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.

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.

Amide Proton Transfer-Weighted Imaging in Assessing the Aggressive and Proliferative Potential of Bladder Cancer.

BACKGROUND: Ki-67 and human epidermal growth factor receptor 2 (HER2) are known oncogenes involved in bladder cancer (BCa) patient risk stratification. Preoperative assessment of their expression level can assist in clinical treatment decision-making. Recently, amide proton transfer-weighted (APTw) MRI has shown promising potential in the diagnosis of several malignancies. However, few studies reported the value of APTw imaging in evaluating Ki-67 and HER2 status of BCa. PURPOSE: To investigate the feasibility of APTw MRI in assessing the aggressive and proliferative potential regarding the expression levels of Ki-67 and HER2 in BCa. STUDY TYPE: Retrospective. SUBJECTS: 114 patients (mean age, 64.78 ± 11.93 [SD] years; 97 men) were studied. FIELD STRENGTH/SEQUENCE: APTw MRI acquired by a three-dimensional fast-spin-echo sequence at 3.0 T MRI system. ASSESSMENT: Patient pathologic findings, included histologic grade and the expression status of Ki-67 and HER2, were reviewed by one uropathologist. The APTw values of BCa were independently measured by two radiologists and were compared between high-/low-tumor grade group, high-/low-Ki-67 expression group, and high-/low-HER2 expression group. STATISTICAL TESTS: The interclass correlation coefficient, independent sample t-test, Mann-Whitney U test, Spearman's rank correlation, and receiver operating characteristic curve (ROC) analysis were used. P < 0.05 was considered statistically significant. RESULTS: Significantly higher APTw values were found in high-grade BCa patients (7.72% vs. 4.29%, P < 0.001), high-Ki-67 expression BCa patients (8.40% vs. 3.25%, P < 0.001) and HER2 positive BCa patients (8.24% vs. 5.40%, P = 0.001). APTw values were positively correlated with Ki-67 (r = 0.769) and HER2 (r = 0. 356) expression status. The area under the ROC curve of the APTw values for detecting Ki-67 and HER2 expression status were 0.883 (95% CI: 0.790-0.945) and 0.713 (95% CI: 0.592-0.816), respectively. DATA CONCLUSIONS: APTw MRI is a potential method to assess the biological and proliferation potential of BCa. TECHNICAL EFFICACY: Stage 2.

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.

A NIR-Light-Activated and Lysosomal-Targeted Pt(II) Metallacycle for Highly Potent Evoking of Immunogenic Cell Death that Potentiates Cancer Immunotherapy of Deep-Seated Tumors.

Though platinum (Pt)-based complexes have been recently exploited as immunogenic cell death (ICD) inducers for activating immunotherapy, the effective activation of sufficient immune responses with minimal side effects in deep-seated tumors remains a formidable challenge. Herein, we propose the first example of a near-infrared (NIR) light-activated and lysosomal targeted Pt(II) metallacycle (1) as a supramolecular ICD inducer. 1 synergistically potentiates immunomodulatory response in deep-seated tumors via multiple-regulated approaches, involving NIR light excitation, boosted reactive oxygen species (ROS) generation, good selectivity between normal and tumor cells, and enhanced tumor penetration/retention capabilities. Specifically, 1 has excellent depth-activated ROS production (~7 mm), accompanied by strong anti-diffusion and anti-ROS quenching ability. In vitro experiments demonstrate that 1 exhibits significant cellular uptake and ROS generation in tumor cells as well as respective multicellular tumor spheroids. Based on these advantages, 1 induces a more efficient ICD in an ultralow dose (i.e., 5 µM) compared with the clinical ICD inducer-oxaliplatin (300 µM). In vivo, vaccination experiments further demonstrate that 1 serves as a potent ICD inducer through eliciting CD8+/CD4+ T cell response and Foxp3+ T cell depletion with negligible adverse effects. This study pioneers a promising avenue for safe and effective metal-based ICD agents in immunotherapy.

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.

Tacrolimus improved the pregnancy outcomes of patients with refractory recurrent spontaneous abortion and immune bias disorders: a randomized controlled trial.

OBJECTIVE: To investigate the effect of tacrolimus treatment on refractory recurrent spontaneous abortion (RSA) patients with elevated serum IL-33/ST2 levels. METHODS: This study was a randomized controlled trial (RCT) of refractory RSA patients with elevated peripheral blood IL-33/ST2 levels or an elevated Th1/Th2 cell ratio. A total of 149 women were enrolled, each of whom had had at least 3 serial miscarriages and was confirmed to have elevated peripheral blood IL-33/ST2 levels or an elevated Th1/Th2 cell ratio. These women were randomly divided into two groups. The tacrolimus group (n = 75) received basic therapy with the addition of tacrolimus (Prograf). Tacrolimus was administered at a dose of 0.05 ~ 0.1 mg/kg/day from the end of the menstrual period to the beginning of the next menstrual period or to the 10th week of pregnancy. In contrast, basic therapy with the addition of placebo was given to the placebo group (n = 74). The main study outcome was the delivery of healthy newborns without deformities. RESULTS: A total of 60 (80.00%) patients in the tacrolimus group and 47 (63.51%) patients in the placebo group delivered healthy newborns [P = 0.03, odds ratio = 2.30; 95% confidence interval (1.10 ~ 4.81)]. The peripheral blood IL-33/ST2 levels and Th1/Th2 cell ratio of the tacrolimus group were much lower than those of the placebo group (P < 0.05). CONCLUSION: We validated our previous finding that serum IL-33 and sST2 concentrations are related to RSA. Immunosuppressive treatment with tacrolimus was demonstrated to be a promising method to treat refractory RSA with immune bias disorders.

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.

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.

Chemical Constituent Analysis of Ranunculus sceleratus L. Using Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole-Orbitrap High-Resolution Mass Spectrometry.

Ranunculus sceleratus L.(RS) has shown various pharmacological effects in traditional Chinese medicine. In our previous study, the positive therapeutic effect on α-naphthylisothiocyanate induced intrahepatic cholestasis in rats was obtained using TianJiu treatment with fresh RS. However, the chemical profile of RS has not been clearly clarified, which impedes the research progress on the therapeutic effect of RS. Herein, an ultra-high performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) method was developed to rapidly separate and identify multiple constituents in the 80% methanol extract of RS. A total of sixty-nine compounds (19 flavonoids, 22 organic acids, 6 coumarins, 4 lignans, 14 nitrogenous compounds, and 4 anthraquinones) were successfully characterized. A total of 12 of these compounds were unambiguously identified by standard samples. Their mass spectrometric fragmentation pathways were investigated. It is worth noting that flavonoids and lignans were identified for the first time in RS. In this study, we successfully provide the first comprehensive report on identifying major chemical constituents in RS by UHPLC-Q-Orbitrap HRMS. The obtained results enrich the RS chemical profile, paving the way for further phytochemical study, quality control, and pharmacological investigation of RS.

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.

The protective impact of education on brain structure and function in Alzheimer's disease.

BACKGROUND: The Cognitive Reserve (CR) theory posits that brains with higher reserve can cope with more cerebral damage to minimize clinical manifestations. The aim of this study was to examine the effect of education (CR proxy) on brain structure and function in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients and in cognitively healthy elderly (HC) individuals. METHODS: Fifty-seven AD patients, 57 aMCI patients and 48 HCs were included to investigate the relationships between education years and gray matter volume (GMV), regional homogeneity (ReHo) and functional connectivity (FC) in brain regions to show associations with both structure and function. Taking the severity of the disease into account, we further assessed the relationships in AD stratified analyses. RESULTS: In AD group, the GMV of the dorsal anterior cingulate cortex (dACC) and ReHo in the left inferior temporal cortex (ITC) were inversely associated with education years, after adjustment for age, sex, Mini-Mental State Examination (MMSE), and total intracranial volume or head motion parameters. Seed-based FC analyses revealed that education years were negatively correlated with the FC between the left anterior ITC and left mid frontal cortex as well as right superior frontal cortex and right angular gyrus. Stratified analyses results indicated that this negative relation between education and GMV, ReHo, FC was mainly present in mild AD, which was attenuated in moderate AD and aMCI groups. CONCLUSIONS: Our results support the CR theory, and suggest that CR may be protective against AD related brain pathology at the early stage of clinical dementia. These findings could provide the locus of CR-related functional brain mechanisms and a specific time-window for therapeutic interventions to help AD patients to cope better with the brain pathological damage by increasing CR.

MoCpa1-mediated arginine biosynthesis is crucial for fungal growth, conidiation, and plant infection of Magnaporthe oryzae.

Arginine is an important amino acid involved in processes such as cell signal transduction, protein synthesis, and sexual reproduction. To understand the biological roles of arginine biosynthesis in pathogenic fungi, we used Cpa1, the carbamoyl phosphate synthase arginine-specific small chain subunit in Saccharomyces cerevisiae as a query to identify its ortholog in the Magnaporthe oryzae genome and named it MoCpa1. MoCpa1 is a 471-amino acid protein containing a CPSase_sm_chain domain and a GATase domain. MoCpa1 transcripts were highly expressed at the conidiation, early-infection, and late-infection stages of the fungus. Targeted deletion of the MoCPA1 gene resulted in a ΔMocpa1 mutant exhibiting arginine auxotrophy on minimum culture medium (MM), confirming its role in de novo arginine biosynthesis. The ΔMocpa1 mutant presented significantly decreased sporulation with some of its conidia being defective in morphology. Furthermore, the ΔMocpa1 mutant was nonpathogenic on rice and barley leaves, which was a result of defects in appressorium-mediated penetration and restricted invasive hyphal growth within host cells. Addition of exogenous arginine partially rescued conidiation and pathogenicity defects on the barley and rice leaves, while introduction of the MoCPA1 gene into the ΔMocpa1 mutant fully complemented the lost phenotype. Further confocal microscopy examination revealed that MoCpa1 is localized in the mitochondria. In summary, our results demonstrate that MoCpa1-mediated arginine biosynthesis is crucial for fungal development, conidiation, appressorium formation, and infection-related morphogenesis in M. oryzae, thus serving as an attractive target for mitigating obstinate fungal plant pathogens. KEY POINTS: • MoCpa1 is important for aerial hyphal growth and arginine biosynthesis. • MoCpa1 is pivotal for conidial morphogenesis and appressorium formation. • MoCpa1 is crucial for full virulence in M. oryzae.

Clinicopathological and Prognostic Significance of Cancer Stem Cell Markers in Ovarian Cancer Patients: Evidence from 52 Studies.

BACKGROUND/AIMS: Relevant markers of cancer stem cells (CSCs) may serve as commonly used biomarkers of ovarian cancer (OC). However, their actual clinicopathological and prognostic significance remains inconclusive. Thus, we conducted a meta-analysis to quantitatively evaluate the association between the expression of CSC-relevant markers (ALDH1, CD117, CD133, and CD44) and OC. METHODS: We used an odds ratio (OR) and a hazard ratio (HR) with a 95% confidence interval (CI) to estimate the effects by analyzing 52 studies from a literature search. Heterogeneity and sensitivity were evaluated, as well. Publication bias was assessed using funnel plots and Egger tests. RESULTS: ALDH1 expression was statistically associated with FIGO stage (OR=1.872, 95%CI=1.14-3.076, P=0.013) and lymph invasion (OR=2.78, 95%CI=1.08-7.152, P=0.034). CD117 expression was significantly associated with FIGO stage (OR=2.01, 95%CI=1.35-2.98, P=0.001). CD133 expression was correlated with FIGO stage (OR=3.410, 95%CI=2.196-5.294, P< 0.001) and differentiation grade (OR=2.672, 95%CI=1.354-5.272, P=0.005). CD44s was related to chemotherapy resistance (OR=3.218, 95%CI=1.148-9.016, P=0.026). Furthermore, overexpression of ALDH1 (HR=1.494, 95%CI=1.207-1.849, P< 0.001), CD117 (HR=1.395, 95%CI=1.025-1.898, P=0.034) or CD44s (HR=1.725, 95%CI=1.135-2.623, P=0.011) was associated with poor OS. Further, overexpression of both ALDH1 (HR=1.524, 95%CI=1.158-2.007, P=0.003) and CD44s (HR=2.12, 95%CI=1.692-2.657, P< 0.001) was correlated with worse DFS. CONCLUSION: CSC markers are useful predictive or prognostic biomarkers for OC in clinical assessments. Combined detection of CSC marker expression may be a powerful tool for prognostic predictions in clinical practice for patients with OC.

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.

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.

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.