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Covering: 2000 to up to 2023α,ß-Dehydroamino acids (dhAAs) are unsaturated nonproteinogenic amino acids found in a wide array of naturally occurring peptidyl metabolites, predominantly those from bacteria. Other organisms, such as fungi, higher plants and marine invertebrates, have also been found to produce dhAA-containing peptides. The α,ß-unsaturation in dhAAs has profound effects on the properties of these molecules. They display significant synthetic flexibility, readily undergoing reactions such as Michael additions, transition-metal-catalysed cross-couplings, and cycloadditions. These residues in peptides/proteins also exhibit great potential in bioorthogonal applications using click chemistry. Peptides containing contiguous dhAA residues have been extensively investigated in the field of foldamers, self-assembling supermolecules that mimic biomacromolecules such as proteins to fold into well-defined conformations. dhAA residues in these peptidyl materials tend to form a 2.05-helix. As a result, stretches of dhAA residues arrange in an extended conformation. In particular, peptidyl foldamers containing ß-enamino acid units display interesting conformational, electronic, and supramolecular aggregation properties that can be modulated by light-dependent E-Z isomerization. Among approximately 40 dhAAs found in the natural product inventory, dehydroalanine (Dha) and dehydrobutyrine (Dhb) are the most abundant. Dha is the simplest dehydro-α-amino acid, or α-dhAA, without any geometrical isomers, while its re-arranged isomer, 3-aminoacrylic acid (Aaa or ΔßAla), is the simplest dehydro-ß-amino acid, or ß-enamino acid, and displays E/Z isomerism. Dhb is the simplest α-dhAA that exhibits E/Z isomerism. The Z-isomer of Dhb (Z-Dhb) is sterically favourable and is present in the majority of naturally occurring peptides containing Dhb residues. Dha and Z-Dhb motifs are commonly found in ribosomally synthesized and post-translationally modified peptides (RiPPs). In the last decade, the formation of Dha and Dhb motifs in RiPPs has been extensively investigated, which will be briefly discussed in this review. The formation of other dhAA residues in natural products (NPs) is, however, less understood. In this review, we will discuss recent advances in the biosynthesis of peptidyl NPs containing unusual dhAA residues and cryptic dhAA residues. The proposed biosynthetic pathways of these natural products will also be discussed.
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Productos Biológicos , Aminoácidos/química , Péptidos/química , Proteínas , IsomerismoRESUMEN
Antimony selenide (Sb2 Se3 ) is a highly promising photovoltaic material thanks to its outstanding optoelectronic properties, as well as its cost-effective and eco-friendly merits. However, toxic CdS is widely used as an electron transport layer (ETL) in efficient Sb2 Se3 solar cells, which largely limit their development toward market commercialization. Herein, an effective green Cd-free ETL of SnOx is introduced and deposited by atomic layer deposition method. Additionally, an important post-annealing treatment is designed to further optimize the functional layers and the heterojunction interface properties. Such engineering strategy can optimize SnOx ETL with higher nano-crystallinity, higher carrier density, and less defect groups, modify Sb2 Se3 /SnOx heterojunction with better interface performance and much desirable "spike-like" band alignment, and also improve the Sb2 Se3 light absorber layer quality with passivated bulk defects and prolonged carrier lifetime, and therefore to enhance carrier separation and transport while suppressing non-radiative recombination. Finally, the as-fabricated Cd-free Mo/Sb2 Se3 /SnOx /ITO/Ag thin-film solar cell exhibits a stimulating efficiency of 7.39%, contributing a record value for Cd-free substrate structured Sb2 Se3 solar cells reported to date. This work provides a viable strategy for developing and broadening practical applications of environmental-friendly Sb2 Se3 photovoltaic devices.
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Mechano growth factor (MGF) is a splicing variant of insulin-like growth factor 1 (IGF-1). The unique C-terminal E domain of MGF (MGF-E) makes it distinct from the other variants of IGF-1. Our previous work demonstrated that MGF-25E induces the migration of rat bone marrow-derived mesenchymal stem cells (rMSCs) by altering their mechanical properties, which is accompanied by the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. However, the relationship between ERK1/2 activation and the change in mechanical properties has not been illustrated. In the present study, we determined that MGF-25E induced the migration of rMSCs by modulating CXCR4 to activate the ERK1/2 pathway. The analysis of the Young's modulus and F-actin remodeling indicated that MGF-25E increased the stiffness and the F-actin polymerization of rMSCs through the activation of the CXCR4-ERK1/2 pathway. For the first time, this study clarified the signaling pathway that regulates the mechanical properties of rMSCs and is responsible for MGF-25E-promoted migration.
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Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Células Madre Mesenquimatosas/fisiología , Receptores CXCR4/metabolismo , Animales , Bencilaminas , Células de la Médula Ósea/fisiología , Movimiento Celular , Células Cultivadas , Ciclamas , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Flavonoides/farmacología , Compuestos Heterocíclicos/farmacología , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/farmacología , Sistema de Señalización de MAP Quinasas , Microscopía de Fuerza Atómica , Ratas , Ratas Sprague-Dawley , Receptores CXCR4/antagonistas & inhibidoresRESUMEN
The interplay between flexoelectric and optoelectronic characteristics provides a paradigm for studying emerging phenomena in various 2D materials. However, an effective way to induce a large and tunable strain gradient in 2D devices remains to be exploited. Herein, we propose a strategy to induce large flexoelectric effect in 2D ferroelectric CuInP2S6 by constructing a 1D-2D mixed-dimensional heterostructure. The strong flexoelectric effect is induced by enormous strain gradient up to 4.2 × 106 m-1 resulting from the underlying ZnO nanowires, which is further confirmed by the asymmetric coercive field and the red-shift in the absorption edge. The induced flexoelectric polarization efficiently boosts the self-powered photodetection performance. In addition, the improved photoresponse has a good correlation with the induced strain gradient, showing a consistent size-dependent flexoelectric effect. The mechanism of flexoelectric and optoelectronic coupling is proposed based on the Landau-Ginzburg-Devonshire double-well model, supported by density functional theory (DFT) calculations. This work provides a brand-new method to induce a strong flexoelectric effect in 2D materials, which is not restricted to crystal symmetry and thus offers unprecedented opportunities for state-of-the-art 2D devices.
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Mechano-growth factor (MGF) generated by cells in response to mechanical stimulation has been identified as a mechano effector molecule, playing a key role in regulating mesenchymal stem cell (MSC) function, including proliferation and migration. However, the mechanism(s) underlying how MGF-induced MSC migration occurs is still unclear. In the present study, MGF motivated migration of rat MSCs (rMSCs) in a concentration-dependent manner and optimal concentration of MGF at 50 ng/mL (defined as MGF treatment in this paper) was demonstrated. Notably, enhancement of mechanical properties that is pertinent to cell migration, such as cell traction force and cell stiffness were found to respond to MGF treatment. Furthermore, MGF increased phosphorylation of extracellular signal-regulated kinase (ERK), ERK inhibitor (i.e., PD98059) suppressed ERK phosphorylation, and abolished MGF-induced rMSC migration were found, demonstrating that ERK is involved molecule for MGF-induced rMSC migration. These in vitro evidences of MGF-induced rMSC migration and its direct link to altering rMSC mechanics and activating the ERK pathway, uncover the underlying biomechanical and biological mechanisms of MGF-induced rMSC migration, which may help find MGF-based application of MSC in clinical therapeutics.
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Fenómenos Biomecánicos/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/enzimología , Animales , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Activación Enzimática/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
Two-dimensional CuCrP2S6 possesses significant potential for low-power non-volatile devices owing to its multiferroic properties. Nonetheless, comprehensive investigations regarding the modulation of CuCrP2S6 polarization for enhancing semiconductor photodetection capabilities and its potential applications in ferroelectric non-volatile devices are still relatively scarce. In this study, we present a novel, non-volatile, tunable photodetector engineered through the integration of a ferroelectric heterostructure comprising CuCrP2S6 and InSe. Our findings reveal that distinct ferroelectric polarization states of CuCrP2S6 exert varying modulation effects on the InSe photodetection performance. Notably, optimized results give a responsivity of 1839 A W-1 and a detectivity of 1.9 × 1012 Jones at a 300 nm wavelength, featuring a substantial 20.7-fold difference in responsivity between the two polarization states. This investigation underscores the immense potential of CuCrP2S6 in the development of non-volatile, multi-state optoelectronic devices.
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The ferroelectric field effect transistor (Fe-FET) is considered to be one of the most important low-power and high-performance devices. It is promising to combine a ferroelectric field effect with a photodetector to improve the photodetection performance. This study proposes a strategy for ZnO ultraviolet (UV) photodetectors regulated by a ferroelectric gate. The ZnO nanowire (NW) UV photodetector was tuned by a 2D CuInP2S6 (CIPS) ferroelectric gate, which decreased the dark current and enhanced the responsivity and detectivity to 2.40 × 104 A/W and 7.17 × 1011 Jones, respectively. This strategy was also applied to a ZnO film UV photodetector that was tuned by a P(VDF-TrFE) ferroelectric gate. Lower power consumption and higher performance can be enabled by ferroelectric tuning of ZnO ultraviolet photodetectors, providing new inspiration for the fabrication of high-performance photodetectors.
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Non-Ribosomal Peptide Synthetases (NRPSs) assemble a diverse range of natural products with important applications in both medicine and agriculture. They consist of several multienzyme subunits that must interact with each other in a highly controlled manner to facilitate efficient chain transfer, thus ensuring biosynthetic fidelity. Several mechanisms for chain transfer are known for NRPSs, promoting structural diversity. Herein, we report the first biochemically characterized example of a type II thioesterase (TEII) domain capable of catalysing aminoacyl chain transfer between thiolation (T) domains on two separate NRPS subunits responsible for installation of a dehydrobutyrine moiety. Biochemical dissection of this process reveals the central role of the TEII-catalysed chain translocation event and expands the enzymatic scope of TEII domains beyond canonical (amino)acyl chain hydrolysis. The apparent co-evolution of the TEII domain with the NRPS subunits highlights a unique feature of this enzymatic cassette, which will undoubtedly find utility in biosynthetic engineering efforts.
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Ácido Graso Sintasas/química , Ácido Graso Sintasas/metabolismo , Péptido Sintasas/metabolismo , Tioléster Hidrolasas/química , Tioléster Hidrolasas/metabolismo , Catálisis , Escherichia coli/genética , Ácido Graso Sintasas/genética , Ingeniería Metabólica , Dominios Proteicos , Tioléster Hidrolasas/genéticaRESUMEN
Objective: The pathogenesis of schizophrenia is associated with neuropeptide Y (NPY) gene polymorphism to explore the relationship between rs16141, rs16145, and rs5573 polymorphisms in the NPY gene and antipsychotics response in the Chinese population. Methods: The unrelated 228 Chinese Han patients with schizophrenia were enrolled in the present study. Genotypisation within NPY gene was performed using the KASP genotyping assays. Before treatment and on the weekends of the 2nd, 4th, and 8th weeks after treatment, the medication status of the patients was recorded and the positive and negative syndrome scale (PANSS) was used to evaluate the clinical effect. A reduction in total PANSS scores ≥50% were classified as good responders, while others were poor responders. We evaluated the association between NPY gene and antipsychotic efficacy by comparing allele and genotype distribution, correlation analysis, linkage imbalance, and five genetic models between the two groups. Results: No significant associations were found in the rs16141, rs16145, and rs5573 of NPY and antipsychotic treatment response (all p > 0.05). There was no significant relationship between the three SNPs polymorphisms in the NPY gene and the changes of positive, negative and general psychopathology subscales scores at each stage (all p > 0.05). The distribution of genotype and allele frequencies of locus rs16141 was not statistically difference between good responders and poor responders (genotype: χ2 =4.088, p=0.043, p-correction = 0.129; allele: χ2 = 4.088, p = 0.027, p-correction = 0.081). The allele distribution of rs5573 was significantly different between groups, yet the difference was disappeared after correcting (χ2 = 4.136, p = 0.042, p-correction =0.126). The distribution frequencies of TA/TG and GG haplotypes constituted by rs16141 and rs5573 showed no statistical difference between the two groups (p > 0.05). In recessive inheritance mode, NPYrs5573 was found to be associated with antipsychotic drug response (G/G vs. A/A +A/G: p = 0.028, AIC = 197.2, BIC = 210.9). Conclusions: This study didn't found association between polymorphisms in the NPY gene locus (rs16141, rs16145, and rs5573) and the response to antipsychotics after Bonferroni correction. The polymorphism of NPY gene and the efficacy of antipsychotic drugs in patients with schizophrenia need further study.
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Ribosomally synthesized and post-translationally modified peptides (RiPPs) are structurally complex natural products with diverse bioactivities. Here we report discovery of a RiPP, kintamdin, for which the structure is determined through spectroscopy, spectrometry and genomic analysis to feature a bis-thioether macrocyclic ring and a ß-enamino acid residue. Biosynthetic investigation demonstrated that its pathway relies on four dedicated proteins: phosphotransferase KinD, Lyase KinC, kinase homolog KinH and flavoprotein KinI, which share low homologues to enzymes known in other RiPP biosynthesis. During the posttranslational modifications, KinCD is responsible for the formation of the characteristic dehydroamino acid residues including the ß-enamino acid residue, followed by oxidative decarboxylation on the C-terminal Cys and subsequent cyclization to provide the bis-thioether ring moiety mediated by coordinated action of KinH and KinI. Finally, conserved genomic investigation allows further identification of two kintamdin-like peptides among the kin-like BGCs, suggesting the occurrence of RiPPs from actinobacteria.
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Actinobacteria , Productos Biológicos , Péptidos , Procesamiento Proteico-Postraduccional , SulfurosRESUMEN
For this study, 461 Chinese Han patients with depressive disorder were recruited. The AKT1 genotype and allele distribution were determined by PCR amplification and direct sequencing. UNPHASED software was used to analyze associations between the 17-item Hamilton Depression Rating Scale, total score, four factors and the AKT1 rs2494746 and rs3001371 polymorphisms. The results indicate that there is a significant association between suicidal ideation and anxiety symptoms in depressed patients and the rs2494746 polymorphism. The other AKT1 polymorphism, rs3001371, was significantly associated with work and activities. Patients with the rs3001371-A allele had a significantly more severe illness compared to patients with the rs3001371-G allele. Thus, AKT1 polymorphisms appear to be associated with depression severity, anxiety symptoms, work and activities, and suicide attempts in patients with depressive disorder.