Pan-cancer dissection of vasculogenic mimicry characteristic to provide potential therapeutic targets.

Introduction: Vasculogenic mimicry (VM) represents a novel form of tumor angiogenesis that is associated with tumor invasiveness and drug resistance. However, the VM landscape across cancer types remains poorly understood. In this study, we elucidate the characterizations of VM across cancers based on multi-omics data and provide potential targeted therapeutic strategies. Methods: Multi-omics data from The Cancer Genome Atlas was used to conduct comprehensive analyses of the characteristics of VM related genes (VRGs) across cancer types. Pan-cancer vasculogenic mimicry score was established to provide a depiction of the VM landscape across cancer types. The correlation between VM and cancer phenotypes was conducted to explore potential regulatory mechanisms of VM. We further systematically examined the relationship between VM and both tumor immunity and tumor microenvironment (TME). In addition, cell communication analysis based on single-cell transcriptome data was used to investigate the interactions between VM cells and TME. Finally, transcriptional and drug response data from the Genomics of Drug Sensitivity in Cancer database were utilized to identify potential therapeutic targets and drugs. The impact of VM on immunotherapy was also further clarified. Results: Our study revealed that VRGs were dysregulated in tumor and regulated by multiple mechanisms. Then, VM level was found to be heterogeneous among different tumors and correlated with tumor invasiveness, metastatic potential, malignancy, and prognosis. VM was found to be strongly associated with epithelial-mesenchymal transition (EMT). Further analyses revealed cancer-associated fibroblasts can promote EMT and VM formation. Furthermore, the immune-suppressive state is associated with a microenvironment characterized by high levels of VM. VM score can be used as an indicator to predict the effect of immunotherapy. Finally, seven potential drugs targeting VM were identified. Conclusion: In conclusion, we elucidate the characteristics and key regulatory mechanisms of VM across various cancer types, underscoring the pivotal role of CAFs in VM. VM was further found to be associated with the immunosuppressive TME. We also provide clues for the research of drugs targeting VM. Our study provides an initial overview and reference point for future research on VM, opening up new avenues for therapeutic intervention.

Polyvinylpyrrolidone hydrogel coating for ureteral stent: Safety and performance evaluation.

BACKGROUND: Ureteral stents are commonly used in urology. However, complications such as encrustation and infection on the surface of the stent, and injury to the ureteral mucosa can occur after implantation, causing discomfort for patients. OBJECTIVE: We intend to confirm the biosafety of polyvinylpyrrolidone (PVP) hydrophilic coating and its lubrication properties for surface modification of ureteral stents to reduce friction and improve patient comfort. METHODS: Based on our previous studies, we have developed a PVP hydrophilic coating for surface modification of ureteral stents. We firstly investigated the cytotoxicity, intradermal irritation, delayed type hypersensitivity, and acute systemic reactions of stent coating extracts. We further characterized the break strength, retention strength, and dynamic friction of the stent. RESULTS: The cell survival rate of all experimental groups was greater than 70%. No hypersensitivity reaction, systemic toxicity reaction, or obvious intradermal reaction were observed. The above results indicate that the test results of the modified stent meet the requirements of ISO 10993-5: 2009 (Cytotoxicity); ISO 10993-10:2021 (Sensitization and Irritation); ISO 10993-11:2017 (Acute Systemic Toxicity). After soaking in artificial urine for an extended period, there was no obvious change in its super-slip performance. CONCLUSION: Our results confirm the safety and lubrication characteristics of PVP hydrophilic coating for ureteral stent surface modification. The performance of this coating has the potential to reduce complications after stent implantation, thereby improving patient comfort, reducing medical burden, and has a good clinical application prospect.

Manipulating Coupled Field Enhancement in Slot-under-Groove Nanoarrays for Universal Surface-Enhanced Raman Scattering.

Surface-enhanced Raman scattering (SERS) is an ultrasensitive spectroscopic technique that can identify materials and chemicals based on their inelastic light-scattering properties. In general, SERS relies on sub-10 nm nanogaps to amplify the Raman signals and achieve ultralow-concentration identification of analytes. However, large-sized analytes, such as proteins and viruses, usually cannot enter these tiny nanogaps, limiting the practical applications of SERS. Herein, we demonstrate a universal SERS platform for the reliable and sensitive identification of a wide range of analytes. The key to this success is the prepared "slot-under-groove" nanoarchitecture arrays, which could realize a strongly coupled field enhancement with a large spatial mode distribution via the hybridization of gap-surface plasmons in the upper V-groove and localized surface plasmon resonance in the lower slot. Therefore, our slot-under-groove platform can simultaneously deliver high sensitivity for small-sized analytes and the identification of large-sized analytes with a large Raman gain.

Advances in 3D Printed Electronics: Materials, Processes, Properties and Applications.

The current Special Issue entitled "Advances in 3D printed electronics: materials, processes, properties and applications" aims to discuss the latest developments in the field of the AM of structures or components with reinforcements [...].

Spontaneous Redox-Reaction-Driven Growth of Ag Nanoparticles on Co(OH)2 Nanoflower Arrays for Surface-Enhanced Raman Scattering.

A simple and reliable method is developed to fabricate Ag-nanoparticle-decorated Co(OH)2 nanoflowers grafted on polyacrylonitrile (PAN) nanopillar arrays as uniform and sensitive surface-enhanced Raman scattering (SERS) substrates. First, Co(OH)2-nanosheet-assembled nanoflowers are achieved on the highly uniform PAN nanopillar arrays via electrochemical deposition. Then, Ag nanoparticles (Ag-NPs) are decorated onto the Au-nanoparticle-precoated Co(OH)2 nanoflowers based on a spontaneous redox reaction (SRR) between the silver ions and Co(OH)2 nanosheets at room temperature. Ag-NPs can be successfully in situ synthesized on the Co(OH)2 nanoflowers, and Au nanoparticles precoated on the surface of the Co(OH)2 nanosheets can ensure that the Co(OH)2 nanoflower structure does not collapse. Because of the highly uniform PAN nanopillar arrays and the high-density sub-10 nm gaps between the neighboring Ag-NPs on the surface of the Co(OH)2 nanoflowers, the hierarchical three-dimensional Ag@Co(OH)x grown on PAN nanopillar arrays can produce a reproducible and sensitive SERS effect. To verify the SERS performance of the substrate, 4-aminothiophenol (4-ATP) is used as the probe molecule, and the Ag@Co(OH)x grown on PAN nanopillar arrays is employed as the SERS substrate. As a result, 4-ATP concentrations as low as 10-10 M can still be identified, exhibiting high SERS activity. Additionally, the relative standard deviation value of the main characteristic peak of 10-5 M 4-ATP is 9.43%, indicating good uniformity of the SERS signal of the substrate. The SRR between silver ions and Co(OH)2 can provide a simple route to prepare heterostructures as SERS substrates, which has great potential for application in the field of analysis.

Plasmonic Cavity for Self-Powered Chemical Detection and Performance Boosted Surface-Enhanced Raman Scattering Detection.

With the popularization of the Internet of Things, the application of chemical sensors has become more and more extensive. However, it is difficult for a single functional sensor to meet multiple needs at the same time. For the next generation of chemical sensors, in addition to rapid qualitative and quantitative detection, it is also necessary to solve the problem of a distributed sensor power supply. Triboelectric nanogenerator (TENG) and surface-enhanced Raman scattering (SERS) are two emerging technologies that can be used for chemical testing. The combination of TENG and SERS technology is proposed to be an attractive research strategy to implement qualitative and quantitative analysis, as well as self-powered detection in one device. Herein, the Ag nanoparticle (NP)@polydimethylsiloxane (PDMS) plasmonic cavity is demonstrated, which can be exploited not only as a SERS substrate for qualitative analysis of the target molecules but also as a TENG based self-powered chemical sensor for rapid quantitative analysis. More importantly, the as-designed plasmonic cavity enables prolonged triboelectric field generated by the phenomena of triboelectricity, which in turn enhances the "hot spot" intensities from Ag NPs in the cavity and boosts the SERS signals. In this way, the device can have good feasibility and versatility for chemical detection. Specifically, the measurement of the concentration of many analytes can be successfully realized, including ions and small molecules. The results verify that the proposed sensor system has the potential for self-powered chemical sensors for environmental monitoring and analytical chemistry.

Single-cell multi-omics analysis reveals dysfunctional Wnt signaling of spermatogonia in non-obstructive azoospermia.

Background: Non-obstructive azoospermia (NOA) is the most severe type that leads to 1% of male infertility. Wnt signaling governs normal sperm maturation. However, the role of Wnt signaling in spermatogonia in NOA has incompletely been uncovered, and upstream molecules regulating Wnt signaling remain unclear. Methods: Bulk RNA sequencing (RNA-seq) of NOA was used to identify the hub gene module in NOA utilizing weighted gene co-expression network analyses (WGCNAs). Single-cell RNA sequencing (scRNA-seq) of NOA was employed to explore dysfunctional signaling pathways in the specific cell type with gene sets of signaling pathways. Single-cell regulatory network inference and clustering (pySCENIC) for Python analysis was applied to speculate putative transcription factors in spermatogonia. Moreover, single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) determined the regulated genes of these transcription factors. Finally, spatial transcriptomic data were used to analyze cell type and Wnt signaling spatial distribution. Results: The Wnt signaling pathway was demonstrated to be enriched in the hub gene module of NOA by bulk RNA-seq. Then, scRNA-seq data revealed the downregulated activity and dysfunction of Wnt signaling of spermatogonia in NOA samples. Conjoint analyses of the pySCENIC algorithm and scATAC-seq data indicated that three transcription factors (CTCF, AR, and ARNTL) were related to the activities of Wnt signaling in NOA. Eventually, spatial expression localization of Wnt signaling was identified to be in accordance with the distribution patterns of spermatogonia, Sertoli cells, and Leydig cells. Conclusion: In conclusion, we identified that downregulated Wnt signaling of spermatogonia in NOA and three transcription factors (CTCF, AR, and ARNTL) may be involved in this dysfunctional Wnt signaling. These findings provide new mechanisms for NOA and new therapeutic targets for NOA patients.

Screen printing and laser-induced flexible sensors for the simultaneous sensitive detection of uric acid, tyrosine, and ascorbic acid in sweat.

A wearable sweat sensor, which could continuously monitor biomolecules related to the human physiological state, is emerging as a promising piece of health surveillance equipment. However, current sensors cannot simultaneously achieve a detection performance that equates to that of traditional sensors and satisfactory mechanical strength. Herein, a wearable sweat sensor with excellent detection performance and mechanical stability is designed and fabricated. Based on the integration of laser-induced graphene electrodes and a screen printing technique, this wearable sweat sensor could realize both the separate and simultaneous detection of uric acid (UA), tyrosine (Tyr), and ascorbic acid (AA) with high sensitivity. Good UA sensing performance in artificial sweat could be maintained even after 20 000 bends. In addition, the sensor can operate well in the wearing state or in a complex bovine whole blood sample. For the detection of human sweat, the changes in UA concentration after a purine-rich meal are continuously monitored and the results are in accordance with the corresponding serum UA detection results tested with a commercial serum UA meter. These results suggest its application potential in health monitoring for both gout patients and healthy humans.

Cu-Sn Aerogels for Electrochemical CO2 Reduction with High CO Selectivity.

This work reports the synthesis of CuxSny alloy aerogels for electrochemical CO2 reduction catalysts. An in situ reduction and the subsequent freeze-drying process can successfully give CnxSny aerogels with tuneable Sn contents, and such aerogels are composed of three-dimensional architectures made from inter-connected fine nanoparticles with pores as the channels. Density functional theory (DFT) calculations show that the introduction of Sn in Cu aerogels inhibits H2 evolution reaction (HER) activity, while the accelerated CO desorption on the catalyst surface is found at the same time. The porous structure of aerogel also favors exposing more active sites. Counting these together, with the optimized composition of Cu95Sn5 aerogel, the high selectivity of CO can be achieved with a faradaic efficiency of over 90% in a wide potential range (-0.7 V to -1.0 V vs. RHE).

Cell-cell communications shape tumor microenvironment and predict clinical outcomes in clear cell renal carcinoma.

BACKGROUND: Cell-cell communications of various cell populations within tumor microenvironment play an essential role in primary tumor growth, metastasis evolution, and immune escape. Nevertheless, comprehensive investigation of cell-cell communications in the ccRCC (Clear cell renal carcinoma) microenvironment and how this interplay affects prognosis still remains limited. METHODS: Intercellular communications were characterized by single-cell data. Firstly, we employed "CellChat" package to characterize intercellular communications across all types of cells in microenvironment in VHL mutated and non-mutated samples from 8 patients, respectively. And pseudotime trajectory analyses were performed with monocle analyses. Finally clinical prognosis and immunotherapy efficacy with different landscapes of intercellular interplay are evaluated by TCGA-KIRC and immunotherapy cohort. RESULTS: Firstly, the VHL phenotype may be related to the intercellular communication landscape. And trajectory analysis reveals the potential relationship of cell-cell communication molecules with T cells and Myeloid cells differentiation. Furthermore, those molecules also correlate with the infiltration of T cells and Myeloid cells. A tumor cluster with highly expressed ligands was defined by quantitative analysis and transcription factor enrichment analysis, which was identified to be pivotal for intercellular communications in tumor microenvironment. Finally, bulk data indicates bulk that different clusters with different intercellular communications have significant predictive value for prognosis and distinguished immunotherapy efficiency. CONCLUSIONS: The intercellular communication landscapes of VHL wild and VHL mutant ccRCC vary. Intercellular communications within the tumor microenvironment also influence T cell and myeloid cell development and infiltration, as well as predict clinical prognosis and immunotherapy efficacy in ccRCC.

CT Three-Dimensional Visualization Model in Diagnosis and Treatment of Stress Urinary Incontinence: A Retrospective Study.

OBJECTIVE: To study the clinical effect of stress urinary incontinence sling surgery based on CT 3-dimensional visualization model, and to explore the value of three-dimensional visualization model in the diagnosis and treatment of stress urinary incontinence. METHODS: Patients with stress urinary incontinence in our center from October 2020 to March 2022 were studied retrospectively. Among them, 16 cases received preoperative 3-dimensional visualization model construction, 18 cases did not use preoperative 3-dimensional model construction. The perioperative results, the postoperative results and the correlation between some related parameters of 3-dimensional visualization model and the severity of stress urinary incontinence were analyzed. RESULTS: Compared with traditional surgery, the operation time of 3D group is significantly shorter (P < 0.05). There was no significant difference in intraoperative blood loss, perioperative fever, bleeding, micturition, pudendal or inguinal pain and postoperative symptom improvement. The posterior vesicourethral angle measured by 3-dimensional reconstruction model was correlated with ICI-Q-SF score. CONCLUSIONS: The construction of three-dimensional visualization model of stress urinary incontinence can be used in clinic as a safe and effective new preoperative evaluation technique, and more potential applications can be further explored.

SERS spectral evolution of azo-reactions mediated by plasmonic Au@Ag core-shell nanorods.

The mechanism and application of localized surface plasmon resonance induced photocatalytic reactions remain an issue of interest. In this work, we used Au@Ag core-shell nanorods as a platform for plasmon-driven photocatalysis, which was in situ investigated by surface-enhanced Raman scattering (SERS) spectroscopy. The para-aminothiophenol (PATP) and para-nitrothiophenol (PNTP) adsorbed on the nanorods were irradiated with different excitation wavelengths (633 nm, 785 nm) and transformed into 4,4'-dimercaptoazobenzene (DMAB) as evidenced by the emerging Raman peaks at 1142 cm-1, 1390 cm-1, 1440 cm-1, and 1477 cm-1, corresponding to hot carrier dominated oxidation of PATP and reduction of PNTP. Preliminary azo-reaction kinetics and in situ SERS measurements were conducted by comparing the relative intensity ratio of SERS peaks at 1440 cm-1 (DMAB stretching of N[double bond, length as m-dash]N) and 1080 cm-1 (C-S stretching of PATP and PNTP). These results indicate that the catalytic efficiency was dominated by the excitation wavelength as well as the resonance condition between the plasmon band of the nanorods and the excitation line. As a proof of concept, the Au@Ag core-shell nanorods were used to catalyze 4-nitrophenol molecules, and 4-hydroxyazobenzene molecules as the product were confirmed by in situ SERS spectra as well theoretical predictions, showing potential in plasmon driven catalysis and degradation of organic molecules.

Necroptosis of nucleus pulposus cells involved in intervertebral disc degeneration through MyD88 signaling.

Background context: Low back pain, affecting nearly 40% of adults, mainly results from intervertebral disc degeneration (IVDD), while the pathogenesis of IVDD is still not fully elucidated. Recently, some researches have revealed that necroptosis, a programmed necrosis, participated in the progression of IVDD, nevertheless, the underlying mechanism remains unclear. Purpose: To study the mechanism of necroptosis of Nucleus Pulposus (NP) cells in IVDD, focusing on the role of MyD88 signaling. Study design: The expression and co-localization of necroptotic indicators and MyD88 were examined in vivo, and MyD88 inhibitor was applied to determine the role of MyD88 signaling in necroptosis of NP cells in vitro. Methods: Human disc specimens were collected from patients receiving diskectomy for lumbar disc herniation (LDH) or traumatic lumbar fractures after MRI scanning. According to the Pfirrmann grades, they were divided into normal (Grades 1, 2) and degenerated groups (4, 5). Tissue slides were prepared for immunofluorescence to assess the co-localization of necroptotic indicators (RIP3, MLKL, p-MLKL) and MyD88 histologically. The combination of TNFα, LPS and Z-VAD-FMK was applied to induce necroptosis of NP cells. Level of ATP, reactive oxygen species (ROS), live-cell staining and electron microscope study were employed to study the role of MyD88 signaling in necroptosis of NP cells. Results: In vivo, the increased expression and co-localization of necroptotic indicators (RIP3, MLKL, p-MLKL) and MyD88 were found in NP cells of degenerated disc, while very l low fluorescence intensity in tissue of traumatic lumbar fractures. In vitro, the MyD88 inhibitor effectively rescued the necroptosis of NP cells, accompanied by increased viability, ATP level, and decreased ROS level. The effect of MyD88 inhibition on necroptosis of NP cells was further confirmed by ultrastructure of mitochondria shown by Transmission Electron Microscope (TEM). Conclusion: Our results indicated that the involvement of MyD88 signaling in the necroptosis of NP cells in IVDD, which will replenish the pathogenesis of IVDD and provide a novel potential therapeutic target for IVDD.

Effects of the cone angle on the SERS detection sensitivity of tapered fiber probes.

In this paper, we investigate the effects of taper angle on the SERS detection sensitivity using tapered fiber probes with single-layer uniform gold spherical nanoparticles (GSNs). We show that the photothermal damage caused by excessive excitation laser power is the main factor that restricts the improvement of detection sensitivity of tapered fiber probes. Only when the cone angle is appropriate can a balance be achieved between increasing the excitation laser power and suppression of the transmission and scattering losses of the nanoparticles on the tapered fiber surface, thereby obtaining the best SERS detection sensitivity. Furthermore, the optimal cone angle depends on the complex refractive index of the equivalent composite dielectric (ECD) layer containing GSNs. For three SERS fiber probes with different ECD layers, the optimal cone angles measured are between 11-13°.

Arrays of Ag-nanoparticles decorated TiO2 nanotubes as reusable three-dimensional surface-enhanced Raman scattering substrates for molecule detection.

Three-dimensional surface-enhanced Raman scattering (SERS) substrates usually provide more hot spots in the excitation light beam and higher sensitivity when compared with the two-dimensional counterpart. Here a simple approach is presented for the fabrication of arrays of Ag-nanoparticles decorated TiO2 nanotubes. Arrays of ZnO nanorods were fabricated in advance by a hydrothermal method. Then TiO2 nanotube arrays were achieved by immersing the arrays of ZnO nanorods in an aqueous solution of (NH4)2TiF6 for 1.5 h. Vertically aligned TiO2 nanotube arrays were modified with dense Ag nanoparticles by Ag mirror reaction. High density of Ag nanoparticles decorated on the fabricated TiO2 nanotubes provide plenty of hotspots for Raman enhancement. In addition, the fabricated array of Ag nanoparticles modified TiO2 nanotubes can serve as a reusable SERS substrate because of the photocatalytic activity of the TiO2 nanotubes. The SERS substrate adsorbed with analyte molecules can realize self-cleaning in deionized water after UV irradiation for 2.5 h. The sensitivity of the fabricated SERS substrate was investigated by the detection of organic dye molecules. The detectable concentration limits of rhodamine 6G (R6G), malachite green (MG) and methylene blue (MB) were found to be 10-12 M, 10-9 M and 10-8 M, respectively. The enhancement factor (EF) of the three-dimensional SERS substrate was estimated to be as high as ∼1.4×108. Therefore, the prepared Ag nanoparticles modified TiO2 nanotube arrays have promising potentials to be applied to rapid and trace SERS detection of organic chemicals.

Exosomes derived from olfactory ensheathing cells provided neuroprotection for spinal cord injury by switching the phenotype of macrophages/microglia.

Transplantation of olfactory ensheathing cells (OECs) has been demonstrated to be beneficial for spinal cord injury (SCI) by modulating neuroinflammation, supporting neuronal survival and promoting angiogenesis. Besides OECs, the conditioned medium (CM) from OECs has also been proved to have therapeutic effects for SCI, indicating that the bioactive substances secreted by OECs are essential for its protective effects. Nevertheless, there is still little information regarding the underlying mechanisms. Considering that exosomes are crucial for intercellular communication and could be secreted by different types of cells, we speculated that the therapeutic potential of OECs for SCI might be partially based on their exosomes. To examine whether OECs could secret exosomes, we isolated exosomes by polyethylene glycol-based method, and identified them by electron microscopy study, nanoparticle tracking analysis (NTA) and western blotting. In view of phagocytic ability of microglia and its distinct roles in microenvironment regulation after SCI, we then focused the effects of OECs-derived exosomes (OECs-Exo) on microglial phenotypic regulation. We found that the extracted OECs-Exo could be engulfed by microglia and partially reverse the LPS-induced pro-inflammatory polarization through inhibiting NF-κB and c-Jun signaling pathways in vitro. Furthermore, OECs-Exo were found to inhibit the polarization of pro-inflammatory macrophages/microglia while increased the numbers of anti-inflammatory cells after SCI. Considering that the neuronal injury is closely related to the activation state of macrophages/microglia, co-culture of microglia and neurons were performed. Neuronal death induced by LPS-treated microglia could be significantly alleviated when microglia treated by LPS plus OECs-Exo in vitro. After SCI, NeuN-immunostaining and axonal tract-tracing were performed to assess neuronal survival and axon preservation. Our data showed that the OECs-Exo promoted the neuronal survival and axon preservation, and facilitated functional recovery after SCI. Our findings provide a promising therapeutic strategy for SCI based on exosome-immunomodulation.

Case Report: Metastatic Signet-Ring-Cell Carcinoma of the Bladder From Breast Invasive Lobular Carcinoma Detected by Computed Tomography.

Secondary bladder tumors are relatively rare among all bladder tumors, while bladder metastases from breast cancer have been rarely reported. Furthermore, signet-ring differentiation may appear in the metastases from a breast invasive lobular carcinoma regardless of whether the primary breast tumor had signet-ring cells, which may cause diagnostic uncertainty. We report a case of a 55-year-old female patient with diffuse bladder thickening as the chief complaint and no specific clinical manifestations. While the cystoscopy showed multiple scattered red protuberances, the biopsy suggested signet-ring-cell carcinoma. The gastroscopy results suggested poorly differentiated adenocarcinoma with signet-ring cells. Considering the patient's history of invasive lobular carcinoma of the breast, chronic myeloid leukemia, and metastatic endometrial carcinoma from the breast, we performed an immunohistochemical analysis and the results indicated that signet-ring-cell carcinomas of the stomach and bladder originated from the invasive lobular carcinoma of the breast. We performed positron emission tomography/computed tomography and the results showed that there were multiple bone metastases already present. This was the first English case report of invasive lobular carcinoma of the breast metastasizing to the uterus, stomach, bladder, and bones with multiple signet-ring-cell variations. This study shares our reasons for misdiagnosing and opinions on diagnosing and treating for this kind of cases.

Efficient electrocatalytic reduction of nitrate to nitrogen gas by a cubic Cu2O film with predominant (111) orientation.

A (111) predominant cubic Cu2O film terminated with nanopyramids was electrodeposited on copper foam as the cathode for electrocatalytic reduction of nitrate. The nitrate removal efficiency reached 94.3% and the selectivity for nontoxic nitrogen gas was 49.2%, 99% and 64.2% in neutral solution, alkaline solution and spiked actual lake water, respectively.

Determination of trans-fatty acids in food samples based on the precolumn fluorescence derivatization by high performance liquid chromatography.

Trans-fatty acids are unsaturated fatty acids that are considered to have health risks. 1,3,5,7-Tetramethyl-8-butyrethylenediamine-difluoroboradiaza-s-indacene is a highly sensitive fluorescent labeling reagent for carboxylic acids developed by our lab. In this study, using this precolumn fluorescent derivatization reagent, a rapid and accurate high-performance liquid chromatography with fluorescence detection method was developed for the determination of two trans-fatty acids in food samples. Under the optimized derivative conditions, two trans-fatty acids were tagged with the fluorescent labeling reagent in the presence of 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide at 25°C for 30 min. Then, the baseline separation of trans- and cis-fatty acids and their saturated fatty acid with similar structures was achieved with less interference using a reversed-phased C18 column with isocratic elution in 14 min. With fluorescence detection at λex /λem  = 490 /510 nm, the linear range of the TFAs was 1.0-200 nM with low detection limits in the range of 0.1-0.2 nM (signal-to-noise ratio = 3). In addition, the proposed approach was successfully applied for the detection of trans-fatty acids in food samples, and the recoveries using this method ranged from 96.02 to 109.22% with low relative standard deviations of 1.2-4.3% (n = 6).

Comprehensive analysis of necroptosis-related long noncoding RNA to predict prognosis, immune status, and immunotherapeutic response in clear cell renal cell carcinoma.

Background: Necroptosis has been found to be associated with tumorigenesis and tumor progression. However, the prognostic effect of long noncoding RNAs (lncRNAs) associated with necroptosis in clear cell renal cell carcinoma (ccRCC) is still unclear. Methods: Pearson correlation analysis was used to identify necroptosis-related genes and lncRNAs obtained from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression analyses were used to identify a novel necroptosis-associated lncRNAs signature that significantly correlated with survival of ccRCC. Next, single sample gene set enrichment analysis (ssGSEA) was employed to assess the extent of infiltration with immune cells. Analyses to predict the half-maximal inhibitory concentration (IC50) of patients in different risk groups were also conducted. Moreover, follow-up data of an immunotherapy cohort were used to test for differences in the immunotherapeutic efficiency between two risk groups. Finally, patients with ccRCC were divided into two groups based on 6 prognostic lncRNAs. Results: We developed a signature of necroptosis-related lncRNAs, which was verified as an independent prognostic factor that can predict prognosis up to 7 years. Patients with higher risk scores were shown to have higher immune suppressive cell infiltration levels and expression of immune checkpoint genes, which suggests that these patients were in a state of immunosuppression. Patients in the low-risk group were found to have an increased response to immunotherapy. A prognostic prediction nomogram was conducted to predict long-term survival of patients. Cluster A tumors were considered hot tumors, since they were correlated with higher levels of immune infiltration and were more sensitive to immunotherapy. Conclusions: A comprehensive bioinformatics analysis was conducted, which found that the necroptosis-associated lncRNA signature might be a potent prognostic factor for patients with ccRCC, which could contribute to improved prognosis of these patients.