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1.
Proc Natl Acad Sci U S A ; 121(17): e2314201121, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38635631

ABSTRACT

To effectively protect the host from viral infection while avoiding excessive immunopathology, the innate immune response must be tightly controlled. However, the precise regulation of antiviral innate immunity and the underlying mechanisms remain unclear. Here, we find that sirtuin3 (SIRT3) interacts with mitochondrial antiviral signaling protein (MAVS) to catalyze MAVS deacetylation at lysine residue 7 (K7), which promotes MAVS aggregation, as well as TANK-binding kinase I and IRF3 phosphorylation, resulting in increased MAVS activation and enhanced type I interferon signaling. Consistent with these findings, loss of Sirt3 in mice and zebrafish renders them more susceptible to viral infection compared to their wild-type (WT) siblings. However, Sirt3 and Sirt5 double-deficient mice exhibit the same viral susceptibility as their WT littermates, suggesting that loss of Sirt5 in Sirt3-deficient mice may counteract the increased viral susceptibility displayed in Sirt3-deficient mice. Thus, we not only demonstrate that SIRT3 positively regulates antiviral immunity in vitro and in vivo, likely via MAVS, but also uncover a previously unrecognized mechanism by which SIRT3 acts as an accelerator and SIRT5 as a brake to orchestrate antiviral innate immunity.


Subject(s)
Sirtuin 3 , Sirtuins , Virus Diseases , Animals , Mice , Adaptor Proteins, Signal Transducing/genetics , Immunity, Innate , Lysine , Sirtuin 3/genetics , Sirtuins/genetics , Zebrafish , Zebrafish Proteins
3.
Gene ; 893: 147935, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38381506

ABSTRACT

Hypoxia, an inadequate supply of tissue oxygen tension, has been reported to induce apoptosis of spermatogenic cells and is associated with male infertility. Neddylation, a post-translational modification similar to ubiquitination, has been shown to be involved in the hypoxia stress response. However, the functions of neddylation in hypoxia-induced apoptosis of spermatogenic cells and its association with male infertility remain largely unexplored. In this study, aiming to explore the role of neddylation in male infertility, we used the specific neddylation inhibitor MLN4924 for treatment in mouse type B spermatogonia GC-2 cells. Our results showed that MLN4924 had no apparent effect on GC-2 cell apoptosis under normoxia, but significantly increased apoptotic cells under hypoxia. Transcriptomic analysis and qPCR assay confirmed that MLN4924 could suppress the expression of hypoxia target genes in GC-2 cells under hypoxia. In addition, MLN4924 could enhance the induction of intracellular and mitochondrial reactive oxygen species (ROS) under hypoxia. These results indicate that the neddylation inhibitor MLN4924 potentiates hypoxia-induced apoptosis of mouse type B spermatogonia GC-2 cells, and neddylation may play an important role in promoting spermatogenic cells to adapt to hypoxia stress.


Subject(s)
Cyclopentanes , Infertility, Male , Pyrimidines , Spermatogonia , Male , Animals , Mice , Humans , Apoptosis , Hypoxia
4.
Acta Radiol ; : 2841851231221912, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38232946

ABSTRACT

BACKGROUND: The overlapping nature of thyroid lesions visualized on ultrasound (US) images could result in misdiagnosis and missed diagnoses in clinical practice. PURPOSE: To compare the diagnostic effectiveness of US coupled with three mathematical models, namely logistic regression (Logistics), partial least-squares discriminant analysis (PLS-DA), and support vector machine (SVM), in discriminating between malignant and benign thyroid nodules. MATERIAL AND METHODS: A total of 588 thyroid nodules (287 benign and 301 malignant) were collected, among which 80% were utilized for constructing the mathematical models and the remaining 20% were used for internal validation. In addition, an external validation cohort comprising 160 nodules (80 benign and 80 malignant) was employed to validate the accuracy of these mathematical models. RESULTS: Our study demonstrated that all three models exhibited effective predictive capabilities for distinguishing between benign and malignant nodules, whose diagnostic effectiveness surpassed that of the TI-RADS classification, particularly in terms of true negative diagnoses. SVM achieved a higher diagnostic rate for malignant thyroid nodules (93.8%) compared to Logistics (91.5%) and PLS-DA (91.6%). PLS-DA exhibited higher diagnostic rates for benign thyroid nodules (91.9%) compared to Logistics (86.7%) and SVM (88.7%). Both the area under the receiver operating characteristic curve (AUC) values of PLS-DA (0.917) and SVM (0.913) were higher than that of Logistics (0.891). CONCLUSION: Our findings indicate that SVM had significantly higher rates of true positive diagnoses and PLS-DA exhibited significantly higher rates of true negative diagnoses. All three models outperformed the TI-RADS classification in discriminating between malignant and benign thyroid nodules.

5.
J Environ Manage ; 351: 119997, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38160546

ABSTRACT

We report a novel modified semi-carbonized fiber (CF) prepared using cotton and acrylic clothes for derisking contaminated water to realize the resource utilization of discarded clothes in wastewater treatment. In this study, amphoteric and auxiliary modifiers were used to modify CFs for preparing amphoteric and amphoteric-auxiliary CFs. The basic physicochemical properties of different modified CFs were determined, and the microscopic morphology of modified CFs was detected. The isothermal adsorption characteristics of Cu(II) and Pb(II) on different modified CFs were investigated by the batch method, and the effect mechanisms of temperature, pH, ionic strength, and material dose were compared. Physicochemical properties and microscopic morphology results proved that amphoteric and auxiliary modifiers were modified on the CF surface and changed the surface properties of CF. The adsorption capacities of Cu(II) and Pb(II) on modified CFs increased with the increase in equilibrium concentration of Cu(II) and Pb(II), and the isotherm was more suitable for Freundlich model fitting than that of the Langmuir model. The maximum adsorption capacities (qm) of Cu(II) and Pb(II) on different modified CFs were 60.72-81.26 mg/g and 102.58-161.72 mg/g, respectively, and presented the trend of amphoteric-auxiliary CFs > amphoteric CFs > CFs. Increasing pH and temperature and decreasing ionic strength and material dose were beneficial to Cu(II) and Pb(II) adsorption. The Cu(II) and Pb(II) adsorption process was a spontaneous, endothermic, and entropy-increasing reaction, and the adsorption rate was controlled by chemisorption. The adsorption amount of amphoteric-auxiliary CFs maintained about 65% of original materials after 3 times of regeneration. Electrostatic attraction, precipitation, complexation, and ion exchange were the main adsorption mechanisms. The cation exchange capacity and total pore volume of modified CFs were key to determining qm of Cu(II) and Pb(II).


Subject(s)
Lead , Water Pollutants, Chemical , Temperature , Cations , Adsorption , Water , Clothing , Water Pollutants, Chemical/chemistry , Kinetics , Hydrogen-Ion Concentration
6.
Cell Rep ; 43(1): 113606, 2024 01 23.
Article in English | MEDLINE | ID: mdl-38127621

ABSTRACT

Activation of type I interferon (IFN-1) signaling is essential to protect host cells from viral infection. The full spectrum of IFN-I induction requires the activation of a number of cellular factors, including IκB kinase epsilon (IKKϵ). However, the regulation of IKKϵ activation in response to viral infection remains largely unknown. Here, we show that factor inhibiting hypoxia-inducible factor (HIF) (FIH), an asparaginyl hydroxylase, interacts with IKKϵ and catalyzes asparagine hydroxylation of IKKϵ at Asn-254, Asn-700, and Asn-701, resulting in the suppression of IKKϵ activation. FIH-mediated hydroxylation of IKKϵ prevents IKKϵ binding to TBK1 and TRAF3 and attenuates the cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex-catalyzed K63-linked polyubiquitination of IKKϵ at Lys-416. In addition, Fih-deficient mice and zebrafish are more resistant to viral infection. This work uncovers a previously unrecognized role of FIH in suppressing IKKϵ activation for IFN signaling and antiviral immune responses.


Subject(s)
I-kappa B Kinase , Virus Diseases , Animals , Mice , I-kappa B Kinase/metabolism , Repressor Proteins/metabolism , Amino Acid Sequence , Hydroxylation , Zebrafish/metabolism , Immunity, Innate
7.
Front Psychol ; 14: 1287891, 2023.
Article in English | MEDLINE | ID: mdl-38106401

ABSTRACT

Objective: This study aimed to evaluate the effects of self-help mindfulness-based cognitive therapy (MBCT-SH) on mindfulness, symptom change, and suicidal ideation in patients with depression. Methods: For this randomized controlled study, 97 patients were randomly assigned to either the MBCT-SH (n = 48) or control (n = 49) group. The Five Facet Mindfulness Questionnaire (FFMQ), Hamilton Depression Rating Scale (HAMD-24), and Suicide Attitude Questionnaire (SAQ) were used to assess mindfulness, depression symptoms, and suicidal ideation, respectively, at baseline (T0), intervention week 4 (T1), intervention week 8 (T2), and 3-month follow-up (T3). The groups were also compared on treatment costs and readmission rates at a 6-month follow-up. Results: In the MBCT-SH group, 46 of 48 participants (96%) completed the eight-week program. At T0, there were no statistically significant between-group differences in demographics, clinical characteristics, FFMQ, HAMD-24, or SAQ. Nor were there statistically significant differences on the HAMD-24 or SAQ between the MBCT-SH and control groups at T1 (p = 0.18 and p = 0.59, respectively), while mindfulness was significantly higher in the MBCT-SH group (t = 2.383, p = 0.019). At T2, there were significant between-group differences on the FFMQ, HAMD-24, and SAQ, all of which remained significant at T3. At the 6-month follow-up, per capita treatment costs were 5,298 RMB lower in the MBCT-SH group compared with the control group, while their readmission rates (6.1% and 4.2%, respectively) did not differ significantly. Conclusion: These findings support the feasibility and effectiveness of MBCT-SH among patients with depression. Clinical trial registration: http://www.chictr.org.cn, ChiCTR2300077850.

8.
J Biol Chem ; 299(12): 105420, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37923141

ABSTRACT

Prolyl hydroxylase domain (PHD)-containing enzyme 3 (PHD3) belongs to the Caenorhabditis elegans gene egl-9 family of prolyl hydroxylases. PHD3 catalyzes proline hydroxylation of hypoxia-inducible factor α (HIF-α) and promotes HIF-α proteasomal degradation through coordination with the pVHL complex under normoxic conditions. However, the relationship between PHD3 and the hypoxic response is not well understood. In this study, we used quantitative real-time PCR assay and O-dianisidine staining to characterize the hypoxic response in zebrafish deficient in phd3. We found that the hypoxia-responsive genes are upregulated and the number of erythrocytes was increased in phd3-null zebrafish compared with their wild-type siblings. On the other hand, we show overexpression of phd3 suppresses HIF-transcriptional activation. In addition, we demonstrate phd3 promotes polyubiquitination of zebrafish hif-1/2α proteins, leading to their proteasomal degradation. Finally, we found that compared with wild-type zebrafish, phd3-null zebrafish are more resistant to hypoxia treatment. Therefore, we conclude phd3 has a role in hypoxia tolerance. These results highlight the importance of modulation of the hypoxia signaling pathway by phd3 in hypoxia adaptation.


Subject(s)
Hypoxia-Inducible Factor-Proline Dioxygenases , Oxygen , Procollagen-Proline Dioxygenase , Zebrafish Proteins , Zebrafish , Animals , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor-Proline Dioxygenases/genetics , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Procollagen-Proline Dioxygenase/genetics , Procollagen-Proline Dioxygenase/metabolism , Proline/metabolism , Zebrafish/genetics , Zebrafish/metabolism , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Gene Deletion , Oxygen/metabolism
9.
Acta Biochim Pol ; 70(3): 609-614, 2023 Sep 06.
Article in English | MEDLINE | ID: mdl-37672760

ABSTRACT

Vitamin D deficiency (VDD) causes a wide range of health problems, including anemia in infants. If not treated promptly, it may create serious issues for infants with long-term impacts. Therefore, a satisfactory solution to this problem is required. This investigation was to explore the correlation between the blood 25-hydroxyvitamin D (25(OH)D) levels and childhood anemia. In this investigation, a cross-sectional examination was performed on 2,942 babies ranging in age from 2 to 36 months and classified into three cohorts: VDD (Vitamin D deficiency), VDI (Vitamin D insufficiency), and VDS (Vitamin D sufficiency). Multiple-variables and multinomially-related logistic regressions for examining the anemia status-vitamin D (Vit-D) relationship of the baseline as the interpretable visual quality models were examined. The median serum 25(OH)D level in 2,942 infants was 24.72±4.26 ng/l, with 661 cases (22.5%) of VDD and 1710 cases of deficiency (58.1%), and a noticeable seasonal variation (p<0.05). Anemia was present in 28.5% of the VDD group compared with 3.3% in vit-D sufficient infants (p<0.0001). Lower levels of 25(OH)D were found to be associated with an increased risk of anemia in a multiple-variable regression analysis. In healthy children, low 25(OH)D levels were associated with increased risk of anemia. Biologically inspired, primary care physicians should assess Vit-D levels and place a greater emphasis on adequate supplementation for deficiency prevention.


Subject(s)
Anemia , Vitamin D Deficiency , Infant , Child , Humans , Child, Preschool , Biomechanical Phenomena , Bionics , Cross-Sectional Studies , Vitamin D , Vitamins , Vitamin D Deficiency/diagnosis , Anemia/diagnosis
10.
Sci Rep ; 13(1): 16047, 2023 09 25.
Article in English | MEDLINE | ID: mdl-37749121

ABSTRACT

This study compared the diagnostic efficiency of benign and malignant breast nodules using ultrasonographic characteristics coupled with several machine-learning models, including logistic regression (Logistics), partial least squares discriminant analysis (PLS-DA), linear support vector machine (Linear SVM), linear discriminant analysis (LDA), K-nearest neighbor (KNN), artificial neural network (ANN) and random forest (RF). The clinical information and ultrasonographic characteristics of 926 female patients undergoing breast nodule surgery were collected and their relationships were analyzed using Pearson's correlation. The stepwise regression method was used for variable selection and the Monte Carlo cross-validation method was used to randomly divide these nodule cases into training and prediction sets. Our results showed that six independent variables could be used for building models, including age, background echotexture, shape, calcification, resistance index, and axillary lymph node. In the prediction set, Linear SVM had the highest diagnosis rate of benign nodules (0.881), and Logistics, ANN and LDA had the highest diagnosis rate of malignant nodules (0.910~0.912). The area under the ROC curve (AUC) of Linear SVM was the highest (0.890), followed by ANN (0.883), LDA (0.880), Logistics (0.878), RF (0.874), PLS-DA (0.866), and KNN (0.855), all of which were better than that of individual variances. On the whole, the diagnostic efficacy of Linear SVM was better than other methods.


Subject(s)
Calcification, Physiologic , Calcinosis , Female , Humans , Area Under Curve , Cluster Analysis , Models, Theoretical
11.
J Mech Behav Biomed Mater ; 144: 105988, 2023 08.
Article in English | MEDLINE | ID: mdl-37406484

ABSTRACT

The long-term successes of implant restorations rely on both appropriate osseointegration and robust soft tissue integration (STI). Numerous studies have reported that titanium dioxide nanotube (TNT) arrays formed by electrochemical anodization (EA) can promote early osteogenesis, but the mechanical stability of such modifications is often ignored and remains underexplored. In addition, relatively little research has been done on their effects on soft tissues integration. In this study, we developed mechanically robust TNT arrays using an optimized EA system. Subsequently, we immobilized a peptide, specifically D-amino K122-4, onto the anodized TNTs via polydopamine (PDA) films to enhance their mechanical properties. Surface morphology and composition were characterized by scanning electron microscopy (SEM), atomic force microscopy, and X-ray photoelectron spectroscopy. Mechanical properties, including the elastic modulus and hardness of TNTs modified Ti surfaces, were assessed using the nano-indention test. The adhesive strength of TNTs films to the substrate was measured using the nano scratch test. Furthermore, we evaluated the adhesion, spreading, and proliferation of human gingival fibroblasts (HGFs) and periodontal pathogenic bacteria such as Streptococcus mutans (S.m) and F. nucleatum (F.n) on the surface. Results showed that the elastic modulus, hardness, and adhesive strength of anodized TNTs were significantly enhanced by the incorporation of the D-amino K122-4 peptide. Live-dead staining and SEM observation suggested a decreased surface colonization by both bacterial species. The antibacterial rate of S.m and F. n was 81.5% and 71.7%, respectively, evaluated by colony counting method. Additionally, results of CCK8 assay showed that modified TNTs slightly stimulated HGFs attachment and proliferation while producing enhanced fluorescence of integrin ß1 and F-actin, confirmed by laser confocal microscopy observation. Thus, D-amino K122-4 biofunctionalized TNTs present significantly improved mechanical properties, and the mechanically robust structures modulate HGFs proliferation and alignment, resulting in decreased bacteria growth. This novel strategy has the potential to create a surface coating for implants that exhibits superior mechanical robustness and enhanced surface-to-implant interactions.


Subject(s)
Dental Implants , Nanotubes , Humans , Peptides , Titanium/chemistry , Nanotubes/chemistry , Fibroblasts , Bacteria , Surface Properties , Cell Adhesion
12.
J Biol Chem ; 299(8): 105074, 2023 08.
Article in English | MEDLINE | ID: mdl-37481210

ABSTRACT

SIRT7 is a member of the sirtuin family proteins with nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase activity, which can inhibit the activity of hypoxia-inducible factors independently of its enzymatic activity. However, the role of SIRT7 in affecting hypoxia signaling in vivo is still elusive. Here, we find that sirt7-null zebrafish are more resistant to hypoxic conditions, along with an increase of hypoxia-responsive gene expression and erythrocyte numbers, compared with their wildtype siblings. Overexpression of sirt7 suppresses the expression of hypoxia-responsive genes. Further assays indicate that sirt7 interacts with zebrafish hif-1αa, hif-1αb, hif-2αa, and hif-2αb to inhibit their transcriptional activity and mediate their protein degradation. In addition, sirt7 not only binds to the hypoxia responsive element of hypoxia-inducible gene promoters but also causes a reduction of H3K18Ac on these promoters. Sirt7 may regulate hypoxia-responsive gene expression through its enzymatic and nonenzymatic activities. This study provides novel insights into sirt7 function and sheds new light on the regulation of hypoxia signaling by sirt7.


Subject(s)
Oxygen , Sirtuins , Zebrafish Proteins , Zebrafish , Animals , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Proteolysis , Sirtuins/genetics , Sirtuins/metabolism , Zebrafish/genetics , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Anaerobiosis , Oxygen/metabolism
13.
J Radiat Res ; 2023 May 08.
Article in English | MEDLINE | ID: mdl-37154691

ABSTRACT

This study aimed to assess the severity of acute radiodermatitis (ARD) by ultrasound quantitative parameters and to try to identify the influencing factors of skin toxicity. A total of 55 patients who underwent radiotherapy after unilateral breast-conserving surgery (BCS) were included in the study. The irradiated side of the breast was used as the research object and the quantitative ultrasound parameters (skin thickness, shear wave elasticity) were evaluated before radiotherapy, every week during radiotherapy. Two weeks after radiotherapy, the patients were divided into two groups, according to the World Health Organization scoring standard: mild (0-2 grade) and severe (3-4 grade). The differences in the parameters between the groups and the changes during radiotherapy were compared, and the relationship between these parameters and the severity of ARD was analyzed. In addition, some clinical factors that may affect ARD were also included in our study. Ninety-eight percent of patients developed different degrees of ARD, and Group 2 accounted for ~31%. At the end of 5 weeks of radiotherapy, the difference in thickness between the two groups was statistically significant (P < 0.05). There was no significant change in the elastic modulus of breast skin between the two groups (P > 0.05). Body mass index >25 kg/m2, breast thickness ≥18 mm, skin basic elastic modulus <23 kPa and skin thickness increment >0.3 mm were considered to be associated with severe skin reactions (P < 0.05). Ultrasound can be a useful tool for the non-invasive and objective assessment of skin changes during radiotherapy, documenting quantitative changes in the skin of breast cancer patients following BCS undergoing radiotherapy.

14.
Sci Rep ; 13(1): 3346, 2023 02 27.
Article in English | MEDLINE | ID: mdl-36849532

ABSTRACT

The purpose of this paper was to assess the value of ultrasonography in the prognosis of diffuse large b-cell lymphoma (DLBCL) by developing a new prognostic model. One hundred and eleven DLBCL patients with complete clinical information and ultrasound findings were enrolled in our study. Univariate and multivariate regression analyses were used to identify independent risk factors for progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curves were plotted and the corresponding area under the curve (AUC) was calculated to assess the accuracy of the international prognostic index (IPI) and new model in DLBCL risk stratification. The results suggested that hilum loss and ineffective treatment were independent risk variables for both PFS and OS in DLBCL patients. Additionally, the new model that added hilum loss and ineffective treatment to IPI had a better AUC for PFS and OS than IPI alone (AUC: 0.90, 0.88, and 0.82 vs. 0.71, 0.74, and 0.68 for 1-, 3-, and 5-year PFS, respectively; AUC: 0.92, 0.85 and 0.86 vs. 0.71, 0.75 and 0.76, for 1-, 3-, and 5-year OS, respectively). The model based on ultrasound images could better suggest PFS and OS of DLBCL, allowing for better risk stratification.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Humans , Prognosis , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Ultrasonography , Area Under Curve , Multivariate Analysis
15.
J Biol Chem ; 299(4): 103054, 2023 04.
Article in English | MEDLINE | ID: mdl-36822329

ABSTRACT

The deubiquitinating enzyme OTUB1 possesses canonical deubiquitinase (DUB) activity and noncanonical, catalytic-independent activity, which has been identified as an essential regulator of diverse physiological processes. Posttranslational modifications of OTUB1 affect both its DUB activity and its noncanonical activity of binding to the E2 ubiquitin-conjugation enzyme UBC13, but further investigation is needed to characterize the full inventory of modifications to OTUB1. Here, we demonstrate that SET7, a lysine monomethylase, directly interacts with OTUB1 to catalyze OTUB1 methylation at lysine 122. This modification does not affect DUB activity of OTUB1 but impairs its noncanonical activity, binding to UBC13. Moreover, we found using cell viability analysis and intracellular reactive oxygen species assay that SET7-mediated methylation of OTUB1 relieves its suppressive role on ferroptosis. Notably, the methylation-mimic mutant of OTUB1 not only loses the ability to bind to UBC13 but also relieves its suppressive role on Tert-Butyl hydroperoxide-induced cell death and Cystine starvation/Erastin-induced cellular reactive oxygen species. Collectively, our data identify a novel modification of OTUB1 that is critical for inhibiting its noncanonical activity.


Subject(s)
Deubiquitinating Enzymes , Ferroptosis , Histone-Lysine N-Methyltransferase , Ubiquitin-Conjugating Enzymes , Deubiquitinating Enzymes/metabolism , Lysine/metabolism , Protein Binding , Reactive Oxygen Species/metabolism , Ubiquitination , Humans , Histone-Lysine N-Methyltransferase/metabolism
16.
Front Oncol ; 12: 991948, 2022.
Article in English | MEDLINE | ID: mdl-36568168

ABSTRACT

Objectives: To develop and validate a nomogram to predict the overall survival (OS) of patients with primary nodal diffuse large B-cell lymphoma(N-DLBCL) based on radiomic features and clinical features. Materials and methods: A retrospective analysis was performed on 145 patients confirmed with N-DLBCL and they were randomly assigned to training set(n=78), internal validation set(n=33), external validation set(n=34). First, a clinical model (model 1) was established according to clinical features and ultrasound (US) results. Then, based on the radiomics features extracted from conventional ultrasound images, a radiomic signature was constructed (model 2), and the radiomics score (Rad-Score) was calculated. Finally, a comprehensive model was established (model 3) combined with Rad-score and clinical features. Receiver operating characteristic (ROC) curves were employed to evaluate the performance of model 1, model 2 and model 3. Based on model 3, we plotted a nomogram. Calibration curves were used to test the effectiveness of the nomogram, and decision curve analysis (DCA) was used to asset the nomogram in clinical use. Results: According to multivariate analysis, 3 clinical features and Rad-score were finally selected to construct the model 3, which showed better predictive value for OS in patients with N-DLBCL than mode 1 and model 2 in training (AUC,0. 891 vs. 0.779 vs.0.756), internal validation (AUC, 0.868 vs. 0.713, vs.0.756) and external validation (AUC, 914 vs. 0.866, vs.0.789) sets. Decision curve analysis demonstrated that the nomogram based on model 3 was more clinically useful than the other two models. Conclusion: The developed nomogram is a useful tool for precisely analyzing the prognosis of N-DLBCL patients, which could help clinicians in making personalized survival predictions and assessing individualized clinical options.

17.
J Biol Chem ; 298(12): 102633, 2022 12.
Article in English | MEDLINE | ID: mdl-36273580

ABSTRACT

Hypoxia-inducible factor (HIF)1α, a main transcriptional regulator of the cellular response to hypoxia, also plays important roles in oxygen homeostasis of aerobic organisms, which is regulated by multiple mechanisms. However, the full cellular response to hypoxia has not been elucidated. In this study, we found that expression of SMYD3, a methyltransferase, augments hypoxia signaling independent of its enzymatic activity. We demonstrated SMYD3 binds to and stabilizes HIF1α via co-immunoprecipitation and Western blot assays, leading to the enhancement of HIF1α transcriptional activity under hypoxia conditions. In addition, the stabilization of HIF1α by SMYD3 is independent of HIF1α hydroxylation by prolyl hydroxylases and the intactness of the von Hippel-Lindau ubiquitin ligase complex. Furthermore, we showed SMYD3 induces reactive oxygen species accumulation and promotes hypoxia-induced cell apoptosis. Consistent with these results, we found smyd3-null zebrafish exhibit higher hypoxia tolerance compared to their wildtype siblings. Together, these findings define a novel role of SMYD3 in affecting hypoxia signaling and demonstrate that SMYD3-mediated HIF1α stabilization augments hypoxia signaling, leading to the impairment of hypoxia tolerance.


Subject(s)
Histone-Lysine N-Methyltransferase , Hypoxia , Methyltransferases , Zebrafish Proteins , Animals , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Methyltransferases/metabolism , Signal Transduction , Von Hippel-Lindau Tumor Suppressor Protein/genetics , Von Hippel-Lindau Tumor Suppressor Protein/metabolism , Zebrafish/metabolism , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism
18.
Vascular ; : 17085381221124708, 2022 Sep 05.
Article in English | MEDLINE | ID: mdl-36063574

ABSTRACT

PURPOSE: To evaluate the method of thrombin injection under B-flow and ultrasound guidance (BUGTI) for the treatment of pseudoaneurysms. MATERIALS AND METHODS: Twenty-one patients suffering from pseudoaneurysm (PSA) were retrospectively reviewed at the First Affiliated Hospital of Nanjing Medical University in Nanjing, China, from January 2018 to August 2019. The patients were treated using an ultrasound-guided injection of thrombin (500 IU/mL) combined with B-mode blood flow imaging (B-flow). The information on the PSA, including the size of the arterial rupture and sac, flow rate, thrombin dose, and treatment outcome, was recorded during the procedure. Follow-up evaluation was performed at 1, 3, and 6 months after the treatment. Pearson's correlation analysis was performed among the characteristics of PSA and the dose of thrombin. RESULT: The age of patients ranged from 34 to 80 years and averaged 62.8 years. The maximum cross-sectional area of PSA ranged from 208 to 1148 mm2. All patients were treated with thrombin injections. The dose of thrombin ranged from 300 to 1667 IU. No reperfusions were detected at follow-up 6 months, and the BUGTI treatment was successful in all 21 cases. Pearson's correlation analysis demonstrated that the dose of thrombin was positively correlated with the width (r = 0.449, p < .05) and maximum cross-sectional area (r = 0.504, p < .05) of PSA. CONCLUSION: Thrombin injection under B-flow and ultrasound guidance is a rapid and effective treatment for PSA. Additionally, the sac size could be used to estimate the dose of thrombin.

19.
J Environ Manage ; 321: 115970, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-35969972

ABSTRACT

Plant litter causes a serious waste of resources. Thus, plant litter extract (LE) should be used in the soil remediation of heavy metals. In this study, different proportions of LE from the Alternanthera philoxeroides were used to modify dodecyl dimethyl betaine (BS)-modified purple soil (P). The basic physicochemical properties of LE + BS-modified Ps (LE + BS-Ps) were determined, and the microscopic morphology of LE + BS-Ps was studied by using scanning electron microscopy (SEM), energy dispersion spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy, and specific surface area detection. The isothermal adsorption characteristics of heavy metal ions (Pb2+, Cu2+, and Cr6+) on different LE + BS-Ps were investigated by the batch method, and the effect mechanisms of temperature, pH, ionic strength, and LE + BS-P's property were compared. Results showed that the cation exchange capacity and specific surface area of LE + BS-Ps increased, pH of LE + BS-Ps decreased, and TOC of LE + BS-Ps increased first and then decreased with increasing proportion of LE. FTIR, SEM, and EDS results proved that LE was modified on the surface of BS-P. Langmuir and Freundlich models could be used to describe the adsorption isotherms of heavy metal ions on different LE + BS-Ps, and the fitting correlation of the Langmuir model was higher than that of the Freundlich model. The maximum adsorption capacity (qm) of Pb2+, Cu2+, and Cr6+ were 107.60-295.66, 133.00-342.11, and 33.59-75.41 mmol/kg, respectively. The qm of Pb2+, Cu2+, and Cr6+ on LE + BS-Ps all increased first and then decreased with increasing proportion of LE, and the peak value was observed in 20%LE + BS-Ps. High pH improved Pb2+ and Cu2+ adsorption but inhibited Cr6+ adsorption. The adsorption amounts of Pb2+, Cu2+, and Cr6+ all increased first and then decreased with incresing ionic strength and were maintained at the maximum value of 0.1-0.2 mol/L. The Pb2+, Cu2+, and Cr6+ adsorption mechanisms on different LE + BS-Ps showed a positive temperature effect and presented spontaneous, exothermic and entropy-adding processes.


Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Adsorption , Hydrogen-Ion Concentration , Ions , Kinetics , Lead , Metals, Heavy/chemistry , Soil/chemistry , Spectroscopy, Fourier Transform Infrared , Water Pollutants, Chemical/chemistry
20.
Front Endocrinol (Lausanne) ; 13: 902130, 2022.
Article in English | MEDLINE | ID: mdl-35966086

ABSTRACT

Diabetic foot ulcer(DFU) is one of the most severe chronic complications of type 2 diabetes mellitus, which is mainly caused by peripheral vascular occlusion with various degrees of infection. Treatment of DFU is difficult, and ulcer formation in lower limbs and deep-tissue necrosis might lead to disability or even death. Insulin resistance is the major mechanism of type 2 diabetes mellitus development, largely caused by adipose tissue dysfunction. However, adipose tissue was recently identified as an important endocrine organ that secretes bio-active factors, such as adipokines and extracellular vesicles(EVs). And adipose tissue-derived stem cells(ADSCs) are abundant in adipose tissue and have become a hot topic in the tissue engineering field. In particular, EVs derived from ADSCs contain abundant biomarkers and mediators. These EVs exert significant effects on distant cells and organs, contributing to metabolic homeostasis. In this review, we aim to elaborate on the mechanisms of diabetic non-healing wound development and the role of ADSCs-EVs in wound repair, which might provide a new therapy for treating DFU.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Foot , Extracellular Vesicles , Adipose Tissue , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/therapy , Diabetic Foot/therapy , Humans , Stem Cells
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