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2.
Sci Rep ; 14(1): 4683, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409246

RESUMO

Due to the high incidence and inconspicuous initial characteristics of rotor unbalance faults, the detection of incipient unbalance faults is becoming a very challenging problem. In this paper, a new method of small rotor unbalance fault diagnosis based on RIME-VMD and modified wavelet kernel network (modified-WKN) is proposed. Firstly, in order to extract the small unbalance fault information from the vibration signals with low signal-to-noise ratio (SNR) more efficiently, the RIME algorithm is used to search for the optimal location of the penalty factor and decomposition layer in the variable mode decomposition (VMD). Secondly, the most relevant decomposition components to the small unbalance fault information are selected by using Pearson Correlation Coefficients and utilized to reconstruct the signal. Finally, the modified-WKN diagnostic model that is used for multi-sensor data fusion is constructed. The model can acquire features of vibration signals from multiple position sensors, which enhances the ability of the modified WKN diagnostic model to deal with incipient fault modes. Based on the experimental analysis of rotor unbalance fault datasets with different SNRs, it is verified that the detection performance of the proposed method is better than the traditional WKN and VMD-WKN methods. Specifically, the proposed method is more sensitive to the initial unbalance faults.

3.
Small ; : e2309086, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321834

RESUMO

Ferroptosis therapy, which uses ferroptosis inducers to produce lethal lipid peroxides and induce tumor cell death, is considered a promising cancer treatment strategy. However, challenges remain regarding how to increase the accumulation of reactive oxygen species (ROS) in the tumor microenvironment (TME) to enhance antitumor efficacy. In this study, a hyaluronic acid (HA) encapsulated hollow mesoporous manganese dioxide (H-MnO2 ) with double-shell nanostructure is designed to contain iron coordinated cyanine near-infrared dye IR783 (IR783-Fe) for synergistic ferroptosis photodynamic therapy against tumors. The nano photosensitizer IR783-Fe@MnO2 -HA, in which HA actively targets the CD44 receptor, subsequently dissociates and releases Fe3+ and IR783 in acidic TME. First, Fe3+ consumes glutathione to produce Fe2+ , which promotes the Fenton reaction in cells to produce hydroxyl free radicals (·OH) and induce ferroptosis of tumor cells. In addition, MnO2 catalyzes the production of O2 from H2 O2 and enhances the production of singlet oxygen (1 O2 ) by IR783 under laser irradiation, thus increasing the production and accumulation of ROS to provide photodynamic therapy. The highly biocompatible IR783-Fe@MnO2 -HA nano-photosensitizers have exhibited tumor-targeting ability and efficient tumor inhibition in vivo due to the synergistic effect of photodynamic and ferroptosis antitumor therapies.

4.
Eur J Nucl Med Mol Imaging ; 51(6): 1651-1661, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38182838

RESUMO

PURPOSE: MRI-negative children with focal cortical dysplasia type II (FCD II) are one of the most challenging cases in surgical epilepsy management. We aimed to utilize quantitative positron emission tomography (QPET) analysis to complement [18F]SynVesT-1 and [18F]FDG PET imaging and facilitate the localization of epileptogenic foci in pediatric MRI-negative FCD II patients. METHODS: We prospectively enrolled 17 MRI-negative children with FCD II who underwent [18F]SynVesT-1 and [18F]FDG PET before surgical resection. The QPET scans were analyzed using statistical parametric mapping (SPM) with respect to healthy controls. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of [18F]SynVesT-1 PET, [18F]FDG PET, [18F]SynVesT-1 QPET, and [18F]FDG QPET in the localization of epileptogenic foci were assessed. Additionally, we developed a multivariate prediction model based on dual trace PET/QPET assessment. RESULTS: The AUC values of [18F]FDG PET and [18F]SynVesT-1 PET were 0.861 (sensitivity = 94.1%, specificity = 78.2%, PPV = 38.1%, NPV = 98.9%) and 0.908 (sensitivity = 82.4%, specificity = 99.2%, PPV = 93.3%, NPV = 97.5%), respectively. [18F]FDG QPET showed lower sensitivity (76.5%) and NPV (96.6%) but higher specificity (95.0%) and PPV (68.4%) than visual assessment, while [18F]SynVesT-1 QPET exhibited higher sensitivity (94.1%) and NPV (99.1%) but lower specificity (97.5%) and PPV (84.2%). The multivariate prediction model had the highest AUC value (AUC = 0.996, sensitivity = 100.0%, specificity = 96.6%, PPV = 81.0%, NPV = 100%). CONCLUSIONS: The multivariate prediction model based on [18F]SynVesT-1 and [18F]FDG PET/QPET assessments holds promise in noninvasively identifying epileptogenic regions in MRI-negative children with FCD II. Furthermore, the combination of visual assessment and QPET may improve the sensitivity and specificity of diagnostic tests in localizing epileptogenic foci and achieving a preferable surgical outcome in MRI-negative FCD II.


Assuntos
Epilepsia , Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Humanos , Criança , Masculino , Feminino , Tomografia por Emissão de Pósitrons/métodos , Pré-Escolar , Adolescente , Malformações do Desenvolvimento Cortical do Grupo I/diagnóstico por imagem , Displasia Cortical Focal
5.
Eur J Nucl Med Mol Imaging ; 51(6): 1544-1557, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38276986

RESUMO

PURPOSE: Several studies have demonstrated the advantages of heterodimers over their corresponding monomers due to the multivalency effect. This effect leads to an increased number of effective targeted receptors and, consequently, improved tumor uptake. Fibroblast activation protein (FAP) and integrin αvß3 are found to be overexpressed in different components of the tumor microenvironment. In our pursuit of enhancing tumor uptake and retention, we designed and developed a novel peptidic heterodimer that synergistically targets both FAP and integrin αvß3. METHODS: FAP-RGD was synthesized from FAP-2286 and c(RGDfK) through a multi-step organic synthesis. The dual receptor binding property of 68Ga-FAP-RGD was investigated by cell uptake and competitive binding assays. Preclinical pharmacokinetics were determined in HT1080-FAP and U87MG tumor models using micro-positron emission tomography/computed tomography (micro-PET/CT) and biodistribution studies. The antitumor efficacy of 177Lu-FAP-RGD was assessed in U87MG tumor models. The radiation exposure and clinical diagnostic performance of 68 Ga-FAP-RGD were evaluated in healthy volunteers and cancer patients. RESULTS: Bi-specific radiotracer 68Ga-FAP-RGD exhibited high binding affinity for both FAP and integrin αvß3. In comparison to 68Ga-FAP-2286 and 68Ga-RGDfK, 68Ga-FAP-RGD displayed enhanced tumor uptake and longer tumor retention time in preclinical models. 177Lu-FAP-RGD could efficiently suppress the growth of U87MG tumor in vivo when applied at an activity of 18.5 and 29.6 MBq. The effective dose of 68Ga-FAP-RGD was 1.06 × 10-2 mSv/MBq. 68Ga-FAP-RGD demonstrated low background activity and stable accumulation in most neoplastic lesions up to 3 h. CONCLUSION: Taking the advantages of multivalency effect, the bi-specific radiotracer 68Ga-FAP-RGD showed superior tumor uptake and retention compared to its corresponding monomers. Preclinical studies with 68Ga- or 177Lu-labeled FAP-RGD showed favorable image contrast and effective antitumor responses. Despite the excellent performance of 68Ga-FAP-RGD in clinical diagnosis, experimental efforts are currently underway to optimize the structure of FAP-RGD to increase its potential for clinical application in endoradiotherapy.


Assuntos
Endopeptidases , Integrina alfaVbeta3 , Proteínas de Membrana , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Serina Endopeptidases , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Dimerização , Endopeptidases/metabolismo , Endopeptidases/farmacologia , Radioisótopos de Gálio/química , Integrina alfaVbeta3/química , Integrina alfaVbeta3/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/farmacologia , Oligopeptídeos/química , Oligopeptídeos/farmacocinética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Traçadores Radioativos , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/química , Serina Endopeptidases/metabolismo , Distribuição Tecidual , Peptídeos/metabolismo , Peptídeos/farmacologia
6.
Eur J Nucl Med Mol Imaging ; 51(2): 369-379, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37759096

RESUMO

PURPOSE: PD-L1 PET imaging, as a non-invasive procedure, can perform a real-time, dynamic and quantitative analysis of PD-L1 expression at tumor sites. In this study, we developed a novel peptide-based PET tracer, [68 Ga]Ga-AUNP-12, for preclinical and first-of-its-kind imaging of PD-L1 expression in patients. METHODS: Radiosynthesis of [68 Ga]Ga-AUNP-12 was conducted. Assays for cellular uptake and binding were conducted on the PANC02, CT26, and B16F10 cell lines. Preclinical models were used to investigate its biodistribution, imaging capacity, and pharmacokinetics. Furthermore, interferon-γ (IFN-γ) was used for development of an animal model with high PD-L1 expression for targeted PET imaging and efficacy evaluation of PD-L1 blocking therapy. In healthy volunteers and cancer patients, the PD-L1 imaging, radiation dosimetry, safety, and biodistribution were further evaluated. RESULTS: In vitro and in vivo animal studies showed that [68 Ga]Ga-AUNP-12 PET imaging displayed a high specificity in evaluating PD-L1 expression. The radiochemical yield of [68 Ga]Ga-AUNP-12 was 71.7 ± 8.2%. Additionally, its molar activity and radiochemical purity were satisfactory. The B16F10 tumor was visualized with the tumor uptake of 6.86 ± 0.71% ID/g and tumor-to-muscle ratio of 6.83 ± 0.36 at 60 min after [68 Ga]Ga-AUNP-12 injection. Furthermore, [68 Ga]Ga-AUNP-12 PET imaging could sensitively detect the PD-L1 dynamic changes in CT26 tumor xenograft models regulated by IFN-γ treatment, and correspondingly can effectively guide immunotherapy. Regarding radiation dosimetry, [68 Ga]Ga-AUNP-12 is safe for human use. The first human study found that [68 Ga]Ga-AUNP-12 can be rapidly cleared from blood and other nonspecific organs through the kidney excretion, leading to form a clear imaging contrast in the clinical framework. The specificity of [68 Ga]Ga-AUNP-12 was validated and tumor uptake strongly correlated with the high PD-L1 expression in patients with lung adenocarcinoma and oesophageal squamous cell carcinoma (OSCC). CONCLUSION: [68 Ga]Ga-AUNP-12 was successfully developed as a PD-L1-specific PET imaging tracer in preclinical and first-in-human studies.


Assuntos
Radioisótopos de Gálio , Neoplasias , Humanos , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
7.
Eur Radiol ; 34(2): 887-898, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37581655

RESUMO

OBJECTIVES: To investigate [18F]FDG PET patterns of mesial temporal lobe epilepsy (MTLE) patients with distinct pathologic types and provide possible guidance for predicting long-term prognoses of patients undergoing epilepsy surgery. METHODS: This was a retrospective review of MTLE patients who underwent anterior temporal lobectomy between 2016 and 2021. Patients were classified as having chronic inflammation and gliosis (gliosis, n = 44), hippocampal sclerosis (HS, n = 43), or focal cortical dysplasia plus HS (FCD-HS, n = 13) based on the postoperative pathological diagnosis. Metabolic patterns and the severity of metabolic abnormalities were investigated among MTLE patients and healthy controls (HCs). The standardized uptake value (SUV), SUV ratio (SUVr), and asymmetry index (AI) of regions of interest were applied to evaluate the severity of metabolic abnormalities. Imaging processing was performed with statistical parametric mapping (SPM12). RESULTS: With a mean follow-up of 2.8 years, the seizure freedom (Engel class IA) rates of gliosis, HS, and FCD-HS were 54.55%, 62.79%, and 69.23%, respectively. The patients in the gliosis group presented a metabolic pattern with a larger involvement of extratemporal areas, including the ipsilateral insula. SUV, SUVr, and AI in ROIs were decreased for patients in all three MTLE groups compared with those of HCs, but the differences among all three MTLE groups were not significant. CONCLUSIONS: MTLE patients with isolated gliosis had the worst prognosis and hypometabolism in the insula, but the degree of metabolic decrease did not differ from the other two groups. Hypometabolic regions should be prioritized for [18F]FDG PET presurgical evaluation rather than [18F]FDG uptake values. CLINICAL RELEVANCE STATEMENT: This study proposes guidance for optimizing the operation scheme in patients with refractory MTLE and emphasizes the potential of molecular neuroimaging with PET using selected tracers to predict the postsurgical histology of patients with refractory MTLE epilepsy. KEY POINTS: • MTLE patients with gliosis had poor surgical outcomes and showed a distinct pattern of decreased metabolism in the ipsilateral insula. • In the preoperative assessment of MTLE, it is recommended to prioritize the evaluation of glucose hypometabolism areas over [18F]FDG uptake values. • The degree of glucose hypometabolism in the epileptogenic focus was not associated with the surgical outcomes of MTLE.


Assuntos
Epilepsia do Lobo Temporal , Humanos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Fluordesoxiglucose F18 , Gliose/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Glucose , Imageamento por Ressonância Magnética
8.
Clin Nucl Med ; 49(2): 180-181, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38049966

RESUMO

ABSTRACT: A 54-year-old man presented with a 2-month history of urination disturbances. Serum prostate-specific antigen level was 4.96 ng/mL, and a possibility of benign prostate hyperplasia was raised by outside medical CT. Histopathology revealed adenosquamous carcinoma. Staging workup showed large areas of high PSMA uptake and focal intense hypermetabolism in the prostate, multiple lymphatics, bone, and pulmonary heterogenic metastases on 68 Ga-PSMA and 18 F-FDG PET/CT imaging.


Assuntos
Carcinoma Adenoescamoso , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Próstata/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Carcinoma Adenoescamoso/diagnóstico por imagem , Carcinoma Adenoescamoso/patologia
9.
BJU Int ; 133(4): 442-450, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37983593

RESUMO

OBJECTIVES: To investigate the safety and efficacy of indocyanine green (ICG) fluorescence-guided inguinal lymph node dissection (ILND) in patients with penile cancer. PATIENTS AND METHODS: A prospective, single-blind, randomised controlled clinical trial (ChiCTR2100044584) was performed among patients with penile caner who underwent bilateral modified ILND at four centres in China between 1 April 2021 and 30 June 2022. Patients aged 18-80 years and diagnosed with squamous cell carcinomas were included. Each enrolled patient was randomly assigned to either ICG fluorescence-guided ILND by a laparoscopic or robot-assisted approach in one groin, with non-ICG fluorescence-guided ILND in the other groin acting as a control. The primary outcome was the number of retrieved ILNs. Secondary outcomes included complications according to the Clavien-Dindo classification and the ILN non-compliance (inadequate removal of ILNs) rate. RESULTS: A total of 45 patients were included in the intention-to-treat (ITT) analysis, and the 42 who completed the entire study were included in the per protocol (PP) analysis. There were no ICG-related complications in any of the patients. The results of the ITT and PP analyses indicated that the total number of unilateral ILNs retrieved was higher on the ICG side than on the non-ICG side (mean 13 vs 9 ILNs, difference 4 ILNs [95% CI 2.7-4.4], P = 0.007), and the number of unilateral deep and superficial ILNs was higher on the ICG side. Furthermore, the LN non-compliance rate was lower on the ICG side than on the non-ICG side. Additionally, there was no significant difference in local complications in the groins between the two sides (P > 0.05). CONCLUSION: An ICG fluorescence-guided ILND was safe for patients with penile cancer. This procedure can improve the number of ILNs retrieved and reduce the LN non-compliance rate without increased complications. ICG fluorescence-guided ILND is beneficial and recommended for selected patients with penile cancer.


Assuntos
Verde de Indocianina , Neoplasias Penianas , Masculino , Humanos , Neoplasias Penianas/cirurgia , Neoplasias Penianas/patologia , Estudos Prospectivos , Método Simples-Cego , Excisão de Linfonodo/métodos , Linfonodos/patologia , Biópsia de Linfonodo Sentinela
10.
ACS Appl Mater Interfaces ; 16(1): 605-613, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38131347

RESUMO

The catalytic oxidation of carbon monoxide (CO) under ambient conditions plays a crucial role in the abatement of indoor CO, which poses risks to human health. Despite the notable activity exhibited by Pt-based catalysts in CO oxidation, their efficacy is usually diminished by the CO self-poisoning issue. In this work, three different Pt/CeO2-based catalysts, which have distinct coordinative environments of Pt but an identical Pt/CeO2 substrate structure, were synthesized by activating the catalyst with CO using different temperatures and durations. Compared with clean and graphite-covered Pt on CeO2, the one modified by epoxy carbon showed higher activity and stability. The combination of characterizations and density functional theory modeling demonstrated that the clean Pt on CeO2 rapidly deactivated due to the CO self-poisoning albeit high initial activity, and conversely, low initial activity was observed for the more stable graphite-covered catalyst due to the obstruction of the Pt site. In contrast, epoxy carbon species on Pt shifted the d-band of Pt to lower energy, weakening the Pt-CO binding strength. Such a modification mitigated the self-poisoning effect while maintaining ample active sites and enabling the complete oxidative removal of CO under ambient conditions. This work may provide a general approach to tackling the self-poisoning issue.

11.
J Environ Sci (China) ; 138: 709-718, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38135433

RESUMO

Formaldehyde (HCHO) is a common indoor pollutant that is detrimental to human health. Its efficient removal has become an urgent demand to reduce the public health risk. In this work, Ag-MnOx-based catalysts were prepared and activated under different atmosphere (i.e., air, hydrogen (H2) and carbon monoxide (CO)) for efficient oxidation of HCHO. The catalyst activated with CO (Ag/Mn-CO) displayed the highest activity among the tested samples with 90% conversion at 100°C under a gas space velocity of 75,000 mL/(gcat·hr). Complementary characterizations demonstrate that CO reduction treatment resulted in synergically regulated content of surface oxygen on support to adsorb/activate HCHO and size of Ag particle to dissociate oxygen to oxidize the adsorbed HCHO. In contrast, other catalysts lack for either abundant surface oxygen species or metallic silver with the appropriate particle size, so that the integrate activity is limited by one specific reaction step. This study contributes to elucidating the mechanisms regulating the oxidation activity of Ag-based catalysts.


Assuntos
Oxigênio , Prata , Humanos , Óxidos , Oxirredução , Formaldeído , Catálise
12.
Int J Nanomedicine ; 18: 7637-7646, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38106445

RESUMO

Background: Sentinel lymph node (SLN) mapping-guided biopsy is crucial for cancer staging and treatment. Optical/nuclide dual-modality imaging agents for mapping SLN are ideal for preoperative planning and intraoperative biopsy, which are enabled by penetration-depth unlimited nuclide imaging and dynamic real-time optical imaging, respectively. However, commonly reported dual-modality imaging agents are composed of novel but safety-unproven materials, making their quick clinical translation challenging. Herein, we report a novel nanoparticle composed of facile hospital-available drugs and isotope for single-photon emission computed tomography (SPECT)/near-infrared (NIR) fluorescence imaging to detect SLNs. Methods: Indocyanine green-human serum albumin (ICG-HSA) nanoparticles (NPs) were synthesized by ICG-induced HSA self-assembly and further 99mTc-labeling via a one-step, facile hospital-available method. After injecting 99mTc-ICG-HSA into the rats' forepaw pads, the rats' draining axillary lymph nodes were visualized by preoperative mapping with SPECT/CT and intraoperative biopsy with NIR fluorescence. The axillary lymph nodes of rats were identified by pathology and fluorescent staining after execution. Additionally, its toxicity testing and comparison with 99mTc-sulfur colloid imaging were also explored. Results: The study reported a self-assembled 99mTc-ICG-HSA with a high radiochemical yield (85.6 ± 3.8%). Compared with conventional 99mTc-sulfur colloid, 99mTc-ICG-HSA NPs showed faster SLN identification, higher renal clearance, and lower hepatic retention. Furthermore, NIRF imaging allowed for the accurate visualization of the SLN and guided SLN biopsy intraoperatively. Notably, the 99mTc-ICG-HSA NPs were composed of hospital-available drugs and isotope, which are safe for acute toxicity evaluation by a certified institute. Conclusion: The proposed 99mTc-ICG-HSA NPs are safe and capable of noninvasive SLN identification and biopsy guidance with multi-modal imaging strategies and could be a promising tool for clinically assisted SLN biopsy.


Assuntos
Linfonodo Sentinela , Humanos , Animais , Ratos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Linfonodos/patologia , Verde de Indocianina , Tomografia Computadorizada de Emissão de Fóton Único , Compostos Radiofarmacêuticos , Imagem Óptica/métodos , Albumina Sérica Humana , Coloides , Enxofre , Corantes
13.
Cytotechnology ; 75(6): 517-532, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37841956

RESUMO

N6-methyladenosine (m6A) modification is the most common internal modification in eukaryotic mRNA and an important mechanism for post-transcriptional regulation of genes. This study focuses on the role of the m6A reader insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in the malignant behaviors of non-small-cell lung cancer (NSCLC) cells and especially the cancer stem cells (CSCs). We obtained IGF2BP1 as an aberrantly upregulated gene linking to poor survival of patients with NSCLC by bioinformatics, and then confirmed increased IGF2BP1 expression in NSCLC tissues and cells, especially in the enriched CSCs. Knockdown of IGF2BP1 suppressed proliferation, mobility and epithelial-mesenchymal transition activity of NSCLC cells and CSCs, and it reduced stemness, self-renewal ability, xenograft tumorigenesis and immune resistance of the CSCs. IGF2BP1 was predicted to have a positive correlation with BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B), and it upregulated BUB1B expression through m6A modification. Further overexpression of BUB1B in CSCs counteracted the effects of IGF2BP1 silencing and restored the malignant phenotype, self-renewal, and immune resistance of CSCs in vitro and in vivo. Taken together, this work demonstrates that IGF2BP1 manipulates BUB1B expression to affect malignant behaviors, stem cell properties and immune resistance of NSCLC stem cells.

14.
J Urol ; 210(6): 854-855, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37795825
15.
ACS Nano ; 17(20): 19740-19752, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37831945

RESUMO

Immunotherapy has revolutionized the field of cancer treatment through invigorating robust antitumor immune response. Here, we report the development of a therapeutic vaccine [consisting of high mobility group nucleosome-binding protein 1 (HMGN1), resiquimod/R848, and anti-PD-L1 (αPD-L1)]-loaded reactive oxygen species (ROS)-responsive mesoporous silica nanoparticle (MSN@TheraVac) for curative therapy of colon cancer. In MSN@TheraVac, αPD-L1 conjugated onto the surface of MSNs via a diselenide bond, which can be rapidly released under the oxidative condition of the tumor microenvironment to avert immunosuppression and effector T cell exhaustion while coloaded HMGN1 and R848 would cooperatively trigger robust tumor-infiltrating dendritic cell (TiDC) maturation and elicitation of antitumor immune responses. Indeed, MSN@TheraVac induced the maturation and activation of dendritic cells (DCs) by promoting the surface expression of CD80, CD86, and CD103 as well as the production of pro-inflammatory cytokines, including TNFα, IL-12, and IL-1ß. Importantly, treatment with intravenous MSN@TheraVac led to a complete cure of 100% of BALB/c mice bearing large colon tumors and induced the generation of tumor-specific protective memory without apparent toxicity. Thus, MSN@TheraVac provides a timely release of TheraVac for the curative treatment of colon tumors and holds potential for translation into a clinical therapy for patients with immunologically "cold" colorectal cancers. This ROS-responsive MSN platform may also be tailored for the selective delivery of other cancer vaccines for effective immunotherapy.


Assuntos
Neoplasias do Colo , Proteína HMGN1 , Nanopartículas , Humanos , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/química , Nanopartículas/química , Neoplasias do Colo/tratamento farmacológico , Imunidade , Porosidade , Microambiente Tumoral
16.
Gen Psychiatr ; 36(5): e101112, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37829163

RESUMO

Background: Internet gaming disorder (IGD) is an ideal model to study the mechanisms underlying synaptic deficits in addiction as it eliminates the confounding effects of substance use. Synaptic loss and deficits are hypothesised to underlie the enduring maladaptive behaviours and impaired cognitive function that contribute to IGD. Aims: This study aimed to determine whether subjects with IGD have lower synaptic density than control subjects and the relationship between synaptic density and IGD severity. Methods: Eighteen unmedicated subjects diagnosed with current IGD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and 16 demographically matched healthy controls (HCs) participated in the study and underwent 18F-labelled difluoro-analogue of UCB-J (18F-SynVesT-1) positron emission tomography scans to assess the density of synaptic vesicle glycoprotein 2A (SV2A). The Internet Gaming Disorder Scale-Short Form (IGDS9-SF), Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Rating Scale (HAMA), Barratt Impulsiveness Scale Version 11 (BIS-11), Stroop Colour-Word Test (SCWT), stop-signal paradigms and N-back tasks were administered to all subjects. Results: Patients with IGD had significantly higher scores on the IGDS9-SF, HAMD, HAMA and BIS-11 than HCs. HCs performed better on the two-back and SCWT tests as well as in terms of stop-signal reaction times (SSRTs) in the stop-signal paradigms than patients with IGD. Lower uptake was found in the bilateral putamen, right pregenual anterior cingulate cortex and Rolandic operculum of patients with IGD compared with HCs. Furthermore, in the IGD group, IGDS9-SF scores and daily gaming hours were negatively correlated with the standardised uptake value ratios of 18F-SynVesT-1 in the bilateral putamen. Longer SSRTs were significantly associated with lower SV2A density in the right pregenual anterior cingulate cortex and right Rolandic operculum. Conclusions: The in vivo results in this study suggest that lower synaptic density contributes to the severity and impairments in inhibitory control of IGD. These findings may provide further incentive to evaluate interventions that restore synaptic transmission and plasticity to treat IGD.

17.
Lung Cancer ; 186: 107389, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37820538

RESUMO

OBJECTIVES: To investigate whether the combination of inflammatory biomarkers and metabolic parameters of 18F-FDG PET/CT could predict the major pathological reactions (MPR) in resectable NSCLC patients after neoadjuvant immunochemotherapy more accurately and screen out patients who may benefit from the neoadjuvant therapy. MATERIALS AND METHODS: 114 resectable NSCLC patients who underwent neoadjuvant immunochemotherapy and radical surgery were retrospectively enrolled. Detailed clinical characteristics, B-R and 18F-FDG PET/CT images were collected for analyzing their correlation with MPR. A metabolic-inflammation comprehensive prognostic index (MICPI) combined 18F-FDG PET/CT metabolic parameters and inflammatory index was proposed to predict MPR. RESULTS: 66.7 % patients achieved MPR. Smoking history, gender and ILO were influencing factors for MPR acquisition in NSCLC patients. High absolute neutrophils count (PreN ≥ 3.65), metabolic parameters (PreSUVmax ≥ 11.73) before treatment and ΔSUVmean (≥54.18) were significantly associated with MPR (P<0.01, P<0.05 and P<0.001 respectively). MICPI-B based on PreN and PreSUVmax categorized NSCLC patients into three groups and among the groups of high, intermediate and low MICPI-B score, MPR accounted for 80.00 %, 51.72 % and 28.57 % respectively (P < 0.01). In high, intermediate and low MICPI-P groups which based on PreN and ΔSUVmean, MPR accounted for 92.31 %, 53.57 % and 11.11 %, respectively (P < 0.001). CONCLUSION: PreN and metabolic parameter of 18F-FDG PET/CT may be an accurate alternative biomarker for predicting MPR in NSCLC patients after neoadjuvant immunochemotherapy. Moreover, MICPI can stratify patients into different groups based on their likelihood of obtaining MPR, allowing clinicians to identify patients who may most likely benefit from neoadjuvant immunochemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Terapia Neoadjuvante , Estudos Retrospectivos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia
18.
Eur J Nucl Med Mol Imaging ; 51(1): 168-179, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37707571

RESUMO

PURPOSE: Temporal lobe epilepsy (TLE) is a common, polygenic epilepsy syndrome that involves glucose hypometabolism in the epileptogenic zone. However, the transcriptional and cellular signatures underlying the metabolism in TLE remain unclear. METHODS: In this retrospective study, 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) scans of TLE patients (n = 104) who underwent anterior temporal lobectomy were consecutively collected between 2016 and 2021. The transcriptional profiles of TLE risk genes across the brain were identified by the gene expression analyses from six TLE patients and twelve postmortem donors (six from the Allen Human Brain Atlas). Integrating the neuroimaging and transcriptomic data, we examined the relationship between the expression of TLE-associated genes and metabolic alterations in TLE. Furthermore, we performed functional enrichment analyses of the genes with higher weight in partial least squares regression using Metascape. RESULTS: A total of 104 patients with TLE (mean age 29 ± 9 years, 50% male) and 30 healthy controls (HCs) (mean age 31 ± 6 years, 53% male) were enrolled. Compared to that of HCs, patients with TLE showed hypometabolism in the temporal lobes and adjacent structures but hypermetabolism in the thalamus and basal ganglia. The cortical map of inter-group differences in cerebral metabolism was spatially correlated with the expression of a weighted combination of genes enriched in ontology terms and pathways related to neurovascular unit (NVU) integrity and synaptic plasticity. DISCUSSION: Our findings, combined with the analysis of neuroimaging and transcriptional data, suggest that genes related to NVU integrity and synaptic plasticity may drive alterations to brain metabolism that mediate the genetic risk of TLE.


Assuntos
Epilepsia do Lobo Temporal , Humanos , Masculino , Adulto Jovem , Adulto , Feminino , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/genética , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Fluordesoxiglucose F18/metabolismo , Glucose/metabolismo , Imageamento por Ressonância Magnética
19.
Cancer Imaging ; 23(1): 81, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667341

RESUMO

BACKGROUND: The prostate-specific antigen (PSA) has been widely used in screening and early diagnosis of prostate cancer (PCa). However, in the PSA grey zone of 4-10 ng/ml, the sensitivity and specificity for diagnosing PCa are limited, resulting in considerable number of unnecessary and invasive prostate biopsies, which may lead to potential overdiagnosis and overtreatment. We aimed to predict clinically significant PCa (CSPCa) by combining the maximal standardized uptake value (SUVmax) based on 68Ga­PSMA PET/CT and clinical indicators in men with gray zone PSA levels. METHODS: 81 patients with suspected PCa based on increased serum total PSA (TPSA) levels of 4 - 10 ng/mL who underwent transrectal ultrasound/magnetic resonance imaging (MRI)/PET fusion-guided biopsy were enrolled. Among them, patients confirmed by histopathology were divided into the CSPCa group and the non-CSPCa group, and data on PSA concentration, prostate volume (PV), PSA density (PSAD), free PSA (FPSA)/TPSA, Prostate Imaging-Reporting and Data System version 2.1 (PI-RADS v2.1) score, 68Ga-PSMA PET/CT imaging evaluation results and SUVmax were compared. Multivariate logistic regression analysis was performed to identify the independent predictors for CSPCa, thereby establishing a predictive model based on SUVmax that was evaluated by analyzing the receiver operating characteristic (ROC) curve and decision curve analysis. RESULTS: Compared to non-CSPCa, CSPCa patients had smaller PVs (median, 31.40 mL), lower FPSA/TPSA (median, 0.12), larger PSADs (median, 0.21 ng/mL2) and higher PI-RADS scores (P < 0.05). The prediction model comprising 68Ga-PSMA PET/CT maximal standardized uptake value, PV and FPSA/TPSA had the highest AUC of 0.927 compared with that of other predictors alone (AUCs of 0.585 for PSA, 0.652 for mpMRI and 0.850 for 68Ga-PSMA PET/CT). The diagnostic sensitivity and specificity of the prediction model were 86.21% and 86.54%, respectively. CONCLUSION: Given the low diagnostic accuracy of regular PSA tests, a new prediction model based on the 68Ga-PSMA PET/CT SUVmax, PV and FPSA/TPSA was developed and validated, and this model could provide a more satisfactory predictive accuracy for CSPCa. This study provides a noninvasive prediction model with high accuracy for the diagnosis of CSPCa in the PSA gray zone, thus may be better avoiding unnecessary biopsy procedures.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Imageamento por Ressonância Magnética , Biópsia Guiada por Imagem
20.
J Environ Sci (China) ; 134: 117-125, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37673527

RESUMO

Formaldehyde (HCHO) and carbon monoxide (CO) are both common air pollutants and hazardous to human body. It is imperative to develop the catalyst that is able to efficiently remove these pollutants. In this work, we activated Pt-MnO2 under different conditions for highly active oxidation of HCHO and CO, and the catalyst activated under CO displayed superior performance. A suite of complementary characterizations revealed that the catalyst activated with CO created the highly dispersed Pt nanoparticles to maintain a more positively charged state of Pt, which appropriately weakens the Mn-O bonding strength in the adjacent region of Pt for efficient supply of active oxygen during the reaction. Compared with other catalysts activated under different conditions, the CO-activated Pt-MnO2 displays much higher activity for oxidation of HCHO and CO. This research contributes to elucidating the mechanism for regulating the oxidation activity of Pt-based catalyst.


Assuntos
Poluentes Atmosféricos , Oxigênio , Humanos , Compostos de Manganês , Óxidos , Espécies Reativas de Oxigênio
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