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PD-L1 is expressed in many tumors but rarely in normal tissues, therefore, it can be a target of PET imaging. In this work, we developed new peptide-based PET probes [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p with yields of 20-25 % and 40-55 %, respectively. [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p were synthesized within 30 min with high molar activities. [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p showed good stability in vivo and in vitro. In vitro cell studies showed [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p target PD-L1 specifically, with high uptake of 61.52 ± 4.39 and 19.29 ± 2.17 %ID/1 million cells in B16F10 cells at 60 min, respectively. Biodistribution results showed that both [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p had lower liver accumulation. In vivo PET imaging results showed that [18F]AlF-PAI-PDL1p had a high tumor uptake of 4.23 ± 0.81 %ID/g at 2 h and increased uptake of 6.60 ± 1.01 %ID/g at 12 h. [68Ga]Ga-PAI-PDL1p also showed high tumor uptake of 2.30 ± 0.20 %ID/g at 2 h and slightly increased uptake of 3.80 ± 0.26 %ID/g at 6 h. In conclusion, [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1 seemed to be potential tracers for PET imaging of PD-L1 expression.
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PURPOSE: This study was designed to develop and validate a machine learning-based, multimodality fusion (MMF) model using 18F-fluorodeoxyglucose (FDG) PET/CT radiomics and kernelled support tensor machine (KSTM), integrated with clinical factors and nuclear medicine experts' diagnoses to individually predict peritoneal metastasis (PM) in advanced gastric cancer (AGC). METHODS: A total of 167 patients receiving preoperative PET/CT and subsequent surgery were included between November 2006 and September 2020 and were divided into a training and testing cohort. The PM status was confirmed via laparoscopic exploration and postoperative pathology. The PET/CT signatures were constructed by classic radiomic, handcrafted-feature-based model and KSTM self-learning-based model. The clinical nomogram was constructed by independent risk factors for PM. Lastly, the PET/CT signatures, clinical nomogram, and experts' diagnoses were fused using evidential reasoning to establish the MMF model. RESULTS: The MMF model showed excellent performance in both cohorts (area under the curve [AUC] 94.16% and 90.84% in training and testing), and demonstrated better prediction accuracy than clinical nomogram or experts' diagnoses (net reclassification improvement p < 0.05). The MMF model also had satisfactory generalization ability, even in mucinous adenocarcinoma and signet ring cell carcinoma which have poor uptake of 18F-FDG (AUC 97.98% and 89.71% in training and testing). CONCLUSIONS: The 18F-FDG PET/CT radiomics-based MMF model may have significant clinical implications in predicting PM in AGC, revealing that it is necessary to combine the information from different modalities for comprehensive prediction of PM.
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Aprendizado de Máquina , Nomogramas , Neoplasias Peritoneais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radiômica , Compostos Radiofarmacêuticos , Neoplasias Gástricas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fluordesoxiglucose F18 , Seguimentos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/diagnóstico por imagem , Taxa de SobrevidaRESUMO
To investigate the influence of different rhenium contents on the helium desorption behavior in tungsten-rhenium alloys, pure tungsten and tungsten-rhenium alloys were irradiated with helium under the same conditions. All irradiated samples were characterized using TDS and DBS techniques. The results indicate that the addition of rhenium can reduce the total helium desorption quantity in tungsten-rhenium alloys and slightly accelerate the reduction in the concentration of vacancy-type defects accompanying helium dissociation. The desorption activation energy of helium is approximately 2 eV at the low-temperature peak (~785 K) and about 4 eV at the high-temperature peak (~1475 K). An increase in rhenium content causes the desorption peak to shift towards higher temperatures (>1473 K), which is attributed to the formation of the stable complex structures between rhenium and vacancies. Besides, the migration of He-vacancy complexes towards traps and dynamic annealing processes both lead to the recovery of vacancy-type defects, resulting in a decrease in the positron annihilation S parameters.
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BACKGROUND: In the present study, we investigated the value of 18F-fibroblast-activation protein inhibitor (FAPI) positron emission tomography/computed tomography (18F-FAPI-42 PET/CT) to preoperative evaluations of appendiceal neoplasms and management for patients. METHODS: This single-center retrospective clinical study, including 16 untreated and 6 treated patients, was performed from January 2022 to May 2023 at Southern Medical University Nanfang Hospital. Histopathologic examination and imaging follow-up served as the reference standard. 18F-FAPI-42 PET/CT was compared to 18F-fluorodeoxyglucose (18F-FDG) PET/CT and contrast-enhanced CT (CE-CT) in terms of maximal standardized uptake value (SUVmax), diagnostic efficacy and impact on treatment decisions. RESULTS: The accurate detection of primary tumors and peritoneal metastases were improved from 28.6% (4/14) and 50% (8/16) for CE-CT, and 43.8% (7/16) and 85.0% (17/20) for 18F-FDG PET/CT, to 87.5% (14/16) and 100% (20/20) for 18F-FAPI-42 PET/CT. Compared to 18F-FDG PET/CT, 18F-FAPI-42 PET/CT detected more regions infiltrated by peritoneal metastases (108 vs. 43), thus produced a higher peritoneal cancer index (PCI) score (median PCI: 12 vs. 5, P < 0.01). 18F-FAPI-42 PET/CT changed the intended treatment plans in 35.7% (5/14) of patients compared to CE-CT and 25% (4/16) of patients compared to 18F-FDG PET/CT but did not improve the management of patients with recurrent tumors. CONCLUSIONS: The present study revealed that 18F-FAPI-42 PET/CT can supplement CE-CT and 18F-FDG PET/CT to provide a more accurate detection of appendiceal neoplasms and improved treatment decision making for patients.
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Neoplasias do Apêndice , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias do Apêndice/diagnóstico por imagem , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Idoso , Adulto , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/secundário , Tomografia Computadorizada por Raios X/métodosRESUMO
A three-dimensional helix geometry unit cell is established to simulate the complex spatial configuration of 3D braided composites. Initially, different types of yarn factors, such as yarn path, cross-sectional shape, properties, and braid direction, are explained. Then, the multiphase finite element method is used to develop a new theoretical calculation procedure based on the unit cell for predicting the impacts of environmental temperature on the thermophysical properties of 3D four-direction carbon/epoxy braided composites. The changing rule and distribution characteristics of the thermophysical properties for 3D four-direction carbon/epoxy braided composites are obtained at temperatures ranging from room temperature to 200 °C. The influences of environmental temperature on the coefficients of thermal expansion (CTE) and the coefficients of thermal conduction (CTC) are evaluated, by which some important conclusions are drawn. A comparison is conducted between theoretical and experimental results, revealing that variations in temperature exert a notable influence on the thermophysical characteristics of 3D four-directional carbon/epoxy braided composites. The theoretical calculation procedure is an effective tool for the mechanical property analysis of composite materials with complex geometries.
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BACKGROUND: The strategy for preventing colorectal cancer is screening by colonoscopy, which offers a direct way for detection and removal of adenomatous polyps (APs). American College of Gastroenterology guidelines recommend that people aged ≥ 45 years should undergo colonoscopy; however, how to deal with people aged ≤ 45 years is still unknown. AIM: To compare the prevalence of APs and high-grade neoplasia between the left and right colon in patients ≤ 45 years. METHODS: A retrospective observational study was conducted at a single tertiary III hospital in China. This study included patients aged 18-45 years with undergoing initial colonoscopy dissection and pathological diagnosis AP or high-grade neoplasia between February 2014 and January 2021. The number of APs in the entire colon while screening and post-polypectomy surveillance in following 1-3 years were evaluated. RESULTS: A total of 3053 cases were included. The prevalence of APs in the left and right colon was 55.0% and 41.6%, respectively (OR 1.7, 95%CI 1.6-2.4; P < 0.05). For APs with high-grade neoplasia, the prevalence was 2.7% and 0.9%, respectively (OR 3.0, 95%CI 2.0-4.6; P < 0.05). Therefore, the prevalence of APs and high-grade neoplasia in the left colon was significantly higher than in the right colon in patients aged ≤ 45 years. There were 327 patients who voluntarily participated in post-polypectomy surveillance in following 1-3 years, and APs were found in 216 cases (66.1%); 170 cases had 1-3 polyps (52.0%) and 46 cases had > 3 polyps (14.1%; OR 0.3, 95%CI 0.1-0.6; P < 0.05). CONCLUSION: This study suggests that flexible sigmoidoscopy would be an optimal approach for initial screening in people aged ≤ 45 years and would be a more cost-effective and safe strategy.
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BACKGROUND: Inflammatory processes could potentially impact both mood and suicide risk, however, the relationship between cytokines and suicidal ideation remains unclear. This study aimed to investigate the association between plasma levels of cytokines and suicidal ideation in population with major depressive disorders (MDD). METHODS: A cross-sectional study was performed to assess the peripheral plasma levels of interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α) in 88 Chinese Han first-episode drug-naïve MDD patients. Suicidal ideation in the past week were identified using the Beck Scale for Suicide Ideation-Chinese Version (BSI-CV). The Hamilton Depression Rating Scale-17 (HAMD-17), the Hamilton Anxiety Rating Scale-14 (HAMA-14) and the Childhood Trauma Questionnaire (CTQ) was used to assess depression, anxiety and childhood trauma. Multivariable logistic regression models were used to estimate the association between cytokines and suicidal ideation. Interaction and stratified analyses were conducted according to age, sex, marital status, education, smoking status, BMI and physical activity. RESULTS: Among the 88 participants, 42 individuals (47.7%) reported suicidal ideation within the past week. In the fully adjusted model, a statistically significant trend was observed in the association between IL-2 level and suicidal ideation (OR: 1.40, 95% CI: 1.00-1.97). The stratified analysis showed a statistically significant association between IL-6 level and suicidal ideation among younger people (OR: 1.17, 95% CI: 1.01-1.36) and a significant positive association between IL-8 (OR: 1.59, 95% CI: 1.03-2.44) and IL-10 (OR: 2.51, 95% CI: 1.27-4.96) levels and suicide ideation among higher educated populations. LIMITATIONS: The cross-sectional design, residual confounding effects and small sample size CONCLUSION: Our findings indicate a significant positive association between plasma IL-2 level and suicidal ideation in MDD patients. IL-2 has the potential to be a biomarker of suicidal ideation in patients with depression.
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Citocinas , Transtorno Depressivo Maior , Interleucina-2 , Ideação Suicida , Humanos , Masculino , Feminino , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/psicologia , Adulto , Estudos Transversais , Citocinas/sangue , Interleucina-2/sangue , Pessoa de Meia-Idade , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue , Interleucina-10/sangue , Interleucina-8/sangue , Interleucina-1beta/sangue , China , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
GRP78, a member of the HSP70 superfamily, is an endoplasmic reticulum chaperone protein overexpressed in various cancers, making it a promising target for cancer imaging and therapy. Positron emission tomography (PET) imaging offers unique advantages in real time, noninvasive tumor imaging, rendering it a suitable tool for targeting GRP78 in tumor imaging to guide targeted therapy. Several studies have reported successful tumor imaging using PET probes targeting GRP78. However, existing PET probes face challenges such as low tumor uptake, inadequate in vivo distribution, and high abdominal background signal. Therefore, this study introduces a novel peptide PET probe, [18F]AlF-NOTA-c-DVAP, for targeted tumor imaging of GRP78. [18F]AlF-NOTA-c-DVAP was radiolabeled with fluoride-18 using the aluminum-[18F]fluoride ([18F]AlF) method. The study assessed the partition coefficients, stability in vitro, and metabolic stability of [18F]AlF-NOTA-c-DVAP. Micro-PET imaging, pharmacokinetic analysis, and biodistribution studies were carried out in tumor-bearing mice to evaluate the probe's performance. Docking studies and pharmacokinetic analyses of [18F]AlF-NOTA-c-DVAP were also performed. Immunohistochemical and immunofluorescence analyses were conducted to confirm GRP78 expression in tumor tissues. The probe's binding affinity to GRP78 was analyzed by molecular docking simulation. [18F]AlF-NOTA-c-DVAP was radiolabeled in just 25 min with a high yield of 51 ± 16%, a radiochemical purity of 99%, and molar activity within the range of 20-50 GBq/µmol. [18F]AlF-NOTA-c-DVAP demonstrated high stability in vitro and in vivo, with a logD value of -3.41 ± 0.03. Dynamic PET imaging of [18F]AlF-NOTA-c-DVAP in tumors showed rapid uptake and sustained retention, with minimal background uptake. Biodistribution studies revealed rapid blood clearance and excretion through the kidneys following a single-compartment reversible metabolic model. In PET imaging, the T/M ratios for A549 tumors (high GRP78 expression), MDA-MB-231 tumors (medium expression), and HepG2 tumors (low expression) at 60 min postintravenous injection were 10.48 ± 1.39, 6.25 ± 0.47, and 3.15 ± 1.15% ID/g, respectively, indicating a positive correlation with GRP78 expression. This study demonstrates the feasibility of using [18F]AlF-NOTA-c-DVAP as a PET tracer for imaging GRP78 in tumors. The probe shows promising results in terms of stability, specificity, and tumor targeting. Further research may explore the clinical utility and potential therapeutic applications of this PET tracer for cancer diagnosis.
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Chaperona BiP do Retículo Endoplasmático , Radioisótopos de Flúor , Proteínas de Choque Térmico , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Animais , Camundongos , Humanos , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos de Flúor/farmacocinética , Distribuição Tecidual , Proteínas de Choque Térmico/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/administração & dosagem , Linhagem Celular Tumoral , Camundongos Nus , Feminino , Camundongos Endogâmicos BALB C , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/farmacocinética , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacocinéticaRESUMO
STUDY OBJECTIVE: To determine the sex-specific associations between postoperative haemoglobin and mortality or complications reflecting ischaemia or inadequate oxygen supply after major noncardiac surgery. DESIGN: A retrospective cohort study with prospective validation. SETTING: A large university hospital health system in China. PATIENTS: Men and women undergoing elective major noncardiac surgery. INTERVENTIONS AND MEASUREMENTS: The primary exposure was nadir haemoglobin within 48 h after surgery. The outcome of interest was a composite of postoperative mortality or ischaemic events including myocardial injury, acute kidney injury and stroke within hospitalisation. MAIN RESULTS: The study included 26,049 patients (15,757 men and 10,292 women). Low postoperative haemoglobin was a strong predictor of the composite outcome in both sexes, with the risk progressively increasing as the nadir haemoglobin concentration dropped below 130 g l-1 in men and 120 g l-1 in women (adjusted odds ratio [OR] 1.43, 95% CI 1.37-1.50 in men, and OR 1.45, 95% CI 1.35-1.55 in women, per 10 g l-1 decrease in postoperative nadir haemoglobin). Above these sex-specific thresholds, the change of nadir haemoglobin was no longer associated with odds of the composite outcome in either men or women. There was no significant interaction between patient sex and the association between postoperative haemoglobin and the composite outcome (Pinteraction = 0.673). Validation in an external prospective cohort (n = 2120) with systematic postoperative troponin and creatinine measurement confirmed our findings. CONCLUSIONS: Postoperative haemoglobin levels following major noncardiac surgery were nonlinearly associated with ischaemic complications or mortality, without any clinically important interaction with patient sex.
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Anemia , Hemoglobinas , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Hemoglobinas/análise , Pessoa de Meia-Idade , Anemia/etiologia , Anemia/epidemiologia , Anemia/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/sangue , Estudos Retrospectivos , Idoso , Fatores Sexuais , China/epidemiologia , Estudos Prospectivos , Estudos de Coortes , Adulto , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/sangue , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Isquemia/etiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/epidemiologiaRESUMO
OBJECTIVE: This study is performed to investigate the imaging characteristics of the International Association for the Study of Lung Cancer grade 3 invasive adenocarcinoma (IAC) on PET/CT and the value of PET/CT for preoperative predicting this tumor. MATERIALS AND METHODS: We retrospectively enrolled patients with IAC from August 2015 to September 2022. The clinical characteristics, serum tumor markers, and PET/CT features were analyzed. T test, Mann-Whitney U test, χ 2 test, Logistic regression analysis, and receiver operating characteristic analysis were used to predict grade 3 tumor and evaluate the prediction effectiveness. RESULTS: Grade 3 tumors had a significantly higher maximum standardized uptake value (SUV max ) and consolidation-tumor-ratio (CTR) ( P â <â 0.001), while Grade 1 - 2 tumors were prone to present with air bronchogram sign or vacuole sign ( P â <â 0.001). A stepwise logistic regression analysis revealed that smoking history, CEA, SUV max , air bronchogram sign or vacuole sign and CTR were useful predictors for Grade 3 tumors. The established prediction model based on the above 5 parameters generated a high AUC (0.869) and negative predictive value (0.919), respectively. CONCLUSION: Our study demonstrates that grade 3 IAC has a unique PET/CT imaging feature. The prognostication model established with smoking history, CEA, SUV max , air bronchogram sign or vacuole sign and CTR can effectively predict grade 3 tumors before the operation.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologiaRESUMO
Endothelial dysfunction is a common complication of diabetes mellitus (DM) and contributes to the high incidence and mortality of cardiovascular and cerebrovascular diseases. Aberrant epigenetic regulation under diabetic conditions, including histone modifications, DNA methylation, and non-coding RNAs (ncRNAs) play key roles in the initiation and progression of diabetic vascular complications. ASH2L, a H3K4me3 regulator, triggers genetic transcription, which is critical for physiological and pathogenic processes. In this study we investigated the role of ASH2L in mediating diabetic endothelial dysfunction. We showed that ASH2L expression was significantly elevated in vascular tissues from diabetic db/db mice and in rat aortic endothelial cells (RAECs) treated with high glucose medium (11 and 22 mM). Knockdown of ASH2L in RAECs markedly inhibited the deteriorating effects of high glucose, characterized by reduced oxidative stress and inflammatory responses. Deletion of endothelial ASH2L in db/db mice by injection of an adeno-associated virus (AAV)-endothelial specific system carrying shRNA against Ash2l (AAV-shAsh2l) restored the impaired endothelium-dependent relaxations, and ameliorated DM-induced vascular dysfunction. We revealed that ASH2L expression activated reductase STEAP4 transcription in vitro and in vivo, which consequently elevated Cu(I) transportation into ECs by the copper transporter CTR1. Excess copper produced by STEAP4-mediated copper uptake triggered oxidative stress and inflammatory responses, resulting in endothelial dysfunction. Our results demonstrate that hyperglycemia triggered ASH2L-STEAP4 axis contributes to diabetic endothelial dysfunction by modulating copper uptake into ECs and highlight the therapeutic potential of blocking the endothelial ASH2L in the pathogenesis of diabetic vascular complications.
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Diabetes Mellitus , Angiopatias Diabéticas , Ratos , Camundongos , Animais , Cobre/metabolismo , Cobre/farmacologia , Regulação para Cima , Células Endoteliais/metabolismo , Epigênese Genética , Células Cultivadas , Angiopatias Diabéticas/etiologia , Glucose/metabolismo , Endotélio VascularAssuntos
Neoplasias Cardíacas , Leiomiomatose , Neoplasias Uterinas , Doenças Vasculares , Humanos , Feminino , Leiomiomatose/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Veia Cava Inferior/diagnóstico por imagem , Átrios do Coração/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico por imagemRESUMO
Plant defensins are widely distributed in the leaves, fruits, roots, stems, seeds, and tubers. Research shows that defensin in plants play a significant role in physiological metabolism, growth and development. Plant defensins can kill and suppress a variety of pathogenic bacteria. In this study, we understand the phylogenetic relationships, protein characterization, chromosomal localization, promoter and gene structural features of the TaPDFs family through sequence alignment and conserved protein structural domain analysis. A total of 73 PDF gene members in wheat, 15 PDF genes in maize, and 11 PDF genes in rice were identified. A total of 35, 65, and 34 PDF gene members were identified in the genomes of Ae. tauschii, T. urartu, and T. dicoccoides, respectively. TaPDF4.9 and TaPDF2.15 were constructed into pART27 vector with YFP by homologous recombination for subcellular localization analysis. Subcellular localization results showed that TaPDF4.9 and TaPDF2.15 were basically located in the cell membrane and cytoplasm, and TaPDF4.9 was also located in the nucleus. TaPDF4.9 and TaPDF2.15 could inhibit the infection of Phytophthora infestans strain '88069'. The results suggest that TaPDFs may be able to improve disease resistance. The study of wheat defensins will be beneficial for improving wheat yield and provides a theoretical basis for research on resistance to wheat diseases.
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OBJECTIVE: In this study, the potential advantage of FAPI over 18 F-labelled deoxyglucose ( 18 F-FDG) in evaluation of the initial staging colorectal cancer (CRC) was investigated. MATERIALS AND METHODS: Thirty-two patients with histopathologically confirmed primary CRC were included in our study. They all underwent both 18 F-FDG and FAPI PET/CT. Lesion detectability and tracer uptakes, mainly quantified by maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR), were compared for paired lesions between both modalities using the Wilcoxon signed-rank test and paired t-test. RESULTS: Thirty-five CRC lesions in 32 patients were diagnosed. The sensitivity of FAPI PET/CT in diagnosis of the CRC lesions was 100% while 93.8% of 18 F-FDG PET/CT. FAPI and 18 F-FDG had a similar uptake in CRC lesion (mean SUVmax: 14.3â ±â 8.6 vs. 15.4â ±â 9.8, P â =â 0.604), but lesions contained mucus and/or signet-ring cell carcinoma seemed to have a trend of higher FAPI uptake although there was no statistical difference (mean SUVmax: 12.7â ±â 5.6 vs. 8.5â ±â 4.1, P â =â 0.152) and higher TBR (13.4â ±â 6.2 vs. 4.9â ±â 2.2, P â =â 0.004) than those of 18 F-FDG. For regional lymph node metastases, both FAPI and FDG PET/CTs showed high sensitivity (7/8 vs. 7/8), specificity (7/8 vs. 6/8) and accuracy (14/16 vs. 13/16) (all P â >â 0.05). For distant metastasis, FAPI PET/CT depicted more positive lesions in distant lymph node (46 vs. 26), liver (13 vs. 7) and peritoneum (107 vs. 45) than 18 F-FDG PET/CT. FAPI PET/CT also had a higher peritoneal cancer index score (median 11 vs 4; P â <â 0.001) than 18 F-FDG PET/CT in evaluation of peritoneal metastases. CONCLUSION: FAPI PET/CT showed high sensitivity in detection of primary CRC and superiority to 18 F-FDG PET/CT in detection of metastases to distant lymph node, liver and peritoneum.
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Neoplasias Colorretais , Quinolinas , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Neoplasias Colorretais/diagnóstico por imagem , Fibroblastos , Radioisótopos de GálioRESUMO
PURPOSE: Research on fibroblast activating protein (FAP)-targeting inhibitor (FAPI) has become an important focus for cancer imaging and radiotherapy. Quinoline-based tracers [68 Ga]FAPI-04 and [18F]FAPI-42 have been widely used for positron emission tomography (PET) imaging of most tumors. However, there exist some limitations of these tracers with high uptake in biliary duct system and unstable uptake in pancreas, unsuitable for abdominal tumors PET imaging. Here we developed a [18F]-labeled glycopeptide-containing FAPI tracer (named [18F]FAPT) for PET imaging of FAP in cancers. METHODS: [18F]FAPT was synthesized manually and automatically. The competitive binding to FAP, cellular internalization, and efflux characteristics were examined in vitro using A549-FAP cells. Dynamic MicroPET and biodistribution studies of [18F]FAPT were then conducted in A549-FAP and U87MG xenograft tumor mouse models compared with [18F]FAPI-42. Five healthy volunteers and three patients with cancer underwent [18F]FAPT PET/CT. RESULTS: Preclinical and clinical studies showed specific binding of [18F]FAPT to FAP and favorable pharmacokinetic properties with better hydrophilicity, lower uptake in biliary duct system, higher tumor uptake and longer tumor retention compared with [18F]FAPI-42. The biodistribution of [18F]FAPT in healthy volunteers and patients with cancer displayed low uptake in most normal tissues except for pancreas, thyroid and salivary gland, which could contribute to high tumor-to-background ratios in most cancers. CONCLUSION: [18F]FAPT is better PET tracer than [18F]FAPI-42 for imaging of biliary duct system cancer, potentially providing a tool to examine FAP expression in most cancers with high tumor-to-background ratios.
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Neoplasias Abdominais , Quinolinas , Humanos , Animais , Camundongos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Distribuição Tecidual , Tomografia por Emissão de Pósitrons , Fibroblastos , Modelos Animais de Doenças , Radioisótopos de GálioRESUMO
PURPOSE: Our purpose was to develop a deep learning model (AbsegNet) that produces accurate contours of 16 organs at risk (OARs) for abdominal malignancies as an essential part of fully automated radiation treatment planning. METHODS AND MATERIALS: Three data sets with 544 computed tomography scans were retrospectively collected. Data set 1 was split into 300 training cases and 128 test cases (cohort 1) for AbsegNet. Data set 2, including cohort 2 (n = 24) and cohort 3 (n = 20), were used to validate AbsegNet externally. Data set 3, including cohort 4 (n = 40) and cohort 5 (n = 32), were used to clinically assess the accuracy of AbsegNet-generated contours. Each cohort was from a different center. The Dice similarity coefficient and 95th-percentile Hausdorff distance were calculated to evaluate the delineation quality for each OAR. Clinical accuracy evaluation was classified into 4 levels: no revision, minor revisions (0% < volumetric revision degrees [VRD] ≤ 10%), moderate revisions (10% ≤ VRD < 20%), and major revisions (VRD ≥20%). RESULTS: For all OARs, AbsegNet achieved a mean Dice similarity coefficient of 86.73%, 85.65%, and 88.04% in cohorts 1, 2, and 3, respectively, and a mean 95th-percentile Hausdorff distance of 8.92, 10.18, and 12.40 mm, respectively. The performance of AbsegNet outperformed SwinUNETR, DeepLabV3+, Attention-UNet, UNet, and 3D-UNet. When experts evaluated contours from cohorts 4 and 5, 4 OARs (liver, kidney_L, kidney_R, and spleen) of all patients were scored as having no revision, and over 87.5% of patients with contours of the stomach, esophagus, adrenals, or rectum were considered as having no or minor revisions. Only 15.0% of patients with colon and small bowel contours required major revisions. CONCLUSIONS: We propose a novel deep-learning model to delineate OARs on diverse data sets. Most contours produced by AbsegNet are accurate and robust and are, therefore, clinically applicable and helpful to facilitate radiation therapy workflow.
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6-O-[18F]Fluoroethylerlotinib (6-O-[18F]FEE), with a suitable half-life for commercial distribution, may be a good replacement for [11C]erlotinib to identify epidermal growth factor receptor (EGFR) positive tumors with activating mutations to tyrosine kinase inhibitors therapy. In this study, we explored the fully automated synthesis of 6-O-[18F]FEE and investigated its pharmacokinetics in tumor-bearing mice. 6-O-[18F]FEE with high specific activity (28-100 GBq/µmol) and radiochemistry purity (over 99 %) was obtained by two-step reaction and Radio-HPLC separation in PET-MF-2 V-IT-1 automated synthesizer. PET imaging of 6-O-[18F]FEE in HCC827, A431, and U87 tumor-bearing mice with different EGFR expression and mutation was performed. Uptake and blocking of PET imaging indicated that the probe specifically targeted exon 19 deleted EGFR (the quantitative analysis of tumor-to-mouse ratio for HCC827, HCC827 blocking, U87, A431 was 2.58 ± 0.24, 1.20 ± 0.15, 1.18 ± 0.19, and 1.05 ± 0.13 respectively). Dynamic imaging was used to study the pharmacokinetics of the probe in tumor-bearing mice. Logan plot graphical analysis demonstrated late linearity and a high fitting correlation coefficient (0.998), supporting reversible kinetics. According to the Akaike Information Criterion (AIC) rule, the 2-compartment reversible model was more consistent with the metabolic properties of 6-O-[18F]FEE. The automated radiosynthesis and pharmacokinetic analysis will promote clinically transformation of 6-O-[18F]FEE.