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1.
Plant Physiol ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701036

ABSTRACT

The strong ability of plants to regenerate wounds is exemplified by grafting when two plants are cut and joined together to grow as one. During graft healing, tissues attach, cells proliferate, and the vasculatures connect to form a graft union. The plant hormone auxin plays a central role, and auxin-related mutants perturb grafting success. Here, we investigated the role of individual cell types and their response to auxin during Arabidopsis (Arabidopsis thaliana) graft formation. By employing a cell-specific inducible misexpression system, we blocked auxin response in individual cell types using the bodenlos mutation. We found that auxin signaling in procambial tissues was critical for successful tissue attachment and vascular differentiation. In addition, we found that auxin signaling was required for cell divisions of the procambial cells during graft formation. Loss of function mutants in cambial pathways also perturbed attachment and phloem reconnection. We propose that cambial and procambial tissues drive tissue attachment and vascular differentiation during successful grafting. Our study thus refines our knowledge of graft development and furthers our understanding of the regenerative role of the cambium.

2.
FASEB J ; 38(1): e23394, 2024 01.
Article in English | MEDLINE | ID: mdl-38149910

ABSTRACT

Neutrophils and their production of neutrophil extracellular traps (NETs) significantly contribute to neuroinflammation and brain damage after intracerebral hemorrhage (ICH). Although Akebia saponin D (ASD) demonstrates strong anti-inflammatory activities and blood-brain barrier permeability, its role in regulating NETs formation and neuroinflammation following ICH is uncharted. Our research focused on unraveling the influence of ASD on neuroinflammation mediated by NETs and the mechanisms involved. We found that increased levels of peripheral blood neutrophils post-ICH are correlated with worse prognostic outcomes. Through network pharmacology, we identified ASD as a promising therapeutic target for ICH. ASD administration significantly improved neurobehavioral performance and decreased NETs production in neutrophils. Furthermore, ASD was shown to upregulate the membrane protein NTSR1 and activate the cAMP signaling pathway, confirmed through transcriptome sequencing, western blot, and immunofluorescence. Interestingly, the NTSR1 inhibitor SR48692 significantly nullified ASD's anti-NETs effects and dampened cAMP pathway activation. Mechanistically, suppression of PKAc via H89 negated ASD's anti-NETs effects but did not affect NTSR1. Our study suggests that ASD may reduce NETs formation and neuroinflammation, potentially involving the NTSR1/PKAc/PAD4 pathway post-ICH, underlining the potential of ASD in mitigating neuroinflammation through its anti-NETs properties.


Subject(s)
Cerebral Hemorrhage , Extracellular Traps , Neuroinflammatory Diseases , Saponins , Network Pharmacology , Gene Expression Profiling , Saponins/pharmacology , Extracellular Traps/drug effects , Neuroinflammatory Diseases/drug therapy , Cerebral Hemorrhage/drug therapy , Humans , Animals , Rats , Rats, Sprague-Dawley , Signal Transduction , Receptors, Neurotensin/metabolism , Protein-Arginine Deiminase Type 4/metabolism
3.
Lancet Oncol ; 25(6): e270-e280, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38821101

ABSTRACT

Although radiotherapy continues to evolve as a mainstay of the oncological armamentarium, research and innovation in radiotherapy in low-income and middle-income countries (LMICs) faces challenges. This third Series paper examines the current state of LMIC radiotherapy research and provides new data from a 2022 survey undertaken by the International Atomic Energy Agency and new data on funding. In the context of LMIC-related challenges and impediments, we explore several developments and advances-such as deep phenotyping, real-time targeting, and artificial intelligence-to flag specific opportunities with applicability and relevance for resource-constrained settings. Given the pressing nature of cancer in LMICs, we also highlight some best practices and address the broader need to develop the research workforce of the future. This Series paper thereby serves as a resource for radiation professionals.


Subject(s)
Developing Countries , Neoplasms , Radiation Oncology , Humans , Developing Countries/economics , Neoplasms/radiotherapy , Radiation Oncology/economics , Biomedical Research/economics , Radiotherapy/economics , Poverty
4.
J Struct Biol ; 216(1): 108059, 2024 03.
Article in English | MEDLINE | ID: mdl-38160703

ABSTRACT

Cryogenic electron microscopy maps are valuable for determining macromolecule structures. A proper quality assessment method is essential for cryo-EM map selection or revision. This article presents DeepQs, a novel approach to estimate local quality for 3D cryo-EM density maps, using a deep-learning algorithm based on map-model fit score. DeepQs is a parameter-free method for users and incorporates structural information between map and its related atomic model into well-trained models by deep learning. More specifically, the DeepQs approach leverages the interplay between map and atomic model through predefined map-model fit score, Q-score. DeepQs can get close results to the ground truth map-model fit scores with only cryo-EM map as input. In experiments, DeepQs demonstrates the lowest root mean square error with standard method Fourier shell correlation metric and high correlation with map-model fit score, Q-score, when compared with other local quality estimation methods in high-resolution dataset (<=5 Å). DeepQs can also be applied to evaluate the quality of the post-processed maps. In both cases, DeepQs runs faster by using GPU acceleration. Our program is available at http://www.csbio.sjtu.edu.cn/bioinf/DeepQs for academic use.


Subject(s)
Deep Learning , Cryoelectron Microscopy/methods , Models, Molecular , Microscopy, Electron , Algorithms , Protein Conformation
5.
J Am Chem Soc ; 146(9): 6397-6407, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38394777

ABSTRACT

Catalyst supports play an essential role in catalytic reactions, hinting at pronounced metal-support effects. Zeolites are a propitious support in heterogeneous catalysts, while their use in the electrocatalytic CO2 reduction reaction has been limited as yet because of their electrically insulating nature and serious competing hydrogen evolution reaction (HER). Enlightened by theoretical prediction, herein, we implant zinc ions into the structural skeleton of a zeolite Y to strategically tailor a favorable electrocatalytic platform with remarkably enhanced electronic conduction and strong HER inhibition capability, which incorporates ultrafine cadmium oxide nanoclusters as guest species into the supercages of the tailored 12-ring window framework. The metal d-bandwidth tuning of cadmium by skeletal zinc steers the extent of substrate-molecule orbital mixing, enhancing the stabilization of the key intermediate *COOH while weakening the CO poisoning effect. Furthermore, the strong cadmium-zinc interplay causes a considerable thermodynamic barrier for water dissociation in the conversion of H+ to *H, potently suppressing the competing HER. Therefore, we achieve an industrial-level partial current density of 335 mA cm-2 and remarkable Faradaic efficiency of 97.1% for CO production and stably maintain Faradaic efficiency above 90% at the industrially relevant current density for over 120 h. This work provides a proof of concept of tailored conductive zeolite as a favorable electrocatalytic support for industrial-level CO2 electrolysis and will significantly enhance the adaptability of conductive zeolite-based electrocatalysts in a variety of electrocatalysis and energy conversion applications.

6.
Int J Cancer ; 154(7): 1143-1157, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38059788

ABSTRACT

Radiotherapy has unique immunostimulatory and immunosuppressive effects. Although high-dose radiotherapy has been found to have systemic antitumor effects, clinically significant abscopal effects were uncommon on the basis of irradiating single lesion. Low-dose radiation therapy (LDRT) emerges as a novel approach to enhance the antitumor immune response due to its role as a leverage to reshape the tumor immune microenvironment (TIME). In this article, from bench to bedside, we reviewed the possible immunomodulatory role of LDRT on TIME and systemic tumor immune environment, and outlined preclinical evidence and clinical application. We also discussed the current challenges when LDRT is used as a combination therapy, including the optimal dose, fraction, frequency, and combination of drugs. The advantage of low toxicity makes LDRT potential to be applied in multiple lesions to amplify antitumor immune response in polymetastatic disease, and its intersection with other disciplines might also make it a direction for radiotherapy-combined modalities.


Subject(s)
Neoplasms , Humans , Neoplasms/radiotherapy , Forecasting , Immunity , Combined Modality Therapy , Immunomodulation , Immunotherapy , Tumor Microenvironment
7.
Mol Biol Evol ; 40(1)2023 01 04.
Article in English | MEDLINE | ID: mdl-36625089

ABSTRACT

Determining the functional consequences of karyotypic changes is invariably challenging because evolution tends to obscure many of its own footprints, such as accumulated mutations, recombination events, and demographic perturbations. Here, we describe the assembly of a chromosome-level reference genome of the gayal (Bos frontalis) thereby revealing the structure, at base-pair-level resolution, of a telo/acrocentric-to-telo/acrocentric Robertsonian translocation (2;28) (T/A-to-T/A rob[2;28]). The absence of any reduction in the recombination rate or genetic introgression within the fusion region of gayal served to challenge the long-standing view of a role for fusion-induced meiotic dysfunction in speciation. The disproportionate increase noted in the distant interactions across pro-chr2 and pro-chr28, and the change in open-chromatin accessibility following rob(2;28), may, however, have led to the various gene expression irregularities observed in the gayal. Indeed, we found that many muscle-related genes, located synthetically on pro-chr2 and pro-chr28, exhibited significant changes in expression. This, combined with genome-scale structural variants and expression alterations in genes involved in myofibril composition, may have driven the rapid sarcomere adaptation of gayal to its rugged mountain habitat. Our findings not only suggest that large-scale chromosomal changes can lead to alterations in genome-level expression, thereby promoting both adaptation and speciation, but also illuminate novel avenues for studying the relationship between karyotype evolution and speciation.


Subject(s)
Chromatin , Genome , Animals , Cattle
8.
Gastroenterology ; 165(3): 629-646, 2023 09.
Article in English | MEDLINE | ID: mdl-37247644

ABSTRACT

BACKGROUND & AIMS: Hyperactivation of ribosome biogenesis leads to hepatocyte transformation and plays pivotal roles in hepatocellular carcinoma (HCC) development. We aimed to identify critical ribosome biogenesis proteins that are overexpressed and crucial in HCC progression. METHODS: HEAT repeat containing 1 (HEATR1) expression and clinical correlations were analyzed using The Cancer Genome Atlas and Gene Expression Omnibus databases and further evaluated by immunohistochemical analysis of an HCC tissue microarray. Gene expression was knocked down by small interfering RNA. HEATR1-knockdown cells were subjected to viability, cell cycle, and apoptosis assays and used to establish subcutaneous and orthotopic tumor models. Chromatin immunoprecipitation and quantitative polymerase chain reaction were performed to detect the association of candidate proteins with specific DNA sequences. Endogenous coimmunoprecipitation combined with mass spectrometry was used to identify protein interactions. We performed immunoblot and immunofluorescence assays to detect and localize proteins in cells. The nucleolus ultrastructure was detected by transmission electron microscopy. Click-iT (Thermo Fisher Scientific) RNA imaging and puromycin incorporation assays were used to measure nascent ribosomal RNA and protein synthesis, respectively. Proteasome activity, 20S proteasome foci formation, and protein stability were evaluated in HEATR1-knockdown HCC cells. RESULTS: HEATR1 was the most up-regulated gene in a set of ribosome biogenesis mediators in HCC samples. High expression of HEATR1 was associated with poor survival and malignant clinicopathologic features in patients with HCC and contributed to HCC growth in vitro and in vivo. HEATR1 expression was regulated by the transcription factor specificity protein 1, which can be activated by insulin-like growth factor 1-mammalian target of rapamycin complex 1 signaling in HCC cells. HEATR1 localized predominantly in the nucleolus, bound to ribosomal DNA, and was associated with RNA polymerase I transcription/processing factors. Knockdown of HEATR1 disrupted ribosomal RNA biogenesis and impaired nascent protein synthesis, leading to reduced cytoplasmic proteasome activity and inhibitory-κB/nuclear factor-κB signaling. Moreover, HEATR1 knockdown induced nucleolar stress with increased nuclear proteasome activity and inactivation of the nucleophosmin 1-MYC axis. CONCLUSIONS: Our study revealed that HEATR1 is up-regulated by insulin-like growth factor 1-mammalian target of rapamycin complex 1-specificity protein 1 signaling in HCC and functions as a crucial regulator of ribosome biogenesis and proteome homeostasis to promote HCC development.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Homeostasis , Hot Temperature , Insulin-Like Growth Factor I/genetics , Liver Neoplasms/pathology , Mechanistic Target of Rapamycin Complex 1/metabolism , Proteasome Endopeptidase Complex/genetics , Proteome/metabolism , Ribosomes/metabolism , Ribosomes/pathology , RNA, Ribosomal/genetics , RNA, Ribosomal/metabolism
9.
Biochem Biophys Res Commun ; 692: 149360, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38081108

ABSTRACT

BACKGROUND: Myocardial infarction (MI) dramatically changes the mechanical stress, which is intensified by the fibrotic remodeling. Integrins, especially the αV subunit, mediate mechanical signal and mechanoparacrine of transforming growth factor ß1 (TGF-ß1) in various organ fibrosis by activating CFs into myofibroblasts (MFBs). We investigated a possible role of integrin αV mediated mechanoparacrine of TGF-ß1 in MFBs activation for fibrous reparation in mice with MI. METHODS: Heart samples from MI, sham, or MI plus cilengitide (14 mg/kg, specific integrin αV inhibitor) treated mice, underwent functional and morphological assessments by echocardiography, and histochemistry on 7, 14 and 28 days post-surgery. The mechanical and ultrastructural changes of the fibrous scar were further evaluated by atomic mechanics microscope (AFM), immunofluorescence, second harmonic generation (SHG) imaging, polarized light and scanning electron microscope, respectively. Hydroxyproline assay was used for total collagen content, and western blot for protein expression profile examination. Fibroblast bioactivities, including cell shape, number, Smad2/3 signal and expression of extracellular matrix (ECM) related proteins, were further evaluated by microscopic observation and immunofluorescence in polyacrylamide (PA) hydrogel with adjustable stiffness, which was re-explored in fibroblast cultured on stiff matrix after silencing of integrin αV. The content of total and free TGF-ß1 was tested by enzyme-linked immunosorbent assay (ELISA) in both infarcted tissue and cell samples. RESULT: Increased stiffness with heterogeneity synchronized with integrin αV and alpha smooth muscle actin (α-SMA) positive MFBs accumulation in those less mature fibrous areas. Cilengitide abruptly reduced collagen content and disrupted collagen alignment, which also decreased TGF-ß1 bioavailability, Smad2/3 phosphorylation, and α-SMA expression in the fibrous area. Accordingly, fibroblast on stiff but not soft matrix exhibited obvious MFB phenotype, as evidenced by enlarged cell, hyperproliferation, well-developed α-SMA fibers, and elevated ECM related proteins, while silencing of integrin αV almost abolished this switch via attenuating paracrine of TGF-ß1 and nuclear translocation of Smad2/3. CONCLUSION: This study illustrated that increased tissue stiffness activates CFs into MFBs by integrin αV mediated mechanoparacrine of TGF-ß1, especially in immature scar area, which ultimately promotes fibrous scar maturation.


Subject(s)
Myocardial Infarction , Myofibroblasts , Animals , Mice , Actins/metabolism , Cicatrix/metabolism , Collagen/metabolism , Extracellular Matrix Proteins/metabolism , Fibroblasts/metabolism , Fibrosis , Integrin alphaV/metabolism , Myocardial Infarction/pathology , Myofibroblasts/metabolism , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1/metabolism
10.
Dev Neurosci ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38955163

ABSTRACT

INTRODUCTION: Neurosteroids have a variety of neurological functions, such as neurite growth, neuroprotection, myelination, and neurogenesis. P450scc, encoded by CYP11A1 gene, is the cholesterol side chain cleavage enzyme that catalyzes the first and rate limiting step in the steroidogenesis. In this study, we examine the dendritic morphology in developing hippocampal neurons of Cyp11a1 null mice at P15, a critical period for synapse formation and maturation. METHODS: Knockout mice were maintained until P15 with hormone administration. The Golgi-Cox method stained CA1 and CA3 pyramidal neurons in the hippocampus to reveal dendritic morphology. RESULTS: We demonstrated that Cyp11a1 null mice usually die within 7 days after birth and thus collected brain samples at postnatal day 5 (P5) for examination. There were significant shrinkage of dendrite size and diminishment of dendritic branching in CA1 and CA3 pyramidal neurons in the hippocampus of Cyp11a1 null mice, suggesting a developmental delay. We wonder if this delay may catch up later in life. Since the age of P15 is a critical period for synapse formation and maturation, the Cyp11a1 null mice were rescued by receiving hormone administration until P15 that the dendritic morphology in the developing hippocampal neurons could be examined. The results indicated that the total dendritic length, number of dendritic branches, as well as dendritic arborization in the CA1 and CA3 pyramidal neurons are significantly decreased in P15 knockout mice when compared to the wild type. The spine densities were also significantly decreased. In addition, the western blot analysis revealed decrease PSD-95 expression levels in the knockout mice compared to the wild type at P15. CONCLUSION: These results suggested that Cyp11a1 deficiency impairs the dendritic structures in the developing hippocampal pyramidal neurons.

11.
Small ; : e2311821, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38597689

ABSTRACT

Lithium-air battery (LAB) is regarded as one of the most promising energy storage systems. However, the challenges arising from the lithium metal anode have significantly impeded the progress of LAB development. In this study, cellulose-based filter paper (FP) is utilized as a separator for ambient Li-air batteries to suppress dendrite growth and prevent H2O crossover. Thermogravimetric analysis and molecular spectrum reveal that FP enables ambient Li-air battery operation due to its surface functional groups derived from cellulose. The oxygen-enriched surface of cellulose not only enhances ion conductivity but also captures water and confines solvent molecules, thereby mitigating anode corrosion and side reactions. Compared with commercial glassfiber (GF) separator, this cellulose-based FP separator is cheaper, renewable, and environmentally friendly. Moreover, it requires less electrolyte while achieving prolonged and stable cycle life under real air environment conditions. This work presents a novel approach to realizing practical Li-air batteries by capturing water on the separator's surface. It also provides insights into the exploration and design of separators for enabling practical Li-air batteries toward their commercialization.

12.
Small ; : e2309646, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38676330

ABSTRACT

The long-term stability of perovskite solar cells (PSCs) is still challenging for commercialization and mainly linked to the life span of perovskite films. Herein, a spontaneous compositional-interfacial co-modification strategy is developed based on the ion exchange reaction by introducing ammonium hexafluorophosphate (NH4PF6) into antisolvent to form gradient structures through a simple one-step solvent engineering. With the assistance of the ion exchange reaction, NH4PF6 forms a multifunctional structure to protect perovskite films from both internal and external factors for the exceptionally long-term stability of photovoltaics. The reason for this is linked to the high hydrophobicity of NH4PF6 for preventing H2O invasion, suppressing ion migration by forming hydrogen bonding, and reducing perovskite defects. The resulting unencapsulated devices show exceptionally long-term stability under standardized the International Summit on Organic Photovoltaic Stability (ISOS) protocols, with over 94%, 81%, and 83% retained power conversion efficiencies after aging tests under N2 (ISOS-D-1I), ambient air (ISOS-D-1), and 85 °C (ISOS-D-2I) for 14016, 2500, and 1248 h, respectively. These performances compare well with the state-of-the-art stability of inverted PSCs. Further investigations are conducted to study the evolution of macroscopic morphology and microscopic crystal structure in aged perovskite films, aiming to provide evidence supporting the aforementioned improvements in stability.

13.
Small ; : e2401921, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813749

ABSTRACT

Lithium-sulfur (Li-S) batteries are one of the most promising energy storage devices due to their environmental friendliness, low cost, and high specific capacity. However, the slow electrochemical kinetics and the "shuttle effect" have seriously hindered their commercialization. Herein, the nanoflower Bi2S3─MoS2 (BMS) heterostructure is synthesized by a two-step hydrothermal method, and then the Bi2S3─MoS2-Polypropylene (BMS-PP) interlayer is constructed. The heterostructure is rich in active sites, in which BMS has strong adsorption to lithium polysulfides (LiPSs) and can effectively anchor LiPSs while catalyzing LiPSs and promote the redox of Li2S at the same time, which can improve the utilization of active substances. More importantly, the d-band center can be tuned by the formation of Bi2S3─MoS2 heterostructure. Thus, Li-S batteries containing the BMS-PP interlayer show excellent rate performance (841.6 mAh g-1 at 5 C) and cycling performance (70.3% capacity retention after 500 cycles at 3 C). This work provides a new route for high-performance lithium-sulfur batteries.

14.
Fungal Genet Biol ; 173: 103908, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38857848

ABSTRACT

Reductive assimilation pathway involves ferric reductase and ferrous iron transporter, which is integral for fungal iron acquisition. A family of ferric reductase-like proteins has been functionally characterized in the filamentous entomopathogenic fungus Beauveria bassiana. In this investigation, two ferrous iron transporter-like proteins (Ftr) were functionally annotated in B. bassiana. BbFtr1 and BbFtr2 displayed high similarity in structure and were associated with the plasma and nuclear membrane. Their losses had no negatively influence on fungal growth on various nutrients and development under the iron-replete condition. Single mutants of BbFTR1 and BbFTR2 displayed the iron-availability dependent developmental defects, and double mutant exhibited the significantly impaired developmental potential under the iron-limited conditions. In insect bioassay, the double mutant also showed the weaker virulence than either of two single disruption mutants. These results suggested that two ferrous iron transporter-like proteins function independently in fungal physiologies under the iron-deficient condition. Intriguingly, a bZIP transcription factor BbHapX was required for expression of BbFTR1 and BbFTR2 under iron-depleted conditions. This study enhances our understanding of the iron uptake system in the filamentous entomopathogenic fungi.

15.
Plant Physiol ; 194(1): 229-242, 2023 Dec 30.
Article in English | MEDLINE | ID: mdl-37311199

ABSTRACT

Parasitic plants are globally prevalent pathogens with important ecological functions but also potentially devastating agricultural consequences. Common to all parasites is the formation of the haustorium which requires parasite organ development and tissue invasion into the host. Both processes involve cell wall modifications. Here, we investigated a role for pectins during haustorium development in the facultative parasitic plant Phtheirospermum japonicum. Using transcriptomics data from infected Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), we identified genes for multiple P. japonicum pectin methylesterases (PMEs) and their inhibitors (PMEIs) whose expression was upregulated by haustoria formation. Changes in PME and PMEI expression were associated with tissue-specific modifications in pectin methylesterification. While de-methylesterified pectins were present in outer haustorial cells, highly methylesterified pectins were present in inner vascular tissues, including the xylem bridge that connects parasite to host. Specifically blocking xylem bridge formation in the haustoria inhibited several PME and PMEI genes from activating. Similarly, inhibiting PME activity using chemicals or by overexpressing PMEI genes delayed haustoria development. Our results suggest a dynamic and tissue-specific regulation of pectin contributes to haustoria initiation and to the establishment of xylem connections between parasite and host.


Subject(s)
Arabidopsis , Orobanchaceae , Pectins/metabolism , Plants/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Orobanchaceae/metabolism , Cell Wall/metabolism , Carboxylic Ester Hydrolases/metabolism , Gene Expression Regulation, Plant
16.
Clin Endocrinol (Oxf) ; 101(1): 32-41, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38691659

ABSTRACT

OBJECTIVE: Somatic variants in the ubiquitin-specific protease 8 (USP8) gene are the most common genetic cause of Cushing disease. We aimed to explore the relationship between clinical outcomes and USP8 status in a single centre. DESIGN, PATIENTS AND MEASUREMENTS: We investigated the USP8 status in 48 patients with pituitary corticotroph tumours. A median of 62 months of follow-up was conducted after surgery from November 2013 to January 2015. The clinical, biochemical and imaging features were collected and analysed. RESULTS: Seven USP8 variants (p.Ser718Pro, p.Ser719del, p.Pro720Arg, p.Pro720Gln, p.Ser718del, p.Ser718Phe, p.Lys713Arg) were identified in 24 patients (50%). USP8 variants showed a female predominance (100% vs. 75% in wild type [WT], p = .022). Patients with p.Ser719del showed an older age at surgery compared to patients with the p.Pro720Arg variant (47- vs. 24-year-olds, p = .033). Patients with p.Pro720Arg showed a higher rate of macroadenoma compared to patients harbouring the p.Ser718Pro variant (60% vs. 0%, p = .037). No significant differences were observed in serum and urinary cortisol and adrenocorticotropin hormone (ACTH) levels. Immediate surgical remission (79% vs. 75%) and long-term hormone remission (79% vs. 67%) were not significantly different between the two groups. The recurrence rate was 21% (4/19) in patients harbouring USP8 variants and 13% (2/16) in WT patients. Recurrence-free survival presented a tendency to be shorter in USP8-mutated individuals (76.7 vs. 109.2 months, p = .068). CONCLUSIONS: Somatic USP8 variants accounted for 50% of the genetic causes in this cohort with a significant female frequency. A long-term follow-up revealed a tendency toward shorter recurrence-free survival in USP8-mutant patients.


Subject(s)
ACTH-Secreting Pituitary Adenoma , Endopeptidases , Endosomal Sorting Complexes Required for Transport , Neuroendocrine Tumors , Ubiquitin Thiolesterase , Humans , Ubiquitin Thiolesterase/genetics , Female , Male , Endosomal Sorting Complexes Required for Transport/genetics , Middle Aged , Adult , Prognosis , ACTH-Secreting Pituitary Adenoma/genetics , ACTH-Secreting Pituitary Adenoma/pathology , ACTH-Secreting Pituitary Adenoma/surgery , Endopeptidases/genetics , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/pathology , Mutation , Young Adult , Adrenocorticotropic Hormone/blood , Aged , Adolescent
17.
Plant Cell ; 33(8): 2716-2735, 2021 08 31.
Article in English | MEDLINE | ID: mdl-34043798

ABSTRACT

Reactive oxygen species (ROS) are unstable reactive molecules that are toxic to cells. Regulation of ROS homeostasis is crucial to protect cells from dysfunction, senescence, and death. In plant leaves, ROS are mainly generated from chloroplasts and are tightly temporally restricted by the circadian clock. However, little is known about how ROS homeostasis is regulated in nonphotosynthetic organs, such as petals. Here, we showed that hydrogen peroxide (H2O2) levels exhibit typical circadian rhythmicity in rose (Rosa hybrida) petals, consistent with the measured respiratory rate. RNA-seq and functional screening identified a B-box gene, RhBBX28, whose expression was associated with H2O2 rhythms. Silencing RhBBX28 accelerated flower senescence and promoted H2O2 accumulation at night in petals, while overexpression of RhBBX28 had the opposite effects. RhBBX28 influenced the expression of various genes related to respiratory metabolism, including the TCA cycle and glycolysis, and directly repressed the expression of SUCCINATE DEHYDROGENASE 1, which plays a central role in mitochondrial ROS (mtROS) homeostasis. We also found that PHYTOCHROME-INTERACTING FACTOR8 (RhPIF8) could activate RhBBX28 expression to control H2O2 levels in petals and thus flower senescence. Our results indicate that the circadian-controlled RhPIF8-RhBBX28 module is a critical player that controls flower senescence by governing mtROS homeostasis in rose.


Subject(s)
Flowers/physiology , Mitochondria/metabolism , Plant Proteins/metabolism , Reactive Oxygen Species/metabolism , Rosa/physiology , Circadian Rhythm/physiology , Gene Expression Regulation, Plant , Homeostasis , Hydrogen Peroxide/metabolism , Mitochondria/genetics , Plant Proteins/genetics , Plant Senescence , Plants, Genetically Modified , Succinate Dehydrogenase/genetics , Succinate Dehydrogenase/metabolism
18.
Opt Lett ; 49(11): 2954-2957, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824301

ABSTRACT

Low-cost nanocomposite metasurfaces have demonstrated attractive potential to replace the equivalent dielectric metasurfaces for light engineering. However, the resonance characteristics of embedded structures in nanocomposite metasurfaces have not been further analyzed beyond the effective refractive index. Herein, we have proposed customizable polarization-selective narrowband meta-filters using ultraviolet-curable (UV) nanocomposites. As an additional degree of freedom, near-field effects between highly concentrated doped nanoparticles can enhance the Mie resonance of the low aspect ratio (AR = 0.2) meta-units. The surface lattice resonances (SLRs) of meta-filters can be coupled with enhanced Mie resonances of individual meta-units to realize tunable narrowband (FWHM ∼0.007λ) reflections with intensities near unity. Meanwhile, the polarization-selective properties of the reflection peaks can be tuned by optimizing the asymmetric lattice. Such proposed new-generation customizable meta-filters will offer, to our knowledge, novel strategies for filtering specific near-infrared polarized fluorescence in the integrated imaging systems.

19.
Oncology ; 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38471461

ABSTRACT

INTRODUCTION: The study explored the failure pattern and clinical outcomes in patients with ependymoma undergoing radiotherapy. METHODS: Between January 2004 and June 2022, we included 32 patients with ependymoma who underwent radiotherapy as part of the multimodality treatment at our institution. Of these, 27 (84.4%) underwent adjuvant radiotherapy, four received radiotherapy after local recurrence, and one received definitive CyberKnife radiotherapy (21 Gy in three fractions). The median prescribed dose was 54 Gy in patients who received conventional radiotherapy. We analyzed the local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and potential prognostic factors. RESULTS: The median age was 29.8 years. Approximately 28.1% were pediatric patients. Fifteen tumors (46.9%) were World Health Organization (WHO) grade II, 10 (31.3%) were WHO grade III, and seven (22.8%) were WHO grade I. Among them, 15 patients (46.9%) had posterior fossa tumors, 10 (31.3%) had supratentorial tumors, and seven (22.8%) had spinal tumors. Of the 31 patients who underwent upfront surgical resection, 19 (61.3%) underwent gross total resection or near total resection. Seventeen of 19 patients with first failures (89.5%) had isolated local recurrences. Of the 19 patients with disease progression, 11 (57.9%) were disease-free or had stable disease after salvage therapy, and five (26.3%) had disease-related mortality. Most of the first local recurrences after radiotherapy occurred in the infield (13 of 16, 81.3%). The 5-year LPFS, DMFS, PFS, and OS rates were 48.5%, 89.6%, 45.1%, and 88.4%, respectively, at a median follow-up of 6.25 years. Subtotal resection was associated with poorer LPFS and PFS in patients with intracranial ependymoma (hazard ratio = 3.69, p = 0.018 for LPFS; hazard ratio = 3.20, p = 0.029 for PFS). CONCLUSION: Incorporating radiotherapy into multimodal treatment has led to favorable outcomes in patients with ependymoma, and the extent of resection is a prognostic factor for the local control of intracranial ependymoma.

20.
J Magn Reson Imaging ; 59(3): 1034-1042, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37272790

ABSTRACT

BACKGROUND: The assessment of resectability after neoadjuvant chemotherapy of hepatoblastoma is dependent on Post-Treatment EXTENT of Disease (POSTTEXT) staging and its annotation factors P (portal venous involvement) and V (hepatic venous/inferior vena cava [IVC] involvement), but MR performance in assessing them remains unclear. PURPOSE: To assess the diagnostic performance of contrast-enhanced MR imaging for preoperative POSTTEXT staging and diagnosing vascular involvement in terms of annotation factors P and V in pediatric hepatoblastoma following neoadjuvant chemotherapy. STUDY TYPE: Retrospective. SUBJECTS: Thirty-five consecutive patients (17 males, median age, 24 months; age range, 6-98 months) with proven hepatoblastoma underwent preoperative MR imaging following neoadjuvant chemotherapy. FIELD STRENGTH/SEQUENCE: 3.0 T; T2-weighted imaging (T2WI), T2WI with fat suppression, diffusion weighted imaging, radial stack-of-the-star/Cartesian 3D Dixon T1-weighted gradient echo imaging. ASSESSMENT: Three radiologists independently assessed the POSTTEXT stages and annotation factors P and V based on the 2017 PRE/POSTTEXT system. The sensitivities and specificities were calculated for 1) diagnosing each POSTTEXT stage; 2) discrimination of stages III and IV (advanced) from those stages I and II (non-advanced) hepatoblastomas; and 3) annotation factors P and V. The combination of pathologic findings and surgical records served as the reference standard. STATISTICAL TESTS: Sensitivity, specificity, Fleiss kappa test. RESULTS: The sensitivity and specificity ranges for discriminating advanced from non-advanced hepatoblastomas were 73.3%-80.0% and 80.0%-90.0%, respectively. For annotation factor P, they were 66.7%-100.0% and 90.6%, respectively. For factor V, they were 75.0% and 67.7%-83.9%, respectively. There was excellent, substantial, and moderate agreement on POSTTEXT staging (Fleiss kappa = 0.82), factors P (Fleiss kappa = 0.64), and factors V (Fleiss kappa = 0.60), respectively. DATA CONCLUSION: MR POSTTEXT provides reliable discrimination between advanced and non-advanced tumors, and MR has moderate to excellent specificity at identifying portal venous and hepatic venous/IVC involvement. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.


Subject(s)
Hepatoblastoma , Liver Neoplasms , Male , Child , Humans , Child, Preschool , Infant , Hepatoblastoma/drug therapy , Hepatoblastoma/pathology , Hepatoblastoma/surgery , Neoadjuvant Therapy , Retrospective Studies , Magnetic Resonance Imaging/methods , Hepatic Veins , Sensitivity and Specificity , Liver Neoplasms/pathology , Neoplasm Staging
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