Most renal cell carcinoma (RCC) patients die from metastasis or recurrence after the spread of cancer to another organ, but the mechanisms underlying the intravascular survival of circulating tumor cells (CTCs) have not been completely deciphered. Additionally, although elevated plasma C-reactive protein (CRP) levels and thrombocytosis are strongly correlated and both indicate a poor prognosis for RCC patients, the bridge connecting inflammation and coagulation remains poorly understood. To explore the complicated relationship among inflammation, the coagulation system and CTC survival, we obtained viable CTC counts and clinical information from 106 treatment-naïve patients. In addition, we performed RNA sequencing on peripheral blood leukocytes from 21 of these patients. Patients with elevated CRP and fibrinogen (FIB) levels had higher CTC counts than patients with normal levels of these indexes. Each pair of the three variables (CTC count, CRP level and FIB level) was positively correlated. According to transcriptomic analysis of blood leukocytes, the functions of the 257 genes identified as being positively correlated with the CTC count indicated neutrophil extracellular trap (NET) formation. Indeed, gene set enrichment analysis (GSEA) suggested that NET formation or increased levels of NET markers would promote CTC viability. Additionally, the calculated NET score was positively correlated with the plasma FIB concentration, and both of these values were increased in patients with elevated CRP levels. Moreover, immunofluorescence staining showed that NETs were entangled with viable renal cancer cells and that the NET frameworks were decorated with NET-derived tissue factor (TF). Finally, analysis of 533 RCC samples from The Cancer Genome Atlas (TCGA) indicated that the NET score and TF value are independent prognostic factors for RCC patients. Collectively, NETs formed by intravascular neutrophils further activate the coagulation system. Both the DNA scaffold sprouted and fibrin net triggered by NETs anchor and shield CTCs from attack. Thus, degrading this framework maybe could destroy the double shelter of CTCs, the pioneers of metastasis.
Herein, a unique hierarchically structured composite nanofiber membrane, consisting of a zeolitic imidazolate framework-8-embedded polyethersulfone (PES@ZIF8) fiber layer and a polysulfonamide/polyethersulfone (PSA/PES) fiber layer, was successfully developed to cope with the complex environments during the actual filtration/separation process and overcome the conflict between high filtration efficiency and low air pressure resistance. Due to the advantages of the synergistic effect of multicomponents and the bi-layer hierarchical structure, the integrated PES@ZIF8−PSA/PES filter possesses an extremely high air filtration efficiency (up to 99.986%) under a very low pressure drop (only 15 Pa), superior PM 0.3 purification capacity (close to 99.95%), long-term recycling ability for purifying real smoke PM 2.5 from >800 to <10 μg/m 3 , extremely high temperature resistance (exceed 200 °C), flame retardancy, good chemical stability, satisfactory transmittance, and robust self-cleaning ability. Apart from these, it achieves effective separation of oil−water mixtures and oil−water emulsions as a result of selective wettability including hydrophobicity and superoleophilicity. In particular, the PES@ZIF8−PSA/PES nanofiber membranes maintain outstanding air filtration and oil/water separation properties under the high temperature or strong acid/alkali conditions. This special comprehensive performance gives the PES@ZIF8−PSA/PES-based filtration/separation membranes a wider application prospect ranging from environmental governance to individual protection and industrial security.
These authors contributed equally to this work.
AbstractThe co-evolving tumour cells and the systemic immune environment are mutually dysregulated. Tumours affect the immune response in a complex manner. For example, although lymphocytes are mobilized in response to tumours, their function is impaired by tumour progression. This study aimed to explore how the baseline and dynamic renal cell carcinoma (RCC) tumour burdens affect the T-cell repertoire, and whether the baseline T-cell receptor β-chain (TCRB) diversity predicts prognosis. To characterise the TCRB repertoire, the baseline and follow-up peripheral TCRB repertoires of 45 patients with RCC and 2 patients with benign renal disease patients were examined using highthroughput TCRB sequencing. To explain the significance of TCRB diversity, 56 peripheral leukocyte samples from 28 patients before and after surgery were subjected to transcriptome sequencing. To validate the results, an advanced RCC patient's sample was subjected to single-cell RNA sequencing (scRNA, 10x Genomics). Higher TCRB diversity was found to be correlated with a higher lymphocyte-to-neutrophil ratio, especially indicating more naïve T cells. Highbaseline TCRB diversity predicted a better prognosis for stage IV patients, and different tumour burdens exerted distinct effects on the immune status. The pre-operative TCRB diversity was significantly higher in benign and stage I (low tumour burden) RCC patients than in stage IV (high tumour burden) patients. After the tumour burden of advanced patients was mostly relieved, we observed that the TCRB diversity was restored, T-cell exhaustion was reduced, and naïve T-cells were mobilized. It was demonstrated that the circulating TCRB repertoire could reflect the immune status and predict prognosis, and to some extent that cytoreductive nephrectomy (CN) reduces the burden of the immune system in advanced patients, which might provide a good opportunity for immunotherapy. No conflicts of interest were declared. (TCRB) comprises variable (V), diversity (D), joining (J), and constant (C) regions. The amount of TCRB diversity arises from the recombination of VDJ regions Journal of Pathology
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