15 representative accessions correctly revealed the pedigree of the accessions, and the biparental progeny datasets correctly constructed the linkage maps of the SNPs. The 10K panel was also used to genotype two parent-derived populations and analyze QTLs controlling 100-seed weight, resulting in the identification of the stable associated genetic locus Locus_OSW_06 on chromosome 06. The markers flanking the QTL explained 7.05% and 9.83% of the phenotypic variation, respectively. Compared with GBS and DNA chips, the 40K, 20K, and 10K panels reduced costs by 5.07% and 58.28%, 21.44% and 65.48%, and 35.74% and 71.76%, respectively. Low-cost genotyping panels could facilitate soybean germplasm assessment, genetic linkage map construction, QTL identification, and genomic selection. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01372-6.

Mean platelet volume modifies the contribution of homocysteine to cardiovascular disease: A real-world study.

BACKGROUND AND AIMS: The effect of reductions in homocysteine (Hcy) on cardiovascular disease (CVD) was suggested to be modified by platelet activation, but the interaction between Hcy and platelet activation on CVD events is not well studied. Here, we aimed to examine the interaction between Hcy and platelet activation on CVD in a large, real-world population. METHODS AND RESULTS: A total of 27,234 patients with hypertension (mean 63 years, 48% male) who were registered in Taicang city and free of CVD were prospectively followed up for new CVD events from 2017 to 2020. Hcy and platelet indices including mean platelet volume (MPV) were assayed at baseline. A total of 1063 CVD events were recorded during follow-up. Hcy at baseline was significantly associated with a higher risk of CVD (HR = 1.85, P < 0.001 for log-transformed Hcy). MPV showed a significant interaction effect with Hcy on CVD (HR = 1.20, P = 0.030 for the interaction term). The association between Hcy and CVD was significantly stronger in participants with a large (vs. small) MPV (HR = 2.71 vs. 1.32, P = 0.029 for log-transformed Hcy). For participants with both elevated Hcy and a large MPV, the attributable proportion of CVD events due to their interaction was 0.26 (95% CI: 0.06-0.45). CONCLUSIONS: The association between Hcy and CVD was significantly stronger in patients with hypertension with a larger MPV. MPV may modify the contribution of Hcy to CVD events through synergistic interactions with Hcy. These findings suggest that MPV could be monitored and controlled in the prevention of CVD.

Extracting Traffic Signage by Combining Point Clouds and Images.

Recognizing traffic signs is key to achieving safe automatic driving. With the decreasing cost of LiDAR, the accurate extraction of traffic signs using point cloud data has received wide attention. In this study, we propose combining point cloud and image traffic sign extraction: firstly, we use the improved YoloV3 model to detect traffic signs in panoramic images. The specific improvement is that the convolution block attention module is added to the algorithm framework, the traditional K-means clustering algorithm is improved, and Focal Loss is introduced as the loss function. It shows higher accuracy on the TT100K dataset, with a 1.4% improvement in accuracy compared to the previous YoloV3. Then, the point cloud of the area where the traffic sign is located is extracted by combining the image detection results. On this basis, the outline of the traffic sign is accurately extracted using the reflection intensity, spatial geometry and other information. Compared with the traditional method, the proposed method can effectively reduce the missed detection rate, narrow the range of point cloud, and improve the detection accuracy by 10.2%.

Dual-Responsive Supramolecular Chiral Assemblies from Amphiphilic Dendronized Tetraphenylethylenes.

Supramolecular assembly of amphiphilic molecules in aqueous solutions to form stimuli-responsive entities is attractive for developing intelligent supramolecular materials for bioapplications. Here we report on the supramolecular chiral assembly of amphiphilic dendronized tetraphenylethylenes (TPEs) in aqueous solutions. Hydrophobic TPE moieties were connected to the hydrophilic three-fold dendritic oligoethylene glycols (OEGs) through a tripeptide proline-hydroxyproline-glycol (POG) to afford the characteristic topological structural effects of dendritic OEGs and the peptide linker. Both ethoxyl- and methoxyl-terminated dendritic OEGs were used to modulate the overall hydrophilicity of the dendronized TPEs. Their supramolecular aggregates exhibited thermoresponsive behavior that originated from the dehydration and collapse of the dendritic OEGs, and their cloud point temperatures (Tcps) were tailored by solution pH conditions. Furthermore, aggregation-induced fluorescent emission (AIE) from TPE moieties was used as an indicator to follow the assembly, which was reversibly tuned by temperature variation at different pH conditions. Supramolecular assemblies from these dendronized amphiphiles exhibited enhanced supramolecular chirality, which was dominated mainly by the interaction balance between TPE with dendritic OEG and TPE with POG moieties and was modulated through different solvation by changing solution temperature or pH conditions. More interestingly, ethoxyl-terminated dendritic OEG provided a much stronger shielding effect than its methoxyl-terminated counterpart to prevent amino groups within the peptide from protonation, even in strong acidic conditions, resulting in different responsive behavior to the solution temperature and pH conditions for these supramolecular aggregates.

Exploring the Release of Elastin Peptides Generated from Enzymatic Hydrolysis of Bovine Elastin via Peptide Mapping.

To enhance the understanding of enzymatic hydrolysis and to accelerate the discovery of key bioactive peptides within enzymatic products, this research focused on elastin as the substrate and investigated the variations in peptide profiles and the production of key bioactive peptides (those exceeding 5% of the total) and their impacts on the biological activity of the hydrolysates. Through the application of advanced analytical techniques, such as stop-flow two-dimensional liquid chromatography and ultra-high-performance liquid chromatography-tandem mass spectrometry, the research tracks the release and profiles of peptides within elastin hydrolysates (EHs). Despite uniform peptide compositions, significant disparities in peptide concentrations were detected across the hydrolysates, hinting at varying levels of bioactive efficacy. A comprehensive identification process pinpointed 403 peptides within the EHs, with 18 peptides surpassing 5% in theoretical maximum content, signaling their crucial role in the hydrolysate's bioactivity. Of particular interest, certain peptides containing sequences of alanine, valine, and glycine were released in higher quantities, suggesting Alcalase® 2.4L's preference for these residues. The analysis not only confirms the peptides' dose-responsive elastase inhibitory potential but also underscores the nuanced interplay between peptide content, biological function, and their collective synergy. The study sets the stage for future research aimed at refining enzymatic treatments to fully exploit the bioactive properties of elastin.