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BACKGROUND: Berberine (BBR), the main active component of Coptis chinensis Franch., has a variety of pharmacological effects, notably anti-inflammatory, which make it a potential treatment for ulcerative colitis (UC). Nevertheless, the specific target and the mode of action of BBR against UC are still unclear. PURPOSE: Here, we aim to identify BBR's anti-inflammatory target and its mode of action in UC treatment. METHODS: The therapeutic effects of BBR and Coptis chinensis Franch. extract were first assessed in UC mice. Then, stable isotope labeling using amino acids in cell culture-activity-based protein profiling (SILAC-ABPP) was applied to identify the anti-inflammatory target proteins of BBR in an inflammation model of RAW264.7 cells stimulated by LPS. Molecular docking, drug affinity responsive target stability (DARTS), molecular dynamics simulation, cellular thermal shift assay (CETSA), and biological layer interference (BLI) measurement were employed to study the interaction between BBR and its targets. Lentiviral transfection was used to knock down the target protein and investigate BBR's anti-inflammatory mechanism. RESULTS: BBR and Coptis chinensis Franch. extracts both significantly alleviated UC in mice. SILAC-ABPP identified IRGM1 as BBR's anti-inflammatory target, with its overexpression reduced by BBR treatment in both RAW264.7 cell inflammation models stimulated by LPS and UC mice. BBR significantly reduced inflammatory cytokines in LPS-induced RAW264.7 cells by blocking the PI3K/AKT/mTOR pathway. Knockdown of IRGM1 weakened BBR's effects on cytokine expression and pathway regulation. CONCLUSION: For the first time, IRGM1 was identified as the direct anti-inflammatory target of BBR. BBR has the potential to inhibit IRGM1 expression in vitro as well as in vivo. The molecular mechanism of BBR's anti-inflammatory activity was inhibiting the PI3K/AKT/mTOR pathway by targeting IRGM1.
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Electrolyte cations have been demonstrated to effectively enhance the rate and selectivity of the electrochemical CO2 reduction reaction (CO2RR), yet their implementation in electrolyte-free membrane electrode assembly (MEA) electrolyzer presents significant challenges. Herein, an anchored cation strategy that immobilizes Cs+ on carbon vacancies was designed and innovatively implemented in MEA electrolyzer, enabling highly efficient CO2 electroreduction over commercial silver catalyst. Our approach achieves a CO partial current density of approximately 500â mA cm-2 in the MEA electrolyzer, three-fold enhancement compared to pure Ag. In situ Raman and theoretical analyses, combined with machine learning potentials, reveal anchored Cs induces an electric field that significantly promotes the adsorption of *CO2 - intermediates through performing muti-point energy calculations on each structure. Furthermore, reduced adsorption of *OH intermediates effectively hampers competing hydrogen evolution reaction, as clarified by disk electrode experiments and density functional theory studies. Additionally, coupling our system with commercial polysilicon solar cells yields a notable solar-to-CO energy conversion efficiency of 8.3 %. This study opens a new avenue for developing effective cation-promoting strategy in MEA reactors for efficient CO2RR.
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Seed vigour, including rapid, uniform germination and robust seedling establishment under various field conditions, is becoming an increasingly essential agronomic trait for achieving high yield in crops. However, little is known about this important seed quality trait. In this study, we performed a genome-wide association study to identify a key transcription factor ZmRap2.7, which regulates seed vigour through transcriptionally repressing expressions of three ABA signalling genes ZmPYL3, ZmPP2C and ZmABI5 and two phosphatidylethanolamine-binding genes ZCN9 and ZCN10. In addition, ZCN9 and ZCN10 proteins could interact with ZmPYL3, ZmPP2C and ZmABI5 proteins, and loss-of-function of ZmRap2.7 and overexpression of ZCN9 and ZCN10 reduced ABA sensitivity and seed vigour, suggesting a complex regulatory network for regulation of ABA signalling mediated seed vigour. Finally, we showed that four SNPs in ZmRap2.7 coding region influenced its transcriptionally binding activity to the downstream gene promoters. Together with previously identified functional variants within and surrounding ZmRap2.7, we concluded that the distinct allelic variations of ZmRap2.7 were obtained independently during maize domestication and improvement, and responded separately for the diversities of seed vigour, flowering time and brace root development. These results provide novel genes, a new regulatory network and an evolutional mechanism for understanding the molecular mechanism of seed vigour.
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Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Transducción de Señal , Zea mays , Ácido Abscísico/metabolismo , Estudio de Asociación del Genoma Completo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polimorfismo de Nucleótido Simple , Semillas/genética , Semillas/metabolismo , Semillas/crecimiento & desarrollo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Zea mays/genética , Zea mays/metabolismo , Zea mays/crecimiento & desarrolloRESUMEN
Maize plastid terminal oxidase1 (ZmPTOX1) plays a pivotal role in seed development by upholding redox balance within seed plastids. This study focuses on characterizing the white kernel mutant 3735 (wk3735) mutant, which yields pale-yellow seeds characterized by heightened protein but reduced carotenoid levels, along with delayed germination compared to wild-type (WT) seeds. We successfully cloned and identified the target gene ZmPTOX1, responsible for encoding maize PTOX-a versatile plastoquinol oxidase and redox sensor located in plastid membranes. While PTOX's established role involves regulating redox states and participating in carotenoid metabolism in Arabidopsis leaves and tomato fruits, our investigation marks the first exploration of its function in storage organs lacking a photosynthetic system. Through our research, we validated the existence of plastid-localized ZmPTOX1, existing as a homomultimer, and established its interaction with ferredoxin-NADP+ oxidoreductase 1 (ZmFNR1), a crucial component of the electron transport chain (ETC). This interaction contributes to the maintenance of redox equilibrium within plastids. Our findings indicate a propensity for excessive accumulation of reactive oxygen species (ROS) in wk3735 seeds. Beyond its known role in carotenoids' antioxidant properties, ZmPTOX1 also impacts ROS homeostasis owing to its oxidizing function. Altogether, our results underscore the critical involvement of ZmPTOX1 in governing seed development and germination by preserving redox balance within the seed plastids.
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Germinación , Homeostasis , Oxidación-Reducción , Proteínas de Plantas , Plastidios , Semillas , Zea mays , Semillas/crecimiento & desarrollo , Semillas/genética , Semillas/metabolismo , Germinación/genética , Plastidios/metabolismo , Plastidios/genética , Plastidios/enzimología , Zea mays/genética , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Zea mays/enzimología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Oxidorreductasas/metabolismo , Oxidorreductasas/genética , Regulación de la Expresión Génica de las Plantas , Carotenoides/metabolismoRESUMEN
BACKGROUND: Inositol polyphosphate 4-phosphatase type II (INPP4B) has been identified as a tumor repressor in several human cancers while its role in endometrial cancer has not been investigated yet. Therefore, the current study was designed to determine whether INPP4B participates in the progression of endometrial cancer by utilizing clinical data and experimental determination. MATERIALS AND METHODS: We first include six chemotherapy-treated patients with recurrent and metastatic endometrioid carcinoma to determine the relationship between INPP4B mutation and relative tumor burden. By using siRNA-mediated gene silencing and vector-mediated gene overexpression, we further determined the effect of manipulating INPP4B expression on the proliferation, invasion, and survival of endometrial cancer cells. Furthermore, the repressing effect of INPP4B together with its role in chemotherapy was further validated by xenograft tumor-bearing mice models. Western blot analysis was used to explore further downstream signaling modulated by INPP4B expression manipulation. RESULTS: Two of the patients were found to have INPP4B mutations and the mutation frequency of INPP4B increased during the progression of chemotherapy resistance. Endometrial cancer cells with silenced INPP4B expression were found to have promoted tumor cell proliferation, invasion, and survival. Endometrial cancer cells overexpressing INPP4B were found to have decreased tumor cell proliferation, invasion, and survival. An in vivo study using six xenograft tumor-bearing mice in each group revealed that INPP4B overexpression could suppress tumor progression and enhance chemosensitivity. Furthermore, INPP4B overexpression was found to modulate the activation of Wnt3a signaling. CONCLUSION: The current study suggested that INPP4B could be a suppressor in endometrial cancer progression and might be a target for endometrial cancer treatment. Also, INPP4B might serve as a predictor of chemosensitivity determination.
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Movimiento Celular , Proliferación Celular , Neoplasias Endometriales , Invasividad Neoplásica , Monoéster Fosfórico Hidrolasas , Humanos , Femenino , Neoplasias Endometriales/patología , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/metabolismo , Animales , Línea Celular Tumoral , Ratones , Ratones Desnudos , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/metabolismo , Persona de Mediana Edad , Supervivencia Celular , Regulación Neoplásica de la Expresión Génica , MutaciónRESUMEN
OBJECTIVES: Combination of Breast Cancer 1 protein-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) in the peritoneal mesothelioma (PeM) has yet to be explored. We aim to assess the diagnostic value of combined BAP1 and MTAP to distinguish biphasic mesothelioma (BM) from epithelioid mesothelioma (EM) with reactive stroma in peritoneum, as well as its prognostic value in PeM. METHODS: This is a retrospective study from June 2014 to December 2021. This study included 18 cases of BM and 27 cases of EM with reactive stroma, excluded sarcomatoid, and EM without reactive stroma cases, and clinicopathological information was collected. The associations between MTAP and BAP1 levels and clinicopathological features or prognosis were analyzed. Clinical follow-up data were reviewed to correlate with pathological prognostic factors using Kaplan-Meier estimator and univariate/multivariate Cox proportional hazards regression models. RESULTS: Loss/decrease of BAP1/MTAP was observed in 6 (33.3%) BM cases and 12 (44.4%) EM cases. In 5 (27.8%) cases, loss of or decreased BAP1/MTAP expression was observed in both EC and SC of BM. BAP1/MTAP loss/decrease was observed in 12 (44.4%) cases of only EC of EM but not in reactive stroma. Compared with histology alone, a combination of BAP1 and MTAP immunohistochemistry (IHC) in spindled PeM provides a more objective mean to distinguish BM from EM with reactive stroma. Loss/decrease of BAP1/MTAP was associated with peritoneal cancer index (PCI) score (P = 0.047) and completeness of cytoreduction (CC) score (P = 0.038). BM patients have worse overall survival (OS) than EM with reactive stroma (P = 0 .007). CONCLUSIONS: Combination of BAP1/MTAP by IHC is helpful for differential diagnosis of peritoneal BM from EM with reactive stroma. Nevertheless, BAP1/MTAP may help to evaluate the biological behavior of PeM.
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Neoplasias de la Mama , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Femenino , Humanos , Biomarcadores de Tumor/metabolismo , Proteína BRCA1 , Neoplasias de la Mama/diagnóstico , Neoplasias Pulmonares/patología , Mesotelioma/diagnóstico , Mesotelioma/metabolismo , Mesotelioma/patología , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/metabolismo , Neoplasias Pleurales/patología , Estudios Retrospectivos , Proteínas Supresoras de Tumor/metabolismoRESUMEN
The Myodural Bridge (MDB) is a physiological structure that is highly conserved in mammals and many of other tetrapods. It connects the suboccipital muscles to the cervical spinal dura mater (SDM) and transmits the tensile forces generated by the suboccipital muscles to the SDM. Consequently, the MDB has broader physiological potentials than just fixing the SDM. It has been proposed that MDB significantly contributes to the dynamics of cerebrospinal fluid (CSF) movements. Animal models of suboccipital muscle atrophy and hyperplasia were established utilizing local injection of BTX-A and ACE-031. In contrast, animal models with surgical severance of suboccipital muscles, and without any surgical operation were set as two types of negative control groups. CSF secretion and reabsorption rates were then measured for subsequent analysis. Our findings demonstrated a significant increase in CSF secretion rate in rats with the hyperplasia model, while there was a significant decrease in rats with the atrophy and severance groups. We observed an increase in CSF reabsorption rate in both the atrophy and hyperplasia groups, but no significant change was observed in the severance group. Additionally, our immunohistochemistry results revealed no significant change in the protein level of six selected choroid plexus-CSF-related proteins among all these groups. Therefore, it was indicated that alteration of MDB-transmitted tensile force resulted in changes of CSF secretion and reabsorption rates, suggesting the potential role that MDB may play during CSF circulation. This provides a unique research insight into CSF dynamics.
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Duramadre , Músculos del Cuello , Animales , Ratas , Hiperplasia , Duramadre/fisiología , Músculos del Cuello/fisiología , Movimiento , Mamíferos , Atrofia , Líquido CefalorraquídeoRESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects millions of people worldwide. Positron emission tomography/magnetic resonance (PET/MR) imaging is a promising technique that combines the advantages of PET and MR to provide both functional and structural information of the brain. Deep learning (DL) is a subfield of machine learning (ML) and artificial intelligence (AI) that focuses on developing algorithms and models inspired by the structure and function of the human brain's neural networks. DL has been applied to various aspects of PET/MR imaging in AD, such as image segmentation, image reconstruction, diagnosis and prediction, and visualization of pathological features. In this review, we introduce the basic concepts and types of DL algorithms, such as feed forward neural networks, convolutional neural networks, recurrent neural networks, and autoencoders. We then summarize the current applications and challenges of DL in PET/MR imaging in AD, and discuss the future directions and opportunities for automated diagnosis, predictions of models, and personalized medicine. We conclude that DL has great potential to improve the quality and efficiency of PET/MR imaging in AD, and to provide new insights into the pathophysiology and treatment of this devastating disease.
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Anthocyanin, a kind of flavonoid, plays a crucial role in plant resistance to abiotic stress. Salt stress is a kind of abiotic stress that can damage the growth and development of plant seedlings. However, limited research has been conducted on the involvement of maize seedlings in salt stress resistance via anthocyanin accumulation, and its potential molecular mechanism is still unclear. Therefore, it is of great significance for the normal growth and development of maize seedlings to explore the potential molecular mechanism of anthocyanin improving salt tolerance of seedlings via transcriptome analysis. In this study, we identified two W22 inbred lines (tolerant line pur-W22 and sensitive line bro-W22) exhibiting differential tolerance to salt stress during seedling growth and development but showing no significant differences in seedling characteristics under non-treatment conditions. In order to identify the specific genes involved in seedlings' salt stress response, we generated two recombinant inbred lines (RILpur-W22 and RILbro-W22) by crossing pur-W22 and bro-W22, and then performed transcriptome analysis on seedlings grown under both non-treatment and salt treatment conditions. A total of 6100 and 5710 differentially expressed genes (DEGs) were identified in RILpur-W22 and RILbro-W22 seedlings, respectively, under salt-stressed conditions when compared to the non-treated groups. Among these DEGs, 3160 were identified as being present in both RILpur-W22 and RILbro-W22, and these served as commonly stressed EDGs that were mainly enriched in the redox process, the monomer metabolic process, catalytic activity, the plasma membrane, and metabolic process regulation. Furthermore, we detected 1728 specific DEGs in the salt-tolerant RILpur-W22 line that were not detected in the salt-sensitive RILbro-W22 line, of which 887 were upregulated and 841 were downregulated. These DEGs are primarily associated with redox processes, biological regulation, and the plasma membrane. Notably, the anthocyanin synthesis related genes in RILpur-W22 were strongly induced under salt treatment conditions, which was consistented with the salt tolerance phenotype of its seedlings. In summary, the results of the transcriptome analysis not only expanded our understanding of the complex molecular mechanism of anthocyanin in improving the salt tolerance of maize seedlings, but also, the DEGs specifically expressed in the salt-tolerant line (RILpur-W22) provided candidate genes for further genetic analysis.
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Maize (Zea mays) kernel size is an important factor determining grain yield; although numerous genes regulate kernel development, the roles of RNA polymerases in this process are largely unclear. Here, we characterized the defective kernel 701 (dek701) mutant that displays delayed endosperm development but normal vegetative growth and flowering transition, compared to its wild type. We cloned Dek701, which encoded ZmRPABC5b, a common subunit to RNA polymerases I, II and III. Loss-of-function mutation of Dek701 impaired the function of all three RNA polymerases and altered the transcription of genes related to RNA biosynthesis, phytohormone response and starch accumulation. Consistent with this observation, loss-of-function mutation of Dek701 affected cell proliferation and phytohormone homeostasis in maize endosperm. Dek701 was transcriptionally regulated in the endosperm by the transcription factor Opaque2 through binding to the GCN4 motif within the Dek701 promoter, which was subjected to strong artificial selection during maize domestication. Further investigation revealed that DEK701 interacts with the other common RNA polymerase subunit ZmRPABC2. The results of this study provide substantial insight into the Opaque2-ZmRPABC5b transcriptional regulatory network as a central hub for regulating endosperm development in maize.
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ARN Polimerasas Dirigidas por ADN , Endospermo , Zea mays , ARN Polimerasas Dirigidas por ADN/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , Endospermo/genética , Endospermo/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Zea mays/genética , Zea mays/metabolismoRESUMEN
BACKGROUND: The aim of this study is to search for the predictive value of 3D fat analysis and calculation technique (FACT) and intravoxel incoherent motion (IVIM) parameters in identifying osteoporosis in women. METHODS: We enrolled 48 female subjects who underwent 3.0 T MRI, including 3D FACT and IVIM sequences. Bone mineral density (BMD) values and Fracture Risk Assessment (FRAX) scores were obtained. Proton density fat fraction (PDFF) in the bone marrow and the real diffusion (D) value of intervertebral discs were measured on 3D FACT and IVIM images, respectively. Accuracy and bias were assessed by linear regression analysis and Bland-Altman plots. Intraclass correlation coefficients were used to assess the measurements' reproducibility. Spearman's rank correlation was applied to explore the correlation. MRI-based parameters were tested for significant differences among the three groups using ANOVA analyses. A receiver operating characteristic (ROC) analysis was performed. RESULTS: The PDFF of the vertebral body showed a negative correlation with BMD (R = -0.393, p = 0.005) and a positive correlation with the FRAX score (R = 0.706, p < 0.001). The D value of intervertebral discs showed a positive correlation with BMD (R = 0.321, p = 0.024) and a negative correlation with the FRAX score (R = -0.334, p = 0.019). The area under the curve values from the ROC analysis showed that the 3D FACT and IVIM sequences could accurately differentiate between normal and osteoporosis (AUC = 0.88 using the PDFF; AUC = 0.77 using the D value). The PDFF value demonstrated a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 78.6%, 89.5%, 84.6%, and 85.0%, respectively, in its ability to predict osteoporosis. The D value had a sensitivity, specificity, PPV, and NPV of 63.16%, 92.9%, 65.0%, and 77.8%, respectively, for predicting osteoporosis. CONCLUSIONS: The 3D FACT- and IVIM-measured PDFF and D values are promising biomarkers in the assessment of bone quality and fracture risk.
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OBJECTIVES: To establish a Bayesian network (BN) model to predict the survival of patients with malignant peritoneal mesothelioma (MPM) treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: The clinicopathological data of 154 MPM patients treated with CRS + HIPEC at our hospital from April 2015 to November 2022 were retrospectively analyzed. They were randomly divided into two groups in a 7:3 ratio. Survival analysis was conducted on the training set and a BN model was established. The accuracy of the model was validated using a confusion matrix of the testing set. The receiver operating characteristic (ROC) curve and area under the curve were used to evaluate the overall performance of the BN model. RESULTS: Survival analysis of 107 patients (69.5%) in the training set found ten factors affecting patient prognosis: age, Karnofsky performance score, surgical history, ascites volume, peritoneal cancer index, organ resections, red blood cell transfusion, pathological types, lymphatic metastasis, and Ki-67 index (all p < 0.05). The BN model was successfully established after the above factors were included, and the BN model structure was adjusted according to previous research and clinical experience. The results of confusion matrix obtained by internal validation of 47 cases in the testing set showed that the accuracy of BN model was 72.7%, and the area under ROC was 0.74. CONCLUSIONS: The BN model was established successfully with good overall performance and can be used as a clinical decision reference.
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Hipertermia Inducida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneales , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Teorema de Bayes , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/métodos , Hipertermia Inducida/métodos , Quimioterapia Intraperitoneal Hipertérmica , Mesotelioma/tratamiento farmacológico , Mesotelioma/cirugía , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Background: Alzheimer's disease is a common neurodegenerative disease, and patients with early-onset Alzheimer's disease (onset age < 65 years) often have atypical symptoms, which are easily misdiagnosed and missed. Multimodality neuroimaging has become an important diagnostic and follow-up method for AD with its non-invasive and quantitative advantages. Case presentation: We report a case of a 59-year-old female with a diagnosis of depression at the age of 50 after a 46-year-old onset and a 9-year follow-up observation, who developed cognitive dysfunction manifested by memory loss and disorientation at the age of 53, and eventually developed dementia. Combined with neuropsychological scales (MMSE and MOCA scores decreased year by year and finally reached the dementia criteria) and the application of multimodal imaging. MRI showed that the hippocampus atrophied year by year and the cerebral cortex was extensively atrophied. 18F-FDG PET image showed hypometabolism in right parietal lobes, bilateral frontal lobes, bilateral joint parieto-temporal areas, and bilateral posterior cingulate glucose metabolism. The 18F-AV45 PET image showed the diagnosis of early-onset Alzheimer's disease was confirmed by the presence of Aß deposits in the cerebral cortex. Conclusion: Early-onset Alzheimer's disease, which starts with depression, often has atypical symptoms and is prone to misdiagnosis. The combination of neuropsychological scales and neuroimaging examinations are good screening tools that can better assist in the early diagnosis of Alzheimer's disease. Graphical Abstract.
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BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignant tumor with a high mortality rate and extremely poor prognosis. TOP2A expression is associated with cell proliferation and cell cycle progression. We aimed to demonstrate the expression profile of TOP2A in MPM and its correlation with clinicopathological features. METHODS: Clinicopathological information from 100 MPM cases was collected at Beijing Shijitan Hospital, Capital Medical University. Immunohistochemistry (IHC) was performed to evaluate TOP2A levels. The associations between TOP2A levels and clinicopathological features or prognosis were analyzed. Clinical follow-up data were reviewed to determine correlations among the pathological prognostic factors using the Kaplan-Meier estimator and univariate/multivariate Cox proportional hazards regression models. RESULTS: Among the 100 MPM patients, there were 48 males and 52 females, with a median age of 54 years (range: 24-72 years). The cutoff curve was used to find the boundary value of the TOP2A-positive rate. TOP2A positive rate ≥ 11.97 % accounted for 48 % in tumor tissue. The TOP2A-positive rate was not associated with sex, age, asbestos exposure, peritoneal carcinomatosis index (PCI) score, or completeness of cytoreduction (CC) score in MPM. Univariate analysis revealed survival-related pathological parameters, including asbestos exposure, CA125, histological type, PCI score, CC score, Ki-67 index, and TOP2A positive rate. Multivariate analysis identified that asbestos exposure history, PCI score, Ki-67 proliferation index and TOP2A positive rate in tissue are independent prognostic factors. CONCLUSIONS: High expression of TOP2A is linked to better prognosis of MPM.
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Amianto , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneales , Neoplasias Pleurales , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/patología , Mesotelioma/diagnóstico , Neoplasias Pleurales/metabolismo , Neoplasias Pleurales/patología , PronósticoRESUMEN
During the pathogenesis of heart failure with preserved ejection fraction (HFpEF), fibroblasts are activated and express the fibroblast activation protein (FAP). Targeted imaging of FAP can qualitatively and quantitatively assess the fibroblast activity. This study aimed to use [18F]AlF-NOTA-FAPI-04 (AlF = aluminum fluoride; NOTA = 1,4,7-triazacyclononane-1,4,7-triacetic acid; FAPI = FAP inhibitor) positron emission tomography/computed tomography (PET/CT) imaging to detect activated fibroblasts in a rat HFpEF model. The rat HfpEF model was established by feeding a high-fat diet plus l-NAME (Nω-nitro-l-arginine methyl ester) for 10 weeks. Blood pressure, echocardiography, and [18F]AlF-NOTA-FAPI-04 PET/CT were used to assess the progression of HfpEF. The biodistribution of [18F]AlF-NOTA-FAPI-04 in healthy rats was obtained. Cardiac tissue sections were also analyzed using Masson's, hematoxylin and eosin (H&E), and FAP immunohistochemistry (IHC) staining. The echocardiography and blood pressure data indicated that the rat HfpEF model was successfully established. [18F]AlF-NOTA-FAPI-04 PET/CT imaging showed obvious radiotracer accumulation in the left ventricular wall of the HfpEF rats from the seventh week. A biodistribution test showed that the tracer was cleared mainly via renal and intestinal excretion. Percentage of injected dose per gram tissue (% ID) of the heart and its surrounding organs was lower in normal rats, which was conducive to image analysis. Masson's and H&E stainings showed large areas of vascular and interstitial fibrosis in the HfpEF rat hearts. IHC staining also confirmed the presence of FAP-positive cardiac fibroblasts of the HfpEF rat hearts, with a good correlation with FAPI PET. Thus, [18F]AlF-NOTA-FAPI-04 PET/CT is a promising and non-invasive method to assess the progression of fibrosis in HfpEF to facilitate the clinical management.
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Insuficiencia Cardíaca , Tomografía Computarizada por Tomografía de Emisión de Positrones , Ratas , Animales , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Insuficiencia Cardíaca/diagnóstico por imagen , Distribución Tisular , Volumen Sistólico , Fibroblastos , Radioisótopos de Galio , Tomografía de Emisión de Positrones/métodosRESUMEN
Background: Stewart-Treves Syndrome in Primary Limb Lymphedema (STS-PLE) is an extremely rare malignant tumor. A retrospective analysis was conducted to elucidate the relationship between magnetic resonance imaging (MRI) findings and signs compared to pathology. Methods: Seven patients with STS-PLE were enrolled at Beijing Shijitan Hospital, Capital Medical University, from June 2008 to March 2022. All cases were examined by MRI. The surgical specimens were subjected to histopathological and immunohistochemical staining for CD31, CD34, D2-40, and Ki-67. Results: There were two different types of MRI findings. One was mass shape (STS-PLE I type) in three male patients, and the other was the "trash ice" d sign (STS-PLE II type) observed in four female patients. The average duration of lymphedema (DL) of STS-PLE I type (18 months) was shorter than that of STS-PLE II type (31 months). The prognosis for the STS-PLE I type was worse than that for the STS-PLE II type. Regarding overall survival (OS), the STS-PLE I type (17.3 months) was three times shorter than that of the STS-PLE II type (54.5 months). For STS-PLE I type, the older the STS-PLE onset, the shorter the OS. However, there was no significant correlation in STS-PLE II type. MRI was compared to histological results to provide an explanation for the differences in MR signal changes, especially on T2WI. Against a background of dense tumor cells, the richer the lumen of immature vessels and clefts, the higher the T2WI MRI signal (taking muscle signal as the internal reference standard) and the worse the prognosis, and vice versa. We also found that younger patients with a lower Ki-67 index (<16%) had better OS, especially for the STS-PLE I type. Those with stronger positive expression of CD31 or CD34 had shorter OS. However, the expression of D2-40 was positive in nearly all cases, and seemed not to be associated with prognosis. Conclusions: In lymphedema, the richer the lumen of immature vessels and clefts based on dense tumor cells, the higher the T2WI signal on the MRI. In adolescent patients, the tumor often showed a "trash ice" sign (STS-PLE II-type) and prognosis was better than for the STS-PLE I type. While in middle-aged and older patients, tumors showed a mass shape (STS-PLE I type). The expression of immunohistochemical indicators (CD31, CD34, and KI-67) correlated with clinical prognosis, especially decreased Ki-67 expression. In this study, we determined it was possible to predict prognosis comparing MRI findings with pathological results.
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The phenomenon of foam-induced inactivation is a common challenge during foam fractionation of proteins. In this work, we attempted to use ultrasound to treat foam out of the foam fractionation column with the aim of minimizing the foam-induced protein inactivation using pepsin as a model protein. Firstly, the mechanisms by which ultrasound prevented the foam-induced pepsin inactivation during defoaming were explored. The results showed that ultrasound promoted the refolding of unfolded pepsin molecules at the gas-liquid interface to restore their activities during the desorption process from the interface and before dissolving into the foamate. Subsequently, the effects of ultrasonic power on the pepsin renaturation were analyzed, which revealed that the unfolding degree of pepsin in the foamate gradually decreased and then increased as the ultrasonic power increased. Correspondingly, the specific activity of pepsin in the foamate increased and then decreased. Finally, we explored the effects of defoaming efficiency, type of gas and pH. The results indicated that the decrease in defoaming efficiency and gas solubility in water facilitated the ultrasound-assisted pepsin renaturation in the pH range from 1.0 to 2.5. When air was applied in the foaming process, the specific activity of pepsin in the foamate with ultrasonic treatment was not significantly different from that in the feed solution at ultrasonic power of 400 W and pH 2.0. Collectively, these results indicate the ultrasonic treatment of foam effectively prevented the foam-induced pepsin inactivation.
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Fraccionamiento Químico , Pepsina A , Fraccionamiento Químico/métodos , Ultrasonido , Aerosoles , AguaRESUMEN
Venous cystic adventitial disease (VCAD) is a rare vascular anomaly located in the common femoral vein in most cases. We describe the case of a 59-year-old female patient with right leg edema who was misdiagnosed with deep vein thrombosis of the lower extremity at another hospital. Magnetic resonance angiography revealed a round mass in the popliteal vein, with a narrow lumen. Considering the location of the lesion, absence of a history of deep venous thrombosis and trauma, and clinical manifestations, the diagnosis is likely a popliteal vein adventitial cyst. Segmental popliteal vein resection and reconstruction were performed using a cylindrical great saphenous vein graft. No joint connection was found during the operation, and the postoperative pathology confirmed VCAD.
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Quistes , Enfermedades Vasculares , Femenino , Humanos , Persona de Mediana Edad , Vena Poplítea/diagnóstico por imagen , Vena Poplítea/cirugía , Quistes/diagnóstico por imagen , Quistes/cirugía , Resultado del Tratamiento , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/cirugía , Vena Femoral/diagnóstico por imagen , Vena Femoral/cirugía , Vena Femoral/patologíaRESUMEN
Anthocyanins are a class of antioxidants that scavenge free radicals in cells and play an important role in promoting human health and preventing many diseases. Here, we characterized a maize Bronze gene (BZ1) from the purple colored W22 introgression line, which encodes an anthocyanin 3-O-glucosyltransferase, a key enzyme in the anthocyanin synthesis pathway. Mutation of ZmBZ1 showed bronze-colored seeds and reduced anthocyanins in seeds aleurone layer, seedlings coleoptile, and stem of mature plants by comparison with purple colored W22 (WT). Furthermore, we proved that maize BZ1 is an aleurone layer-specific expressed protein and sub-located in cell nucleus. Real-time tracing of the anthocyanins in developing seeds demonstrated that the pigment was visible from 16 DAP (day after pollination) in field condition, and first deposited in the crown part then spread all over the seed. Additionally, it was transferred along with the embryo cell activity during seed germination, from aleurone layer to cotyledon and coleoptile, as confirmed by microscopy and real-time qRT-PCR. Finally, we demonstrated that the ZmBZ1 contributes to stress tolerance, especially salinity. Further study proved that ZmBZ1 participates in reactive oxygen scavenging (ROS) by accumulating anthocyanins, thereby enhancing the tolerance to abiotic stress.