Genome-based analysis of the family Paracoccaceae and description of Ostreiculturibacter nitratireducens gen. nov., sp. nov., isolated from an oyster farm on a tidal flat.

Two bacterial strains, designated FR2A1T and MT2-5-38, were isolated from the surface sediments of an oyster farm on a tidal flat in Quanzhou Bay, China. Both strains were Gram-stain-negative, rod-shaped, aerobic, catalase-positive, and oxidase-positive. The 16S rRNA gene sequences of the two strains were 100% identical and had the highest similarity (97.1%) with Phaeovulum vinaykumarii JA123T. The average nucleotide identity (ANI) value and digital DNA-DNA hybridization (DDH) value indicated that the two strains belonged to a single species. Gene annotation revealed that the two strains contained a gene cluster for nitrate reduction and a gene cluster for sulfur oxidation, indicating a possible role in N and S cycling in the tidal flat sediment. The phylogeny inferred from the 16S rRNA gene and 120 conserved proteins indicated that the two strains formed a distinct monophyletic clade within the family Paracoccaceae. The respiratory quinone was Q-10. The major fatty acids consisted of summed feature 8 (C18:1ω7c and/or C18:1ω6c) and C18:0. The polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, and several unidentified phospholipids. Based on the above characteristics, strains FR2A1T and MT2-5-38 represent a novel genus and a novel species, for which we propose the name Ostreiculturibacter nitratireducens gen. nov., sp. nov. The type strain is FR2A1T (=MCCC 1K08809T = KCTC 8317T). Phylogenomic analysis of 1,606 high-quality genomes of the family Paracoccaceae, including type strains, non-type strains, and uncultivated bacteria, was performed using the Genome Taxonomic Database Toolkit (GTDB-Tk), and the average amino acid identity (AAI) value of the phylogenetic clade was estimated. We found that 35 species of the family Paracoccaceae needed re-classification, and an AAI value of 70% was chosen as the genus boundary within the family Paracoccaceae.

Molecular Stratification and Treatment Monitoring of Lung Cancer Using a Small Extracellular Vesicle-Activated Nanocavity Architecture.

Development of molecular diagnostics for lung cancer stratification and monitoring is crucial for the rational planning and timely adjustment of treatments to improve clinical outcomes. In this regard, we propose a nanocavity architecture to sensitively profile the protein signature on small extracellular vesicles (sEVs) to enable accurate, noninvasive staging and treatment monitoring of lung cancer. The nanocavity architecture is formed by molecular recognition through the binding of sEVs with the nanobox-based core-shell surface-enhanced Raman scattering (SERS) barcodes and mirrorlike, asymmetric gold microelectrodes. By imposing an alternating current on the gold microelectrodes, a nanofluidic shear force was stimulated that supported the binding of sEVs and the efficient assembly of the nanoboxes. The binding of sEVs further induced a nanocavity between the nanobox and the gold microelectrode that significantly amplified the electromagnetic field to enable the simultaneous enhancement of Raman signals from four SERS barcodes and generate patient-specific molecular sEV signatures. Importantly, evaluated on a cohort of clinical samples (n = 76) on the nanocavity architecture, the acquired patient-specific sEV molecular signatures achieved accurate identification, stratification, and treatment monitoring of lung cancer patients, highlighting its potential for transition to clinical utility.

A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm with Orbital Tumor as the Initial Symptom.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. It is a rare and challenging clinical presentation. For decades, there has been no treatment course for managing BPDCN and its overall prognosis is poor. METHODS AND RESULTS: We report a 27-year-old man who was admitted to the hospital due to an orbital tumor as the first symptom. Progressive enlargement of the orbital tumor was accompanied by multiple purple circular nodules on the body trunk. Pathological confirmation of BPDCN after resection of the orbital mass. Bone marrow smear and flow cytometry on examination indicate AML-M5. Performance of chemotherapy and peripheral blood autologous stem cell transplantation. CONCLUSIONS: The clinical manifestations of blastic plasmacytoid dendritic cell neoplasms are diverse. The diagnosis of BPDCN can be difficult due to overlapping morphologic, immunophenotypic, and clinical features of other hematologic AML. Relapsed and refractory BPDCN remains an elusive therapeutic challenge. The future of new targeted therapeutic drugs is expected.

Cost-effective prognostic evaluation of breast cancer: using a STAR nomogram model based on routine blood tests.

Background: Breast cancer (BC) is the most common and prominent deadly disease among women. Predicting BC survival mainly relies on TNM staging, molecular profiling and imaging, hampered by subjectivity and expenses. This study aimed to establish an economical and reliable model using the most common preoperative routine blood tests (RT) data for survival and surveillance strategy management. Methods: We examined 2863 BC patients, dividing them into training and validation cohorts (7:3). We collected demographic features, pathomics characteristics and preoperative 24-item RT data. BC risk factors were identified through Cox regression, and a predictive nomogram was established. Its performance was assessed using C-index, area under curves (AUC), calibration curve and decision curve analysis. Kaplan-Meier curves stratified patients into different risk groups. We further compared the STAR model (utilizing HE and RT methodologies) with alternative nomograms grounded in molecular profiling (employing second-generation short-read sequencing methodologies) and imaging (utilizing PET-CT methodologies). Results: The STAR nomogram, incorporating subtype, TNM stage, age and preoperative RT data (LYM, LYM%, EOSO%, RDW-SD, P-LCR), achieved a C-index of 0.828 in the training cohort and impressive AUCs (0.847, 0.823 and 0.780) for 3-, 5- and 7-year OS rates, outperforming other nomograms. The validation cohort showed similar impressive results. The nomogram calculates a patient's total score by assigning values to each risk factor, higher scores indicating a poor prognosis. STAR promises potential cost savings by enabling less intensive surveillance in around 90% of BC patients. Compared to nomograms based on molecular profiling and imaging, STAR presents a more cost-effective, with potential savings of approximately $700-800 per breast cancer patient. Conclusion: Combining appropriate RT parameters, STAR nomogram could help in the detection of patient anemia, coagulation function, inflammation and immune status. Practical implementation of the STAR nomogram in a clinical setting is feasible, and its potential clinical impact lies in its ability to provide an early, economical and reliable tool for survival prediction and surveillance strategy management. However, our model still has limitations and requires external data validation. In subsequent studies, we plan to mitigate the potential impact on model robustness by further updating and adjusting the data and model.

Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle.

Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with minimal side effects in deep-seated tumors remains challenging. Herein, we introduce a novel self-assembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105 (λem = 1105 nm), as a first example of a Ru(II) supramolecular ICD inducer. Ru1105 synergistically potentiates immunomodulatory responses and reduces adverse effects in deep-seated tumors through multiple regulated approaches, including NIR-light excitation, increased reactive oxygen species (ROS) generation, selective targeting of tumor cells, precision organelle localization, and improved tumor penetration/retention capabilities. Specifically, Ru1105 demonstrates excellent depth-activated ROS production (∼1 cm), strong resistance to diffusion, and anti-ROS quenching. Moreover, Ru1105 exhibits promising results in cellular uptake and ROS generation in cancer cells and multicellular tumor spheroids. Importantly, Ru1105 induces more efficient ICD in an ultralow dose (10 µM) compared to the conventional anticancer agent, oxaliplatin (300 µM). In vivo experiments further confirm Ru1105's potency as an ICD inducer, eliciting CD8+ T cell responses and depleting Foxp3+ T cells with minimal adverse effects. Our research lays the foundation for the design of secure and exceptionally potent metal-based ICD agents in immunotherapy.

Amide Proton Transfer-Weighted MRI and Diffusion-Weighted Imaging in Bladder Cancer: A Complementary Tool to the VI-RADS.

RATIONALE AND OBJECTIVES: To investigate the feasibility of amide proton transfer-weighted (APTw) and diffusion-weighted Magnetic Resonance Imaging (MRI) as a means by which to add value to the Vesical Imaging Reporting and Data System (VI-RADS) for discriminating muscle invasive bladder cancer (MIBC) from nonmuscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: This prospective study enrolled participants with pathologically confirmed bladder cancer (BCa) who underwent preoperative multiparametric MRI, including APTw and diffusion-weighted MRI, from July 2020 to January 2023. The exclusion criteria were lesions smaller than 10 mm, missing smooth muscle layer in the operation specimen, neoadjuvant therapy before MRI, inadequate image quality, and malignancy other than urothelial neoplasm. Two radiologists independently assigned the VI-RADS score for each participant. Quantitative parameters derived from APTw and diffusion-weighted MRI were obtained by another two radiologists. Receiver operating characteristic (ROC) curve analysis with the area under the ROC curve (AUC) was performed to evaluate the diagnostic performances of quantitative parameters for discriminating BCa detrusor muscle invasion status. RESULTS: A total of 106 participants were enrolled (mean age, 64 ± 12 years [SD]; 90 men): 32 with MIBC and 74 with NMIBC. Lower apparent diffusion coefficient (ADC) values (0.88 × 10-3 mm2/s ± 0.12 vs. 1.08 × 10-3 mm2/s ± 0.25; P < 0.001) and higher APTw values (6.89% [interquartile range {IQR}, 5.05%-12.17%] vs. 3.61% [IQR, 2.23%-6.83%]; P < 0.001) were observed in the MIBC group. Compared to VI-RADS alone, both APTw (P = 0.003) and ADC (P = 0.020) values could improve the diagnostic performance of VI-RADS in differentiating MIBC from NMIBC. The combination of the three yielded the highest diagnostic performance (AUC, 0.93; 95% CI:0.87,0.97) for evaluating muscle invasion status. The addition of the APTw values to the combination of VI-RADS and ADC values notably improved the diagnostic performance for differentiating NMIBC from MIBC (VI-RADS+ADC vs. VI-RADS+APTw+ADC, P = 0.046). CONCLUSION: MRI parameters derived from APTw and diffusion-weighted MRI can be used to accurately assess muscle invasion status in BCa and provide additional value to VI-RADS.

Natural killer cell-related prognosis signature predicts immune response in colon cancer patients.

Background: Natural killer (NK) cells are crucial components of the innate immune system that fight tumors and viral infections. Patients with colorectal cancer (CRC) have a poor prognosis, and immunotherapeutic tools play a key role in the treatment of CRC. Methods: Public data on CRC patients was collected from the TCGA and the GEO databases. Tissue data of CRC patients were collected from Guangxi Medical University Affiliated Cancer Hospital. An NK-related prognostic model was developed by the least absolute shrinkage and selection operator (LASSO) and Cox regression method. Validation data were collected from different clinical subgroups and an external independent validation cohort to verify the model's accuracy. In addition, multiple external independent immunotherapy datasets were collected to further examine the value of NK-related risk scores (NKRS) in the prediction of immunotherapy response. Potential biological functions of key genes were examined by methods of cell proliferation, apoptosis and Western blotting. Results: A novel prognostic model for CRC patients based on NK-related genes was developed and NKRS was generated. There was a significantly poorer prognosis among the high-NKRS group. Based on immune response prediction, patients with low NKRS may be more suitable for immunotherapy and they are more sensitive to immunotherapy. The proliferation rate of CRC cells was significantly reduced and apoptosis of CRC cells was increased after SLC2A3 was knocked down. SLC2A3 was also found to be associated with the TGF-ß signaling pathway. Conclusion: NKRS has potential applications for predicting prognostic status and response to immunotherapy in CRC patients. SLC2A3 has potential as a therapeutic target for CRC.

Potential clinical feasibility of synthetic MRI in bladder tumors: a comparative study with conventional MRI.

Background: Synthetic magnetic resonance imaging (MRI) can provide quantitative information about inherent tissue properties and synthesize tailored contrast-weighted images simultaneously in a single scan. This study aimed to investigate the clinical feasibility of synthetic MRI in bladder tumors. Methods: A total of 47 patients (37 males; mean age: 66±10 years old) with postoperative pathology-confirmed papillary urothelial neoplasms of the bladder were enrolled in this retrospective study. A 2-dimensional (2D) multi-dynamic multi-echo pulse sequence was performed for synthetic MRI at 3T. The overall image quality, lesion conspicuity, contrast resolution, resolution of subtle anatomic structures, motion artifact, blurring, and graininess of images were subjectively evaluated by 2 radiologists independently using a 5-point Likert scale for qualitative analysis. The signal intensity ratio (SIR), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured for quantitative analysis. Linear weighted Kappa, Wilcoxon's signed-rank test, and the Mann-Whitney U-test were used for statistical analysis. Results: The interobserver consistency was excellent (κ values: 0.607-1). Synthetic T1-weighted (syn-T1w) and synthetic T2-weighted (syn-T2w) images obtained scores of 4 in most subjective terms, which were relatively smaller than those of conventional images. The SIR and SNR of syn-T1w were significantly higher than those of con-T1w images (SIR 2.37±0.86 vs. 1.47±0.20, P<0.001; SNR 21.83±9.43 vs. 14.81±3.30, P<0.001). No difference was found in SIR between syn-T2w and conventional T2-weighted (con-T2w) images, whereas the SNR of the syn-T2w was significantly lower (8.79±4.06 vs. 26.49±6.80, P<0.001). Additionally, the CNR of synthetic images was significantly lower than that of conventional images (T1w 1.41±0.72 vs. 2.68±1.04; T2w 1.40±0.87 vs. 4.03±1.55, all P<0.001). Conclusions: Synthetic MRI generates morphologic magnetic resonance (MR) images with diagnostically acceptable image quality in bladder tumors, especially T1-weighted images with high image contrast of tumors relative to urine. Further technological improvements are needed for synthetic MRI to reduce noise. Combined with T1, T2, and proton density (PD) quantitative data, synthetic MRI has potential for clinical application in bladder tumors.

Harnessing dual-energy CT for glycogen quantification: a phantom analysis.

Background: Non-invasive glycogen quantification in vivo could provide crucial information on biological processes for glycogen storage disorder. Using dual-energy computed tomography (DECT), this study aimed to assess the viability of quantifying glycogen content in vitro. Methods: A fast kilovolt-peak switching DECT was used to scan a phantom containing 33 cylinders with different proportions of glycogen and iodine mixture at varying doses. The virtual glycogen concentration (VGC) was then measured using material composition images. Additionally, the correlations between VGC and nominal glycogen concentration (NGC) were evaluated using least-square linear regression, then the calibration curve was constructed. Quantitative estimation was performed by calculating the linearity, conversion factor (inverse of curve slope), stability, sensitivity (limit of detection/limit of quantification), repeatability (inter-class correlation coefficient), and variability (coefficient of variation). Results: In all conditions, excellent linear relationship between VGC and NGC were observed (P<0.001, coefficient of determination: 0.989-0.997; residual root-mean-square error of glycogen: 1.862-3.267 mg/mL). The estimated conversion factor from VGC to NGC was 3.068-3.222. In addition, no significant differences in curve slope were observed among different dose levels and iodine densities. The limit of detection and limit of quantification had respective ranges of 6.421-15.315 and 10.95-16.46 mg/mL. The data demonstrated excellent scan-repeat scan agreement (inter-class correlation coefficient, 0.977-0.991) and small variation (coefficient of variation, 0.1-0.2%). Conclusions: The pilot phantom analysis demonstrated the feasibility and efficacy of detecting and quantifying glycogen using DECT and provided good quantitative performance with significant stability and reproducibility/variability. Thus, in the future, DECT could be used as a convenient method for glycogen quantification to provide more reliable information for clinical decision-making.

The association of serum IL-33/ST2 expression with hepatocellular carcinoma.

BACKGROUND: IL-33 is a multifunctional cytokine with dual functions. However, the clinicopathological and prognostic significance of IL-33 in cancer patients, especially in patients with hepatocellular carcinoma (HCC), remains controversial. Therefore, we conducted a study of 565 patients with HCC and 561 healthy controls and performed a meta-analysis to quantitatively evaluate the above problems. METHODS: We collected blood from 565 patients with HCC and 561 healthy controls. ELISA was used to detect the concentrations of IL-33 and ST2 in the serum, and RT‒PCR was used to detect the levels of IL-33 and ST2 mRNA. Meanwhile, we collected comprehensive literature on IL-33 and the clinical characteristics of cancer patients retrieved from the PubMed, Web of Science and CNKI databases as of December 2022. An odds ratio (OR) with a 95% confidence interval (CI) was used to estimate the impact through overall and stratified analyses. RESULTS: Compared with the healthy control group, the levels of ST2 mRNA and serum in the peripheral blood of HCC patients increased (p < 0.05), while the levels of IL-33 mRNA and serum showed no significant difference between the two groups (p > 0.05). In the meta-analysis section, at the tissue level, the overall analysis showed that the expression of IL-33 was positively correlated with tumor stage, histological grade, distant metastasis, and tumor size. Compared with patients with low IL-33 expression, the 3-year overall survival (OS) rate (OR = 3.467, p < 0.001) and 5-year OS rate (OR = 2.784, p < 0.001) of patients with high IL-33 expression were lower. At the serum expression level, the overall analysis showed that the expression of IL-33 increased the risk of cancer, and the serum level of IL-33 was positively correlated with tumor stage and vascular invasion. CONCLUSION: IL-33/ST2 is a useful predictive or prognostic biomarker in clinical evaluation and may be used as a potential therapeutic target, but much research is needed to verify this hypothesis.

Recent developments in carbon dots: a biomedical application perspective.

Recently, newly developed carbon-based nanomaterials known as carbon dots (CDs) have generated significant interest in nanomedicine. However, current knowledge regarding CD research in the biomedical field is still lacking. An overview of the most recent development of CDs in biomedical research is given in this review article. Several crucial CD applications, such as biosensing, bioimaging, cancer therapy, and antibacterial applications, are highlighted. Finally, CD-based biomedicine's challenges and future potential are also highlighted to enrich biomedical researchers' knowledge about the potential of CDs and the need for overcoming various technical obstacles.

Colorectal Cancer Cell Differentiation Trajectory Predicts Patient Immunotherapy Response and Prognosis.

OBJECTIVES: This study aimed to investigate the differentiation state and clinical significance of colorectal cancer cells, as well as to predict the immune response and prognosis of patients based on differentiation-related genes of colorectal cancer. INTRODUCTION: Colorectal cancer cells exhibit different differentiation states under the influence of the tumor microenvironment, which determines the cell fates. METHODS: We combined single-cell sequencing (scRNA-seq) data from The Cancer Genome Atlas source with extensive transcriptome data from the Gene Expression Omnibus database. We obtained colorectal cancer differentiation-related genes using cell trajectory analysis and developed a colorectal cancer differentiation-related gene based molecular typing and prognostic model to predict the immune response and prognosis of patients with colorectal cancer. RESULTS: We identified 5 distinct cell differentiation subsets and 620 colorectal cancer differentiation-related genes. Colorectal cancer differentiation-related genes were significantly associated with metabolism, angiogenesis, and immunity. We separated patients into 3 subtypes based on colorectal cancer differentiation-related gene expression in the tumor and found differences among the different subtypes in immune infiltration status, immune checkpoint gene expression, clinicopathological features, and overall survival. Immunotherapeutic interventions involving a highly expressed immune checkpoint blockade may be selectively effective in the corresponding cancer subtypes. We built a risk score prediction model (5-year AUC: .729) consisting of the 4 most important predictors of survival (TIMP1, MMP1, LGALS4, and ITLN1). Finally, we generated and validated a nomogram consisting of the risk score and clinicopathological variables. CONCLUSION: This study highlights the significance of genes involved in cell differentiation for clinical prognosis and immunotherapy in patients and provides prospective therapeutic targets for colorectal cancer.

Determining the effects of tencha-ro drying on key volatile compounds in tencha (Camellia sinensis) through gas chromatography-mass spectrometry.

Drying is the key process through which the aroma of tencha forms. However, the effects of drying method on volatiles are unknown. We compared tencha-ro drying with regular drying. Volatiles in tencha infusions were extracted using headspace solid-phase microextraction and solvent-assisted flavor evaporation combined with gas chromatography-mass spectrometry. Partial least squares (PLS), odor activity value (OAV), and heat map analyses were performed to identify the optimal drying method for creating a seaweed-like aroma. Changes in the key volatile compounds of the samples were investigated. The tencha infusions contained 125 volatiles with nine chemical structures. According to the sensory evaluation, tencha-ro drying was the optimal method for producing high-quality tencha with an intense and consistent seaweed-like aroma. The PLS model accurately distinguished among the types of tencha. By combining OAVs with screening through multivariate statistical analysis, six volatile compounds were revealed to contribute substantially to tencha's seaweed-like aroma: 2-ethyl-3,5-dimethylpyrazine, 2-ethyl-6-methylpyrazine, 2-ethyl-5-methylpyrazine, dimethyl sulfide, ß-ionone, and 2-formyl-1-methylpyrrole. The findings provide a theoretical basis and technical guidance for the processing of high-quality tencha with a strong seaweed-like aroma. PRACTICAL APPLICATION: This study demonstrated that tencha-ro drying contributes to the formation of a seaweed-like aroma in tencha and provides theoretical guidance for tea factories to use the appropriate drying methods for high-quality tencha.

Multiparametric MRI Evaluation of VI-RADS for Bladder Tumors Located at the Ureteral Orifice.

Background The Vesical Imaging Reporting and Data System (VI-RADS) based on multiparametric MRI scans standardizes preoperative bladder cancer staging. However, limitations have been reported for VI-RADS, particularly for ureteral orifice tumors. Purpose To investigate the diagnostic performance and interobserver agreement of VI-RADS in evaluating muscle invasion for bladder tumors located at the ureteral orifice. Materials and Methods In this retrospective study, patients with histopathologically confirmed bladder cancer occurring at the ureteral orifice from January 2012 to November 2021 were analyzed. Two blinded radiologists independently scored multiparametric MRI scans according to VI-RADS. Interobserver agreement of the VI-RADS scores was evaluated with weighted κ analysis. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of the VI-RADS scores in the prediction of muscle invasion. Results A total of 78 patients (mean age, 67 years ± 7 [SD]; age range, 46-90 years; 67 men) were included in the final analysis: 25 with non-muscle-invasive bladder cancer and 53 with muscle-invasive bladder cancer (MIBCa). At consensus reading, one (1%) case was scored as VI-RADS 1, 27 cases (35%) were scored as VI-RADS 2, six (8%) were scored as VI-RADS 3, 10 (13%) were scored as VI-RADS 4, and 34 (44%) were scored as VI-RADS 5. On comparison of the VI-RADS score with histopathologic findings, it was confirmed that the presence of muscle invasion was 0% (zero of one) for VI-RADS 1, 15% (four of 27) for VI-RADS 2, 83% (five of six) for VI-RADS 3, 100% (10 of 10) for VI-RADS 4, and 100% (34 of 34) for VI-RADS 5. The area under the receiver operating characteristic curve of VI-RADS in the detection of MIBCa was 0.96 (95% CI: 0.92, 1.00). Conclusion The Vesical Imaging Reporting and Data System could be used to accurately predict muscle invasion for bladder tumors occurring at the ureteral orifice. © RSNA, 2022 Online supplemental material is available for this article.

Amide Proton Transfer-weighted MRI in Predicting Histologic Grade of Bladder Cancer.

Background Bladder cancer is classified into high and low grades with different clinical treatments and prognoses. Thus, accurate preoperative evaluation of the histologic grade through imaging techniques is essential. Purpose To investigate the potential of amide proton transfer-weighted (APTw) MRI in evaluating the grade of bladder cancer and to evaluate whether APTw MRI can add value to diffusion-weighted imaging (DWI) at MRI. Materials and Methods In this single-center prospective study, participants with pathologic analysis-confirmed bladder cancer with no previous treatment, lesions larger than 10 mm, and adequate MRI quality were enrolled from July 2020 to September 2021 in a university teaching hospital. All participants underwent preoperative multiparametric MRI, including APTw MRI and DWI. The mean APTw and apparent diffusion coefficient (ADC) values of the primary tumor were measured independently by two radiologists. Receiver operating characteristic curves were generated to evaluate the diagnostic performance of these quantitative parameters. Results In total, 83 participants (mean age, 64 years ± 13 [SD]; 72 men) were evaluated: 51 with high-grade and 32 with low-grade bladder cancer. High-grade bladder cancer showed higher APTw values (6% [IQR, 4%-12%] vs 2% [IQR, 1%-3%]; P < .001) and lower ADC values (0.92 × 10-3 mm2/sec ± 0.17 vs 1.21 × 10-3 mm2/sec ± 0.25; P < .001) than low-grade bladder cancer. The area under the receiver operating characteristic curve (AUC) of APTw and ADC for differentiating low- and high-grade bladder cancer was similar (0.84 for both; P = .94). Moreover, the combination of the two techniques improved the diagnostic performance (AUC, 0.93; all P = .01). Conclusion The combination of amide proton transfer-weighted and diffusion-weighted MRI has the potential to improve the histologic characterization of bladder cancer by differentiating low- from high-grade cancers. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Milot in this issue. An earlier incorrect version appeared online. This article was corrected on July 7, 2022.

Investigation of Synthetic Magnetic Resonance Imaging Applied in the Evaluation of the Tumor Grade of Bladder Cancer.

BACKGROUND: The histological grade of bladder cancer (BCa) is an important factor associated with the treatment and prognosis. However, accurate determination of the preoperative histological grade of BCa remains a challenge. PURPOSE: To investigate the diagnostic potential of synthetic MRI (SyMRI) in evaluating the histological grade of BCa. STUDY TYPE: Prospective. SUBJECTS: Sixty patients (48 men and 12 women; mean age, 65 ± 11 years) with pathologically confirmed BCa (33 with high-grade BCa and 27 with low-grade BCa) were enrolled. FIELD STRENGTH/SEQUENCE: Diffusion-weighted imaging (DWI) acquired by a single-shot echo-planar sequence and SyMRI acquired by a multidynamic multiecho (MDME) sequence at 3.0 T. ASSESSMENT: Preoperative quantitative longitudinal relaxation time (T1 ), transverse relaxation time (T2 ), proton density (PD), and apparent diffusion coefficient (ADC) values of BCa were independently measured by two radiologists. STATISTICAL TESTS: Interclass correlation coefficient (ICC), independent sample t-test, Mann-Whitney U test, Delong test, and receiver operating characteristic curve (ROC) analysis were used. RESULTS: Significant differences were found in the mean of all the T1 , T2 , PD, and ADC values between high- and low-grade BCa. The best diagnostic performance was found for the mean ADC value with an area under the ROC curve (AUC) of 0.869, while the AUC values of the mean PD, T1 , and T2 values were 0.755, 0.740, and 0.723, respectively. DATA CONCLUSION: SyMRI may be a potential noninvasive technique for evaluating the histological grade of BCa. However, the overall diagnostic performance of SyMRI-derived parameters was inferior to the ADC value. LEVELS OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

CD44, IL-33, and ST2 Gene Polymorphisms on Hepatocellular Carcinoma Susceptibility in the Chinese Population.

The interleukin- (IL-) 33/ST2 axis plays a pivotal role in tumorigenesis through influencing cancer stemness and other mechanisms. CD44 is one of the critical markers of hepatocellular carcinoma (HCC) among the cancer stem cells (CSCs). There is still a lack of CD44 gene single-nucleotide polymorphisms (SNPs) combined with IL-33/ST2 pathway single-nucleotide polymorphisms in HCC susceptibility analysis literature, although CD44 and IL-33/ST2 have been reported separately in human cancers. This study is aimed at investigating the relationship between CD44, IL-33, and ST2 SNPs and HCC susceptibility and clinicopathological features. We analyzed 565 HCC patients and 561 healthy controls in the Chinese population. The genes for CD44rs187115A>G, IL-33 rs1929992A>G, and ST2 rs3821204G>C were typed using the SNaPshot method. We found that the distribution frequencies of CD44 and ST2 alleles and genotypes in both the HCC case group and the control group were statistically significant (p < 0.05). The results showed that individuals carrying at least one G allele of the CD44 rs187115 gene were at a higher risk than the AA genotype carriers (p = 0.007, odds ratio (OR) = 1.429, 95% confidence interval (CI): 1.102-1.854). Similarly, individuals with at least one C allele of ST2 rs3821204 had a higher risk of HCC than those with GG genes (p ≤ 0.001, OR = 1.647, 95% CI: 1.296-2.093). Combining the haplotype analysis of the 3 loci suggested that CD44 rs187115, IL-33 rs1929992, and ST2 rs3821204 are associated with the risk of HCC and could potentially serve as useful genetic markers for HCC in some populations of China.

Aluminum-induced "mixed" cell death in mice cerebral tissue and potential intervention.

The brain is one of organs vulnerable to aluminum insult. Aluminum toxicity is involved in neurobehavioral deficit, neuronal cell dysfunction, and death. The aim of this study are as follows: (1) to evaluate the repairing efficiency of Necrostatin-1 (Nec-1), a cell death inhibitor, and Z-VAD-FMK, a pan-caspase inhibitor, on Al-induced neurobehavioral deficit and neuronal cell death, in order to evidence the cell death inducing ability of aluminum, and (2) to primarily explore the possibility of treating neuronal cell loss-related disease, such as Alzheimer's disease, with Nec-1 and Z-VAD in Al-induced dementia animal model. We found Nec-1 and Z-VAD-FMK alone or in combination could reduce aluminum-induced learning and memory impairment in mice. Pathohistological results indicated that Nec-1 and Z-VAD-FMK can decrease Al-induced neuronal death cell. In addition, some cell death-associated proteins in cell death signal pathway were inhibited by Nec-1 and Z-VAD-FMK in Al-exposed mice. In conclusions, Nec-1 and Z-VAD-FMK can repair the injury of learning and memory induced by aluminum in mice. Furthermore, Nec-1 was more obvious to repair the injury of learning and memory function compared with Z-VAD-FMK. Nec-1 and Z-VAD-FMK can repair the Al-induced morphological injury of cell and reduce the amounts of dead cell, and repairing effects were more significant at higher doses. The effect of Nec-1 was stronger than Z-VAD-FMK, though their mechanism was different. The combination of them had the strongest effect. Our study evidenced Al-induced neuronal necroptosis and apoptosis existing in animal model and suggested potential therapeutic effects of Nec-1 and Z-VAD-FMK on neuronal cell death in neurodegenerative diseases.

The Association between PON1 (Q192R and L55M) Gene Polymorphisms and Risk of Cancer: A Meta-Analysis Based on 43 Studies.

Q192R and L55M polymorphism were considered to be associated with the development of multiple cancers. Nevertheless, the results of these researches were inconclusive and controversial. Therefore, we conducted a meta-analysis of all eligible case-control studies to assess the association between PON1 (Q192R and L55M) gene polymorphisms and risk of cancer. With the STATA 14.0 software, we evaluated the strength of the association by using the odds ratios (ORs) and 95% confidence intervals (CIs). A total of 43 case-control publications 19887 cases and 23842 controls were employed in our study. In all genetic models, a significant association between PON1-L55M polymorphisms and overall cancer risk was observed. Moreover, in the stratified analyses by cancer type, polymorphism of PON1-L55M played a risk factor in the occurrence of breast cancer, hematologic cancer, and prostate cancer. Similarly, an increased risk was observed in the Caucasian and Asian population as well as hospital-based group and population-based group. For PON1-Q192R polymorphisms, in the stratified analyses by cancer type, PON1-Q192R allele was associated with reduced cancer risks in breast cancer. Furthermore, for racial stratification, there was a reduced risk of cancer in recession model in Caucasian population. Similarly, in the stratification analysis of control source, the overall risk of cancer was reduced in the heterozygote comparison and dominant model in the population-based group. In conclusion, PON1-Q192R allele decreased the cancer risk especially breast cancer; there was an association between PON1-L55M allele and increased overall cancer risk. However, we need a larger sample size, well-designed in future and at protein levels to confirm these findings.