ABSTRACT
The similarity test of ship stiffened plate structures under underwater explosions is a cost-effective and efficient method to evaluate the vitality of ships and guide the design of their shock resistance. This study focuses on the nonlinear impact response model tests of ship stiffened plate structures and their similarity laws with actual ships. The vertical motion of the ship stiffened plate structure is characterized by the Hurst index, and an equivalent relationship between the Hurst index of the model and the prototype is derived from classical similarity law. Based on the Hurst index, a similarity transformation relationship between the strain signals of the model and prototype is established. To verify the conclusions, similarity experiments of underwater explosions were conducted on both the model and the prototype. The original signals were grouped by the natural vibration period to determine the variation of the Hurst index over time. The model experiment strain signals for each natural vibration period were converted and compared with the prototype experiment results to verify the method's effectiveness. Simultaneously, the Hurst index of the stiffened plate structure under explosive shock load and its similarity transformation relationship with the prototype were simulated and analyzed. This provides theoretical and technical support for conducting analogous nonlinear response experiments for ship underwater explosions.
ABSTRACT
Psoriasis is a common inflammatory skin disorder with no cure. Mesenchymal stem cells (MSCs) have immunomodulatory properties for psoriasis, but the therapeutic efficacies varied, and the molecular mechanisms were unknown. In this study, we improved the efficacy by enhancing the immunomodulatory effects of umbilical cord-derived MSCs (UC-MSCs). UC-MSCs stimulated by TNF-α and IFN-γ exhibited a better therapeutic effect in a mouse model of psoriasis. Single-cell RNA sequencing revealed that the stimulated UC-MSCs overrepresented a subpopulation expressing high tryptophanyl-tRNA synthetase 1 (WARS1). WARS1-overexpressed UC-MSCs treat psoriasis-like skin inflammation more efficiently than control UC-MSCs by restraining the proinflammatory macrophages. Mechanistically, WARS1 maintained a RhoA-Akt axis and governed the immunomodulatory properties of UC-MSCs. Together, we identify WARS1 as a master regulator of UC-MSCs with enhanced immunomodulatory capacities, which paves the way for the directed modification of UC-MSCs for escalated therapeutic efficacy.
Subject(s)
Immunomodulation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Mesenchymal Stem Cells/immunology , Animals , Mice , Humans , Mesenchymal Stem Cell Transplantation/methods , Tryptophan-tRNA Ligase/genetics , Psoriasis/immunology , Psoriasis/therapy , Disease Models, Animal , Single-Cell Analysis , Sequence Analysis, RNA , Umbilical Cord/cytology , Umbilical Cord/immunology , Mice, Inbred C57BL , Cells, CulturedABSTRACT
A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.
Subject(s)
Fructose , Humans , Animals , Mice , Fructose/metabolism , Chromatin/metabolism , Aldehyde Reductase/metabolism , Aldehyde Reductase/genetics , Leukemia/metabolism , Leukemia/pathology , Leukemia/genetics , Chromosomal Proteins, Non-Histone/metabolism , Chromosomal Proteins, Non-Histone/genetics , Chromatin Assembly and Disassembly , Carcinogenesis/metabolism , Carcinogenesis/pathology , Carcinogenesis/genetics , Cell Line, Tumor , Transcription Factors/metabolism , Transcription Factors/genetics , Adenosine TriphosphatasesABSTRACT
Chromothripsis, a type of complex chromosomal rearrangement originally known as chromoanagenesis, has been a subject of extensive investigation due to its potential role in various diseases, particularly cancer. Chromothripsis involves the rapid acquisition of tens to hundreds of structural rearrangements within a short period, leading to complex alterations in one or a few chromosomes. This phenomenon is triggered by chromosome missegregation during mitosis. Errors in accurate chromosome segregation lead to formation of aberrant structural entities such as micronuclei or chromatin bridges. The association between chromothripsis and cancer has attracted significant interest, with potential implications for tumorigenesis and disease prognosis. This review aims to explore the intricate mechanisms and consequences of chromothripsis, with a specific focus on its association with mitotic perturbations. Herein, we discuss a comprehensive analysis of crucial molecular entities and pathways, exploring the intricate roles of the CIP2A-TOPBP1 complex, micronuclei formation, chromatin bridge processing, DNA damage repair, and mitotic checkpoints. Moreover, the review will highlight recent advancements in identifying potential therapeutic targets and the underlying molecular mechanisms associated with chromothripsis, paving the way for future therapeutic interventions in various diseases.
ABSTRACT
A long-standing hypothesis proposes that certain RNA(s) must exhibit structural roles in microtubule assembly. Here, we identify a long noncoding RNA (TubAR) that is highly expressed in cerebellum and forms RNA-protein complex with TUBB4A and TUBA1A, two tubulins clinically linked to cerebellar and myelination defects. TubAR knockdown in mouse cerebellum causes loss of oligodendrocytes and Purkinje cells, demyelination, and decreased locomotor activity. Biochemically, we establish the roles of TubAR in promoting TUBB4A-TUBA1A heterodimer formation and microtubule assembly. Intriguingly, different from the hypomyelination-causing mutations, the non-hypomyelination-causing mutation TUBB4A-R2G confers gain-of-function for an RNA-independent interaction with TUBA1A. Experimental use of R2G/A mutations restores TUBB4A-TUBA1A heterodimer formation, and rescues the neuronal cell death phenotype caused by TubAR knockdown. Together, we uncover TubAR as the long-elusive structural RNA for microtubule assembly and demonstrate how TubAR mediates microtubule assembly specifically from αß-tubulin heterodimers, which is crucial for maintenance of cerebellar myelination and activity.
ABSTRACT
The main challenges (sluggish electron transfer, low energy density) hinder the future application of enzymatic biofuel cells (EBFCs), which urgent to take effective measures to solve these issues. In this work, a composite of Au nanoparticles decorated graphdiyne (AuNPs@GDY) is fabricated and employed as the carrier of enzyme (G6PDH), and a mechanism based on π-π interaction of electron transfer is proposed to understand bioelectrocatalysis processes. The results show that the AuNPs@GDY composite exhibits the highest current density among the three materials (GDY, AuNPs, and AuNPs@GDY), which is 3.4 times higher than that of GDY and 2.5 times higher than that of AuNPs. Furthermore, the results reveal that the AuNPs could increase the loading of enzymes and provide more active site for reaction, while GDY provides highly π-conjugated structure and unique sp/sp2-hybridized linkages interface. This work provides new insights to explore a theoretical basis for the development of more efficient bioelectrocatalytic systems.
Subject(s)
Bioelectric Energy Sources , Gold , Metal Nanoparticles , Gold/chemistry , Metal Nanoparticles/chemistry , Biocatalysis , Graphite/chemistry , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Electrochemical Techniques/methodsABSTRACT
The microbial hybrid system modified by magnetic nanomaterials can enhance the interfacial electron transfer and energy conversion under the stimulation of a magnetic field. However, the bioelectrocatalytic performance of a hybrid system still needs to be improved, and the mechanism of magnetic field-induced bioelectrocatalytic enhancements is still unclear. In this work, γ-Fe2O3 magnetic nanoparticles were coated on a Shewanella putrefaciens CN32 cell surface and followed by placing in an electromagnetic field. The results showed that the electromagnetic field can greatly boost the extracellular electron transfer, and the oxidation peak current of CN32@γ-Fe2O3 increased to 2.24 times under an electromagnetic field. The enhancement mechanism is mainly due to the fact that the surface modified microorganism provides an elevated contact area for the high microbial catalytic activity of the outer cell membrane's cytochrome, while the magnetic nanoparticles provide a networked interface between the cytoplasm and the outer membrane for boosting the fast multidimensional electron transport path in the magnetic field. This work sheds fresh scientific light on the rational design of magnetic-field-coupled electroactive microorganisms and the fundamentals of an optimal interfacial structure for a fast electron transfer process toward an efficient bioenergy conversion.
ABSTRACT
Salinity, as one of the most challenging environmental factors restraining crop growth and yield, poses a severe threat to global food security. To address the rising food demand, it is urgent to develop crop varieties with enhanced yield and greater salt tolerance by delving into genes associated with salt tolerance and high-yield traits. MiR396b/GRF6 module has previously been demonstrated to increase rice yield by shaping the inflorescence architecture. In this study, we revealed that miR396b/GRF6 module can significantly improve salt tolerance of rice. In comparison with the wild type, the survival rate of MIM396 and OE-GRF6 transgenic lines increased by 48.0% and 74.4%, respectively. Concurrent with the increased salt tolerance, the transgenic plants exhibited reduced H2O2 accumulation and elevated activities of ROS-scavenging enzymes (CAT, SOD and POD). Furthermore, we identified ZNF9, a negative regulator of rice salt tolerance, as directly binding to the promoter of miR396b to modulate the expression of miR396b/GRF6. Combined transcriptome and ChIP-seq analysis showed that MYB3R serves as the downstream target of miR396b/GRF6 in response to salt tolerance, and overexpression of MYB3R significantly enhanced salt tolerance. In conclusion, this study elucidated the potential mechanism underlying the response of the miR396b/GRF6 network to salt stress in rice. These findings offer a valuable genetic resource for the molecular breeding of high-yield rice varieties endowed with stronger salt tolerance.
Subject(s)
Gene Expression Regulation, Plant , MicroRNAs , Oryza , Plant Proteins , Plants, Genetically Modified , Salt Tolerance , Oryza/genetics , Oryza/metabolism , Oryza/physiology , Oryza/growth & development , Salt Tolerance/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Plants, Genetically Modified/genetics , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
Protein domains with conserved amino acid sequences and uncharacterized functions are called domains of unknown function (DUF). The DUF640 gene family plays a crucial role in plant growth, particularly in light regulation, floral organ development, and fruit development. However, there exists a lack of systematic understanding of the evolutionary relationships and functional differentiation of DUF640 within the Oryza genus. In this study, 61 DUF640 genes were identified in the Oryza genus. The expression of DUF640s is induced by multiple hormonal stressors including abscisic acid (ABA), cytokinin (CK), ethylene (ETH), and indole-3-acetic acid (IAA). Specifically, OiDUF640-10 expression significantly increased after ETH treatment. Transgenic experiments showed that overexpressing OiDUF640-10 lines were sensitive to ETH, and seedling length was obstructed. Evolutionary analysis revealed differentiation of the OiDUF640-10 gene in O. sativa ssp. indica and japonica varieties, likely driven by natural selection during the domestication of cultivated rice. These results indicate that OiDUF640-10 plays a vital role in the regulation of rice seedling length.
Subject(s)
Gene Expression Regulation, Plant , Oryza , Plant Proteins , Oryza/genetics , Oryza/growth & development , Plant Proteins/genetics , Plant Proteins/metabolism , Phylogeny , Plant Growth Regulators/metabolism , Plants, Genetically Modified/genetics , Evolution, Molecular , Indoleacetic Acids/metabolism , Genes, Plant , Seedlings/genetics , Seedlings/growth & development , Abscisic Acid/metabolism , Abscisic Acid/pharmacology , Ethylenes/metabolismABSTRACT
Although the dynamic instability of microtubules (MTs) is fundamental to many cellular functions, quiescent MTs with unattached free distal ends are commonly present and play important roles in various events to power cellular dynamics. However, how these free MT tips are stabilized remains poorly understood. Here, we report that centrosome and spindle pole protein 1 (CSPP1) caps and stabilizes both plus and minus ends of static MTs. Real-time imaging of laser-ablated MTs in live cells showed deposition of CSPP1 at the newly generated MT ends, whose dynamic instability was concomitantly suppressed. Consistently, MT ends in CSPP1-overexpressing cells were hyper-stabilized, while those in CSPP1-depleted cells were much more dynamic. This CSPP1-elicited stabilization of MTs was demonstrated to be achieved by suppressing intrinsic MT catastrophe and restricting polymerization. Importantly, CSPP1-bound MTs were resistant to mitotic centromere-associated kinesin-mediated depolymerization. These findings delineate a previously uncharacterized CSPP1 activity that integrates MT end capping to orchestrate quiescent MTs.
Subject(s)
Microtubule-Associated Proteins , Microtubules , Microtubules/metabolism , Humans , Microtubule-Associated Proteins/metabolism , Animals , Kinesins/metabolism , Kinesins/genetics , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Spindle Apparatus/metabolismABSTRACT
In eukaryotes, microtubule polymers are essential for cellular plasticity and fate decisions. End-binding (EB) proteins serve as scaffolds for orchestrating microtubule polymer dynamics and are essential for cellular dynamics and chromosome segregation in mitosis. Here, we show that EB1 forms molecular condensates with TIP150 and MCAK through liquid-liquid phase separation to compartmentalize the kinetochore-microtubule plus-end machinery, ensuring accurate kinetochore-microtubule interactions during chromosome segregation in mitosis. Perturbation of EB1-TIP150 polymer formation by a competing peptide prevents phase separation of the EB1-mediated complex and chromosome alignment at the metaphase equator in both cultured cells and Drosophila embryos. Lys220 of EB1 is dynamically acetylated by p300/CBP-associated factor in early mitosis, and persistent acetylation at Lys220 attenuates the phase separation of the EB1-mediated complex, dissolves droplets in vitro, and harnesses accurate chromosome segregation. Our data suggest a novel framework for understanding the organization and regulation of eukaryotic spindle for accurate chromosome segregation in mitosis.
ABSTRACT
Micropeptides encoded by short open reading frames (sORFs) within long noncoding RNAs (lncRNAs) are beginning to be discovered and characterized as regulators of biological and pathological processes. Here, we find that lncRNA Dleu2 encodes a 17-amino-acid micropeptide, which we name Dleu2-17aa, that is abundantly expressed in T cells. Dleu2-17aa promotes inducible regulatory T (iTreg) cell generation by interacting with SMAD Family Member 3 (Smad3) and enhancing its binding to the Foxp3 conserved non-coding DNA sequence 1 (CNS1) region. Importantly, the genetic deletion of Dleu2-17aa in mice by start codon mutation impairs iTreg generation and worsens experimental autoimmune encephalomyelitis (EAE). Conversely, the exogenous supplementation of Dleu2-17aa relieves EAE. Our findings demonstrate an indispensable role of Dleu2-17aa in maintaining immune homeostasis and suggest therapeutic applications for this peptide in treating autoimmune diseases.
Subject(s)
Encephalomyelitis, Autoimmune, Experimental , RNA, Long Noncoding , Animals , Mice , Autoimmunity , Peptides/metabolism , RNA, Long Noncoding/genetics , T-Lymphocytes, Regulatory/metabolismABSTRACT
Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules. Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network (CCAN) during chromosome segregation. CCAN contains 16 subunits, including CENP-W and CENP-T. However, the molecular recognition and mitotic regulation of the CCAN assembly remain elusive. Here, we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T. Aurora B phosphorylates CENP-W at Thr60, which enhances the interaction between CENP-W and CENP-T to ensure robust metaphase chromosome alignment and accurate chromosome segregation in mitosis. These findings delineate a conserved signaling cascade that integrates protein phosphorylation with CCAN integrity for the maintenance of genomic stability.
ABSTRACT
Camellia oleifera Abel, a woody oil plant, that is endemic to China. Tea oil, also referred to as "oriental olive oil," is a superior quality plant-based cooking oil. The production of tea oil accounts for 8% of the total edible vegetable oil production in the country. Since 2022, the annual output value of C. oleifera industry has exceeded 100 billion yuan, making it one of the major economic contributors to China's rural revitalization development strategy. In recent years, demand and production have grown in parallel. However, this has led to an increase in the incidence levels of pest and diseases. Pests and diseases significantly reduce the quality and yield of C. oleifera. C. oleifera diseases are mainly caused by pathogenic fungi. C. oleifera anthracnose, soft rot, leaf spot, coal stain, leaf gall disease, and root rot are the most important fungal diseases affecting the C. oleifera industry. However, the same disease may be caused by different pathogenic fungi. C. oleifera can be found in half of China and is found in several climatic zones. The geographical distribution of woody plant diseases is consistent with the distribution of the tree species and the ecology of the range, which also results in a highly complex distribution of fungal diseases of C. oleifera. The management of fungal diseases in C. oleifera is extremely challenging due to the variety of pathogenic fungal species, multiple routes of transmission, the lack of resistant plants, and the environmental safety of chemical measures. The optimal strategy for addressing fungal diseases in C. oleifera is to develop and apply an integrated disease management plan. This review provides a brief overview of the pathogenic species, pathogenesis, pathogenesis, geographical distribution, current management strategies, and potentially new methods of C. oleifera fungal diseases, to provide direction for the development of comprehensive management measures for C. oleifera fungal diseases in the future.
ABSTRACT
Shugoshin-1 (Sgo1) is necessary for maintaining sister centromere cohesion and ensuring accurate chromosome segregation during mitosis. It has been reported that the localization of Sgo1 at the centromere is dependent on Bub1-mediated phosphorylation of histone H2A at T120. However, it remains uncertain whether other centromeric proteins play a role in regulating the localization and function of Sgo1 during mitosis. Here, we show that CENP-A interacts with Sgo1 and determines the localization of Sgo1 to the centromere during mitosis. Further biochemical characterization revealed that lysine and arginine residues in the C-terminal domain of Sgo1 are critical for binding CENP-A. Interestingly, the replacement of these basic amino acids with acidic amino acids perturbed the localization of Sgo1 and Aurora B to the centromere, resulting in aberrant chromosome segregation and premature chromatid separation. Taken together, these findings reveal a previously unrecognized but direct link between Sgo1 and CENP-A in centromere plasticity control and illustrate how the Sgo1-CENP-A interaction guides accurate cell division.
ABSTRACT
Microplastics/nanoplastics (MNPs) pollution in different environmental media and its adverse effects on organisms have received increasing attention from researchers. This paper compares the effects of natural concentrations of three different sizes (20 nm, 200 nm, and 2 µm) of MNPs on Vallisneria natans and sediments. MNPs with smaller sizes adhere more readily to V. natans roots, further promoting root elongation. In addition, the larger the particle size of MNPs, the higher the reactive oxygen species level in the roots, and the malondialdehyde level increased accordingly. In the sediment, 20 nm, and 200 nm MNPs increased the activity of related enzymes, including acid phosphatase, urease, and nitrate reductase. In addition, the dehydrogenase content in the treated sediments increased, and the content changes were positively correlated with the size of MNPs. Changes in microorganisms were only observed on the root surface. The addition of MNPs reduced the abundance of Proteobacteria and increased the abundance of Chloroflexi. In addition, at the class level of species composition on the root surface, the abundance of Gammaproteobacteria under the 20 nm, 200 nm, and 2 µm MNP treatments decreased by 21.19%, 16.14%, and 17.03%, respectively, compared with the control group, while the abundance of Anaerolineae increased by 44.63%, 26.31%, and 62.52%, respectively. These findings enhance the understanding of the size effects of MNPs on the roots of submerged plants and sediment.
Subject(s)
Chloroflexi , Hydrocharitaceae , Microbiota , Microplastics , PlasticsABSTRACT
Background: Current expectations are that surgeons should be technically proficient in minimally invasive low anterior resection (LAR)-both laparoscopic and robotic-assisted surgery. However, methods to effectively train surgeons for both approaches are under-explored. We aimed to compare two different training programs for minimally invasive LAR, focusing on the learning curve and perioperative outcomes of two trainee surgeons. Methods: We reviewed 272 consecutive patients undergoing laparoscopic or robotic LAR by surgeons A and B, who were novices in conducting minimally invasive colorectal surgery. Surgeon A was trained by first operating on 80 cases by laparoscopy and then 56 cases by robotic-assisted surgery. Surgeon B was trained by simultaneously performing 80 cases by laparoscopy and 56 by robotic-assisted surgery. The cumulative sum (CUSUM) method was used to evaluate the learning curves of operative time and surgical failure. Results: For laparoscopic surgery, the CUSUM plots showed a longer learning process for surgeon A than surgeon B (47 vs. 32 cases) for operative time, but a similar trend in surgical failure (23 vs. 19 cases). For robotic surgery, the plots of the two surgeons showed similar trends for both operative times (23 vs. 25 cases) and surgical failure (17 vs. 19 cases). Therefore, the learning curves of surgeons A and B were respectively divided into two phases at the 47th and 32nd cases for laparoscopic surgery and at the 23rd and 25th cases for robotic surgery. The clinicopathological outcomes of the two surgeons were similar in each phase of the learning curve for each surgery. Conclusions: For surgeons with rich experience in open colorectal resections, simultaneous training for laparoscopic and robotic-assisted LAR of rectal cancer is safe, effective, and associated with accelerated learning curves.
ABSTRACT
Atopic dermatitis (AD) is a common inflammatory skin disorder. Mast cells play an important role in AD because they regulate allergic reactions and inflammatory responses. However, whether and how the modulation of mast cell activity affects AD has not been determined. In this study, we aimed to determine the effects and mechanisms of 3-O-cyclohexanecarbonyl-11-keto-ß-boswellic acid (CKBA). This natural compound derivative alleviates skin inflammation by inhibiting mast cell activation and maintaining skin barrier homeostasis in AD. CKBA markedly reduced serum IgE levels and alleviated skin inflammation in calcipotriol (MC903)-induced AD mouse model. CKBA also restrained mast cell degranulation both in vitro and in vivo. RNA-seq analysis revealed that CKBA downregulated the extracellular signal-regulated kinase (ERK) signaling in BM-derived mast cells activated by anti-2,4-dinitrophenol/2,4-dinitrophenol-human serum albumin. We proved that CKBA suppressed mast cell activation via ERK signaling using the ERK activator (t-butyl hydroquinone) and inhibitor (selumetinib; AZD6244) in AD. Thus, CKBA suppressed mast cell activation in AD via the ERK signaling pathway and could be a therapeutic candidate drug for AD.
Subject(s)
Dermatitis, Atopic , Mice , Humans , Animals , Dermatitis, Atopic/drug therapy , Mast Cells/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Immunoglobulin E/metabolism , Signal Transduction , Inflammation/metabolism , Dinitrophenols/metabolism , Dinitrophenols/pharmacology , Dinitrophenols/therapeutic use , Cytokines/metabolismABSTRACT
[This corrects the article DOI: 10.3389/fpls.2023.1174955.].