A conserved but plant-specific CDK-mediated regulation of DNA replication protein A2 in the precise control of stomatal terminal division

The R2R3-MYB transcription factor FOUR LIPS (FLP) controls the stomatal terminal division through transcriptional repression of the cell cycle genes CYCLIN-DEPENDENT KINASE (CDK) B1s (CDKB1s), CDKA; 1, and CYCLIN A2s (CYCA2s). We mutagenized the weak mutant allele flp-1 seeds with ethylmethane sulfonate and screened out a flp-1 suppressor 1 (fsp1) that suppressed the flp-1 stomatal cluster phenotype. FSP1 encodes RPA2a subunit of Replication Protein A (RPA) complexes that play important roles in DNA replication, recombination, and repair. Here, we show that FSP1/RPA2a functions together with CDKB1s and CYCA2s in restricting stomatal precursor proliferation, ensuring the stomatal terminal division and maintaining a normal guard-cell size and DNA content. Furthermore, we provide direct evidence for the existence of an evolutionarily conserved, but plant-specific, CDK-mediated RPA regulatory pathway. Serine-11 and Serine-21 at the N terminus of RPA2a are CDK phosphorylation target residues. The expression of the phosphorylation-mimic variant RPA2a(S11,21/D) partially complemented the defective cell division and DNA damage hypersensitivity in cdkb1;1 1;2 mutants. Thus, our study provides a mechanistic understanding of the CDK-mediated phosphorylation of RPA in the precise control of cell cycle and DNA repair in plants

Triperyleno[3,3,3]propellane Triimides: Achieving a New Generation of Quasi-\u3cem\u3eD\u3c/em\u3e\u3csub\u3e3h\u3c/sub\u3e Symmetric Nanostructures in Organic Electronics

Rigid three-dimensional (3D) polycyclic aromatic hydrocarbons (PAHs), in particular 3D nanographenes, have garnered interest due to their potential use in semiconductor applications and as models to study through-bond and through-space electronic interactions. Herein we report the development of a novel 3D-symmetric rylene imide building block, triperyleno[3,3,3]propellane triimides (6), that possesses three perylene monoimide subunits fused on a propellane. This building block shows several promising characteristics, including high solubility, large π-surfaces, electron-accepting capabilities, and a variety of reactive sites. Further, the building block is compatible with different reactions to readily yield quasi-D3h symmetric nanostructures (9, 11, and 13) of varied chemistries. For the 3D nanostructures we observed red-shift absorption maxima and amplification of the absorption coefficients when compared to the individual subunits, indicating intramolecular electronic coupling among the subunits. In addition, the microplates of 9 exhibit comparable mobilities in different directions in the range of 10−3 cm2 V−1 s−1, despite the rather limited intermolecular overlap of the π-conjugated moieties. These findings demonstrate that these quasi-D3h symmetric rylene imides have potential as 3D nanostructures for a range of materials applications, including in organic electronic devices

Modélisation numérique d'assemblages collés (application à la réparation de structures en composites)

Cette étude fait partie d'un programme de recherche concernant la réparation de structures composites par collage de patchs externes. Les objectifs principaux de ce programme sont d'une part l'identification de l'ensemble des facteurs susceptibles d influencer les performances à long terme de ce type de réparation, et d autre part de déterminer dans quelle mesure l utilisation de tels assemblages peuvent s'avérer une solution optimale. La conception d'un tel système passe obligatoirement par le développement d'un outil de simulation et de prédiction robuste du fait des divers mécanismes d endommagement pouvant intervenir de fa?on très complexe et de la rupture finale du système résultant d une propagation des zones endommagées. Cette étude compose d une et d autre l aspect de la modélisation numérique, et l'aspect expérimental. Le dialogue entre les résultats numériques et expérimentaux permet, d une part de comprendre les mécanismes d endommagement et l évolution de ce dernier dans le système réparé, d autre part de valider le modèle numérique. En particulier, nos efforts ont été concentrés, en utilisant le logiciel LS-dyna, sur l application des modèles de zone cohésive (MZC). Le comportement au délaminage d un composite carbone/époxyde et de l adhésif sont étudié avec les essais en mode I, mode II et mode mixte. Une étude paramétrique de MZC est effectuée. Le modèle de zone cohésive validé est utilisé pour modéliser le comportement en traction des composites réparés par collage de patches externesThis study is one part of a program of research with regard to the repair of composite structure with extern bonded-patches. The principal objectives of this program are, on one side, the identification of all the factors susceptible to influence the long-term performance of this type of repair, on the other, to determine the extent to which the use of such assemblage can be proved to be an optimal solution. The conception of such a system needs essentially the development of a tool of simulation and of robust prediction because various mechanisms of damage can take place in a very complex way and the final fracture of the system arise from the propagation of damage zones. This study consists of both numerical simulation and experimental aspect which can help us, on one side, understand the mechanisms of damage and its evolution in a repair structure, on the other, valid the numerical model. In particular, we concentrate in the application of cohesive zone model using LS-dyna. The behavior of delamination of carbon/epoxy composite and the adhesive is studied with the experiments in mode I, mode II and mode mixed. A parametric study is carried out. The validated cohesive zone model is used to simulate the tensile behavior of composite repaired by extern bonded-patchesDIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

Comprehensive identification of alternative back-splicing in human tissue transcriptomes

Circular RNAs (circRNAs) are covalently closed RNAs derived from back-splicing of genes across eukaryotes. Through alternative back-splicing (ABS), a single gene produces multiple circRNAs sharing the same back-splice site. Although many ABS events have recently been discovered, to what extent ABS involves in circRNA biogenesis and how it is regulated in different human tissues still remain elusive. Here, we reported an in-depth analysis of ABS events in 90 human tissue transcriptomes. We observed that ABS occurred for about 84% circRNAs. Interestingly, alternative 5\u27 back-splicing occurs more prevalently than alternative 3\u27 back-splicing, and both of them are tissue-specific, especially enriched in brain tissues. In addition, the patterns of ABS events in different brain regions are similar to each other and are more complex than the patterns in non-brain tissues. Finally, the intron length and abundance of Alu elements positively correlated with ABS event complexity, and the predominant circRNAs had longer flanking introns and more Alu elements than other circRNAs in the same ABS event. Together, our results represent a resource for circRNA research-we expanded the repertoire of ABS events of circRNAs in human tissue transcriptomes and provided insights into the complexity of circRNA biogenesis, expression, and regulation

Folate receptor-targeted mixed polysialic acid micelles for combating rheumatoid arthritis: in vitro and in vivo evaluation

Objective: Rheumatoid arthritis (RA) is associated with chronic inflammation. The suppression of inflammation is key to the treatment of RA. Glucocorticoids (GCs) are classical anti-inflammatory drugs with several disadvantages such as poor water solubility and low specificity in the body. These disadvantages are the reasons for the quick elimination and side effects of GCs in vivo. Micelles are ideal carriers for GCs delivery to inflamed synovium. We set out to improve the targeting and pharmacokinetic profiles of GCs by preparing a targeting micelle system. Methods: In this study, natural chlosterol (CC) and folic acid (FA) were used to fabricate polysialic acid (PSA) micelles for the targeted delivery of Dexamethasone (Dex). The biodistribution and therapeutic efficacy of the resulting micelles were evaluated in vitro and in vivo. Results: PSA-CC and FA-PSA-CC micelles showed a size below 100 nm and a moderate negative charge. PSA-CC and FA-PSA-CC micelles could also enhance the intracellular uptake of Dex and the suppression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in vitro and in vivo. Arthritis mice showed reduced paw thickness and clinical arthritis index using PSA-CC and FA-PSA-CC micelle treatment. Micellized Dex demonstrated a 4 ∼ 5 fold longer elimination half-life and a 2 ∼ 3 folds higher bioavailability than commercial Dex injection. FA modification significantly improved the anti-inflammatory efficacy of PSA-CC micelles. Conclusion: FA-PSA-CC micelles demonstrated significant advantages in terms of the suppression of inflammation and the treatment of inflammatory arthritis. These reliable and stable micelles possess a high potential to be transferred for clinical use

Cognition Impairment Prior to Errors of Working Memory Based on Event-Related Potential

Cognitive impairment contributes to errors in different tasks. Poor attention and poor cognitive control are the two neural mechanisms for performance errors. A few studies have been conducted on the error mechanism of working memory. It is unclear whether the changes in memory updating, attention, and cognitive control can cause errors and, if so, whether they can be probed at the same time in one single task. Therefore, this study analyzed event-related potentials in a two-back working memory task. A total of 40 male participants finished the task. The differences between the error and the correct trials in amplitudes and latencies of N1, P2, N2, and P3 were analyzed. The P2 and P3 amplitudes decreased significantly in the error trials, while the N2 amplitude increased. The results showed that impaired attention, poor memory updating, and impaired cognitive control were consistently associated with the error in working memory. Furthermore, the results suggested that monitoring the neurophysiological characteristics associated with attention and cognitive control was important for studying the error mechanism and error prediction. The results also suggested that the P3 and N2 amplitudes could be used as indexes for error foreshadowing

Indication and adverse event profiles of denosumab and zoledronic acid: based on U.S. FDA adverse event reporting system (FAERS)

Objective: To investigate adverse events (AEs) associated with denosumab (Dmab) and zoledronic acid (ZA), compare their association strengths, and explore potential applications to provide clinical reference.Methods: We collected data from FAERS from January 2004 to November 2022 and mined AE signals for Dmab and ZA using ROR values. We compared signal intensity for same AEs and investigated off-label use. We also examined their AEs in adjuvant therapy for breast and prostate cancer.Results: 154,735 reports of primary suspect drugs were analyzed in the FAERS database (Dmab: 117,857; ZA: 36,878). Dmab and ZA had 333 and 1,379 AE signals, with 189 overlaps. The AEs of Dmab included death (ROR:3.478), osteonecrosis of jaw (ROR:53.025), back pain (ROR:2.432), tooth disorder (ROR:16.18), bone pain (ROR:6.523). For ZA, the AEs included osteonecrosis (ROR:104.866), death (ROR: 3.645), pain (ROR:3.963), osteonecrosis of jaw (ROR: 91.744), tooth extraction (ROR: 142.143). Among overlap signals, Dmab showed higher strength in exostosis of the jaw (ROR: 182.66 vs. 5.769), atypical fractures (ROR: 55.589 vs. 9.123), and atypical femur fractures (ROR:49.824 vs. 4.968). And ZA exhibited stronger associations in abscess jaw (ROR: 84.119 vs. 11.12), gingival ulceration (ROR: 74.125 vs. 4.827), increased bone formation (ROR: 69.344 vs. 3.218). Additionally, we identified 528 off-label uses for Dmab and 206 for ZA, with Dmab mainly used in prostate cancer (1.04%), breast cancer (1.03%), and arthritis (0.42%), while ZA in breast cancer (3.21%), prostate cancer (2.48%), and neoplasm malignant (0.52%). For Dmab in breast cancer treatment, AEs included death (11.6%), disease progression (3.3%), and neutropenia (2.7%), while for ZA included death (19.8%), emotional disorder (12.9%), osteomyelitis (11.7%). For prostate cancer treatment, Dmab`s AEs were death (8.9%), prostate cancer metastatic (1.6%), renal impairment (1.7%), while ZA`s included death (34.4%), general physical health deterioration (19.9%), and hemoglobin decreased (18.9%).Conclusion: Our analysis of FAERS database provided postmarketing surveillance data and revealed different strengths of reported AE signals between Dmab and ZA in some of their common AEs. It’s also worth noting that both drugs have potential off-label applications, which could introduce new AEs. This highlights the necessity for safety monitoring when using Dmab and ZA off-label

Time-sequential color code division multiplexing holographic display with metasurface

Color metasurface holograms are powerful and versatile platforms for modulating the amplitude, phase, polarization, and other properties of light at multiple operating wavelengths. However, the current color metasurface holography can only realize static manipulation. In this study, we propose and demonstrate a multiplexing metasurface technique combined with multiwavelength code-division multiplexing (CDM) to realize dynamic manipulation. Multicolor code references are utilized to record information within a single metasurface and increase the information capacity and security for anti-cracks. A total of 48 monochrome images consisting of pure color characters and multilevel color video frames were reconstructed in dual polarization channels of the birefringent metasurface to exhibit high information density, and a video was displayed via sequential illumination of the corresponding code patterns to verify the ability of dynamic manipulation. Our approach demonstrates significant application potential in optical data storage, optical encryption, multiwavelength-versatile diffractive optical elements, and stimulated emission depletion microscopy