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1.
PLoS Pathog ; 20(2): e1012027, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38377149

ABSTRACT

Newcastle disease virus (NDV) has been extensively studied as a promising oncolytic virus for killing tumor cells in vitro and in vivo in clinical trials. However, the viral components that regulate the oncolytic activity of NDV remain incompletely understood. In this study, we systematically compared the replication ability of different NDV genotypes in various tumor cells and identified NP protein determines the oncolytic activity of NDV. On the one hand, NDV strains with phenylalanine (F) at the 450th amino acid position of the NP protein (450th-F-NP) exhibit a loss of oncolytic activity. This phenotype is predominantly associated with genotype VII NDVs. In contrast, the NP protein with a leucine amino acid at this site in other genotypes (450th-L-NP) can facilitate the loading of viral mRNA onto ribosomes more effectively than 450th-F-NP. On the other hand, the NP protein from NDV strains that exhibit strong oncogenicity interacts with eIF4A1 within its 366-489 amino acid region, leading to the inhibition of cellular mRNA translation with a complex 5' UTR structure. Our study provide mechanistic insights into how highly oncolytic NDV strains selectively promote the translation of viral mRNA and will also facilitate the screening of oncolytic strains for oncolytic therapy.


Subject(s)
Newcastle disease virus , Oncolytic Viruses , Animals , Newcastle disease virus/genetics , Amino Acids , Leucine , Oncolytic Viruses/genetics , RNA, Messenger/genetics , Protein Biosynthesis
2.
Proc Natl Acad Sci U S A ; 120(19): e2217887120, 2023 05 09.
Article in English | MEDLINE | ID: mdl-37126704

ABSTRACT

Treatment of HIV-1ADA-infected CD34+ NSG-humanized mice with long-acting ester prodrugs of cabotegravir, lamivudine, and abacavir in combination with native rilpivirine was followed by dual CRISPR-Cas9 C-C chemokine receptor type five (CCR5) and HIV-1 proviral DNA gene editing. This led to sequential viral suppression, restoration of absolute human CD4+ T cell numbers, then elimination of replication-competent virus in 58% of infected mice. Dual CRISPR therapies enabled the excision of integrated proviral DNA in infected human cells contained within live infected animals. Highly sensitive nucleic acid nested and droplet digital PCR, RNAscope, and viral outgrowth assays affirmed viral elimination. HIV-1 was not detected in the blood, spleen, lung, kidney, liver, gut, bone marrow, and brain of virus-free animals. Progeny virus from adoptively transferred and CRISPR-treated virus-free mice was neither detected nor recovered. Residual HIV-1 DNA fragments were easily seen in untreated and viral-rebounded animals. No evidence of off-target toxicities was recorded in any of the treated animals. Importantly, the dual CRISPR therapy demonstrated statistically significant improvements in HIV-1 cure percentages compared to single treatments. Taken together, these observations underscore a pivotal role of combinatorial CRISPR gene editing in achieving the elimination of HIV-1 infection.


Subject(s)
HIV Infections , HIV Seropositivity , Mice , Animals , Humans , Anti-Retroviral Agents/therapeutic use , Gene Editing , Proviruses/genetics , Receptors, CCR5
3.
Immunity ; 44(2): 380-90, 2016 Feb 16.
Article in English | MEDLINE | ID: mdl-26885860

ABSTRACT

Chimeric antigen receptors (CARs) redirect T cell cytotoxicity against cancer cells, providing a promising approach to cancer immunotherapy. Despite extensive clinical use, the attributes of CAR co-stimulatory domains that impact persistence and resistance to exhaustion of CAR-T cells remain largely undefined. Here, we report the influence of signaling domains of coreceptors CD28 and 4-1BB on the metabolic characteristics of human CAR T cells. Inclusion of 4-1BB in the CAR architecture promoted the outgrowth of CD8(+) central memory T cells that had significantly enhanced respiratory capacity, increased fatty acid oxidation and enhanced mitochondrial biogenesis. In contrast, CAR T cells with CD28 domains yielded effector memory cells with a genetic signature consistent with enhanced glycolysis. These results provide, at least in part, a mechanistic insight into the differential persistence of CAR-T cells expressing 4-1BB or CD28 signaling domains in clinical trials and inform the design of future CAR T cell therapies.


Subject(s)
CD28 Antigens/metabolism , CD8-Positive T-Lymphocytes/physiology , Cancer Vaccines/immunology , Immunotherapy , Neoplasms/therapy , Receptors, Antigen, T-Cell/metabolism , Tumor Necrosis Factor Receptor Superfamily, Member 9/metabolism , CD28 Antigens/genetics , Cell Respiration , Cells, Cultured , Glycolysis , Humans , Immunologic Memory , Lipid Metabolism , Mitochondria/metabolism , Neoplasms/immunology , Receptor Cross-Talk , Receptors, Antigen, T-Cell/genetics , Recombinant Fusion Proteins/genetics , Signal Transduction/genetics , Tumor Necrosis Factor Receptor Superfamily, Member 9/genetics
4.
EMBO Rep ; 24(3): e55683, 2023 03 06.
Article in English | MEDLINE | ID: mdl-36660859

ABSTRACT

Unveiling the principles governing embryonic stem cell (ESC) differentiation into specific lineages is critical for understanding embryonic development and for stem cell applications in regenerative medicine. Here, we establish an intersection between LIF-Stat3 signaling that is essential for maintaining murine (m) ESCs pluripotency, and the glycolytic enzyme, the platelet isoform of phosphofructokinase (Pfkp). In the pluripotent state, Stat3 transcriptionally suppresses Pfkp in mESCs while manipulating the cells to lift this repression results in differentiation towards the ectodermal lineage. Pfkp exhibits substrate specificity changes to act as a protein kinase, catalyzing serine phosphorylation of the developmental regulator Lin41. Such phosphorylation stabilizes Lin41 by impeding its autoubiquitination and proteasomal degradation, permitting Lin41-mediated binding and destabilization of mRNAs encoding ectodermal specification markers to favor the expression of endodermal specification genes. This provides new insights into the wiring of pluripotency-differentiation circuitry where Pfkp plays a role in germ layer specification during mESC differentiation.


Subject(s)
Phosphofructokinases , Protein Kinases , Pregnancy , Female , Mice , Animals , Protein Kinases/metabolism , Phosphofructokinases/metabolism , Embryonic Stem Cells/metabolism , Cell Differentiation/genetics , Signal Transduction , Mouse Embryonic Stem Cells/metabolism
5.
Cell Mol Life Sci ; 81(1): 182, 2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38615283

ABSTRACT

BACKGROUND: Stem cell therapy is a promising therapeutic strategy. In a previous study, we evaluated tumorigenicity by the stereotactic transplantation of neural stem cells (NSCs) and embryonic stem cells (ESCs) from experimental mice. Twenty-eight days later, there was no evidence of tumor formation or long-term engraftment in the NSCs transplantation group. In contrast, the transplantation of ESCs caused tumor formation; this was due to their high proliferative capacity. Based on transcriptome sequencing, we found that a long intergenic non-coding RNA (named linc-NSC) with unknown structure and function was expressed at 1100-fold higher levels in NSCs than in ESCs. This finding suggested that linc-NSC is negatively correlated with stem cell pluripotency and tumor development, but positively correlated with neurogenesis. In the present study, we investigated the specific role of linc-NSC in NSCs/ESCs in tumor formation and neurogenesis. METHODS: Whole transcriptome profiling by RNA sequencing and bioinformatics was used to predict lncRNAs that are widely associated with enhanced tumorigenicity. The expression of linc-NSC was assessed by quantitative real-time PCR. We also performed a number of in vitro methods, including cell proliferation assays, differentiation assays, immunofluorescence assays, flow cytometry, along with in vivo survival and immunofluorescence assays to investigate the impacts of linc-NSC on tumor formation and neurogenesis in NSCs and ESCs. RESULTS: Following the knockdown of linc-NSC in NSCs, NSCs cultured in vitro and those transplanted into the cortex of mice showed stronger survival ability (P < 0.0001), enhanced proliferation(P < 0.001), and reduced apoptosis (P < 0.05); the opposite results were observed when linc-NSC was overexpressed in ESCs. Furthermore, the overexpression of linc-NSC in ECSs induced enhanced apoptosis (P < 0.001) and differentiation (P < 0.01), inhibited tumorigenesis (P < 0.05) in vivo, and led to a reduction in tumor weight (P < 0.0001). CONCLUSIONS: Our analyses demonstrated that linc-NSC, a promising gene-edited target, may promote the differentiation of mouse NSCs and inhibit tumorigenesis in mouse ESCs. The knockdown of linc-NSC inhibited the apoptosis in NSCs both in vitro and in vivo, and prevented tumor formation, revealing a new dimension into the effect of lncRNA on low survival NSCs and providing a prospective gene manipulation target prior to transplantation. In parallel, the overexpression of linc-NSC induced apoptosis in ESCs both in vitro and in vivo and attenuated the tumorigenicity of ESCs in vivo, but did not completely prevent tumor formation.


Subject(s)
Embryonic Stem Cells , Neural Stem Cells , Animals , Mice , Prospective Studies , Cell Differentiation/genetics , Carcinogenesis/genetics , Cell Transformation, Neoplastic , Apoptosis/genetics , Cell Proliferation/genetics
6.
Mol Cell Proteomics ; 22(8): 100595, 2023 08.
Article in English | MEDLINE | ID: mdl-37328064

ABSTRACT

B4GALT1 encodes ß-1,4-galactosyltransferase 1, an enzyme that plays a major role in glycan synthesis in the Golgi apparatus by catalyzing the addition of terminal galactose. Studies increasingly suggest that B4GALT1 may be involved in the regulation of lipid metabolism pathways. Recently, we discovered a single-site missense variant Asn352Ser (N352S) in the functional domain of B4GALT1 in an Amish population, which decreases the level of LDL-cholesterol (LDL-c) as well as the protein levels of ApoB, fibrinogen, and IgG in the blood. To systematically evaluate the effects of this missense variant on protein glycosylation, expression, and secretion, we developed a nano-LC-MS/MS-based platform combined with TMT-labeling for in-depth quantitative proteomic and glycoproteomic analyses in the plasma of individuals homozygous for the B4GALT1 missense variant N352S versus non-carriers (n = 5 per genotype). A total of 488 secreted proteins in the plasma were identified and quantified, 34 of which showed significant fold changes in protein levels between N352S homozygotes and non-carriers. We determined N-glycosylation profiles from 370 glycosylation sites in 151 glycoproteins and identified ten proteins most significantly associated with decreased galactosylation and sialyation in B4GALT1 N352S homozygotes. These results further support that B4GALT1 N352S alters the glycosylation profiles of a variety of critical target proteins, thus governing the functions of these proteins in multiple pathways, such as those involved in lipid metabolism, coagulation, and the immune response.


Subject(s)
Galactosyltransferases , Proteomics , Humans , Amish/genetics , Galactosyltransferases/genetics , Galactosyltransferases/chemistry , Galactosyltransferases/metabolism , Glycosylation , Tandem Mass Spectrometry
7.
Am J Transplant ; 24(9): 1610-1622, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38615902

ABSTRACT

The shortage of transplant organs remains a severe global issue. Normothermic machine perfusion (NMP) has the potential to increase organ availability, yet its efficacy is hampered by the inflammatory response during machine perfusion. Mouse liver ischemia-reperfusion injury (IRI) models, discarded human liver models, and porcine marginal liver transplantation models were utilized to investigate whether farnesoid X receptor (FXR) activation could mitigate inflammation-induced liver damage. FXR expression levels before and after reperfusion were measured. Gene editing and coimmunoprecipitation techniques were employed to explore the regulatory mechanism of FXR in inflammation inhibition. The expression of FXR correlates with the extent of liver damage after reperfusion. Activation of FXR significantly suppressed the inflammatory response triggered by IRI, diminished the release of proinflammatory cytokines, and improved liver function recovery during NMP, assisting discarded human livers to reach transplant standards. Mechanistically, FXR disrupts the interaction between p65 and p300, thus inhibiting modulating the nuclear factor kappa-B signaling pathway, a key instigator of inflammation. Our research across multiple species confirms that activating FXR can optimize NMP by attenuating IRI-related liver damage, thereby improving the utilization of marginal livers for transplantation.


Subject(s)
Liver Transplantation , Organ Preservation , Perfusion , Receptors, Cytoplasmic and Nuclear , Reperfusion Injury , Animals , Reperfusion Injury/prevention & control , Reperfusion Injury/metabolism , Mice , Receptors, Cytoplasmic and Nuclear/metabolism , Humans , Swine , Organ Preservation/methods , Male , Mice, Inbred C57BL , Liver/metabolism
8.
BMC Plant Biol ; 24(1): 854, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39266948

ABSTRACT

Casuarina equisetifolia trees are used as windbreaks in subtropical and tropical coastal zones, while C. equisetifolia windbreak forests can be degraded by seawater atomization (SA) and seawater encroachment (SE). To investigate the mechanisms underlying the response of C. equisetifolia to SA and SE stress, the transcriptome and metabolome of C. equisetifolia seedlings treated with control, SA, and SE treatments were analyzed. We identified 737, 3232, 3138, and 3899 differentially expressed genes (SA and SE for 2 and 24 h), and 46, 66, 62, and 65 differentially accumulated metabolites (SA and SE for 12 and 24 h). The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that SA and SE stress significantly altered the expression of genes related to plant hormone signal transduction, plant-pathogen interaction, and starch and sucrose metabolism pathways. The accumulation of metabolites associated with the biosynthetic pathways of phenylpropanoid and amino acids, as well as starch and sucrose metabolism, and glycolysis/gluconeogenesis were significantly altered in C. equisetifolia subjected to SA and SE stress. In conclusion, C. equisetifolia responds to SA and SE stress by regulating plant hormone signal transduction, plant-pathogen interaction, biosynthesis of phenylpropanoid and amino acids, starch and sucrose metabolism, and glycolysis/gluconeogenesis pathways. Compared with SA stress, C. equisetifolia had a stronger perception and response to SE stress, which required more genes and metabolites to be regulated. This study enhances our understandings of how C. equisetifolia responds to two types of seawater stresses at transcriptional and metabolic levels. It also offers a theoretical framework for effective coastal vegetation management in tropical and subtropical regions.


Subject(s)
Seawater , Stress, Physiological , Stress, Physiological/genetics , Seawater/chemistry , Transcriptome , Gene Expression Regulation, Plant , Metabolome , Seedlings/genetics , Seedlings/physiology , Metabolomics , Multiomics
9.
Physiol Plant ; 176(4): e14464, 2024.
Article in English | MEDLINE | ID: mdl-39157882

ABSTRACT

The PIN-FORMED (PIN) proteins mediate the auxin flow throughout the plant and have been identified in many species. However, evolution differences in the PIN gene families have not been systematically analyzed, and their functions under abiotic stresses in grape are largely unexplored. In this study, 373 PIN genes were identified from 25 species and divided into 3 subgroups. Physicochemical properties analysis indicated that most of the PIN proteins were unstable alkaline hydrophobic proteins in nature. The synteny analysis showed that the PINs contained strong gene duplication. Motif composition revealed that PIN gene sequence differences between monocotyledons and dicotyledons were due to evolutionary-induced base loss, and the loss was more common in dicotyledonous. Meanwhile, the codon usage bias showed that the PINs showed stronger codon preference in monocotyledons, monocotyledons biased towards C3s and G3s, and dicotyledons biased towards A3s and T3s. In addition, the VvPIN1 can interact with VvCSN5. Significantly, under freezing treatment, the ion leakage, O 2 · - $$ \left({O}_2^{\cdotp -}\right) $$ , H2O2, and malondialdehyde (MDA) were obviously increased, while the proline (Pro) content, peroxidase (POD) activity, and glutathione (GSH) content were decreased in VvPIN1-overexpressing Arabidopsis compared to the wild type (WT). And quantitative real-time PCR (qRT-PCR) showed that AtICE1, AtICE2, AtCBF1, AtCBF2, and AtCBF3 were down-regulated in overexpression lines. These results demonstrated that VvPIN1 negatively regulated the freezing tolerance in transgenic Arabidopsis. Collectively, this study provides a novel insight into the evolution and a basis for further studies on the biological functions of PIN genes in monocotyledons and dicotyledons.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Freezing , Gene Expression Regulation, Plant , Plants, Genetically Modified , Arabidopsis/genetics , Arabidopsis/physiology , Plants, Genetically Modified/genetics , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Evolution, Molecular , Multigene Family , Plant Proteins/genetics , Plant Proteins/metabolism , Phylogeny , Vitis/genetics , Vitis/physiology , Vitis/metabolism , Stress, Physiological/genetics
10.
J Fluoresc ; 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38613708

ABSTRACT

Acetylcholinesterase (AChE) plays an important role in the treatment of human diseases, environmental security and global food supply. In this study, the simple fluorescent indicators and MnO2 nanosheets were developed and integrated to establish a ratiometric fluorescence sensing system for the detection of AChE activity. Two fluorescence signals could be recorded independently at the same excitation wavelength, which extended the detection range and enhanced the visibility of results. Fluorescence of F-PDA was quenched by MnO2 nanosheets on account of inner filtering effect. Meanwhile, the nonfluorescent OPD was catalytically oxidized to 2,3-diaminophenazine by MnO2 nanosheets. The acetylcholine (ATCh) was catalytically hydrolyzed by AChE to enzymatic thiocholine, which decomposed MnO2 to Mn2+, recovered the fluorescence of F-PDA and reduced the emission of ox-OPD. Utilizing the fluorescence intensity ratio F468/F558 as the signal readout, the ratiometric fluorescence method was established to detect AChE activity. Under the excitation wavelength of 410 nm, the ratio F460/F558 against the AChE concentration demonstrated two linear relationships in the range 0.05 -1.0 and 1.0-50 U·L- 1 with a limit of detection (LOD) of 0.073 U·L- 1. The method was applied to the detection of AChE activity and the analysis of the inhibitor Huperzine-A. Due to the advantages of high sensitivity and favorable selectivity, the method possesses an application prospect in the activity deteceion of AChE and the screening of inhibitors.

11.
J Fluoresc ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874823

ABSTRACT

Tyrosinase inhibitors have the ability to resist melanin formation and can be used for clinical and cosmetic, so it is becoming extremely crucial to search a rapid and effective method for detecting t the activity of tyrosinase. In this study, a sensing probe based on Nitrogen-doped graphene quantum dots (N-GQDs) were prepared with carbamide and citric acid. Tyrosinase can oxidize dopamine to dopamine quinone, which can quench the fluorescence of N-GQDs based on the principle of fluorescence resonance energy transfer (FRET) process, and then the detection of tyrosinase activity can be achieved. The result demonstrated that the fluorescence intensity of N-GQDs was a linear correlation with the activity of tyrosinase. Wide detection linear ranges between 0.05 and 5 U/mL and high selectivity. The detection range of tyrosinase was 0.05 to 5 U/mL and LOD of 0.005 U/mL. According to the above, the fluorescence method established in this work could be successfully used for the trace analysis of tyrosinase and it was verified that KA is an inhibitor of tyrosinase.

12.
Neuroradiology ; 66(9): 1537-1551, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38676749

ABSTRACT

PURPOSE: The Centiloid project helps calibrate the quantitative amyloid-ß (Aß) load into a unified Centiloid (CL) scale that allows data comparison across multi-site. How the smaller regional amyloid converted into CL has not been attempted. We first aimed to express regional Aß deposition in CL using [18F]Flutemetamol and evaluate regional Aß deposition in CL with that in standardized uptake value ratio (SUVr). Second, we aimed to determine the presence or absence of focal Aß deposition by measuring regional CL in equivocal cases showing negative global CL. METHODS: Following the Centiloid project pipeline, Level-1 replication, Level-2 calibration, and quality control were completed to generate corresponding Centiloid conversion equations to convert SUVr into Centiloid at regional levels. In equivocal cases, the regional CL was compared with visual inspection to evaluate regional Aß positivity. RESULTS: 14 out of 16 regional conversions from [18F]Flutemetamol SUVr to Centiloid successfully passed the quality control, showing good reliability and relative variance, especially precuneus/posterior cingulate and prefrontal regions with good stability for Centiloid scaling. The absence of focal Aß deposition could be detected by measuring regional CL, showing a high agreement rate with visual inspection. The regional Aß positivity in the bilateral anterior cingulate cortex was most prevalent in equivocal cases. CONCLUSION: The expression of regional brain Aß deposition in CL with [18F]Flutemetamol has been attempted in this study. Equivocal cases had focal Aß deposition that can be detected by measuring regional CL.


Subject(s)
Amyloid beta-Peptides , Aniline Compounds , Benzothiazoles , Positron-Emission Tomography , Radiopharmaceuticals , Humans , Amyloid beta-Peptides/metabolism , Female , Male , Aged , Positron-Emission Tomography/methods , Reproducibility of Results , Alzheimer Disease/metabolism , Alzheimer Disease/diagnostic imaging , Middle Aged , Brain/metabolism , Brain/diagnostic imaging , Calibration
13.
Int J Med Sci ; 21(13): 2603-2612, 2024.
Article in English | MEDLINE | ID: mdl-39439452

ABSTRACT

Objective: TBC1 domain family member 22A (TBC1D22A) possesses GTPase-activating protein (GAP) activity of Rab family proteins and has not been reported in ovarian serous cystadenocarcinoma (OSC). The research was designed to evaluate the expression and prognostic effect of TBC1D22A in OSC. Methods: TCGA, GTEx, GEO, HPA, and GDSC databases were adopted to explore the oncogenic mechanism of TBC1D22A in OSC, as well as the correlation between TBC1D22A and patient prognosis, IC50, stemness index, immune checkpoint, and immune infiltration. To compare the occurrence of end-point times, Kaplan-Meier survival curves were used. Independent prognostic factors of patients with OSC were analyzed with both univariate as well as multivariate Cox regression analyses, and the overall survival (OS) of the patients at 1, 2 and 3 years was predicted with nomograms. Results: TB1D22A expression was elevated in OSC, and high expression of TBC1D22A was related to poor OS, progression free survival (PFS), disease specific survival (DSS), and disease-free survival (DFS) in OSC. TBC1D22A had predictive value in both univariate and multivariate Cox regression analysis. TBC1D22A was positively correlated with M2 macrophage infiltration and the expression of most immune checkpoint genes. IC50 for cisplatin and paclitaxel increased in patients with overexpression of TBC1D22A. Conclusion: TBC1D22A is an independent prognostic risk factor for patients of ovarian cancer. Future research is required to fully understand the carcinogenic mechanism and clinical utility of TBC1D22A in ovarian cancer.


Subject(s)
Cystadenocarcinoma, Serous , GTPase-Activating Proteins , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Ovarian Neoplasms/mortality , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/mortality , GTPase-Activating Proteins/genetics , GTPase-Activating Proteins/metabolism , Prognosis , Middle Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Kaplan-Meier Estimate , Nomograms , Disease-Free Survival , Paclitaxel/therapeutic use
14.
Acta Radiol ; 65(5): 422-431, 2024 May.
Article in English | MEDLINE | ID: mdl-38584372

ABSTRACT

BACKGROUND: Gallbladder cancer is a rare but aggressive malignancy that is often diagnosed at an advanced stage and is associated with poor outcomes. PURPOSE: To develop a radiomics model to discriminate between benign and malignant gallbladder lesions using enhanced computed tomography (CT) imaging. MATERIAL AND METHODS: All patients had a preoperative contrast-enhanced CT scan, which was independently analyzed by two radiologists. Regions of interest were manually delineated on portal venous phase images, and radiomics features were extracted. Feature selection was performed using mRMR and LASSO methods. The patients were randomly divided into training and test groups at a ratio of 7:3. Clinical and radiomics parameters were identified in the training group, three models were constructed, and the models' prediction accuracy and ability were evaluated using AUC and calibration curves. RESULTS: In the training group, the AUCs of the clinical model and radiomics model were 0.914 and 0.968, and that of the nomogram model was 0.980, respectively. There were statistically significant differences in diagnostic accuracy between nomograms and radiomics features (P <0.05). There was no significant difference in diagnostic accuracy between the nomograms and clinical features (P >0.05) or between the clinical features and radiomics features (P >0.05). In the testing group, the AUC of the clinical model and radiomics model were 0.904 and 0.941, and that of the nomogram model was 0.948, respectively. There was no significant difference in diagnostic accuracy between the three groups (P >0.05). CONCLUSION: It was suggested that radiomics analysis using enhanced CT imaging can effectively discriminate between benign and malignant gallbladder lesions.


Subject(s)
Contrast Media , Gallbladder Neoplasms , Gallbladder , Tomography, X-Ray Computed , Humans , Male , Female , Gallbladder Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Middle Aged , Aged , Diagnosis, Differential , Adult , Gallbladder/diagnostic imaging , Retrospective Studies , Aged, 80 and over , Nomograms , Radiographic Image Enhancement/methods , Reproducibility of Results , Sensitivity and Specificity , Radiomics
15.
Chem Biodivers ; : e202401384, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39172434

ABSTRACT

This study aims to explore the feasibility of using network pharmacology and molecular docking technology to predict the effects of active components from oil tree peony seed meal (PSM) on swine diseases. Ten active components of PSM were screened Screening through literature search and network pharmacology standards, including Betulinic acid, Quercetin, Kaempferol, Luteolin, Isorhamnetin, Hydroxygenkwanin, Hederagenin, Benzoyl Paeoniflorin, Albiflorin, Paeoniflorin. Ten types of swine diseases were selected, including African Swine Fever, Aftosa, Swine Vesicular Disease, Transmissible Gastroenteritis, Swine Streptococcal Infection, Blue Aural Disease, Swine Infectious Atrophic Rhinitis, Swine Influenza, Swine Erysipelas, Swine Epidemic Encephalitis. The results showed that the average number of cross genes between the potential target genes of PSM active components and each swine disease target gene accounted for 7.64 % of the total number of swine disease target genes. The GO enrichment analyses showed that putative targets exist in endosomes, lysosomes, cell membranes, nerves, growth factor activity, receptor tyrosine kinase binding, enzyme binding, growth factor binding, transcription coactivator binding, oxidoreductase activity, prostaglandin E receptor activity and insulin receptor substrate binding. The KEGG enrichment analysis results showed that these putative genes were involved in various cancer progression pathways, signaling pathways, and hormone regulatory pathways. A total of 8 core targets were obtained through protein-protein interaction networks analysis, including Protein Kinase CAMP-Activated Catalytic Subunit Alpha (PRKACA), Non-Receptor Tyrosine Kinase (SRC), Mitogen-Activated Protein Kinase 1 (MAPK1), E1A Binding Protein P300 (EP300), Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A), Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta (PIK3CB), C-X-C chemokine receptor type 4 (CXCR4) and Estrogen Receptor 2 (ESR2). The HIF-1 signaling pathway was found to be associated with all 10 selected swine diseases. The PD-L1 expression, and PD-1 checkpoint pathway in cancer, and thyroid hormone signaling pathway were not only enriches the core target with a quantity of 7, but also associated with 9 Swine diseases. In addition, the molecular docking results indicate that the core ingredients have strong affinity with hub genes. The research suggests that the active components of PSM may intervene in swine diseases through multiple components, targets, and pathways.

16.
Int J Mol Sci ; 25(8)2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38674041

ABSTRACT

Cold stress adversely impacts grape growth, development, and yield. Therefore, improving the cold tolerance of grape is an urgent task of grape breeding. The Jasmonic acid (JA) pathway responsive gene JAZ plays a key role in plant response to cold stress. However, the role of JAZ in response to low temperatures in grape is unclear. In this study, VvJAZ13 was cloned from the 'Pinot Noir' (Vitis vinefera cv. 'Pinot Noir') grape, and the potential interacting protein of VvJAZ13 was screened by yeast two-hybrid (Y2H). The function of VvJAZ13 under low temperature stress was verified by genetic transformation. Subcellular localization showed that the gene was mainly expressed in cytoplasm and the nucleus. Y2H indicated that VvF-box, VvTIFY5A, VvTIFY9, Vvbch1, and VvAGD13 may be potential interacting proteins of VvJAZ13. The results of transient transformation of grape leaves showed that VvJAZ13 improved photosynthetic capacity and reduced cell damage by increasing maximum photosynthetic efficiency of photosystem II (Fv/Fm), reducing relative electrolyte leakage (REL) and malondialdehyde (MDA), and increasing proline content in overexpressed lines (OEs), which played an active role in cold resistance. Through the overexpression of VvJAZ13 in Arabidopsis thaliana and grape calli, the results showed that compared with wild type (WT), transgenic lines had higher antioxidant enzyme activity and proline content, lower REL, MDA, and hydrogen peroxide (H2O2) content, and an improved ability of scavenging reactive oxygen species. In addition, the expression levels of CBF1-2 and ICE1 genes related to cold response were up-regulated in transgenic lines. To sum up, VvJAZ13 is actively involved in the cold tolerance of Arabidopsis and grape, and has the potential to be a candidate gene for improving plant cold tolerance.


Subject(s)
Arabidopsis , Cold-Shock Response , Plant Proteins , Vitis , Arabidopsis/genetics , Arabidopsis/metabolism , Cold Temperature , Cold-Shock Response/genetics , Cyclopentanes/metabolism , Gene Expression Regulation, Plant , Photosynthesis/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified , Vitis/genetics , Vitis/metabolism
17.
BMC Nurs ; 23(1): 134, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38383410

ABSTRACT

BACKGROUND: Academic emotion is a fundamental emotional concept closely linked to academic achievement. Understanding the connection between academic emotion and the personality trait of hardiness is pivotal in maintaining a stable career orientation throughout one's educational career. Therefore, in pursuit of fostering the robust growth of nursing careers, it is imperative to delve into the academic emotions experienced by undergraduate nursing students. This study endeavors to mitigate the impact of gender differences among nursing students while investigating the intricate relationship between academic emotions and the trait of hardiness in their personalities. METHODS: This study employed a cross-sectional research design. We gathered data from a convenient sample of 292 nursing students enrolled at Shanxi University of Chinese Medicine. Each student provided demographic information and responded to a general academic mood questionnaire, as well as a Hardiness Personality Rating Scale. Subsequently, we used canonical correlation analysis to evaluate the correlation between academic emotion and tenacity personality in 292 undergraduate nursing students. RESULTS: We discovered that academic emotions among nursing students are predominantly characterized by feelings of disappointment and boredom. Furthermore, personality hardiness is primarily influenced by the dimensions of engagement and control. It is important to note that a heightened level of negative, low-arousal academic emotions can diminish the level of engagement. The first typical correlation coefficient corresponding to academic emotion and hardiness were 0.660. The linear combination of standardized variables of the first typical variable corresponding to academic emotion (X1) = -0.444*negative hyperarousal -0.443 * positive hyperarousal + 0.694 * negative hypoarousal -0.260 * positive hypoarousal. The standardized variable equation of the first typical variable corresponding to hardiness personality (η1) = 0.235* hardiness -0.433* control -0.530* investment -0.303* challenge. CONCLUSIONS: Nursing students generally believe that their input is out of proportion to the return, and this unbalanced emotional experience will seriously affect their academic emotions in China. It is suggested that paying attention to cultivating their tenacious personality traits in the teaching process may help to enhance their academic emotions and enhance the sense of belonging and identity of nursing students engaged in the nursing profession.

18.
Angew Chem Int Ed Engl ; : e202414721, 2024 Oct 11.
Article in English | MEDLINE | ID: mdl-39392202

ABSTRACT

The development of materials for hydrogen production via seawater electrolysis at high current densities plays a crucial role in producing renewable hydrogen energy. However, during the seawater electrolysis process, the anode inevitably undergoes chloride oxidation reaction (ClOR) due to Cl- adsorption, making the seawater electrolysis process difficult to sustain. Inspired by the selective permeability of cell membranes, we propose a biomimetic design of frustrated Lewis pairs (FLPs) layers. Combining experimental results and molecular dynamics simulations, it has been demonstrated that cerium dioxide layers with FLPs sites can decompose water molecules, capture hydroxyl anions, and repel chloride ions simultaneously. DFT theoretical analysis indicates that the FLP sites regulate the Ce 4f-O 2p-Ni 3d gradient orbital coupling, providing additional oxygen non-bonding (ONB) to stabilize the Ni-O bond and optimize the adsorption strength of intermediates, thereby breaking the *OH and *OOH scaling relationship. Assembled anion exchange membrane electrolyzers exhibit an efficiency of 95.7% at a current density of 0.1 A cm-2 and can stably operate for 250 hours at a current density of 0.2 A cm-2.

19.
BMC Genomics ; 24(1): 665, 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37924006

ABSTRACT

BACKGROUND: Tree peony (Paeonia sect. Moutan DC.) is a famous flower native to China with high ornamental, medicinal, and oil value. However, the low regeneration rate of callus is one of the main constraints for the establishment of a genetic transformation system in tree peony. By histomorphological observation, transcriptomic analysis and metabolite determination, we investigated the molecular mechanism of somatic embryogenesis after the establishment of a culture system and the induction of somatic embryo(SE) formation. RESULTS: We found that SE formation was successfully induced when cotyledons were used as explants. A total of 3185 differentially expressed genes were screened by comparative transcriptomic analysis of embryogenic callus (EC), SE, and non-embryogenic callus (NEC). Compared to NEC, the auxin synthesis-related genes GH3.6 and PCO2 were up-regulated, whereas cytokinin dehydrogenase (CKX6) and CYP450 family genes were down-regulated in somatic embryogenesis. In SE, the auxin content was significantly higher than the cytokinin content. The methyltransferase-related gene S-adenosylmethionine synthase (SAMS) and the flavonoid biosynthesis-related gene (ANS and F3'5'H) were down-regulated in somatic embryogenesis. The determination of flavonoids showed that rhoifolin and hyperoside had the highest content in SE. The results of transcriptome analysis were consistent with the relative expression of 8 candidate genes by quantitative polymerase chain reaction analysis. CONCLUSION: The results revealed that auxin and cytokinin may play a key role in 'Fengdan' somatic embryogenesis. The genes related to somatic embryogenesis were revealed, which has partly elucidated the molecular mechanism of somatic embryogenesis in 'Fengdan'.


Subject(s)
Paeonia , Paeonia/genetics , Paeonia/metabolism , Gene Expression Profiling , Transcriptome , Indoleacetic Acids/metabolism , Embryonic Development , Cytokinins , Flavonoids , Regeneration , Gene Expression Regulation, Plant , Plant Somatic Embryogenesis Techniques
20.
Anal Chem ; 95(48): 17603-17612, 2023 12 05.
Article in English | MEDLINE | ID: mdl-37973790

ABSTRACT

Despite the rapid advances in process analytical technology, the assessment of protein refolding efficiency has largely relied on off-line protein-specific assays and/or chromatographic procedures such as reversed-phase high-performance liquid chromatography and size exclusion chromatography. Due to the inherent time gap pertaining to traditional methods, exploring optimum refolding conditions for many recombinant proteins, often expressed as insoluble inclusion bodies, has proven challenging. The present study describes a novel protein refolding sensor that utilizes liquid crystals (LCs) to discriminate varying protein structures during unfolding and refolding. An LC layer containing 4-cyano-4'-pentylbiphenyl (5CB) intercalated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) is used as a sensing platform, and its proof-of-concept performance is demonstrated using lysozyme as a model protein. As proteins unfold or refold, a local charge fluctuation at their surfaces modulates their interaction with zwitterionic phospholipid DOPE. This alters the alignment of DOPE molecules at the aqueous/LC interface, affecting the orientational ordering of bulk LC (i.e., homeotropic to planar for refolding and planar to homeotropic for unfolding). Differential polarized optical microscope images of the LC layer are subsequently generated, whose brightness directly linked to conformational changes of lysozyme molecules is quantified by gray scale analysis. Importantly, our LC-based refolding sensor is compatible with diverse refolding milieus for real-time analysis of lysozyme refolding and thus likely to facilitate the refolding studies of many proteins, especially those lacking a method to determine structure-dependent biological activity.


Subject(s)
Liquid Crystals , Muramidase , Liquid Crystals/chemistry , Phospholipids/chemistry , Biphenyl Compounds/chemistry
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