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1.
Front Pharmacol ; 15: 1423115, 2024.
Article in English | MEDLINE | ID: mdl-39104384

ABSTRACT

Aim: Plant-derived nanovesicles have emerged as potential agents for combating tumors. In this study, we investigated the inhibitory effects of Panax notoginseng-derived nanovesicles (PnNVs) on the proliferation and migration of squamous cell carcinoma. Additionally, we explored the relationship between plant tuber size and the physical properties, composition and bioactivity of these nanovesicles. Methods: We isolated PnNVs from Panax notoginseng tubers of varying sizes: small-sized (s_PnNVs), medium-sized (m_PnNVs) and large-sized (l_PnNVs), and evaluated for size, potential, and morphology. Cellular uptake efficiency was assessed using confocal microscopy and flow cytometry. The ability of different PnNVs to inhibit oral squamous cell carcinoma cells was evaluated using plate cloning, CCK8 assay, and scratch healing assay. Off-target metabolomics was used to compare metabolic compounds of different PnNVs. Results: Our findings revealed that s_PnNVs exhibited lower potential but had the highest cellular uptake efficiency, whereas m_PnNVs were characterized by the smallest size and lowest cellular uptake efficiency. Notably, m_PnNVs demonstrated the most effective inhibition of squamous cell carcinoma growth and migration. Compositional analyses showed that PnNVs were rich in proteins and contained lower levels of RNA, with l_PnNVs having the highest protein content. Furthermore, untargeted metabolomics analysis revealed a significant increase in the expression of specific antitumour-related metabolites in m_PnNVs compared to s_PnNVs and l_PnNVs. Conclusion: Overall, our results underscore the influence of plant tuber size on the bioactivity of the nanovesicles from which they are derived, emphasizing its importance for experimental design and study reproducibility.

2.
OTO Open ; 8(3): e70002, 2024.
Article in English | MEDLINE | ID: mdl-39206428

ABSTRACT

Due to the anatomic complexity of the head and neck and variable proximity between laboratory and operating room (OR), effective communication during frozen section analysis (FSA) between surgeons and pathologists is challenging. This proof-of-concept study investigates an augmented reality (AR) protocol that allows pathologists to virtually join the OR from the laboratory. Head and neck cancer specimens were scanned ex vivo using a 3-dimensional scanner and uploaded into an AR platform. Eight head and neck specimens were discussed by surgeons and pathologists in an AR environment. AR-guided intraoperative consultation was used for specimen orientation and discussion of FSA margin sampling sites. One patient had positive initial margins on FSA and was re-resected to negative final margins. AR-guided FSA is possible and allows pathologists to join the operating from any location for intraoperative discussion.

3.
J Fungi (Basel) ; 10(7)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-39057337

ABSTRACT

Recent studies have predominantly spotlighted bacterial diversity within coral microbiomes, leaving coral-associated fungi in the shadows of scientific inquiry. This study endeavors to fill this knowledge gap by delving into the biodiversity, distribution and functional differences of fungi associated with soft corals Cladiella krempfi and Sarcophyton tortuosum, gorgonian coral Dichotella gemmacea and stony coral Favia speciosa from the South China Sea. Leveraging high-throughput sequencing of fungal internal transcribed spacer-1 (ITS1) region of the rRNA gene, a total of 431 fungal amplicon sequence variants (ASVs) were identified in this study, which indicated that a large number of fungal communities were harbored in the South China Sea corals. Noteworthy among our findings is that 10 fungal genera are reported for the first time in corals, with Candolleomyces, Exophiala, Fomitopsis, Inaequalispora, Kneiffiella, Paraphaeosphaeria, and Yamadazyma belonging to the Ascomycota, and Cystobasidium, Psathyrella, and Solicoccozyma to the Basidiomycota. Moreover, significant differences (p < 0.05) of fungal communities were observed among the various coral species. In particular, the gorgonian coral D. gemmacea emerged as a veritable haven for fungal diversity, boasting 307 unique ASVs. Contrastingly, soft corals S. tortuosum and C. krempfi exhibited modest fungal diversity, with 36 and 21 unique ASVs, respectively, while the stony coral F. speciosa hosted a comparatively sparse fungal community, with merely 10 unique ASVs in total. These findings not only provide basic data on fungal diversity and function in the South China Sea corals, but also underscore the imperative of nuanced conservation and management strategies for coral reef ecosystems worldwide.

4.
ACS Pharmacol Transl Sci ; 7(7): 2196-2203, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39022367

ABSTRACT

Histone deacetylase 6 (HDAC6) enzyme plays a crucial role in a variety of cellular processes related to cancer, and inhibition of HDAC6 is emerging as an effective strategy for cancer treatment. Although several hydroxamate-based HDAC6 inhibitors showed promising anticancer activities, the intrinsic defects such as poor selectivity, stability, and pharmacokinetics limited their application. In this study, a potent selenocyanide-bearing HDAC6 inhibitor, 5-phenylcarbamoylpentyl selenocyanide (SelSA), was evaluated for its antihepatocellular carcinoma (HCC) activity and further explored for its antitumor mechanisms. In vitro studies demonstrated that SelSA exhibited excellent antiproliferative activity against three HCC cells HepG2 (2.3 ± 0.29 µM), Huh7 (0.83 ± 0.48 µM), and LM3 (2.6 ± 0.24 µM). Further studies indicated that SelSA could downregulate the expression of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, inhibit the growth, invasion, and migration of Huh7 cells, and promote their apoptosis. Moreover, SelSA significantly suppressed tumor growth in Huh7 xenograft mouse models. Our findings suggest that SelSA could be a potential therapeutic agent for HCC.

6.
bioRxiv ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38826470

ABSTRACT

Extracellular communication via the transfer of vesicles and nanoparticles is now recognized to play an important role in tumor microenvironment interactions. Cancer cells upregulate and secrete abundant levels of miR-100 and miR-125b that can alter gene expression by both cell- and non-cell-autonomous mechanisms. We previously showed that these miRNAs activate Wnt signaling in colorectal cancer (CRC) through noncanonical pairing with 5 negative regulators of Wnt signaling. To identify additional targets of miR-100 and miR-125b , we used bioinformatic approaches comparing multiple CRC cell lines, including knockout lines lacking one or both of these miRNAs. From an initial list of 96 potential mRNA targets, we tested 15 targets with 8 showing significant downregulation in the presence of miR-100 and miR-125b . Among these, Cingulin (CGN) and Protein tyrosine phosphatase receptor type-R (PTPRR) are downregulated in multiple cancers, consistent with regulation by increased levels of miR-100 and miR-125b. We also show that increased cellular levels of miR-100 and miR-125b enhance 3D growth and invasiveness in CRC and glioblastoma cell lines. Lastly, we demonstrate that extracellular transfer of miR-100 and miR-125b can silence both reporter and endogenous mRNA targets in recipient cells and also increase the invasiveness of recipient spheroid colonies when grown under 3D conditions in type I collagen.

7.
Cells ; 13(5)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38474367

ABSTRACT

Co-inhibitory receptors (Co-IRs) are essential in controlling the progression of immunopathology in rheumatoid arthritis (RA) by limiting T cell activation. The objective of this investigation was to determine the phenotypic expression of Co-IR T cells and to assess the levels of serum soluble PD-1, PDL-2, and TIM3 in Taiwanese RA patients. METHODS: Co-IRs T cells were immunophenotyped employing multicolor flow cytometry, and ELISA was utilized for measuring soluble PD-1, PDL-2, and TIM3. Correlations have been detected across the percentage of T cells expressing Co-IRs (MFI) and different indicators in the blood, including ESR, high-sensitivity CRP (hsCRP), 28 joint disease activity scores (DAS28), and soluble PD-1/PDL-2/TIM3. RESULTS: In RA patients, we recognized elevated levels of PD-1 (CD279), CTLA-4, and TIGIT in CD4+ T cells; TIGIT, HLA-DR, TIM3, and LAG3 in CD8+ T cells; and CD8+CD279+TIM3+, CD8+HLA-DR+CD38+ T cells. The following tests were revealed to be correlated with hsCRP: CD4/CD279 MFI, CD4/CD279%, CD4/TIM3%, CD8/TIM3%, CD8/TIM3 MFI, CD8/LAG3%, and CD8+HLA-DR+CD38+%. CD8/LAG3 and CD8/TIM3 MFIs are linked to ESR. DAS28-ESR and DAS28-CRP exhibited relationships with CD4/CD127 MFI, CD8/CD279%, and CD8/CD127 MFI, respectively. CD4+CD279+TIM3+% was correlated with DAS28-ESR (p = 0.0084, N = 46), DAS28-CRP (p = 0.007, N = 47), and hsCRP (p = 0.002, N = 56), respectively. In the serum of patients with RA, levels of soluble PD-1, PDL-2, and Tim3 were extremely elevated. CD4+ TIM3+% (p = 0.0089, N = 46) and CD8+ TIM3+% (p = 0.0305, N = 46) were correlated with sTIM3 levels; sPD1 levels were correlated with CD4+CD279+% (p < 0.0001, N = 31) and CD3+CD279+% (p = 0.0084, N = 30). CONCLUSIONS: Co-IR expressions on CD4+ and CD8+ T cells, as well as soluble PD-1, PDL-2, and TIM3 levels, could function as indicators of disease activity and potentially play crucial roles in the pathogenesis of RA.


Subject(s)
Arthritis, Rheumatoid , Programmed Cell Death 1 Receptor , Humans , C-Reactive Protein/metabolism , Hepatitis A Virus Cellular Receptor 2 , Arthritis, Rheumatoid/pathology , HLA-DR Antigens , Receptors, Immunologic
8.
Hum Mol Genet ; 33(8): 677-686, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38224682

ABSTRACT

The metastatic non-small cell lung cancer (NSCLC) is one of the cancers with high incidence, poor survival, and limited treatment. Epithelial-mesenchymal transition (EMT) is the first step by which an early tumor converts to an invasive one. Studying the underlying mechanisms of EMT can help the understanding of cancer metastasis and improve the treatment. In this study, 1013 NSCLC patients and 123 NSCLC cell lines are deeply analyzed for the potential roles of alternative polyadenylation (APA) in the EMT process. A trend of shorter 3'-UTRs (three prime untranslated region) is discovered in the mesenchymal samples. The identification of EMT-related APA events highlights the proximal poly(A) selection of CARM1. It is a pathological biomarker of mesenchymal tumor and cancer metastasis through losing miRNA binding to upregulate the EMT inducer of CARM1 and releasing miRNAs to downregulate the EMT inhibitor of RBM47. The crucial role of this APA event in EMT also guides its effect on drug responses. The patients with shorter 3'-UTR of CARM1 are more benefit from chemotherapy drugs, especially cisplatin. A stratification of NSCLC patients based on this APA event is useful for chemotherapy design in future clinics.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Polyadenylation/genetics , Cell Line, Tumor , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , RNA-Binding Proteins/genetics
9.
New Phytol ; 241(2): 732-746, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37872751

ABSTRACT

Callus formation is important for numerous biological processes in plants. Previously, we revealed that the PdeWRKY75-PdeRBOHB module positively regulates hydrogen peroxide (H2 O2 ) accumulation, thereby affecting callus formation in poplar. In this study, we identified and confirmed a transcription factor, PdeERF114, that interacts with PdeWRKY75 both in vitro and in vivo. Gene expression analysis identified both PdeRBOHB and PdeEXPB2 as downstream genes of PdeERF114 and PdeWRKY75. Overexpression (OE) and reduced-expression (RE) transgenic poplar lines for these four genes were generated, and the observation of callus formation was also performed in all plant materials. We demonstrated that PdeERF114 and PdeWRKY75 formed a protein complex and that this complex could bind W-Box motifs in the promoters of PdeRBOHB and PdeEXPB2, thereby positively regulating the expression of PdeRBOHB and PdeEXPB2. The OE/RE transgenic lines for these four genes also showed enhanced/reduced callus formation. Overall, we revealed a novel gene regulatory network for the regulation of callus formation in plants that involves four genes and regulates callus formation through two pathways: the accumulation of H2 O2 in explants and the relaxation of cell walls. In the future, the four genes could be used to enhance transformation effectiveness in genetic engineering.


Subject(s)
Populus , Transcription Factors , Promoter Regions, Genetic/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Gene Expression Profiling , Cell Wall/metabolism , Gene Expression Regulation, Plant , Populus/genetics , Populus/metabolism , Plants, Genetically Modified/metabolism
10.
Nucleic Acids Res ; 52(D1): D822-D834, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37850649

ABSTRACT

Aging entails gradual functional decline influenced by interconnected factors. Multiple hallmarks proposed as common and conserved underlying denominators of aging on the molecular, cellular and systemic levels across multiple species. Thus, understanding the function of aging hallmarks and their relationships across species can facilitate the translation of anti-aging drug development from model organisms to humans. Here, we built AgeAnnoMO (https://relab.xidian.edu.cn/AgeAnnoMO/#/), a knowledgebase of multi-omics annotation for animal aging. AgeAnnoMO encompasses an extensive collection of 136 datasets from eight modalities, encompassing 8596 samples from 50 representative species, making it a comprehensive resource for aging and longevity research. AgeAnnoMO characterizes multiple aging regulators across species via multi-omics data, comprehensively annotating aging-related genes, proteins, metabolites, mitochondrial genes, microbiotas and age-specific TCR and BCR sequences tied to aging hallmarks for these species and tissues. AgeAnnoMO not only facilitates a deeper and more generalizable understanding of aging mechanisms, but also provides potential insights of the specificity across tissues and species in aging process, which is important to develop the effective anti-aging interventions for diverse populations. We anticipate that AgeAnnoMO will provide a valuable resource for comprehending and integrating the conserved driving hallmarks in aging biology and identifying the targetable biomarkers for aging research.


Subject(s)
Aging , Knowledge Bases , Multiomics , Animals , Humans , Aging/genetics , Biomarkers , Longevity/genetics
11.
Small ; 20(21): e2306865, 2024 May.
Article in English | MEDLINE | ID: mdl-38126669

ABSTRACT

Functional inks enable manufacturing of flexible electronic devices by means of printing technology. Silver nanoparticle (Ag NP) ink is widely used for printing conductive components. A sintering process is required to obtain sufficient conductivity. Thermal sintering is the most commonly used method, but the heat must be carefully applied to avoid damaging low-temperature substrates such as polymer films. In this work, two alternative sintering methods, damp heat sintering and water sintering are systematically investigated for inkjet-printed Ag tracks on polymer substrates. Both methods allow sintering polyvinyl pyrrolidone (PVP) capped Ag NPs at 85°C. In this way, the resistance is significantly reduced to only 1.7 times that of the samples on polyimide sintered in an oven at 250°C. The microstructure of sintered Ag NPs is analyzed. Taking the states of the capping layer under different conditions into account, the explanation of the sintering mechanism of Ag NPs at low temperatures is presented. Overall, both damp heat sintering and water sintering are viable options for achieving high conductivity of printed Ag tracks. They can broaden the range of substrates available for flexible electronic device fabrication while mitigating substrate damage risks. The choice between them depends on the specific application and the substrate used.

12.
Wei Sheng Yan Jiu ; 52(6): 924-929, 2023 Nov.
Article in Chinese | MEDLINE | ID: mdl-38115656

ABSTRACT

OBJECTIVE: To quantitatively assess the concentration and distribution of body iron(BI) in children aged 6 to 17 years in Beijing. METHODS: A total of 1392 children aged 6 to 17 years in Beijing were randomly selected for questionnaire survey and physical examination in 2016-2017. Fasting venous blood was collected, serum ferritin(SF) and serum soluble transferrin receptor(sTfR) were measured by immunoturbidimetric assay. BI were calculated, and the concentration and distribution of BI in children aged 6 to 17 years was assessed. RESULTS: The average BI level of children aged 6 to 17 in Beijing was(5.49±2.94) mg/kg. The average BI level of boys was higher than that of girls, and the average BI level of children with abdominal obesity was higher than that of children without abdominal obesity, and the differences were statistically significant(P<0.05). The concentration of BI in children aged 6 to 17 years in Beijing was 4-7.99 mg/kg, accounting for the highest proportion(57.3%). The concentration of BI<0 mg/kg accounted for the lowest proportion(4.3%). There were significant differences in the distribution of BI concentration in different gender, age and abdominal obesity(P<0.05). The anemia rate of children aged 6 to 17 in Beijing was 2.7%(95%CI 1.9-3.6), the low ferritin rate(SF<25 µg/L) was 22.5%(95%CI 20.0-24.8), and the iron deficiency rate(SF<15 µg/L) was 7.8%(95%CI 6.4-9.3), the negative iron stores(BI<0 mg/kg) rate was 4.3%(95%CI 3.2-5.3). The anemia rate, low ferritin rate, iron deficiency rate and negative iron stores rate were higher in girls than boys, and higher in children aged 12 to 17 years than in children aged 6 to 11 years, and the differences were statistically significant(P<0.01). CONCLUSION: Iron deficiency was still present in children aged 6 to 17 in Beijing from 2016 to 2017. The proportion of low BI level in girls and children aged 12 to 17 is higher, respectively.


Subject(s)
Anemia, Iron-Deficiency , Anemia , Iron Deficiencies , Male , Child , Female , Humans , Ferritins , Anemia, Iron-Deficiency/epidemiology , Beijing , Obesity, Abdominal , Iron , Receptors, Transferrin , Obesity
13.
Health Inf Sci Syst ; 11(1): 50, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37941825

ABSTRACT

Predicting drug-drug interactions (DDIs) has become a major concern in the drug research field because it helps explore the pharmacological function of drugs and enables the development of new therapeutic drugs. Existing prediction methods simply integrate multiple drug attributes or perform tasks on a biomedical knowledge graph (KG). Though effective, few methods can fully utilize multi-source drug data information. In this paper, a multi-view and multichannel attention deep learning (MMADL) model is proposed, which not only extracts rich drug features containing both drug attributes and drug-related entity information from multi-source databases, but also considers the consistency and complementarity of different drug feature representation learning approaches to improve the effectiveness and accuracy of DDI prediction. A single-layer perceptron encoder is applied to encode multi-source drug information to obtain multi-view drug representation vectors in the same linear space. Then, the multichannel attention mechanism is introduced to obtain the attention weight by adaptively learning the importance of drug features according to their contributions to DDI prediction. Further, the representation vectors of multi-view drug pairs with attention weights are used as inputs of the deep neural network to predict potential DDI. The accuracy and precision-recall curves of MMADL are 93.05 and 95.94, respectively. The results indicate that the proposed method outperforms other state-of-the-art methods.

14.
J Nanobiotechnology ; 21(1): 445, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-38001440

ABSTRACT

Tissue damage and aging lead to dysfunction, disfigurement, and trauma, posing significant global challenges. Creating a regenerative microenvironment to resist external stimuli and induce stem cell differentiation is essential. Plant-derived nanovesicles (PDNVs) are naturally bioactive lipid bilayer nanovesicles that contain proteins, lipids, ribonucleic acid, and metabolites. They have shown potential in promoting cell growth, migration, and differentiation into various types of tissues. With immunomodulatory, microbiota regulatory, antioxidant, and anti-aging bioactivities, PDNVs are valuable in resisting external stimuli and facilitating tissue repair. The unique structure of PDNVs provides an optimal platform for drug encapsulation, and surface modifications enhance their stability and specificity. Moreover, by employing synergistic administration strategies, PDNVs can maximize their therapeutic potential. This review summarized the progress and prospects of PDNVs as regenerative tools, provided insights into their selection for repair activities based on existing studies, considered the key challenge for clinical application, and anticipated their continued prominent role in the field of biomedicine.


Subject(s)
Cell Differentiation , Nanoparticles , Plants , Plants/chemistry , Lipid Bilayers
15.
Neuroimage ; 283: 120426, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37898378

ABSTRACT

The level of consciousness undergoes continuous alterations during anesthesia. Prior to the onset of propofol-induced complete unconsciousness, degraded levels of behavioral responsiveness can be observed. However, a reliable index to monitor altered consciousness levels during anesthesia has not been sufficiently investigated. In this study, we obtained 60-channel EEG data from 24 healthy participants during an ultra-slow propofol infusion protocol starting with an initial concentration of 1 µg/ml and a stepwise increase of 0.2 µg/ml in concentration. Consecutive auditory stimuli were delivered every 5 to 6 s, and the response time to the stimuli was used to assess the responsiveness levels. We calculated the spectral slope in a time-resolved manner by extracting 5-second EEG segments at each auditory stimulus and estimated their correlation with the corresponding response time. Our results demonstrated that during slow propofol infusion, the response time to external stimuli increased, while the EEG spectral slope, fitted at 15-45 Hz, became steeper, and a significant negative correlation was observed between them. Moreover, the spectral slope further steepened at deeper anesthetic levels and became flatter during anesthesia recovery. We verified these findings using an external dataset. Additionally, we found that the spectral slope of frontal electrodes over the prefrontal lobe had the best performance in predicting the response time. Overall, this study used a time-resolved analysis to suggest that the EEG spectral slope could reliably track continuously altered consciousness levels during propofol anesthesia. Furthermore, the frontal spectral slope may be a promising index for clinical monitoring of anesthesia depth.


Subject(s)
Anesthesia , Propofol , Humans , Propofol/pharmacology , Consciousness/physiology , Electroencephalography , Unconsciousness/chemically induced , Anesthetics, Intravenous/pharmacology
16.
Mol Ther Nucleic Acids ; 33: 816-831, 2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37675185

ABSTRACT

Disrupted alternative polyadenylation (APA) is frequently involved in tumorigenesis and cancer progression by regulating the gene expression of oncogenes and tumor suppressors. However, limited knowledge of tumor-type- and cell-type-specific APA events may lead to novel APA events and their functions being overlooked. Here, we compared APA events across different cell types in non-small cell lung cancer (NSCLC) and normal tissues and identified functionally related APA events in NSCLC. We found several cell-specific 3'-UTR alterations that regulate gene expression changes showed prognostic value in NSCLC. We further investigated the function of APA-mediated 3'-UTR shortening through loss of microRNA (miRNA)-binding sites, and we identified and experimentally validated several oncogene-miRNA-tumor suppressor axes. According to our analyses, we found SPARC as an APA-regulated oncogene in cancer-associated fibroblasts in NSCLC. Knockdown of SPARC attenuates lung cancer cell invasion and metastasis. Moreover, we found high SPARC expression associated with resistance to several drugs except cisplatin. NSCLC patients with high SPARC expression could benefit more compared to low-SPARC-expression patients with cisplatin treatment. Overall, our comprehensive analysis of cell-specific APA events shed light on the regulatory mechanism of cell-specific oncogenes and provided opportunities for combination of APA-regulated therapeutic target and cell-specific therapy development.

17.
Cancer Lett ; 575: 216404, 2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37739210

ABSTRACT

Elevated expression and genetic aberration of IRTKS, also named as BAIAP2L1, have been observed in many tumors, especially in tumor progression. however, the molecular and cellular mechanisms involved in the IRTKS-enhanced tumor progression are obscure. Here we show that higher IRTKS level specifically increases histone H3 lysine 9 trimethylation (H3K9me3) by promoting accumulation of the histone methyltransferase SETDB1. Furthermore, we reveal that IRTKS recruits the deubiquitinase OTUD4 to remove Lys48-linked polyubiquitination at K182/K1050 sites of SETDB1, thus blocking SETDB1 degradation via the ubiquitin-proteasome pathway. Interestingly, the enhanced IRTKS-OTUD4-SETDB1-H3K9me3 axis leads to a general decrease in chromatin accessibility, which inhibits transcription of CDH1 encoding E-cadherin, a key molecule essential for maintaining epithelial cell phenotype, and therefore results in epithelial-mesenchymal transition (EMT) and malignant cell metastasis. Clinically, the elevated IRTKS levels in tumor specimens correlate with SETDB1 levels, but negatively associate with survival time. Our data reveal a novel mechanism for the IRTKS-enhanced tumor progression, where IRTKS cooperates with OTUD4 to enhance SETDB1-mediated H3K9 trimethylation that promotes tumor metastasis via suppressing E-cadherin expression. This study also provides a potential approach to reduce the activity and stability of the known therapeutic target SETDB1 possibly through regulating IRTKS or deubiquitinase OTUD4.

18.
Front Plant Sci ; 14: 1184489, 2023.
Article in English | MEDLINE | ID: mdl-37645460

ABSTRACT

Endophytic bacterial microbiomes of plants contribute to the physiological health of the host and its adaptive evolution and stress tolerance. Wild rice possesses enriched endophytic bacteria diversity, which is a potential resource for sustainable agriculture. Oryza officinalis is a unique perennial wild rice species in China with rich genetic resources. However, endophytic bacterial communities of this species and their plant growth-promoting (PGP) traits remain largely unknown. In this study, endophytic bacteria in the root, stem, and leaf tissues of O. officinalis were characterized using 16S rRNA gene Illumina sequencing. Culturable bacterial endophytes were also isolated from O. officinalis tissues and characterized for their PGP traits. The microbiome analysis showed a more complex structure and powerful function of the endophytic bacterial community in roots compared with those in other tissue compartments. Each compartment had its specific endophytic bacterial biomarkers, including Desulfomonile and Ruminiclostridium for roots; Lactobacillus, Acinetobacter, Cutibacterium and Dechloromonas for stems; and Stenotrophomonas, Chryseobacterium, Achromobacter and Methylobacterium for leaves. A total of 96 endophytic bacterial strains with PGP traits of phosphate solubilization, potassium release, nitrogen fixation, 1-aminocyclopropane-1-carboxylate (ACC) deaminase secretion, and siderophore or indole-3-acetic acid (IAA) production were isolated from O. officinalis. Among them, 11 strains identified as Enterobacter mori, E. ludwigii, E. cloacae, Bacillus amyloliquefaciens, B. siamensis, Pseudomonas rhodesiae and Kosakonia oryzae were selected for inoculation of perennial rice based on their IAA production traits. These strains showed promising PGP effects on perennial rice seedlings. They promoted plants to form a strong root system, stimulate biomass accumulation, and increase chlorophyll content and nitrogen uptake, which could fulfil the ecologically sustainable cultivation model of perennial rice. These results provide insights into the bacterial endosphere of O. officinalis and its application potential in perennial rice. There is the prospect of mining beneficial endophytic bacteria from wild rice species, which could rewild the microbiome of cultivated rice varieties and promote their growth.

19.
Med Phys ; 50(7): 4651-4663, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37293867

ABSTRACT

BACKGROUND: Magnetic nanoparticles (MNPs) are used as tracers without ionizing radiation in vascular imaging, molecular imaging, and neuroimaging. The relaxation mechanisms of magnetization in response to excitation magnetic fields are important features of MNPs. The basic relaxation mechanisms include internal rotation (Néel relaxation) and external physical rotation (Brownian relaxation). Accurate measurement of these relaxation times may provide high sensitivity for predicting MNP types and viscosity-based hydrodynamic states. It is challenging to separately measure the Néel and Brownian relaxation components using sinusoidal excitation in conventional MPI. PURPOSE: We developed a multi-exponential relaxation spectral analysis method to separately measure the Néel and Brownian relaxation times in the magnetization recovery process in pulsed vascular MPI. METHODS: Synomag-D samples with different viscosities were excited using pulsed excitation in a trapezoidal-waveform relaxometer. The samples were excited at different field amplitudes ranging from 0.5 to 10 mT at intervals of 0.5 mT. The inverse Laplace transform-based spectral analysis of the relaxation-induced decay signal in the field-flat phase was performed by using PDCO, a primal-dual interior method for convex objectives. Néel and Brownian relaxation peaks were elucidated and measured on samples with various glycerol and gelatin concentrations. The sensitivity of viscosity prediction of the decoupled relaxation times was evaluated. A digital vascular phantom was designed to mimic a plaque with viscous MNPs and a catheter with immobilized MNPs. Spectral imaging of the digital vascular phantom was simulated by combining a field-free point with homogeneous pulsed excitation. The relationship between the Brownian relaxation time from different tissues and the number of periods for signal averages was evaluated for a scan time estimation in the simulation. RESULTS: The relaxation spectra of synomag-D samples with different viscosity levels exhibited two relaxation time peaks. The Brownian relaxation time had a positive linear relationship with the viscosity in the range 0.9 to 3.2 mPa · s. When the viscosity was >3.2 mPa · s, the Brownian relaxation time saturated and did not change with increasing viscosity. The Néel relaxation time decreased slightly with an increase in the viscosity. The Néel relaxation time exhibited a similar saturation effect when the viscosity level was >3.2 mPa · s for all field amplitudes. The sensitivity of the Brownian relaxation time increased with the field amplitude and was maximized at approximately 4.5 mT. The plaque and catheter regions were differentiated from the vessel region in the simulated Brownian relaxation time map. The simulation results show that the Néel relaxation time was 8.33±0.09 µs in the plaque region, 8.30±0.08 µs in the catheter region, and 8.46±0.11 µs in the vessel region. The Brownian relaxation time was 36.60±2.31 µs in the plaque region, 30.17±1.24 µs in the catheter region, and 31.21±1.53 µs in the vessel region. If we used 20 excitation periods for image acquisition in the simulation, the total scan time of the digital phantom was approximately 100 s. CONCLUSION: Quantitative assessment of the Néel and Brownian relaxation times through inverse Laplace transform-based spectral analysis in pulsed excitation, highlighting their potential for use in multi-contrast vascular MPI.


Subject(s)
Magnetic Fields , Tomography, X-Ray Computed
20.
Int J Neural Syst ; 33(8): 2350034, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37318536

ABSTRACT

In responding to the calls for revisiting the role that hippocampus (HIP) plays in semantic memory retrieval, this study used functional neuroimaging-based connectivity technique to elucidate the functional brain network involved in retrieving the correct and incorrect science-related semantic memories. Unlike episodic memory retrieval, the 40 scientific concepts learned during middle and high school were selected to assess 46 science majors' semantic memory retrieval and correctness monitoring, which requires neither the support of spatial information nor events to retrieve the memory. Our results demonstrated that HIP was significantly and robustly engaged in the semantic memory retrieval of correct scientific concepts than incorrect ones. Importantly, the Granger causality analysis indicated that effective connectivity of [Formula: see text] and [Formula: see text] was shared by the semantic memory retrieval of both correct and incorrect scientific concepts. On the other hand, the strengths of connectivity in the [Formula: see text] and [Formula: see text] brain networks appeared more pronounced during the processing of correct scientific concepts than of incorrect ones. The shared hippocampal networks highlight the role of the HIP as a hub to coordinate the INS, ACC, and MTG, in turn, support the semantic memory retrieval of scientific concepts.


Subject(s)
Memory, Episodic , Semantics , Magnetic Resonance Imaging , Brain , Hippocampus , Brain Mapping
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