Tumor necrosis factor-α polymorphism and risk of primary nephrotic syndrome: A case-control study and meta-analysis.

BACKGROUND: The current study aims to explore the relationship between tumor necrosis factor-α (TNF-α) polymorphism and the risk of primary nephrotic syndrome (PNS). METHODS: A total of 250 PNS patients were selected for this study, as well as 300 volunteers serving as the control group. TNF-α polymorphism were assessed using the polymerase chain reaction-restriction fragment length polymorphism method. In addition, a meta-analysis was conducted to analyze previously published literature on this topic. RESULTS: No significant differences were observed in the genotypes frequency or alleles frequency among the study populations. Meta-analysis results revealed a positive association between TNF-α rs1800629 polymorphism and allele contrast in African populations (p = 0), homozygote comparison (p = .007), heterozygote comparison (p = .026), recessive genetic model (p = .011), and dominant genetic model (p = .000). CONCLUSIONS: TNF-α rs1800629 polymorphism does not appear to confer any increased risk for PNS.

SPAG5 deficiency activates autophagy to reduce atherosclerotic plaque formation in ApoE-/- mice.

BACKGROUND: Autophagy, as a regulator of cell survival, plays an important role in atherosclerosis (AS). Sperm associated antigen 5 (SPAG5) is closely associated with the classical autophagy pathway, PI3K/Akt/mTOR signaling pathway. This work attempted to investigate whether SPAG5 can affect AS development by regulating autophagy. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with oxidized-low density lipoprotein (ox-LDL) to induce cell damage. ApoE-/- mice were fed a Western diet to establish an AS mouse model. Haematoxylin and eosin (H&E) staining and Oil Red O staining evaluated the pathological changes and in lipid deposition in aortic tissues. CCK-8 and flow cytometry detected cell proliferation and apoptosis. Immunohistochemistry, Enzyme linked immunosorbent assay, qRT-PCR and western blotting assessed the levels of mRNA and proteins. RESULTS: Ox-LDL treatment elevated SPAG5 expression and the expression of autophagy-related proteins, LC3-I, LC3-II, Beclin-1, and p62, in HUVECs. GFP-LC3 dots were increased in ox-LDL-treated HUVECs and LPS-treated HUVECs. SPAG5 knockdown reversed both ox-LDL and LPS treatment-mediated inhibition of cell proliferation and promotion of apoptosis in HUVECs. SPAG5 silencing further elevated autophagy and repressed the expression of PI3K, p-Akt/Akt, and p-mTOR/mTOR in ox-LDL-treated HUVECs. 3-MA (autophagy inhibitor) treatment reversed SPAG5 silencing-mediated increase of cell proliferation and decrease of apoptosis in ox-LDL-treated HUVECs. In vivo, SPAG5 knockdown reduced atherosclerotic plaques in AS mice through activating autophagy and inhibiting PI3K/Akt/mTOR signaling pathway. CONCLUSION: This work demonstrated that SPAG5 knockdown alleviated AS development through activating autophagy. Thus, SPAG5 may be a potential target for AS therapy.

Proteogenomic characterization of primary colorectal cancer and metastatic progression identifies proteome-based subtypes and signatures.

Metastatic progression of colorectal adenocarcinoma (CRC) remains poorly understood and poses significant challenges for treatment. To overcome these challenges, we performed multiomics analyses of primary CRC and liver metastases. Genomic alterations, such as structural variants or copy number alterations, were enriched in oncogenes and tumor suppressor genes and increased in metastases. Unsupervised mass spectrometry-based proteomics of 135 primary and 123 metastatic CRCs uncovered distinct proteomic subtypes, three each for primary and metastatic CRCs, respectively. Integrated analyses revealed that hypoxia, stemness, and immune signatures characterize these 6 subtypes. Hypoxic CRC harbors high epithelial-to-mesenchymal transition features and metabolic adaptation. CRC with a stemness signature shows high oncogenic pathway activation and alternative telomere lengthening (ALT) phenotype, especially in metastatic lesions. Tumor microenvironment analysis shows immune evasion via modulation of major histocompatibility complex (MHC) class I/II and antigen processing pathways. This study characterizes both primary and metastatic CRCs and provides a large proteogenomics dataset of metastatic progression.

A Virus Genetic System to Analyze the Fusogenicity of Human Cytomegalovirus Glycoprotein B Variants.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce the fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

A Retrospective Cohort Study of Factors Influencing Lymph Node Metastasis in Patients With Early Gastric Papillary Adenocarcinoma.

INTRODUCTION: High risk of lymph node metastasis (LNM) in gastric papillary adenocarcinoma causes endoscopists to worry about the suitability of endoscopic resection for early gastric papillary adenocarcinoma (EPAC). We compared risk factors and attempted to establish a scoring system to stratify LNM risk in patients with EPAC. METHODS: A retrospective analysis was performed on 2,513 patients with early gastric carcinoma (EGC) who underwent radical resection in 4 tertiary hospitals in China. Univariate and multivariate analyses were performed to compare the invasiveness in EPAC and other types of EGC and to evaluate potential factors in predicting LNM risk in EPAC groups. RESULTS: Three hundred thirty-five patients with EPAC were enrolled in our study, of which 62 patients were found to have LNM. After comparing clinicopathological characteristics of EPAC with and without LNM, the following factors were included in the risk scoring system: 1 point each for lower stomach location and tumor size >2.0 cm, 3 points for lymphovascular invasion, and 4 points for submucosal invasion; the risk scoring system was validated in a small internal validation set with an area under the curve of 0.844. DISCUSSION: Our results suggested that EPAC was highly invasive compared with other EGCs, especially differentiated EGC types, and need to be treated more rigorously. This proposed risk scoring system could stratify LNM risk in patients with EPAC, and endoscopic resection may only be performed safely on the groups with a low LNM rate.

[68Ga]Ga-PSMA-11 PET/CT has potential application in predicting tumor HIF-2α expression and therapeutic response to HIF-2α antagonists in patients with RCC.

OBJECTIVE: To evaluate the efficacy of parameters derived from [68Ga]Ga-PSMA-11 PET/CT images in predicting pathological HIF-2α expression in primary tumors among patients with renal cell carcinoma (RCC). METHODS: Fifty-three RCC patients with preoperative [68Ga]Ga-PSMA-11 PET/CT scans and complete surgical specimens were retrospectively enrolled in this study. Radiographic parameters were obtained from PET/CT images, and immunohistochemistry was used to measure the expression of HIF-2α and PSMA. Continuous variables and categorical variables were analyzed by the Mann-Whitney U test and chi-square test, respectively. ROC analysis was used to test the efficacy of several preoperative parameters in identifying pathological HIF-2α expression. Univariable logistic regression analyses were performed for significant parameters to predict pathological HIF-2α expression in RCC. RESULTS: Of the 53 tumors, 29 (54.7%) had high expression of HIF-2α. The SUVmax was significantly different in the HIF-2α expression subgroups (p < 0.001). SUVmax emerged as the most significant parameter to differentiate HIF-2α expression subgroups (high vs. low), with the AUC of 0.93 (95% CI 0.85-1.00, p < 0.001), sensitivity of 90%, and specificity of 88%. Furthermore, SUVmax was confirmed as the most significant predictor of HIF-2α expression level by univariable logistic regression model analysis (odds ratio 1.39, 95% CI 1.17-1.65, p < 0.001). Consistent with the radiographic results of [68Ga]Ga-PSMA-11 PET/CT, the staining intensity of pathological PSMA was significantly higher in HIF-2α-high-expressing tumors (p = 0.003). CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT was superior in identifying pathological HIF-2α expression in primary tumors of RCC patients, demonstrating its potential application in predicting responses to HIF-2α antagonists. KEY POINTS: • [68Ga]Ga-PSMA-11 PET/CT could potentially predict the HIF-2α expression of primary tumors among patients with RCC. • SUVmaxof [68Ga]Ga-PSMA-11 PET/CT was the most significant predictor of HIF-2α expression level. • This probability could help predict the therapeutic response of patients with RCC to HIF-2α antagonists.

PSMA uptake on [68Ga]-PSMA-11-PET/CT positively correlates with prostate cancer aggressiveness.

BACKGROUND: Conflicting results have been revealed on the relationship between PSMA uptake values (SUVs) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) and prostate cancer (PCa) aggressiveness. This study is to validate the relationship between SUVs with PCa aggressiveness and its role in evaluation of clinically significant PCa (csPCa) and risk stratification. METHODS: We retrospectively enrolled 51 patients who underwent [68Ga]-PSMA PET/CT (PET/CT) before radical prostatectomy (RP). PET/CT results were corrected with whole mount histology. The relationship between SUVs and aggressiveness related indictors including Gleason score, T stage, initial PSA and tumor size were analyzed. The cutoff value for detection of overall PCa, csPCa and intermediate/high-risk PCa were calculated by receiver operating characteristics (ROC) analysis. RESULTS: Both SUVmax and SUVmean positively correlated with Gleason score (SUVmax Spearman r=0.546 P<0.01, SUVmean Spearman r=0.359 P<0.01), PSA level (SUVmax Spearman r=0.568 P<0.01, SUVmean Spearman r=0.529 P<0.01) and tumor volume SUVmax Spearman r=0.635 P<0.01, SUVmean Spearman r=0.590 P<0.01). Tumors with T3 stage had significant higher SUV uptake than T2 (SUVmax 17.49±10.50 vs 9.90±8.7, P<0.01 and SUVmean 17.49±10.50 vs 9.90±8.7, P<0.01). ROC analysis showed cutoff of SUVmax (3.8) and SUVmean (2.8) for overall PCa detection. ROC analysis showed that csPCa and intermediate/high risk PCa had the same cutoff on both SUVmax (8.4) and SUVmean (6.8). CONCLUSIONS: PSMA uptake on PSMA PET/CT positively correlated with Gleason score, T stage, initial PSA and tumor volume. Both SUVmax and SUVmean can be applied as parameters for csPCa detection and risk classification.

Overexpression of sFlt-1 represses ox-LDL-induced injury of HUVECs by activating autophagy via PI3K/AKT/mTOR pathway.

Soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein, is involved in the pathogenesis of atherosclerosis (AS), and the underlying mechanism is still unclear. Here, we attempted to investigate the mechanism of action of sFlt-1 in AS. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low density lipoprotein (ox-LDL) to induce cell injury. ox-LDL treatment increased LC3-II/LC3-I ratio, Beclin-1 expression and GFP-LC3 puncta in HUVECs, suggesting that ox-LDL may induce autophagic flux impairment in HUVECs. ox-LDL-treated HUVECs displayed a decrease of sFlt-1 levels. Moreover, ox-LDL treatment reduced cell proliferation and elevated apoptosis in HUVECs, which was abrogated by sFlt-1 overexpression. Up-regulation of sFlt-1 repressed the activity of PI3K/AKT/mTOR signaling pathway and enhanced autophagy in HUVECs following ox-LDL treatment. Additionally, sFlt-1 overexpression-mediated increase of autophagy in ox-LDL-treated HUVECs was abolished by 3-methyladenine (autophagy inhibitor). 3-methyladenine abrogated the impact of sFlt-1 overexpression on proliferation and apoptosis in ox-LDL-treated HUVECs. This work confirmed that overexpression of sFlt-1 activated autophagy by repressing PI3K/Akt/mTOR signaling pathway, and thus alleviated ox-LDL-induced injury of HUVECs. Therefore, this study suggests that sFlt-1 may be a potential target for AS treatment.

Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt.

Metformin, traditionally regarded as a hypoglycemic drug, has been studied in other various fields including inflammation. The specific mechanism of metformin's effect on immune cells remains unclear. Herein, it is verified that LPS-induced macrophages are characterized by enhanced endogenous fatty acid synthesis and the inhibition of fatty acid synthase (FASN) downregulates proinflammatory responses. We further show that metformin could suppress such elevation of FASN as well as proinflammatory activation in macrophages. In vivo, metformin treatment ameliorates dextran sulfate sodium (DSS)-induced colitis through impairing proinflammatory activation of colonic lamina propria mononuclear cells (LPMCs). The reduction of FASN by metformin hinders Akt palmitoylation, which further disturbs Akt membrane attachment and its phosphorylation. Metformin-mediated suppression of FASN/Akt pathway and its downstream MAPK signaling contributes to its anti-inflammatory role in macrophages. From the perspective of immunometabolism, our work points towards metformin utilization as an effective and potential intervention against macrophages-involved inflammatory diseases.

One-step hydrothermal synthesis of nitrogen-doped carbon dots for high-sensitivity visual detection of nitrite and ascorbic acid.

Ascorbic acid (AA) is an indispensable vitamin for the human body and is associated with critical processes of human metabolism. However, excessive intake of AA can also have a negative impact on human health. Nitrite is a commonly used food additive, and its overdose can increase the risk of cancer. Therefore, the detection of nitrite and vitamins is generally recognized to be meaningful. In this study, red-fluorescence and yellow-fluorescence CDs (r-CDs/y-CDs) were synthesized by a one-step hydrothermal method using o-phenylenediamine as the only carbon source. These two types of CDs exhibited good detection accuracy, detection limit and selectivity towards nitrite and AA (the detection limits are 0.47 µM and 45.1 µM, respectively). The long wavelength luminescent CDs prepared in this experiment also have high quantum yield (QY), which is of great significance to the visual detection effect. Under weak acidic conditions, the amino group on the surface of r-CDs can coordinate with nitrite and react to generate diazo groups, leading to the fluorescence quenching of CDs. The coordination between the y-CDs and the amino group on the surface of AA connects the adjacent y-CDs to form aggregates, which increases the non-radiative transition of electrons and induces the fluorescence quenching of CDs. This study proposes a new idea for the preparation of carbon dots for the determination of NO2- and AA in solutions, which expands the application of fluorescent CD detection.

Galactosylation of rhamnogalacturonan-II for cell wall pectin biosynthesis is critical for root apoplastic iron reallocation in Arabidopsis.

Apoplastic iron (Fe) in roots represents an essential Fe storage pool. Reallocation of apoplastic Fe is of great importance to plants experiencing Fe deprivation, but how this reallocation process is regulated remains elusive, likely because of the highly complex cell wall structure and the limited knowledge about cell wall biosynthesis and modulation. Here, we present genetic and biochemical evidence to demonstrate that the Cdi-mediated galactosylation of rhamnogalacturonan-II (RG-II) is required for apoplastic Fe reallocation. Cdi is expressed in roots and up-regulated in response to Fe deficiency. It encodes a putative glycosyltransferase localized to the Golgi apparatus. Biochemical and mass spectrometry assays showed that Cdi catalyzes the transfer of GDP-L-galactose to the terminus of side chain A on RG-II. Disruption of Cdi essentially decreased RG-II dimerization and hence disrupted cell wall formation, as well as the reallocation of apoplastic Fe from roots to shoots. Further transcriptomic, Fourier transform infrared spectroscopy, and Fe desorption kinetic analyses coincidently suggested that Cdi mediates apoplastic Fe reallocation through extensive modulation of cell wall components and consequently the Fe adsorption capacity of the cell wall. Our study provides direct evidence demonstrating a link between cell wall biosynthesis and apoplastic Fe reallocation, thus indicating that the structure of the cell wall is important for efficient usage of the cell wall Fe pool.

Loss of neuropilin1 inhibits liver cancer stem cells population and blocks metastasis in hepatocellular carcinoma via epithelial-mesenchymal transition.

It is generally believed that the existence of cancer stem cells (CSCs) is related to tumor recurrence and metastasis of hepatocellular carcinoma (HCC). Neuropilin1 (NRP1) is involved in numerous pathophysiological processes of tumor progression, however, whether NRP1 is involved in the regulation of liver CSCs and metastasis of HCC is still unknown. In the present study, we examined the effect of NRP1 on the population of liver CSCs and the metastasis mechanism of HCC. In NRP1 small hairpin RNA (shRNA)-transduced HCC cells, liver CSCs surface markers (CD133+/ EpCAM+/CD13+/CD44+) expressing cells, which imply the CSCs population, were decreased. Transwell assay and nude mouse liver orthotopic transplantation model confirmed that NRP1 knockdown inhibited HCC cells' migration and lung metastasis. Our data showed that the expression of NRP1 was upregulated in 5 independent cohorts of HCC patients, consequently, high levels of NRP1 correlated with recurrence and poor prognosis in HCC. Mechanism research showed that NRP1 promotes cell spreading through the epithelial-mesenchymal transition (EMT) signaling pathway. In summary, NRP1 enhanced the population of liver CSCs and migration of HCC via EMT, indicating that NRP1 might be a novel target for HCC treatments.

Formyl tetrahydrofolate deformylase affects hydrogen peroxide accumulation and leaf senescence by regulating the folate status and redox homeostasis in rice.

It is well established that an abnormal tetrahydrofolate (THF) cycle causes the accumulation of hydrogen peroxide (H2O2) and leaf senescence, however, the molecular mechanism underlying this relationship remains largely unknown. Here, we reported a novel rice tetrahydrofolate cycle mutant, which exhibited H2O2 accumulation and early leaf senescence phenotypes. Map-based cloning revealed that HPA1 encodes a tetrahydrofolate deformylase, and its deficiency led to the accumulation of tetrahydrofolate, 5-formyl tetrahydrofolate and 10-formyl tetrahydrofolate, in contrast, a decrease in 5,10-methenyl-tetrahydrofolate. The expression of tetrahydrofolate cycle-associated genes encoding serine hydroxymethyl transferase, glycine decarboxylase and 5-formyl tetrahydrofolate cycloligase was significantly down-regulated. In addition, the accumulation of H2O2 in hpa1 was not caused by elevated glycolate oxidation. Proteomics and enzyme activity analyses further revealed that mitochondria oxidative phosphorylation complex I and complex V were differentially expressed in hpa1, which was consistent with the H2O2 accumulation in hpa1. In a further feeding assay with exogenous glutathione (GSH), a non-enzymatic antioxidant that consumes H2O2, the H2O2 accumulation and leaf senescence phenotypes of hpa1 were obviously compensated. Taken together, our findings suggest that the accumulation of H2O2 in hpa1 may be mediated by an altered folate status and redox homeostasis, subsequently triggering leaf senescence.

[Effects of chitinase-3-like protein 1 on the expression of inflammatory damage-related molecules in mouse skeletal muscle satellite cells induced by lipopolysaccharide].

OBJECTIVE: To explore the potential mechanism of chitinase-3-like protein 1 (CHI3L1) involved in skeletal muscle stem cell injury induced by sepsis. METHODS: Six different concentrations of lipopolysaccharide (LPS) were used to stimulate mouse skeletal muscle satellite cells cultured in vitro. Enzyme linked immunosorbent assay (ELISA) and cell counting kit-8 (CCK-8) were used to determine the optimal concentration. The overexpression and interference vectors of CHI3L1 were constructed to transfect skeletal muscle satellite cells, and the transfection efficiency was verified by polymerase chain reaction (PCR) and Western blotting. The cells were randomly divided into blank control group (cells without any intervention), model group (LPS-stimulated untransfected cells), overexpressing CHI3L1 group (LPS-stimulated cells transfected with CHI3L1 plasmid), overexpressing CHI3L1 control group [LPS-stimulated cells transfected with negative control (NC) plasmid], CHI3L1 interference group [LPS-stimulated cells transfected with CHI3L1 small interfering RNA (siRNA)], CHI3L1 interference control group (LPS-stimulated cells transfected with CHI3L1-siRNA NC). The levels of extracellular caspase-1 and interleukin-1ß (IL-1ß) were detected by ELISA. The protein expressions of intracellular IL-1ß, signal transducters and activator of transcription 3 (STAT3), protein kinase B (Akt) and phosphorylated Akt (p-Akt) were detected by Western blotting. RESULTS: According to the results of CCK-8 and ELISA, the best concentration of 5 mg/L LPS was selected for the subsequent experiment. The transfection was validated by PCR and Western blotting. Compared with the blank control group, the levels of extracellular IL-1ß, caspase-1 and the protein expressions of intracellular Akt, p-Akt, and IL-1ß were significantly increased in the model group [IL-1ß (ng/L): 11.22±0.55 vs. 8.63±0.63, caspase-1 (pmol/L): 9.47±0.22 vs. 8.65±0.15, Akt/GAPDH: 1.36±0.12 vs. 1.06±0.15, p-Akt/GAPDH: 0.78±0.07 vs. 0.09±0.01, IL-1ß/GAPDH: 1.38±0.12 vs. 0.18±0.03, all P < 0.05]. Compared with the model group and the overexpressing CHI3L1 control group, the levels of extracellular IL-1ß, caspase-1 and the protein expressions of intracellular p-Akt and IL-1ß were significantly increased in the overexpressing CHI3L1 group [IL-1ß (ng/L): 14.93±0.97 vs. 11.22±0.55, 9.38±0.40, caspase-1 (pmol/L): 10.35±0.03 vs. 9.47±0.22, 8.46±0.24, p-Akt/GAPDH: 1.21±0.04 vs. 0.78±0.07, 0.63±0.04, IL-1ß/GAPDH: 1.87±0.08 vs. 1.38±0.12, 1.51±0.17, all P < 0.05]. Compared with the model group and the CHI3L1 interference control group, the levels of extracellular IL-1ß, caspase-1 and the protein expressions of intracellular p-Akt and IL-1ß were significantly decreased in the CHI3L1 interference group [IL-1ß (ng/L): 8.98±0.73 vs. 11.22±0.55, 10.44±0.65, caspase-1 (pmol/L): 7.61±0.63 vs. 9.47±0.22, 8.37±0.38, p-Akt/GAPDH: 0.50±0.04 vs. 0.78±0.07, 0.94±0.06, IL-1ß/GAPDH: 0.77±0.02 vs. 1.38±0.12, 1.13±0.07, all P < 0.05]. CONCLUSIONS: CHI3L1 may mediate the damage of skeletal muscle stem cells in sepsis by increasing the expression of caspase-1 and IL-1ß. CHI3L1 may be involved in the regulation of Akt signaling pathway in skeletal muscle stem cells, but has no significant effect on STAT3 signaling pathway.

LIGHT of pulmonary NKT cells annihilates tissue protective alveolar macrophages in augmenting severe influenza pneumonia.

CD1d-restricted natural killer T (NKT) cells are innate-like T lymphocytes with protective or pathogenic roles in the development of influenza pneumonia. Here, we show that lung-infiltrated and activated NKT cells are the major cellular source of LIGHT/TNFSF14, which determines the severity of pulmonary pneumonia by highly deteriorative influenza A virus (IAV) infection. Compared to wild-type mice, LIGHT-/- mice exhibit much lower morbidity and mortality to IAV, due to alleviated lung damage and reduced apoptosis of alveolar macrophages (AMs). LIGHT preferentially promotes cell death of lymphotoxin ß receptors positive (LTßR+) AMs but not herpesvirus entry mediator positive (HVEM+) AMs. Therefore, these results suggest that NKT-derived LIGHT augments cell death of the tissue protective AMs in exacerbating lung pathology and susceptibility to fatal influenza infection. Suppression of LIGHT signaling might be a viable option in the treatment of influenza-associated acute respiratory distress syndrome.

Preparation of N/S doped carbon dots and their application in nitrite detection.

Detection of carcinogens is generally recognized to be meaningful, especially for nitrites (NO2 -). Here blue-green fluorescent carbon dots (CDs) were successfully synthesized by using p-aminobenzenesulfonic acid, and their surfaces were identified to be abundant in the functional groups of amino, hydroxyl, and sulfuric acid. Importantly, the sulfuric acid group and aromatic primary ammonia groups on the surfaces of CDs showed the interactions with the nitrites to cause fluorescence quenching. The novel CDs showed high sensitivity and selectivity for NO2 - detection with a low detection limit of 0.03 mM in water due to the fluorescence quenching effect of the CDs. Consequently, the proposed CDs here may provide a new way of monitoring NO2 - in the target samples.

DEAD-box RNA helicase protein DDX21 as a prognosis marker for early stage colorectal cancer with microsatellite instability.

DEAD-box RNA helicase DDX21 (also named nucleolar RNA helicase 2) is a nuclear autoantigen with undefined roles in cancer. To explore possible roles of autoimmune recognition in cancer immunity, we examined DDX21 protein expression in colorectal cancer tissue and its association with patient clinical outcomes. Unbiased deep proteomic profiling of two independent colorectal cancer cohorts using mass spectrometry showed that DDX21 protein was significantly upregulated in cancer relative to benign mucosa. We then examined DDX21 protein expression in a validation group of 710 patients, 619 of whom with early stage and 91 with late stage colorectal cancers. DDX21 was detected mostly in the tumor cell nuclei, with high expression in some mitotic cells. High levels of DDX21 protein were found in 28% of stage I, 21% of stage II, 30% of stage III, and 32% of stage IV colorectal cancer cases. DDX21 expression levels correlated with non-mucinous histology in early stage cancers but not with other clinicopathological features such as patient gender, age, tumor location, tumor grade, or mismatch repair status in any cancer stage. Kaplan-Meier analyses revealed that high DDX21 protein levels was associated with longer survival in patients with early stage colorectal cancer, especially longer disease-free survival in patients with microsatellite instability (MSI) cancers, but no such correlations were found for the microsatellite stable subtype or late stage colorectal cancer. Univariate and multivariate analyses also identified high DDX21 protein expression as an independent favorable prognostic marker for early stage MSI colorectal cancer.

Maspin as a Prognostic Marker for Early Stage Colorectal Cancer With Microsatellite Instability.

Colorectal cancers are among the most common cancers and a leading cause of cancer death. In our pursuit to discover molecular markers for better characterization and precision theranostics of these cancers, we first conducted global deep proteome analyses and identified maspin (serpin B5, peptidase inhibitor 5) as an upregulated protein in tumor tissue. We then validated its expression in a large cohort of 743 patients with colorectal cancers of all stages and found that both cytoplasmic and nuclear expression varied widely between different patients. Comparison with clinicopathological features revealed that maspin expression levels correlate significantly only with mismatch repair (MMR) status but not with other features. To elucidate the prognostic significance of maspin, we analyzed two outcome-annotated cohorts, one of 572 early stage cancer patients and another of 93 late stage cancer patients. Kaplan-Meier survival, univariate, and multivariate analyses revealed that maspin overexpression predicts longer overall and disease-free survival for early stage microsatellite instability (MSI) subtype colorectal cancer, but there is no correlation with survival for patients with early stage cancer of the microsatellite stability (MSS) subtype or late stage cancer. Our study identifies maspin expression as an independent prognostic marker for risk stratification of early stage MSI subtype colorectal cancer and may provide guidance for improved therapeutic management.

Comparison of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and multi-parametric magnetic resonance imaging (MRI) in the evaluation of tumor extension of primary prostate cancer.

BACKGROUND: To compare the diagnostic performance of 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) with multi-parametric magnetic resonance imaging (mpMRI) on extracapsular extension (ECE) and seminal vesicle invasion (SVI) in primary prostate cancer and its impact on therapeutic decisions. METHODS: We retrospectively enrolled 54 patients with both PET/CT and mpMRI before radical prostatectomy. Diagnostic performance of mpMRI, PET/CT and their combination (com-MRI/PET) on ECE and SVI on a patient basis were analyzed. The impact of additional PET/CT scanning on therapeutic decisions were presented. RESULTS: Among the 54 patients, 17 had tumor limited in the prostate gland, 25 only had ECE and 12 patients had both SVI and ECE on pathology. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ECE were 54%, 94%, 95%, 48% on mpMRI, 78%, 94%, 97%, 67% on PET/CT and 83%, 88%, 94%, 71% on com-MRI/PET. Both PET/CT and com-MRI/PET had a higher sensitivity than mpMRI on ECE diagnosis (78% vs. 54%, P<0.05 and 83% vs. 54%, P<0.05). No difference was observed between PET/CT and com-MRI/PET (78% vs. 83%, P=0.17). The Sensitivity, specificity, PPV and NPV of SVI were 67%, 93%, 72%, 91% on mpMRI, 75%, 95%, 82%, 93% on PET/CT and 75%, 88%, 64%, 93% on com-MRI/PET. No difference was found between the three scannings. After the additional evaluation of PET/CT, 18.5% (10/54) turned from nerve-sparing surgery to non-nerve sparing surgery. CONCLUSIONS: 68Ga-PSMA PET/CT has a higher sensitivity on ECE detection than mpMRI but shows no superiority on SVI.