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1.
Artigo em Inglês | MEDLINE | ID: mdl-39325156

RESUMO

PURPOSE: The image-derived input function (IDIF) from the descending aorta has demonstrated performance comparable to arterial blood sampling while avoiding its invasive nature in parametric imaging. However, in conventional PET, large vessels may not always be within the imaging field of view (FOV). This study aims to evaluate the efficacy of dynamic parametric Ki imaging using image-derived input functions (IDIFs) extracted from various arteries, facilitated by total-body PET/CT. METHOD: Twenty-three participants underwent a 60-minute total-body [18F]FDG PET scan. Data from each subject were used to reconstruct both total-body PET images and short-axis field-of-view PET images at different bed positions, each with a 25 cm axial field-of-view (AFOV). Partial volume correction (PVC) was performed using the blurred Van Cittert iterative deconvolution. IDIFs extracted from the descending aorta, carotid artery, abdominal aorta, and iliac artery were employed for Patlak analysis. The resulting Ki images were compared using quantification indicators and subjective assessment. Linear regression analysis was conducted to examine the correlation of Ki values among IDIFs in normal organ and lesion regions of interest (ROIs). RESULT: High similarities were observed in Ki images derived from the IDIFs from the descending aorta and other arteries, with a median structural similarity index measure (SSIM) above 0.98 and a median peak signal-to-noise ratio (PSNR) above 37dB. Linear regression analysis revealed strong correlations in Ki values (r² > 0.88) between the descending aorta and the three alternative vessels, with slopes of the linear fits close to 1. No significant difference in lesion detectability among IDIFs was found, as assessed visually and using metrics such as tumor-to-background ratio (TBR) and contrast-to-noise ratio (CNR) (P < 0.05). CONCLUSION: IDIFs from smaller vessels can reliably reconstruct parametric Ki images without compromising lesion detectability, providing clinically relevant information.

2.
J Pediatr Hematol Oncol ; 46(7): 356-363, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39196630

RESUMO

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN) is an extremely rare inborn error of immunity (IEI) caused by X-linked recessive inheritance and loss-of-function mutations in the MAGT1 gene, resulting in magnesium ion channel defects. This article reports 2 cases of systemic EBV-positive T-cell Lymphoma of childhood (SETLC) associated with XMEN, which have not been reported before. Whole exome sequencing (WES) in their family revealed previously unreported MAGT1 gene mutations (c.77T>C, p.I26T; c.956-957del: p.Ser319Tyrfs) inherited from their mothers. These mutations expand the spectrum of gene mutations in XMEN disease. The importance of genetic testing for MAGT1 mutations in the initial diagnosis of SETLC was emphasized. We also review the literature on this uncommon IEI.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma de Células T , Humanos , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Masculino , Linfoma de Células T/genética , Linfoma de Células T/patologia , Linfoma de Células T/virologia , Linfoma de Células T/complicações , Proteínas de Transporte de Cátions/genética , Mutação , Feminino , Criança , Herpesvirus Humano 4/isolamento & purificação , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/genética , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/complicações , Pré-Escolar , Sequenciamento do Exoma
3.
Urol Oncol ; 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39098476

RESUMO

PURPOSES: To explore the characteristics of PSMA PET/CT and FDG PET/CT images in prostatic ductal adenocarcinoma (DA) patients. METHODS: We retrospectively enrolled prostatic DA patients with PET/CT scans at Tongji Hospital from 2018 to 2022. Patients with prostatic acinar adenocarcinoma (AA) and benign pathology (BP) were enrolled by 1:1 matching. Differences in the uptake of primary and metastatic foci on PET among the groups were analyzed. RESULTS: A total of 42 patients were enrolled: 14 in each group. In primary foci, the mean PSMA uptake in the DA group was lower than that in the AA group (14.2 ± 9.6 vs. 27.1 ± 14.3, P = 0.009) and greater than that in the BP group (14.2 ± 9.6 vs. 4.7 ± 1.3, P = 0.003). The AUCs of the DA-AA ROC curve and DA-BP ROC curve were 0.781 and 0.872, respectively. The median PSMA uptake of metastatic lymph nodes in the DA group was lower than that in the AA group (5.6 vs. 14.2, P = 0.033), with no significant difference in metastatic bone lesions (9.5 vs 19.1, P = 0.485). No significant difference was found in the FDG uptake of primary and metastatic foci between the DA and AA groups (P > 0.05). CONCLUSION: Prostatic DA has greater PSMA uptake than BP diseases, but lower uptake in both primary foci and metastatic lymph nodes than AA on PSMA PET/CT, aiding in the differential diagnosis of DA, AA and BP diseases. Clinicians should combine traditional imaging with PSMA PET/CT to avoid underestimating the clinical stage of DA patients.

4.
Heliyon ; 10(15): e34317, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170180

RESUMO

Background: Gastric cancer (GC) is one of the most common malignant tumors in the world. It has become increasingly difficult to meet the needs of precision therapy using the existing molecular typing system. Therefore, developing a more effective molecular typing system for GC is urgent. Methods: In this study, 100 Chinese GC patients were included. Whole-exome sequencing (WES) and metabolomics analysis were performed to reveal the characteristics of genomic and metabolic changes. Results: In WES, nonsynonymous mutations accounted for the majority. Based on metabolomics, GC has been divided into three subtypes with distinct metabolic features. Importantly, we ultimately divided GC into four subtypes with different metabolic characteristics, genomic alterations, and clinical prognoses by incorporating biomics analysis. Conclusions: Integrating biological features, we constructed a novel molecular system for GC that was closely related to genetics and metabolism, providing new insights for further understanding the heterogeneity and formulating precise treatment strategies.

5.
Transl Androl Urol ; 13(7): 1219-1227, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39100834

RESUMO

Background: Multiparametric magnetic resonance imaging (mpMRI) is a commonly used method to diagnose pelvic lymph node metastasis (PLNM) in prostate cancer (PCa) patients, but there are few comparative studies on mpMRI and 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in locally advanced PCa (LAPC) patients. Therefore, we designed a retrospective study to compare the diagnostic value of 68Ga-PSMA PET/CT and mpMRI for PLNM of LAPC. Methods: A retrospective study was performed on 50 patients with LAPC who underwent radical prostatectomy (RP) in Tongji Hospital from 2021 to 2023. All patients underwent PET/CT and mpMRI examination, and were diagnosed as LAPC before surgery, followed by robot-assisted laparoscopic prostatectomy or laparoscopic RP and extended pelvic lymph node dissection (ePLND). Routine postoperative pathological examination was performed. According to the results, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT and mpMRI for the diagnosis of PLNM of LAPC were compared. Results: Among the 50 patients, the mean age was 65.5±10.3 years, the preoperative total serum prostate-specific antigen (PSA) was 30.7±12.3 ng/mL, and the Gleason score was 7 [7, 8]. The difference in diagnostic efficacy between 68Ga-PSMA PET/CT and mpMRI in the preoperative diagnosis of PLNM of PCa was determined by postoperative pathological results. Based on the number of patients who developed PLNM, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were as follows: 93.75%, 100.00%, 100.00%, 97.14%, and 68.75%, 97.06%, 91.67%, 86.84% for mpMRI, respectively. Based on the number of pelvic metastatic lymph nodes, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were 95.24%, 100.00%, 100.00%, 99.48%, and 65.08%, 99.13%, 89.13%, 96.30% for mpMRI, respectively. It turned out that PET/CT was more sensitive than mpMRI in detecting PLNM of PCa, and the difference was statistically significant. Conclusions: 68Ga-PSMA PET/CT is more sensitive than mpMRI in the detection of PLNM in patients with LAPC. It is a promising method in the diagnosis and preoperative assessment of PLNM in LAPC.

6.
Animals (Basel) ; 14(15)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39123740

RESUMO

Avian primordial germ cells (PGCs) are essential in avian transgenic research, germplasm conservation, and disease resistance breeding. However, cultured PGCs are prone to fragmentation and apoptosis, regulated at transcriptional and translational levels, with N6-methyladenosine (m6A) being the most common mRNA modification. Resveratrol (RSV) is known for its antioxidant and anti-apoptotic properties, but its effects on PGCs and the underlying mechanisms are not well understood. This study shows that RSV supplementation in cultured PGCs improves cell morphology, significantly enhances total antioxidant capacity (p < 0.01), reduces malondialdehyde levels (p < 0.05), increases anti-apoptotic BCL2 expression, and decreases Caspase-9 expression (p < 0.05). Additionally, RSV upregulates the expression of m6A reader proteins YTHDF1 and YTHDF3 (p < 0.05). m6A methylation sequencing revealed changes in mRNA m6A levels after RSV treatment, identifying 6245 methylation sites, with 1223 unique to the control group and 798 unique to the RSV group. Combined analysis of m6A peaks and mRNA expression identified 65 mRNAs with significantly altered methylation and expression levels. Sixteen candidate genes were selected, and four were randomly chosen for RT-qPCR validation, showing results consistent with the transcriptome data. Notably, FAM129A and SFRP1 are closely related to apoptosis, indicating potential research value. Overall, our study reveals the protective effects and potential mechanisms of RSV on chicken PGCs, providing new insight into its use as a supplement in reproductive stem cell culture.

7.
Mol Pharm ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39186477

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by unpredictable progression and limited therapeutic options. Current diagnosis relies on high resolution computed tomography (HRCT), which may not adequately capture early signs of deterioration. The enzyme autotaxin (ATX) emerges as a prominently expressed extracellular secretory enzyme in the lungs of IPF patients. The objective of this study was to evaluate the effectiveness of 18F-labeled ATX-targeted tracer [18F]ATX-1905, in comparison with [18F]FDG, for early fibrosis diagnosis, disease evolution monitoring, and treatment efficacy assessment in bleomycin-induced pulmonary fibrosis (BPF) models. To assess treatment efficacy, mice were treated with two commonly used drugs for IPF, pirfenidone or nintedanib, from Day 9 to Day 23 postbleomycin administration. Lung tissue assessments encompassed inflammation severity via H&E staining, and Ashcroft scoring via Masson staining, alongside quantification of ATX expression through ELISA. Positron emission tomography (PET) imaging employing [18F]FDG and [18F]ATX-1905 tracked disease progression pre- and post-treatment. The extent of pulmonary fibrosis corresponded to changes in ATX expression levels in the BPF mouse model. Notably, [18F]ATX-1905 exhibited elevated uptake in BPF lungs during the progression of the disease, particularly evident at the early stage (Day 9). This uptake was inhibited by an ATX inhibitor, PF-8380, underscoring the specificity of the radiotracer. Conversely, [18F]FDG uptake, peaking at Day 15, decreased subsequently, likely reflective of diminished inflammation. A 2-week treatment regimen using either pirfenidone or nintedanib resulted in notable reductions of ATX expression levels and fibrosis degrees within lung tissues, based on ELISA and Masson staining, as evidenced by PET imaging with [18F]ATX-1905. [18F]FDG uptake also decreased following the treatment period. Additionally, PET/CT imaging extended to a nonhuman primate (NHP) BPF model. The uptake of [18F]ATX-1905 (SUVmax = 2.2) was significantly higher than that of [18F]FDG (SUVmax = 0.7) in fibrotic lung tissue. Using our novel ATX-specific radiotracer [18F]ATX-1905 and PET/CT imaging, we demonstrated excellent ability in early fibrosis detection, disease monitoring, and treatment assessment within lungs of the BPF mouse models. [18F]ATX-1905 displayed remarkable specificity for ATX expression and high sensitivity for ATX alterations, suggesting its potential for monitoring varying ATX expression in lungs of IPF patients.

8.
Hematology ; 29(1): 2381169, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39046131

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) with t(8;21) manifests as a diverse hematological malignancy. Although it was categorized into a favorable subtype, 30-40% of patients experience relapse. The objective of this research was to devise a nomogram for the accurate anticipation of both overall survival (OS) and cancer-specific survival (CSS) in t(8;21) AML. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, individuals diagnosed with t(8;21) AML from 2000 to 2018 were selected. Prognostic factors for t(8;21) AML were identified using Cox regression analysis and Akaike Information Criterion (AIC), forming the basis for constructing prognostic nomograms. RESULTS: Key variables, including first primary tumor, age group, race, and chemotherapy, were identified and integrated into the nomogram. The C-index values for the nomograms predicting OS and CSS were 0.753 (validation: 0.765) and 0.764 (validation: 0.757), respectively. Ultimately, based on nomogram scores, patients were stratified into high-risk and low-risk groups, revealing significant disparities in both OS and CSS between these groups (P < 0.001). CONCLUSION: This study innovatively crafted nomograms, incorporating clinical and therapeutic variables, to forecast the 1-, 3-, and 5-year survival rates for individuals with t(8;21) AML.


Assuntos
Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Leucemia Mieloide Aguda , Nomogramas , Programa de SEER , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Cromossomos Humanos Par 8/genética , Cromossomos Humanos Par 21/genética , Translocação Genética , Prognóstico , Adolescente , Idoso , Adulto Jovem
9.
J Nucl Med ; 65(Suppl 1): 64S-71S, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38719242

RESUMO

Total-body (TB) PET/CT is a groundbreaking tool that has brought about a revolution in both clinical application and scientific research. The transformative impact of TB PET/CT in the realms of clinical practice and scientific exploration has been steadily unfolding since its introduction in 2018, with implications for its implementation within the health care landscape of China. TB PET/CT's exceptional sensitivity enables the acquisition of high-quality images in significantly reduced time frames. Clinical applications have underscored its effectiveness across various scenarios, emphasizing the capacity to personalize dosage, scan duration, and image quality to optimize patient outcomes. TB PET/CT's ability to perform dynamic scans with high temporal and spatial resolution and to perform parametric imaging facilitates the exploration of radiotracer biodistribution and kinetic parameters throughout the body. The comprehensive TB coverage offers opportunities to study interconnections among organs, enhancing our understanding of human physiology and pathology. These insights have the potential to benefit applications requiring holistic TB assessments. The standard topics outlined in The Journal of Nuclear Medicine were used to categorized the reviewed articles into 3 sections: current clinical applications, scan protocol design, and advanced topics. This article delves into the bottleneck that impedes the full use of TB PET in China, accompanied by suggested solutions.


Assuntos
Imagem Corporal Total , Humanos , China , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos
10.
Food Chem ; 452: 139557, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38728895

RESUMO

ß-Galactosidase (ß-gal), an enzyme related to cell wall degradation, plays an important role in regulating cell wall metabolism and reconstruction. However, activatable fluorescence probes for the detection and imaging of ß-gal fluctuations in plants have been less exploited. Herein, we report an activatable fluorescent probe based on intramolecular charge transfer (ICT), benzothiazole coumarin-bearing ß-galactoside (BC-ßgal), to achieve distinct in situ imaging of ß-gal in plant cells. It exhibits high sensitivity and selectivity to ß-gal with a fast response (8 min). BC-ßgal can be used to efficiently detect the alternations of intracellular ß-gal levels in cabbage root cells with considerable imaging integrity and imaging contrast. Significantly, BC-ßgal can assess ß-gal activity in cabbage roots under heavy metal stress (Cd2+, Cu2+, and Pb2+), revealing that ß-gal activity is negatively correlated with the severity of heavy metal stress. Our work thus facilitates the study of ß-gal biological mechanisms.


Assuntos
Brassica , Corantes Fluorescentes , Metais Pesados , Raízes de Plantas , beta-Galactosidase , beta-Galactosidase/metabolismo , beta-Galactosidase/química , Brassica/química , Brassica/metabolismo , Brassica/enzimologia , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Corantes Fluorescentes/química , Metais Pesados/metabolismo , Metais Pesados/análise , Imagem Óptica , Proteínas de Plantas/metabolismo
11.
Langmuir ; 40(20): 10449-10459, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38717310

RESUMO

It is widely acknowledged that doping silicon can significantly enhance the friction performance of diamond-like carbon (DLC) films in a water environment. However, the mechanism of low friction caused by doped silicon is still highly controversial. Therefore, this article compares the interface interaction between DLC and Si-DLC films in a water environment through first-principles calculations of physisorption and chemisorption effects. The results indicate that water molecules are predominantly chemically adsorbed rather than physically adsorbed on the Si-DLC surface. Further study reveals that when OH-termination is formed on the Si-DLC surface, water molecules are predominantly physically adsorbed rather than chemically adsorbed on the Si-DLC hydroxylation surface. Consequently, a more stable hydration layer is formed on the surface through the hydrogen bond network formed by Si-OH groups, ultimately leading to lower friction. Moreover, molecular dynamics simulations further suggest that the lower friction coefficient of Si-DLC films in a water environment may be due to more water molecules at the friction interface and fewer interface covalent bonds. In short, the low-friction coefficient of the Si-DLC film in a water environment may be caused not only by the chemisorption of water molecules on its surface but also by the physisorption of water molecules on the Si-DLC film after surface hydroxylation.

12.
Children (Basel) ; 11(5)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38790600

RESUMO

This retrospective study aimed to analyze the treatment effect and prognostic factors of pediatric acute myeloid leukemia (AML) patients with t(8;21). A total of 268 newly diagnosed pediatric AML (pAML) enrolled from 1 January 2005 to 31 December 2022 were retrospectively reviewed, and 50 (18.7%) patients harbored t(8;21) translocation. CR rate, OS, EFS, and RFS were assessed by multivariate Logistic and Cox regression models in these patients. Of the 50 patients, 2 patients abandoned treatment during the first induction course. Of the remaining 48 patients who received double-induction therapy and were included in the final analyses, CR1 and CR2 were 75.0% (36/48) and 95.8% (46/48), respectively. The overall three-year OS, EFS, and RFS were 68.4% (95% CI, 55.0-85.1), 64.2% (95% CI, 50.7-81.4), and 65.5% (95% CI, 51.9-82.8), respectively. The presence of loss of sex chromosome (LOS) at diagnosis (n = 21) was associated with a better 3-year OS [87.5% (95% CI, 72.7-100) vs. 52.7% (95% CI, 35.1-79.3), p = 0.0089], 3-year EFS [81.6% (95% CI, 64.7-100) vs. 49.7% (95% CI, 32.4-76.4), p = 0.023], and 3-year RFS [81.6% (95% CI, 64.7-100) vs. 51.7% (95% CI, 33.9-78.9), p = 0.036] than those without LOS (n = 27), and it was also an independent good prognostic factor of OS (HR, 0.08 [95% CI, 0.01-0.48], p = 0.005), EFS (HR, 0.22 [95% CI, 0.05-0.85], p = 0.029), and RFS (HR, 0.21 [95% CI, 0.05-0.90], p = 0.035). However, extramedullary leukemia (EML) featured the independent risk factors of inferior OS (HR, 10.99 [95% CI, 2.08-58.12], p = 0.005), EFS (HR, 4.75 [95% CI, 1.10-20.61], p = 0.037), and RFS (HR, 6.55 [95% CI, 1.40-30.63], p = 0.017) in pediatric individuals with t(8;21) AML. Further analysis of combining LOS with EML indicated that the EML+LOS- subgroup had significantly inferior OS (92.9%, [95% CI, 80.3-100]), EFS (86.2%, [95% CI, 70.0-100]), and RFS (86.2%, [95% CI, 80.3-100]) compared to the other three subgroups (all p < 0.001). LOS and EML are independent prognostic factors of OS, EFS, and RFS with t(8;21) pAML patients. LOS combined with EML may help improve risk stratification.

13.
Talanta ; 274: 126081, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38613947

RESUMO

The development of efficient, accurate, and high-throughput technology for gut microbiota sensing holds great promise in the maintenance of health and the treatment of diseases. Herein, we developed a rapid fluorescent sensor array based on surface-engineered silver nanoparticles (AgNPs) and vancomycin-modified gold nanoclusters (AuNCs@Van) for gut microbiota sensing. By controlling the surface of AgNPs, the recognition ability of the sensor can be effectively improved. The sensor array was used to successfully discriminate six gut-derived bacteria, including probiotics, neutral, and pathogenic bacteria and even their mixtures. Significantly, the sensing system has also been successfully applied to classify healthy individuals and colorectal cancer (CRC) patients rapidly and accurately within 30 min, demonstrating its clinically relevant specificity.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Ouro , Nanopartículas Metálicas , Prata , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/diagnóstico , Humanos , Prata/química , Nanopartículas Metálicas/química , Ouro/química , Vancomicina/farmacologia , Propriedades de Superfície , Corantes Fluorescentes/química
14.
Eur J Nucl Med Mol Imaging ; 51(9): 2744-2757, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38587644

RESUMO

PURPOSE: Radiopharmaceutical therapies targeting fibroblast activation protein (FAP) have shown promising efficacy against many tumor types. But radiopharmaceuticals alone in most cases are insufficient to completely eradicate tumor cells, which can partially be attributed to the protective interplay between tumor cells and cancer-associated fibroblasts (CAFs). The C-X-C chemokine receptor type 4/C-X-C motif chemokine 12 (CXCR4/CXCL12) interaction plays an important role in orchestrating tumor cells and CAFs. We hereby investigated the feasibility and efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2, a FAP-targeting radiopharmaceutical, in combination with AMD3100, a CXCR4 antagonist, in a preclinical murine model of triple-negative breast cancer (TNBC). METHODS: Public database was first interrogated to reveal the correlation between CAFs' scores and the prognosis of TNBC patients, as well as the expression levels of FAP and CXCR4 in normal tissues and tumors. In vitro therapeutic efficacy regarding cell proliferation, migration, and colony formation was assessed in BALB/3T3 fibroblasts and 4T1 murine breast cancer cells. In vivo therapeutic efficacy was longitudinally monitored using serial 18F-FDG, [18F]AlF-NOTA-FAPI-04, and [68Ga]Ga-DOTA-Pentixafor PET/CT scans and validated using tumor sections through immunohistochemical staining of Ki-67, α-SMA, CXCR4, and CXCL12. Intratumoral abundance of myeloid-derived suppressive cells (MDSCs) was analyzed using flow cytometry in accordance with the PET/CT schedules. Treatment toxicity was evaluated by examining major organs including heart, lung, liver, kidney, and spleen. RESULTS: CAFs' scores negatively correlated with the survival of TNBC patients (p < 0.05). The expression of CXCR4 and FAP was both significantly higher in tumors than in normal tissues. The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 significantly suppressed cell proliferation, migration, and colony formation in cell culture, and exhibited synergistic effects in 4T1 tumor models along with a decreased number of MDSCs. PET/CT imaging revealed lowest tumor accumulation of 18F-FDG and [18F]AlF-NOTA-FAPI-04 on day 13 and day 14 after treatment started, both of which gradually increased at later time points. A similar trend was observed in the IHC staining of Ki-67, α-SMA, and CXCL12. CONCLUSION: The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 is a feasible treatment against TNBC with minimal toxicity in main organs.


Assuntos
Quimiocina CXCL12 , Receptores CXCR4 , Neoplasias de Mama Triplo Negativas , Receptores CXCR4/metabolismo , Receptores CXCR4/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/radioterapia , Animais , Camundongos , Quimiocina CXCL12/metabolismo , Humanos , Linhagem Celular Tumoral , Feminino , Ciclamos/farmacologia , Ciclamos/uso terapêutico , Lutécio , Benzilaminas/farmacologia , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/química , Compostos Radiofarmacêuticos/uso terapêutico , Compostos Radiofarmacêuticos/farmacologia , Endopeptidases , Proliferação de Células/efeitos dos fármacos , Gelatinases/metabolismo , Proteínas de Membrana/metabolismo , Serina Endopeptidases/metabolismo
15.
Plants (Basel) ; 13(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38611535

RESUMO

Aboveground biomass (AGB) is an important indicator of the grassland ecosystem. It can be used to evaluate the grassland productivity and carbon stock. Satellite remote sensing technology is useful for monitoring the dynamic changes in AGB across a wide range of grasslands. However, due to the scale mismatch between satellite observations and ground surveys, significant uncertainties and biases exist in mapping grassland AGB from satellite data. This is also a common problem in low- and medium-resolution satellite remote sensing modeling that has not been effectively solved. The rapid development of uncrewed aerial vehicle (UAV) technology offers a way to solve this problem. In this study, we developed a method with UAV and satellite synergies for estimating grassland AGB that filled the gap between satellite observation and ground surveys and successfully mapped the grassland AGB in the Hulunbuir meadow steppe in the northeast of Inner Mongolia, China. First, based on the UAV hyperspectral data and ground survey data, the UAV-based AGB was estimated using a combination of typical vegetation indices (VIs) and the leaf area index (LAI), a structural parameter. Then, the UAV-based AGB was aggregated as a satellite-scale sample set and used to model satellite-based AGB estimation. At the same time, spatial information was incorporated into the LAI inversion process to minimize the scale bias between UAV and satellite data. Finally, the grassland AGB of the entire experimental area was mapped and analyzed. The results show the following: (1) random forest (RF) had the best performance compared with simple regression (SR), partial least squares regression (PLSR) and back-propagation neural network (BPNN) for UAV-based AGB estimation, with an R2 of 0.80 and an RMSE of 76.03 g/m2. (2) Grassland AGB estimation through introducing LAI achieved higher accuracy. For UAV-based AGB estimation, the R2 was improved by an average of 10% and the RMSE was reduced by an average of 9%. For satellite-based AGB estimation, the R2 was increased from 0.70 to 0.75 and the RMSE was decreased from 78.24 g/m2 to 72.36 g/m2. (3) Based on sample aggregated UAV-based AGB and an LAI map, the accuracy of satellite-based AGB estimation was significantly improved. The R2 was increased from 0.57 to 0.75, and the RMSE was decreased from 99.38 g/m2 to 72.36 g/m2. This suggests that UAVs can bridge the gap between satellite observations and field measurements by providing a sufficient training dataset for model development and AGB estimation from satellite data.

16.
BMC Complement Med Ther ; 24(1): 156, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605368

RESUMO

BACKGROUND: The clinical application of immune checkpoint inhibitors (ICIs) is limited by their drug resistance, necessitating the development of ICI sensitizers to improve cancer immunotherapy outcomes. Huang Lian Jie Du Decoction (HLJD, Oren-gedoku-to in Japanese, Hwangryunhaedok-tang in Korean), a famous traditional Chinese medicinal prescription, has exhibited potential in the field of cancer treatment. This study aims to investigate the impact of HLJD on the efficacy of ICIs in melanoma and elucidate the underlying mechanisms. METHODS: The potential synergistic effects of HLJD and ICIs were investigated on the tumor-bearing mice model of B16F10 melanoma, and the tumor infiltration of immune cells was tested by flow cytometry. The differential gene expression in tumors between HLJD and ICIs group and ICIs alone group were analyzed by RNA-seq. The effects of HLJD on oxidative stress, TLR7/8, and type I interferons (IFN-Is) signaling were further validated by immunofluorescence, PCR array, and immunochemistry in tumor tissue. RESULTS: HLJD enhanced the anti-tumor effect of ICIs, significantly inhibited tumor growth, and prolonged the survival duration in melanoma. HLJD increased the tumor infiltration of anti-tumor immune cells, especially DCs, CD4+ T cells and CD8+T cells. Mechanically, HLJD activated the oxidative stress and TLR7/8 signaling pathway and IFN-Is-related genes in tumors. CONCLUSIONS: HLJD enhanced the therapeutic benefits of ICIs in melanoma, through increasing reactive oxygen species (ROS), promoting the TLR7/8 pathway, and activating IFN-Is signaling, which in turn activated DCs and T cells.


Assuntos
Medicamentos de Ervas Chinesas , Inibidores de Checkpoint Imunológico , Melanoma , Camundongos , Animais , Inibidores de Checkpoint Imunológico/farmacologia , Coptis chinensis , Receptor 7 Toll-Like , Melanoma/tratamento farmacológico , Transdução de Sinais
17.
BMC Public Health ; 24(1): 1120, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654229

RESUMO

BACKGROUND: Dietary rationality and health concept have certain influence on individual health level. This study aims to explore the characteristics and existing problems of Chinese residents' health behaviors from both macro and micro perspectives, and explore the feasibility and realization path of Healthy China strategy. METHODS: We utilized regression models to evaluate the correlation between diet and the risk of disease causes of death. By use of the linear regression analysis model, we distinguished the impact of each dimension on health literacy index at the individual level. Then, we explored the influential factors of the diet health index using the binary logit regression model. RESULTS: Increased consumption of animal-derived foods in China has contributed to the burden of non-communicable diseases. The individuals' health awareness is still weak, and the health literacy index is greatly affected by the diet, while the individual gender and age are positively correlated with the diet health index, and the individual body mass index (BMI) level is negatively correlated with the diet health index. CONCLUSIONS: This study provided a comprehensive understanding of existing problems of Chinese residents' health behaviors. We have proposed a path model for the implementation of the Healthy China strategy from the perspectives of "diet health, physical health, conceptual health and environmental health," which is also a great contribution to the world.


Assuntos
Comportamentos Relacionados com a Saúde , Humanos , China , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Dieta , Letramento em Saúde , Idoso , Dieta Saudável , Adulto Jovem
18.
Anal Chem ; 96(8): 3436-3444, 2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-38372258

RESUMO

Cerebral ischemia-reperfusion injury (CIRI), a cause of cerebral dysfunction during cerebral infarction treatment, is closely associated with mitochondrial viscosity and hydrogen peroxide (H2O2). However, the accurate measurement of mitochondrial viscosity and H2O2 levels in CIRI is challenging because of the lack of sufficient selectivity and blood-brain barrier (BBB) penetration of existing monitoring tools related to CIRI, hampering the exploration of the role of mitochondrial viscosity and H2O2 in CIRI. To address this issue, we designed an activatable fluorescent probe, mitochondria-targeting styryl-quinolin-ium (Mito-IQS), with excellent properties including high selectivity, mitochondrial targeting, and BBB penetration, for the visualization of mitochondrial viscosity and H2O2 in the brain. Based on the real-time monitoring capabilities of the probe, bursts of mitochondrial viscosity and H2O2 levels were visualized during CIRI. This probe can be used to monitor the therapeutic effects of butylphthalein treatment. More importantly, in vivo experiments further confirmed that CIRI was closely associated with the mitochondrial viscosity and H2O2 levels. This discovery provides new insights and tools for the study of CIRI and is expected to accelerate the process of CIRI diagnosis, treatment, and drug design.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Humanos , Peróxido de Hidrogênio , Corantes Fluorescentes , Viscosidade , Mitocôndrias
19.
Eur Radiol Exp ; 8(1): 12, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270720

RESUMO

BACKGROUND: The low absorption of x-rays in lung tissue and the poor resolution of conventional computed tomography (CT) limits its use to detect lung disease. However, x-ray dark-field imaging can sense the scattered x-rays deflected by the structures being imaged. This technique can facilitate the detection of small alveolar lesions that would be difficult to detect with conventional CT. Therefore, it may provide an alternative imaging modality to diagnose lung disease at an early stage. METHODS: Eight mice were inoculated with lung cancers simultaneously. Each time two mice were scanned using a grating-based dark-field CT on days 4, 8, 12, and 16 after the introduction of the cancer cells. The detectability index was calculated between nodules and healthy parenchyma for both attenuation and dark-field modalities. High-resolution micro-CT and pathological examinations were used to crosscheck and validate our results. Paired t-test was used for comparing the ability of dark-field and attenuation modalities in pulmonary nodule detection. RESULTS: The nodules were shown as a signal decrease in the dark-field modality and a signal increase in the attenuation modality. The number of nodules increased from day 8 to day 16, indicating disease progression. The detectability indices of dark-field modality were higher than those of attenuation modality (p = 0.025). CONCLUSIONS: Compared with the standard attenuation CT, the dark-field CT improved the detection of lung nodules. RELEVANCE STATEMENT: Dark-field CT has a higher detectability index than conventional attenuation CT in lung nodule detection. This technique could improve the early diagnosis of lung cancer. KEY POINTS: • Lung cancer progression was observed using x-ray dark-field CT. • Dark-field modality complements with attenuation modality in lung nodule detection. • Dark-field modality showed a detectability index higher than that attenuation in nodule detection.


Assuntos
Neoplasias Pulmonares , Animais , Camundongos , Neoplasias Pulmonares/diagnóstico por imagem , Raios X , Tomografia Computadorizada por Raios X , Pulmão
20.
Anal Chem ; 96(4): 1795-1802, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38241199

RESUMO

Cytokines are essential components of the immune system and are recognized as significant biomarkers. However, detection of a single cytokine is not precise and reliable enough to satisfy the requirements for diagnosis. Herein, we developed a pattern recognition-based method for the multiplexed sensing of cytokines, which involves three-color-emitting boronic acid-decorated carbon dots (BCDs) and arginine-modified titanium carbide (Ti3C2 MXenes) as the sensor array. Initially, the fluorescence signals of the three BCDs were quenched by Ti3C2 MXenes. In the presence of cytokines, the fluorescence intensity of the BCDs was restored or further quenched by different cytokines. The fluorescence response occurs in two steps: first, boronic acid interacts with cis-diol functional groups of cytokines, and second, arginine headgroup selectively interacts with glycans. By exploiting the different competing binding of the BCDs and the cytokines toward Ti3C2 MXenes, seven cytokines and their mixtures can be effectively discriminated at a concentration of 20 ng mL-1. Furthermore, our sensor array demonstrated an excellent performance in classifying human oral cancer saliva samples from healthy individuals with clinically relevant specificity. The noninvasive method offers a rapid approach to cytokine analysis, benefiting early and timely clinical diagnosis and treatment.


Assuntos
Citocinas , Neoplasias Bucais , Humanos , Carbono , Ácidos Borônicos , Neoplasias Bucais/diagnóstico , Arginina
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