Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is the predominant malignancy of the urinary system. Herein, a comprehensive urine proteomic feature was initially established for the noninvasive diagnosis and recurrence monitoring of bladder cancer. 279 cases (63 primary BCa, 87 nontumor controls (NT), 73 relapsed BCa (BCR), and 56 nonrelapsed BCa (BCNR)) were collected to screen urinary protein biomarkers. 4761 and 3668 proteins were qualified and quantified by DDA and sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis in two discovery sets, respectively. Upregulated proteins were validated by multiple reaction monitoring (MRM) in two independent combined sets. Using the multi-support vector machine-recursive feature elimination (mSVM-RFE) algorithm, a model comprising 13 proteins exhibited good performance between BCa and NT with an AUC of 0.821 (95% CI: 0.675-0.967), 90.9% sensitivity (95% CI: 72.7-100%), and 73.3% specificity (95% CI: 53.3-93.3%) in the diagnosis test set. Meanwhile, an 11-marker classifier significantly distinguished BCR from BCNR with 75.0% sensitivity (95% CI: 50.0-100%), 81.8% specificity (95% CI: 54.5-100%), and an AUC of 0.784 (95% CI: 0.609-0.959) in the test cohort for relapse surveillance. Notably, six proteins (SPR, AK1, CD2AP, ADGRF1, GMPS, and C8A) of 24 markers were newly reported. This paper reveals novel urinary protein biomarkers for BCa and offers new theoretical insights into the pathogenesis of bladder cancer (data identifier PXD044896).

Hotspots and trends of risk factors in gastric cancer: A visualization and bibliometric analysis.

BACKGROUND: The lack of specific symptoms of gastric cancer (GC) causes great challenges in its early diagnosis. Thus it is essential to identify the risk factors for early diagnosis and treatment of GC and to improve the survival rates. AIM: To assist physicians in identifying changes in the output of publications and research hotspots related to risk factors for GC, constructing a list of key risk factors, and providing a reference for early identification of patients at high risk for GC. METHODS: Research articles on risk factors for GC were searched in the Web of Science core collection, and relevant information was extracted after screening. The literature was analyzed using Microsoft Excel 2019, CiteSpace V, and VOSviewer 1.6.18. RESULTS: A total of 2514 papers from 72 countries and 2507 research institutions were retrieved. China (n = 1061), National Cancer Center (n = 138), and Shoichiro Tsugane (n = 36) were the most productive country, institution, or author, respectively. The research hotspots in the study of risk factors for GC are summarized in four areas, namely: Helicobacter pylori (H. pylori) infection, single nucleotide polymorphism, bio-diagnostic markers, and GC risk prediction models. CONCLUSION: In this study, we found that H. pylori infection is the most significant risk factor for GC; single-nucleotide polymorphism (SNP) is the most dominant genetic factor for GC; bio-diagnostic markers are the most promising diagnostic modality for GC. GC risk prediction models are the latest current research hotspot. We conclude that the most important risk factors for the development of GC are H. pylori infection, SNP, smoking, diet, and alcohol.

Discovery of a novel ROS-based signature for predicting prognosis and immunosuppressive tumor microenvironment in lung adenocarcinoma.

The role of reactive oxygen species (ROS) is critical in the emergence and progression of lung adenocarcinoma (LUAD), affecting cell survival, proliferation, angiogenesis, and metastasis. Further investigations are needed to elucidate these effects' precise pathways and devise therapeutic approaches targeting ROS. Moreover, the expression pattern and clinical significance of the ROS-related genes in LUAD remain elusive. Through comprehensive analysis incorporating 1494 LUAD cases from The Cancer Genome Atlas, six Gene Expression Omnibus series, and a Chinese LUAD cohort, we identified a ROS-related signature with substantial predictive value in various LUAD patient cohorts. The ROS-related signature has demonstrated a significant negative relationship with antitumor immunity and dendritic cell maturation and activation. Moreover, The ROS-related signature showed predictive value on immunotherapy outcomes across multiple types of solid tumors, including LUAD. These findings reinforce the ROS-related signature as a predictive tool for LUAD and provide new insights into its link with antitumor immunity and immunotherapy efficacy. These results have implications for refining clinical assessments and tailoring immunotherapeutic strategies for patients with LUAD.

Discussing the safety and effectiveness of transcatheter arterial embolization combined with intravenous chemotherapy in treating locally advanced breast cancer.

To investigate the efficacy and safety of drug-eluting bead-transarterial chemoembolization (DEB-TACE) combined with systemic chemotherapy in HR+/Her2- locally advanced breast cancer (LABC) patients. A controlled study was conducted on LABC patients treated at Jianyang People's Hospital and the First Affiliated Hospital of Chengdu Medical College from December 2020 to June 2022. The patients were randomly divided into the experimental group and the control group. The experimental group received DEB-TACE combined with the TAC regimen (175 mg/m2 paclitaxel-loaded albumin, 50 mg/m2 Doxorubicin, and 500 mg/m2 cyclophosphamide), while the control group received the TAC regimen intravenously. The therapeutic efficacy was evaluated using the mRECIST criteria. Statistical analysis was performed using SPSS 22.0 software, and baseline characteristics, overall response rate (ORR), pathological complete response (PCR), adverse reactions, and complications were compared between the two groups using paired t-test and chi-square test. A total of 60 patients were included, with 30 patients in the experimental group (50%) and 30 patients in the control group (50%). After the first treatment, the ORR was 90% in the experimental group and 60% in the control group (P < 0.05). The overall ORR was 100% in the experimental group and 83% in the control group (P < 0.05). PCR was achieved in 14 patients (47%) in the experimental group and 4 patients (13%) in the control group. The main adverse reactions in the experimental group were skin blistering, pigmentation, and pain. There was no statistically significant difference in vomiting and grade II or above bone marrow suppression between the two groups. No grade III or above adverse events occurred in either group. The comparison of tumor shrinkage between the two groups was P = 0.051, and axillary lymph node shrinkage was P < 0.05. The use of drug-eluting beads in combination with neoadjuvant chemotherapy is a feasible and safe treatment option for locally advanced breast cancer patients.

Transcriptome-wide 1-methyladenosine functional profiling of messenger RNA and long non-coding RNA in bladder cancer.

Introduction: Post-transcriptional RNA modifications are crucial regulators of tumor development and progression. In many biological processes, N1-methyladenosine (m1A) plays a key role. However, little is known about the links between chemical modifications of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) and their function in bladder cancer (BLCA). Methods: Methylated RNA immunoprecipitation sequencing and RNA sequencing were performed to profile mRNA and lncRNA m1A methylation and expression in BLCA cells, with or without stable knockdown of the m1A methyltransferase tRNA methyltransferase 61A (TRMT61A). Results: The analysis of differentially methylated gene sites identified 16,941 peaks, 6,698 mRNAs, and 10,243 lncRNAs in the two groups. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the differentially methylated and expressed transcripts showed that m1A-regulated transcripts were mainly related to protein binding and signaling pathways in cancer. In addition, the differentially genes were identified that were also differentially m1A-modified and identified 14 mRNAs and 19 lncRNAs. Next, these mRNAs and lncRNAs were used to construct a lncRNA-microRNA-mRNA competing endogenous RNA network, which included 118 miRNAs, 15 lncRNAs, and 8 mRNAs. Finally, the m1A-modified transcripts, SCN2B and ENST00000536140, which are highly expressed in BLCA tissues, were associated with decreased overall patient survival. Discussion: This study revealed substantially different amounts and distributions of m1A in BLCA after TRMT61A knockdown and predicted cellular functions in which m1A may be involved, providing evidence that implicates m1A mRNA and lncRNA epitranscriptomic regulation in BLCA tumorigenesis and progression.

Identification of a marine-derived sesquiterpenoid, Compound-8, that inhibits tumour necrosis factor-induced cell death by blocking complex II assembly.

BACKGROUND AND PURPOSE: Tumour necrosis factor (TNF) is a pleiotropic inflammatory cytokine that not only directly induces inflammatory gene expression but also triggers apoptotic and necroptotic cell death, which leads to tissue damage and indirectly exacerbates inflammation. Thus, identification of inhibitors for TNF-induced cell death has broad therapeutic relevance for TNF-related inflammatory diseases. In the present study, we isolated and identified a marine fungus-derived sesquiterpenoid, 9α,14-dihydroxy-6ß-p-nitrobenzoylcinnamolide (named as Cpd-8), that inhibits TNF receptor superfamily-induced cell death by preventing the formation of cytosolic death complex II. EXPERIMENTAL APPROACH: Marine sponge-associated fungi were cultured and the secondary metabolites were extracted to yield pure compounds. Cell viability was measured by ATP-Glo cell viability assay. The effects of Cpd-8 on TNF signalling pathway were investigated by western blotting, immunoprecipitation, and immunofluorescence assays. A mouse model of acute liver injury (ALI) was employed to explore the protection effect of Cpd-8, in vivo. KEY RESULTS: Cpd-8 selectively inhibits TNF receptor superfamily-induced apoptosis and necroptosis. Cpd-8 prevents the formation of cytosolic death complex II and subsequent RIPK1-RIPK3 necrosome, while it has no effect on TNF receptor I (TNFR1) internalization and the formation of complex I in TNF signalling pathway. In vivo, Cpd-8 protects mice against TNF-α/D-GalN-induced ALI. CONCLUSION AND IMPLICATIONS: A marine fungus-derived sesquiterpenoid, Cpd-8, inhibits TNF receptor superfamily-induced cell death, both in vitro and in vivo. This study not only provides a useful research tool to investigate the regulatory mechanisms of TNF-induced cell death but also identifies a promising lead compound for future drug development.

Comparative proteomic profiling of plasma exosomes in lung cancer cases of liver and brain metastasis.

BACKGROUND: Metastases within liver or the brain are the most common causes of mortality from lung cancer (LC). Predicting liver or brain metastases before having evidence from imaging of the tumors is challenging but important for early patient intervention. According to mounting evidence, exosomes circulating within blood may facilitate cancer spread by transporting certain proteins for target cells. METHODS: Using liquid chromatography-MS/MS, we investigated the plasma exosomes' proteomic profiles derived from 42 metastatic LC patients [16 solitary liver metastasis (LM), together with 26 solitary brain metastasis (BM)] and 25 local advanced (LA) lung cancer cases without metastasis, together with five healthy controls (HC), assessing the LM and BM pathogenesis and find potential novel organ-designated proteomic biomarkers. Using ELISA assay, we verified the expression levels of three plasma exosomal protein biomarkers in 110 LC patients, including 40 solitary LM, 32 solitary BM and 38 LA, and 25 HC. RESULTS: In total, 143 and 120 differentially expressed exosome-based proteins (DEEPs) were found to be dysregulated in LM and BM of lung cancer (LM-DEEPs, BM-DEEPs), compared for LA lung cancer samples, respectively. The bioinformatics analyses indicated the heterogeneity and homogeneity in LM-DEEPs and BM-DEEPs. They were primarily engaged within proteomic triggering cascade, ECM-receptor interaction, and the collagen-containing extracellular matrix. Regarding heterogeneity, LM-DEEPs primarily consisted of proteoglycans, lipoprotein, integrin, and heat shock protein, whereas the BM-DEEPs consisted of calcium-dependent/S100 proteins. Furthermore, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)-plasma-stemming exosome proteomics showed heterogeneity, which helped to explain some of the differences between SCLC and NSCLC's metastatic features. We also found that SELL and MUC5B could be used as diagnostic markers of BM, while APOH, CD81, and CCT5 could help diagnose LM in LC patients. Additionally, we demonstrated in a validation cohort that MUC5B and SELL could serve as biomarkers for diagnosing BM, and APOH could be a novel potential diagnostic biomarker of LM. CONCLUSION: We presented the comprehensive and comparative plasma-stemming exosomes' proteomic profiles from cases of LC who had isolated liver and brain metastases for the first time. We also suggested several possible biomarkers and pathogenic pathways that might be a great starting point for future research on LC metastasis.

Mineral Phase Reconstruction and Separation Behavior of Zinc and Iron from Zinc-Containing Dust.

Zinc-containing dust can be found in ironmaking and steelmaking, and it is an important secondary resource of zinc. Zinc-containing dust from an electric furnace was used as a raw material to study the phase transformation behavior of the dust using a calcification roasting process and the zinc-iron separation behavior by using ammonia leaching. The zinc-bearing dust was mixed with CaO and roasted to transform the zinc ferrite into zinc oxide. The results showed that increasing the calcium oxide to dust ratio could promote the conversion of zinc ferrite to zinc oxide. When the calcium oxide ratio reached 60%, the peak of zinc ferrite in the calcined-roasted product in the zinc-containing dust basically disappeared. As the temperature increased, the zinc oxide grains increased but were still smaller than 10 µm. The calcined-roasted product was crushed and ground, and the zinc was leached by ammonia. A zinc-iron recovery rate of 86.12% was achieved by the ammonia leaching. The leachate could be used for zinc extraction by electrolysis. The leaching residue was mainly calcium ferrate, which could be used in sintering production. The proposed process may achieve on-site recovery of zinc-containing dust in steel-making plants.

Selective Mediastinal Lymph Node Dissection Strategy for Clinical T1N0 Invasive Lung Cancer: A Prospective, Multicenter, Clinical Trial.

INTRODUCTION: We aimed to prospectively evaluate our previously proposed selective mediastinal lymph node (LN) dissection strategy for peripheral clinical T1N0 invasive NSCLC. METHODS: This is a multicenter, prospective clinical trial in China. We set six criteria for predicting negative LN stations and finally guiding selective LN dissection. Consolidation tumor ratio less than or equal to 0.5, segment location, lepidic-predominant adenocarcinoma (LPA), negative hilar nodes (stations 10-12), and negative visceral pleural invasion (VPI) were used separately or in combination as predictors of negative LN status in the whole, superior, or inferior mediastinal zone. LPA, hilar node involvement, and VPI were diagnosed intraoperatively. All patients actually underwent systematic mediastinal LN dissection. The primary end point was the accuracy of the strategy in predicting LN involvement. If LN metastasis occurred in certain mediastinal zone that was predicted to be negative, it was considered as an "inaccurate" case. RESULTS: A total of 720 patients were enrolled. The median number of LN dissected was 15 (interquartile range: 11-20). All negative node status in certain mediastinal zone was correctly predicted by the strategy. Compared with final pathologic findings, the accuracy of frozen section to diagnose LPA, VPI, and hilar node metastasis was 94.0%, 98.9%, and 99.6%, respectively. Inaccurate intraoperative diagnosis of LPA, VPI, or hilar node metastasis did not lead to inaccurate prediction of node-negative status. CONCLUSIONS: This is the first prospective trial validating the specific mediastinal LN metastasis pattern in cT1N0 invasive NSCLC, which provides important evidence for clinical applications of selective LN dissection strategy.

WD repeat protein 54-mediator of ErbB2-driven cell motility 1 axis promotes bladder cancer tumorigenesis and metastasis and impairs chemosensitivity.

One of the most abundant protein-protein interaction domains in the human proteome is the WD40 repeat (WDR) domain. A Gene Expression Omnibus dataset revealed 37 differentially expressed WDR domain genes in bladder cancer (BC). WD repeat domain 54 (WDR54), an upregulated WDR domain gene, was selected for further investigation. Sixty pairs of frozen BC tumor and non-malignant bladder tissues and 83 paraffin-embedded BC tissue specimens were obtained. Loss-/gain-of-function experiments were carried out using BC and xenograft tumor models. WDR54 was overexpressed in BC cells, and its high expression was linked to tumor stage and lymph node metastases in patients. WDR54 contributed to the tumorigenesis and metastasis of BC and impaired its chemosensitivity. WDR54 prevented the degradation and ubiquitination of the mediator of ErbB2-driven cell motility 1 (MEMO1). WDR54 also promoted the interaction between MEMO1 and insulin receptor substrate 1 (IRS1) and activated the IRS1/AKT/ß-catenin pathway in BC cells. Particularly, WDR54 depended on MEMO1 to exert its biological functions. Our study demonstrated the relevance of WDR54 in BC and provides insight into the molecular mechanism underlying BC.

WITHDRAWN: Proteomic analysis of plasma-derived exosomes identifies biomarkers that distinguish brain and liver metastasis in lung cancer patients.

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Upper airway flow characteristics of childhood obstructive sleep apnea-hypopnea syndrome.

Revealing the structural morphology and inner flow field of the upper airway is important for understanding obstructive sleep apnea-hypopnea syndrome (OSAHS) incidence phenomena and pathological diagnosis in children. However, prior work on this topic has been focused on adults and the findings cannot be directly extrapolated to children because of different inducing factors. Therefore, this paper employs a simulation method to investigate upper airway flow characteristics of childhood OSAHS. It is found that the Reynold number changes highly throughout the whole upper airway, and the laminar assumption is no longer suitable for low Reynold number flow, which is much unlike classic fluid mechanics. Turbulent models of Standard k-ω and Spalart-Allmaras were developed prior to suggestion. The simulation is validated by experiments with an error of approximately 20%. Additionally, carried out in this analysis is the influence of adenoidal hypertrophy with different narrow levels. The cross-sectional area, flow velocity, pressure drop and volume rate will change greatly when the narrow level is above 64% of the upper airway, which can be a quantitative explanation for medical intervention if adenoid hypertrophy blocks 2/3 of the upper airway in the common clinical judgment of otorhinolaryngology. It is expected that this paper can be a meaningful instruction on OSAHS surgery plan making as well as recovery evaluation postoperatively.

Effects of Pellet Basicity on the Simulated Deposit Formation in Coal-Fired Rotary Kilns for Iron Ore Pellet Production.

Deposit formation in the coal-fired rotary kiln is frequently found in the production of fluxed iron ore pellets by the grate-kiln process and affects normal production. In this paper, the effects of pellet basicity (CaO/SiO2 mass ratio) on the simulated deposit formation were investigated. The results show that the porosity of deposits samples increases from 30.8 to 41.5% as the pellet basicity increases from 0.6 to 1.2, and most of the holes are irregular in shape. The contents of CaO and Fe2O3 in the silicates of the deposit samples increased with increasing basicity. The primary phase of the deposit samples changed from the M2O3 phase region to the clinopyroxene phase region with a lower melting point. As the basicity increased, the calculated proportions of the liquid phases in the deposit samples had an increasing trend. Moreover, the deposit sample adhesion to the refractory brick increases with the increase in pellet basicity.

Long Noncoding RNA HAND2-AS1 Suppresses Cell Proliferation, Migration, and Invasion of Bladder Cancer via miR-17-5p/KLF9 Axis.

Bladder cancer (BC) is the most common type of malignant tumor in the genitourinary system. Through the microarray analysis of clinical samples, long noncoding RNA HAND2-AS1 expression was found to be downregulated in BC tissues. However, the function of HAND2-AS1 on BC and underlying mechanism are unclear. In this study, the correlations of HAND2-AS1 with clinicopathological parameters in BC patients were determined. The gain- and loss-of-function experiments were conducted to examine the role of HAND2-AS1 in malignant behaviors of BC cells in vitro and in vivo. Then, we paid attention to miR-17-5p/KLF9 axis to illustrate the molecular mechanism. Results showed that HAND2-AS1 was downregulated in BC tissues, and its overexpression significantly inhibited cell proliferation, migration, and invasion in vitro, as well as tumor growth in vivo. Knockdown of HAND2-AS1 caused an opposite effect on BC cell malignancies. Furthermore, miR-17-5p was shown to be a direct target of HAND2-AS1, and it reversed the inhibitory effect of HAND2-AS1 on BC malignancies. Also, as a downstream factor of miR-17-5p, KLF9 silencing was demonstrated to mediate the role of miR-17-5p inhibitor in BC cell proliferation and invasion. Thus, it suggests that HAND2-AS1 acts as a suppressor in BC development through miR-17-5p/KLF9 axis.

A Novel CpG Methylation Risk Indicator for Predicting Prognosis in Bladder Cancer.

PURPOSE: Bladder cancer (BLCA) is one of the most common cancers worldwide. In a large proportion of BLCA patients, disease recurs and/or progress after resection, which remains a major clinical issue in BLCA management. Therefore, it is vital to identify prognostic biomarkers for treatment stratification. We investigated the efficiency of CpG methylation for the potential to be a prognostic biomarker for patients with BLCA. PATIENTS AND METHODS: Overall, 357 BLCA patients from The Cancer Genome Atlas (TCGA) were randomly separated into the training and internal validation cohorts. Least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) were used to select candidate CpGs and build the methylation risk score model, which was validated for its prognostic value in the validation cohort by Kaplan-Meier analysis. Hazard curves were generated to reveal the risk nodes throughout the follow-up. Gene Set Enrichment Analysis (GSEA) was used to reveal the potential biological pathways associated with the methylation model. Quantitative real-time polymerase chain reaction (PCR) and western blotting were performed to verify the expression level of the methylated genes. RESULTS: After incorporating the CpGs obtained by the two algorithms, CpG methylation of eight genes corresponding to TNFAIP8L3, KRTDAP, APC, ZC3H3, COL9A2, SLCO4A1, POU3F3, and ADARB2 were prominent candidate predictors in establishing a methylation risk score for BLCA (MRSB), which was used to divide the patients into high- and low-risk progression groups (p < 0.001). The effectiveness of the MRSB was validated in the internal cohort (p < 0.001). In the MRSB high-risk group, the hazard curve exhibited an initial wide, high peak within 10 months after treatment, whereas some gentle peaks around 2 years were noted. Furthermore, a nomogram comprising MRSB, age, sex, and tumor clinical stage was developed to predict the individual progression risk, and it performed well. Survival analysis implicated the effectiveness of MRSB, which remains significant in all the subgroup analysis based on the clinical features. A functional analysis of MRSB and the corresponding genes revealed potential pathways affecting tumor progression. Validation of quantitative real-time PCR and western blotting revealed that TNFAIP8L3 was upregulated in the BLCA tissues. CONCLUSION: We developed the MRSB, an eight-gene-based methylation signature, which has great potential to be used to predict the post-surgery progression risk of BLCA.

[Clinical analysis of treatment and postoperative efficacy in neonatal congenital pyriform sinus fistula].

Objective:To discuss the diagnosis and treatment of congenital pyriform sinus fistula（CPSF） in newborn. Methods:Clinical data of 5 patients with CPSF innewborn were reviewed and the clinical symptoms, auxiliary examinations, surgical methods were analyzed after the operation, patients were followed up closely at different stages. Results:All the 5 neonates successfully completed the surgery without pharyngeal fistula, dysphagia, perifistula and distal fistula infection. Follow-up survey ranged from 3 months to 2 years and no one recurred. Conclusion:Neonatal CPSF is a rare disease with a short course of disease and rapid progression. In severe cases, it may threaten life and should be treated in time.

[Analysis of upper airway flow field between obstructive sleep apnea and normal children based on computational fluid dynamics].

Objective:In this study, the characteristics of the upper airway flow field were analyzed by using computational fluid dynamics（CFD）. The study analyze the differences in the upper airway flow field between normal children and children with obstructive sleep apnea（OSA）, and the pathological characteristics of children with OSA were elaborated from the perspective of airway fluid dynamics. Methods:The upper airway models of a normal child and a child with OSA were constructed. The differences in the same inspiration pressure, such as airflow velocity, airflow pattern, ventilation volume, and pressure, were analyzed. To verify CFD results, rhinomanometry was carried out and an experimental bench based 3D technology was also built. Results:The CFD results are consistent with the in vitro 3D model experiments and clinical measurement results. The adenoid area of nasopharynx is only 11.274 mm²of the child with OSA, about 1/6 of that of normal children. At the area of nasopharyngeal in OSA children, the flow velocity increased but the pressure dropped sharply, which was 69.197% of the total pressure drop, and the resistance value was 6.59 times of that of normal children. Streamline of nasopharyngeal is more disorder. Normal children's inspiratory flow was 116.139 mL/s, while OSA children's inspiratory flow was 47.055 mL/s, with a difference rate as high as 59.48%. Conclusion:The airflow of OSA children in nasopharynx is significantly different from that of normal children. The airflow characteristics of upper airway were discussed in detail with the use of CFD, which can help clinicians intuitively understand the abnormal flow behavior of children with OSA.

Novel thermally activated delayed fluorescence nano-micelle for tumor imaging.

A novel aromatic-imide-based, thermally activated delayed fluorescence material nano-micelle (TADF-NM) compound was prepared after being encapsulated with DSPE-mPEG2000 amphiphilic copolymers. TADF-NM has preferential characteristics such as biocompatibility, non-toxic and targeted ability, and importantly TADF-NM efficiently isolated oxygen to enhance the fluorescence lifetime, and prevented quenching for using time-resolved fluorescence imaging (TRFI) in tumor cells. The fluorescence lifetime of TADF-NM was about 212 µs in PBS and 112 µs in tumor cells, which was the longest in fluorescence lifetime images based on TADF materials. These studies have shown that TADF-NM have excellent potential ability to overcome the interference of auto-fluorescence while being applied in confocal fluorescence tumor imaging.

Identification and Characterization of TF-lncRNA Regulatory Networks Involved in the Tumorigenesis and Development of Adamantinomatous Craniopharyngioma.

Craniopharyngiomas (CPs) are rare tumors arising from the sellar region. Although the best outcome for patients with one subtype, adamantinomatous craniopharyngioma (ACP), is obtained by gross total resection, little is known about the roles of long noncoding RNAs (lncRNAs) and transcription factors (TFs) in ACP tumorigenesis. In total, 12 human ACP and 5 control samples were subjected to transcriptome-level sequencing. We built an integrated algorithm for identifying lncRNAs and TFs regulating the CP-related pathway. Furthermore, ChIP-Seq datasets with binding domain information were used to further verify and identify TF-lncRNA correlations. RT-PCR and immunohistochemistry staining were performed to validate the potential targets. Five pathways associated with ACP were identified and defined by an extensive literature search. Based on the specific pathways and the whole gene expression profile, 266 ACP-related lncRNAs and 39 TFs were identified by our integrating algorithm. Comprehensive analysis of the ChIP-Seq datasets revealed that 29 TFs were targeted by 12000 lncRNAs in a wide range of tissues, including 161 ACP-related lncRNAs that were identified by the computational method. These 29 TFs and 161 lncRNAs, constituting 1004 TF-lncRNA pairs, were shown to potentially regulate different ACP-related pathways. A total of 232 TF-lncRNA networks were consequently established based on differential gene expression. Validation by RT-PCR and immunohistochemistry staining revealed positive expression of the ACP-related TFs E2F2 and KLF5 in ACP. Moreover, the expression of the lncRNA RP11-360P21.2 was shown to be upregulated in ACP tissues. In this study, we introduced an integrated algorithm for identifying lncRNAs and TFs regulating the ACP-related pathway. This is the first comprehensive study to systematically investigate the potential TF and lncRNA regulatory network in ACP. The resulting data serve as a valuable resource for understanding the mechanisms underlying ACP-related lncRNAs and TFs.