Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma.

BACKGROUND: Dysregulation of iron metabolism has been shown to have significant implications for cancer development. We aimed to investigate the prognostic and immunological significance of iron metabolism-related genes (IMRGs) in nasopharyngeal carcinoma (NPC). METHODS: Multiple Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were analyzed to identify key IMRGs associated with prognosis. Additionally, the immunological significance of IMRGs was explored. RESULTS: A novel risk model was established using the LASSO regression algorithm, incorporating three genes (TFRC, SLC39A14, and ATP6V0D1).This model categorized patients into low and high-risk groups, and Kaplan-Meier analysis revealed significantly shorter progression-free survival for the high-risk group (P < 0.0001). The prognostic model's accuracy was additionally confirmed by employing time-dependent Receiver Operating Characteristic (ROC) curves and conducting Decision Curve Analysis (DCA). High-risk patients were found to correlate with advanced clinical stages, specific tumor microenvironment subtypes, and distinct morphologies. ESTIMATE analysis demonstrated a significant inverse relationship between increased immune, stromal, and ESTIMATE scores and lowered risk score. Immune analysis indicated a negative correlation between high-risk score and the abundance of most tumor-infiltrating immune cells, including dendritic cells, CD8+ T cells, CD4+ T cells, and B cells. This correlation extended to immune checkpoint genes such as PDCD1, CTLA4, TIGIT, LAG3, and BTLA. The protein expression patterns of selected genes in clinical NPC samples were validated through immunohistochemistry. CONCLUSION: This study presents a prognostic model utilizing IMRGs in NPC, which could assist in assessing patient prognosis and provide insights into new therapeutic targets for NPC.

Ultra-Broadband Ultraviolet-Visible Light-Short Wavelength Infrared InGaAs Focal Plane Arrays via n-InP Contact Layer Removal.

PIN InGaAs short wavelength infrared (SWIR) focal plane array (FPA) detectors have attracted extensive attention due to their high detectivity, high quantum efficiency, room temperature operation, low dark current, and good radiation resistance. Furthermore, InGaAs FPA detectors have wide applications in many fields, such as aviation safety, biomedicine, camouflage recognition, and infrared night vision. Recently, extensive research has been conducted on the extension of the response spectrum from short wavelength infrared (SWIR) to visible light (VIS) through InP substrate removal and reserving the n-InP contact layer. However, there is little research on the absorption of InGaAs detectors in the ultraviolet (UV) band. In this paper, we present an ultra-broadband UV-VIS-SWIR 640 × 512 15 µm InGaAs FPA detector by removing the n-InP contact layer in the active area and reserving the InP contact layer around the pixels for n contact, creating incident light to be directly absorbed by the In0.53Ga0.47As absorption layer. In addition, the optical absorption characteristics of InGaAs infrared detectors with and without an n-InP contact layer are studied theoretically. The test results show that the spectral response is extended to the range of 200-1700 nm. The quantum efficiency is higher than 45% over a broad wavelength range of 300-1650 nm. The operability is up to 99.98%, and the responsivity non-uniformity is 3.28%. The imaging capability of InGaAs FPAs without the n-InP contact layer has also been demonstrated, which proves the feasibility of simultaneous detection for these three bands.

Identification of hub genes distinguishing subtypes in endometrial stromal sarcoma through comprehensive bioinformatics analysis.

Diagnosing low-grade and high-grade endometrial stromal sarcoma (LG-ESS and HG-ESS) is a challenge. This study aimed to identify biomarkers. 22 ESS cases were analyzed using Illumina microarrays. Differentially expressed genes (DEGs) were identified via Limma. DEGs were analyzed with String and Cytoscape. Core genes were enriched with GO and KEGG, their pan-cancer implications and immune aspects were studied. 413 DEGs were found by exome sequencing, 2174 by GSE85383 microarray. 36 common genes were identified by Venn analysis, and 10 core genes including RBFOX1, PCDH7, FAT1 were selected. Core gene GO enrichment included cell adhesion, T cell proliferation, and KEGG focused on related pathways. Expression was evaluated across 34 cancers, identifying immune DEGs IGF1 and AVPR1A. Identifying the DEGs not only helps improve our understanding of LG-ESS, HG-ESS but also promises to be potential biomarkers for differential diagnosis between LG-ESS and HG-ESS and new therapeutic targets.

Fluorescent carbon dots synthesized by waste wind turbine blade for photocatalytic degradation.

Developing novel waste recycling strategies has become a feasible solution to overcome environmental pollution. In this work, a method of using waste wind turbine blade (WTB) as a carbon source to synthesize blue fluorescent carbon dots (B-CDs) by hydrothermal treatment is proposed. B-CDs are spherical and have an average particle size of 5.2 nm. The surface is rich in C-O, C=O, -CH3 , and N-H bond functional groups, containing five elements: C, O, N, Si, and Ca. The optimal emission wavelength of B-CDs is 463 nm, corresponding to an excitation wavelength of 380 nm. Notably, a relatively high quantum yield of 29.9% and a utilization rate of 40% were obtained. In addition, B-CDs can serve as a photocatalyst to degrade methylene blue dye, with a degradation efficiency of 64% under 40-min irradiation conditions. The presence of holes has a significant influence on the degradation process.

Knockdown of TFRC suppressed the progression of nasopharyngeal carcinoma by downregulating the PI3K/Akt/mTOR pathway.

BACKGROUND: The transferrin receptor (TfR) encoded by TFRC gene is the main cellular iron importer. TfR is highly expressed in many cancers and is expected to be a promising new target for cancer therapy; however, its role in nasopharyngeal carcinoma (NPC) remains unknown. METHODS: The TfR levels were investigated in NPC tissues and cell lines using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. Knockdown of TFRC using two siRNA to investigate the effects on intracellular iron level and biological functions, including proliferation by CKK-8 assay, colony formation, cell apoptosis and cell cycle by flow cytometry, migration and invasion, and tumor growth in vivo by nude mouse xenografts. RNA sequencing was performed to find possible mechanism after TFRC knockdown on NPC cells and further verified by western blotting. RESULTS: TfR was overexpressed in NPC cell lines and tissues. Knockdown of TFRC inhibited cell proliferation concomitant with increased apoptosis and cell cycle arrest, and it decreased intracellular iron, colony formation, migration, invasion, and epithelial-mesenchymal transition in HK1-EBV cells. Western blotting showed that TFRC knockdown suppressed the levels of the iron storage protein FTH1, anti-apoptotic marker BCL-xL, and epithelial-mesenchymal transition markers. We confirmed in vivo that TFRC knockdown also inhibited NPC tumor growth and decreased Ki67 expression in tumor tissues of nude mouse xenografts. RNA sequencing and western blotting revealed that TFRC silencing inhibited the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: These results indicated that TfR was overexpressed in NPC, and TFRC knockdown inhibited NPC progression by suppressing the PI3K/Akt/mTOR signaling pathway. Thus, TfR may serve as a novel biomarker and therapeutic target for NPC.

Clinical Significance of Serum Iron Metabolism-Related Markers in Patients with Nasopharyngeal Carcinoma.

INTRODUCTION: It is known that iron metabolism is dysregulated in nasopharyngeal carcinoma (NPC). However, a meaningful assessment of the iron metabolic status in cancer patient is still under debate. This study aims to evaluate the status of iron metabolism, as well as to explore the correlation between those related serum markers and clinicopathological features of patients with NPC. METHODS: Peripheral blood was collected from 191 pretreatment NPC patients and 191 healthy controls. The red blood cell parameters, plasma Epstein-Barr virus (EBV) DNA load, serum iron (SI), total iron-binding capacity (TIBC), transferrin, soluble transferrin receptor (sTFR), ferritin, and hepcidin were quantitatively detected. RESULTS: The mean levels of hemoglobin and red blood cell count in the NPC group were significantly lower than those in the control group, while no statistical differences in mean MCV were found between the two groups. Median levels of SI, TIBC, transferrin, and hepcidin were significantly lower in the NPC group than in the control group. Compared to patients with the T1-T2 classification, patients with the T3-T4 classification exhibited significantly lower expression levels of SI and TIBC. Serum levels of ferritin and sTFR were significantly higher in patients with M1 classification than those with M0 classification. The EBV DNA load was associated with serum levels of sTFR and hepcidin. CONCLUSION: NPC patients had functional iron deficiency. The degree of iron deficiency was related to the tumor burden and metastasis of NPC. EBV might be involved in the regulation of iron metabolism in the host.

3D hierarchical LDHs-based Janus micro-actuator for detection and degradation of catechol.

Micro/nanomotors that combine the miniaturization and autonomous motion have attracted much research interest for environmental monitoring and water remediation. However, it is still challenging to develop a facile route to produce bifunctional micromotors that can simultaneously detect and remove organic pollutants from water. Herein, we developed a novel Janus micromotor with robust peroxide-like activity for simultaneously colorimetric detection and removal of catechol from water. Such laccase (Lac) functionalized Janus micromotor consisted of calcined MgAl-layered double hydroxides (MgAl-CLDHs) nanosheets and Co3O4-C nanoparticles (Lac-MgAl-CLDHs/Co3O4-C), revealing unique 3D hierarchical microstructure with highly exposed active sites. The obtained Janus micromotors exhibited autonomous motion with a maximum velocity of 171.83 ± 4.07 µm/s in the presence of 7 wt% H2O2 via a chemical propulsion mechanism based on the decomposition of H2O2 by Co3O4-C layer on the hemisphere surface of Janus micromotors. Owing to the combination of autonomous motion and high peroxide-like activity, Lac-MgAl-CLDHs/Co3O4-C Janus micromotors could sensitively detect catechol with the limit of detection of 0.24 µM. In addition, such Janus micromotors also could quickly degrade catechol by •OH generated from a Fenton-like reaction. It is a first step towards using autonomous micromotors for highly selective, sensitive, and facile detection and quick removal of catechol from water.

Surface-Treated Recycling Fibers from Wind Turbine Blades as Reinforcement for Waste Phosphogypsum.

An attempt at the treatment of the waste fiber (WF) from the wind turbine blade (WTB) was made through the modifier of dopamine hydrochloride and the compound modifier of dopamine hydrochloride and 2,5-dihydroxy terephthalic acid or 3,4-dihydroxy cinnamic acid or 3,4-dihydroxy benzonitrile, corresponding to obtain four modified waste fibers (MWF1, MWF2, MWF3, and MWF4). The MWFs samples' microstructure properties were characterized using SEM, EDS, XPS, FTIR analyses, and water contact angle tests. The results revealed that all the MWF surfaces were wrapped by a distinct coating layer and had different elemental compositions and chemical groups, demonstrating the significant effect of the four modifications on the WF surfaces. The hydroxyl, amino, or nitrile groups were grafted onto the WF surfaces causing improvement of the hydrophilicity and reactivity. Furthermore, all the MWFs as the reinforced materials were incorporated into the industrial waste phosphogypsum (PG) to manufacture the phosphorous-building gypsum composites (PBGC). The effects on the micro-morphology and mechanical properties of the PBGC were evaluated. The results also show the improvement in flexural and compressive strength with the addition of MWFs into the PBGC, due to the enhancement of the compactness between the MWF and phosphogypsum matrix. In particular, the effects of three compound modifiers on the flexural and compressive strength are more significant. The highest flexural and compressive strength was contributed by the PBGC-MWF4 with 2% dosage using a compound modifier of dopamine hydrochloride and 3,4-dihydroxy benzonitrile, which were enhanced 61.04% and 25.97% compared with the PBG.

Suppression of the Electrical Crosstalk of Planar-Type High-Density InGaAs Detectors with a Guard Hole.

The resolution of InGaAs FPA detectors is degraded by the electrical crosstalk, which is especially severe in high-density FPAs. We propose a guard-hole structure to suppress the electrical crosstalk in a planar-type 640 × 512 15 µm InGaAs short wavelength infrared FPA detector. For comparison, the frequently used guard ring is also prepared according to the same processing. The calculation results show that the electrical crosstalk with a guard hole is suppressed from 13.4% to 4.5%, reducing by 66%, while the electrical crosstalk with a guard ring is suppressed to 0.4%. Furthermore, we discuss the effects of the guard ring and the guard hole on the dark current, quantum efficiency, and detectivity. Experimental results show the detector with a guard-hole structure has higher performance compared with the detector with a guard-ring structure, the dark current density is reduced by 60%, the QE is increased by 64.5%, and the detectivity is increased by 1.36 times, respectively. The guard-hole structure provides a novel suppression method for the electrical crosstalk of high-density InGaAs detectors.

Integration Profiling Between Plasma Lipidomics, Epstein-Barr Virus and Clinical Phenomes in Nasopharyngeal Carcinoma Patients.

Plasma lipidomics has been commonly used for biomarker discovery. Studies in cancer have suggested a significant alteration of circulating metabolite profiles which is correlated with cancer characteristics and treatment outcome. However, the lipidomics characteristics of nasopharyngeal carcinoma (NPC) have rarely been studied. We previously described the phenomenon of lipid droplet accumulation in NPC cells and showed that such accumulation could be regulated by latent infection of Epstein-Barr virus (EBV). Here, we compared the plasma lipidome of NPC patients to that of healthy controls by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We found 19 lipids (e.g., phosphatidylinositols 18:0/20:4 and 18:0/18:2 and free fatty acid 22:6) to be remarkably decreased, whereas 2 lipids (i.e., diacylglycerols 16:0/16:1 and 16:0/20:3) to be increased, in the plasma of NPC patients, compared with controls. Different lipid profiles were also observed between patients with different titers of EBV antibodies (e.g., EA-IgA and VCA-IgA) as well as between patients with and without lymph node or distant organ metastasis. In conclusion, plasma lipidomics might help to differentiate NPC cases from controls, whereas EBV infection might influence the risk and prognosis of NPC through modulating lipid metabolism in both tumor cells and peripheral blood.

Characteristic analysis of three-ecofriendly reduced graphene oxides (rGOs) and their application in water-ethanol-based fluids with different volume ratios.

In this paper, three-ecofriendly reduced graphene oxides (rGOs) were obtained by using three green reducing agents (beer, wine and cocoa) to reduce the graphene oxide (GO), and were labeled as B-rGO, W-rGO and C-rGO. Meanwhile, rGO nanofluids with different water-ethanol volume ratios (25 : 75, 50 : 50, 75 : 25) were prepared based on three-ecofriendly rGOs. The structure properties of the three-ecofriendly rGOs were investigated by XRD, FR-IT, Raman spectroscopy and XPS analysis. Meanwhile, the thermophysical properties of rGO nanofluids were analyzed. Experimental results indicated that the stability and thermophysical properties of rGO nanofluids were slightly different, indicating that the properties of the nanofluids are dependent on the type of base fluids and nanoparticles. When the water-ethanol volume ratio was maintained at 25 : 75, the stability experiment results showed that W-rGO nanofluids presented excellent stability, which indirectly confirmed their excellent thermal conductivity. Furthermore, the contact angle experiment indicated that the contact angles of rGO nanofluids decreased with the increase of temperature. In a word, these three rGOs and their nanofluids exhibited preferable properties that make them promising in the field of heat transfer.

IFITM1, CD10, SMA, and h-caldesmon as a helpful combination in differential diagnosis between endometrial stromal tumor and cellular leiomyoma.

BACKGROUND: The differential diagnosis of endometrial stromal tumor (EST) and uterine cellular leiomyoma (CL) remains a challenge in clinical practice, especially low grade endometrial stromal sarcoma (ESS) and CL, suggesting the need for novel immunomarkers panels for differential diagnosis. Interferon-induced transmembrane protein 1 (IFITM1) is a novel immunomarker for endometrial stromal cells, h-caldesmon is an immunomarker for smooth muscle cells and has a higher specificity than smooth muscle actin (SMA). So this study aimed to evaluate whether IFITM1, cluster of differentiation 10(CD10), SMA, and h-caldesmon are useful biomarker combinations for the differential diagnosis of EST and CL. METHODS: Tissue microarrays were used to detect IFITM1, CD10, SMA, and h-caldesmon immunohistochemical staining in 30 EST and 33 CL cases. RESULTS: The expressions of IFITM1 and CD10 were high in EST (86.7 and 63.3%, respectively) but low in CL (18.2 and 21.2%), whereas those of h-caldesmon and SMA were high in CL (87.9 and 100%) and low in EST (6.9 and 40%). In diagnosing EST, IFITM1 shows better sensitivity and specificity (86.7 and 81.8%, respectively) than CD10 (63.3 and 78.8%). The specificity of h-caldesmon in diagnosing CL was significantly higher (93.1%) than that of SMA (60%). When all four antibodies were combined for the differential diagnosis, the area-under-the-curve (AUC) predictive value was 0.995. The best combination for diagnosing EST was IFITM1 (+) or CD10 (+) and h-caldesmon (-) (sensitivity 86.7%, specificity 93.9%). CONCLUSION: The best combination for diagnosing CL were h-caldesmon (+) and SMA (+) (sensitivity 87.9%, specificity 100%). IFITM1, CD10, SMA, and h-caldesmon are a good combination for the differential diagnosis of EST and CL.

Epigenetic Inactivation of Acetyl-CoA Acetyltransferase 1 Promotes the Proliferation and Metastasis in Nasopharyngeal Carcinoma by Blocking Ketogenesis.

The dysregulation of epigenetic modification and energy metabolism cooperatively contribute to the tumorigenesis of nasopharyngeal carcinoma (NPC). However, the detailed mechanisms underlying their joint contribution to NPC development and progression remain unclear. Here, we investigate the role of Acy1 Coenzyme A Acyltransferases1 (ACAT1), a key enzyme in the metabolic pathway of ketone bodies, in the proliferation and metastasis of NPC and to elucidate the underlying molecular mechanisms. Ketogenesis, plays a critical role in tumorigenesis. Previously, we reported two enzymes involved in ketone body metabolism mediate epigenetic silencing and act as tumor suppressor genes in NPC. Here, we identify another key enzyme, Acetyl-CoA acetyltransferase 1 (ACAT1), and show that its transcriptional inactivation in NPC is due to promoter hypermethylation. Ectopic overexpression of ACAT1 significantly suppressed the proliferation and colony formation of NPC cells in vitro. The migratory and invasive capacity of NPC cells was inhibited by ACAT1. The tumorigenesis of NPC cells overexpressing ACAT1 was decreased in vivo. Elevated ACAT1 in NPC cells was accompanied by an elevated expression of CDH1 and a reduced expression of vimentin and SPARC, strongly indicating that ACAT1 is involved in regulating epithelial-mesenchymal transition (EMT). We also found that ACAT1 contributes to increased intracellular levels of ß-hydroxybutyrate (ß-HB). Exogenously supplied ß-HB significantly inhibits the growth of NPC cells in a dose-dependent manner. In summary, ACAT1 may function as a tumor suppressor via modulation of ketogenesis and could thus serve as a potential therapeutic target in NPC. In summary, our data suggest that regulation of ketogenesis may serve as adjuvant therapy in NPC.

Synergistic Inhibition of Drug-Resistant Colon Cancer Growth with PI3K/mTOR Dual Inhibitor BEZ235 and Nano-Emulsioned Paclitaxel via Reducing Multidrug Resistance and Promoting Apoptosis.

BACKGROUND: Colon cancer is a top lethal cancer in man and women worldwide and drug resistance is the major cause of cancer-related death. Combinational therapy and drug delivery with nanoparticles have been shown to effectively overcome drug resistance in many cancers. We previously reported that nanoemulsion (NE) loaded paclitaxel (PTX) and BEZ235 could synergistically inhibit colon cancer cell growth. PURPOSE: To investigate whether NE loaded PTX and BEZ235 can overcome drug resistance and synergistically inhibit drug-resistant colon cancer cell growth in vitro and in vivo. METHODS: The in vitro treatment effect on cell viability was assayed using CCK8 kit, cell morphological change was detected by ß-tubulin immunofluorescence staining, drug resistance-related proteins were analyzed by Western blotting, and in vivo tumor growth test was performed in nude mice xeno-transplanted with 2 drug-resistant colon cancer cell lines HCT116-LOHP and HT29-DDP. RESULTS: Both cell lines were sensitive to PTX but relatively insensitive to BEZ235. PTX combined with BEZ235 synergistically inhibited the proliferation of both cell lines. Nanoemulsion loaded PTX (NE-PTX) reduced the IC50 of PTX to approximately 2/5 of free PTX, indicating a high inhibitory efficacy of NE-PTX. When NE-PTX combined with a low concentration of BEZ235 (50 nM), the IC50 was decreased to approximately 2/3 of free PTX. Moreover, NE-PTX+BEZ235 treatment increased apoptosis, decreased Pgp and ABCC1 expression, and reduced tumor weights compared to the single drug treatment and the control group. These results suggest that nanoemulsion loaded PTX+BEZ235 can overcome drug resistance and improve the inhibitory effect on cancer cell proliferation and tumor growth. CONCLUSION: Our study thus provides a possible new approach to treat colon cancer patients with drug resistance.

Circulating PGLYRP1 Levels as a Potential Biomarker for Coronary Artery Disease and Heart Failure.

ABSTRACT: Coronary artery disease (CAD) and associated comorbidities such as heart failure (HF) remain the leading cause of morbidity and mortality worldwide attributed to, at least partially, the lack of biomarkers for efficient disease diagnosis. Here, we evaluated the diagnostic potential of serum peptidoglycan recognition protein 1 (PGLYRP1), an important component of the innate immunity and inflammation system, for both CAD and HF. A machine-learning method (random forest) was used to evaluate the clinical utility of circulating PGLYRP1 for diagnosis of CAD and HF in a total of 370 individuals. Causal links of chronic serum PGLYRP1 elevation to both diseases were further explored in ApoE-/- mice. The serum levels of PGLYRP1 were significantly higher in individuals with either chronic CAD or acute coronary syndrome than those in those without coronary artery stenosis (the control group) and even more pronounced in CAD individuals with concomitant HF. Our random forest classifier revealed that this protein performed better than other recommended clinical indicators in distinguishing the CAD from the control individuals. In addition, this protein associates more with the biomarkers of HF including left ventricular ejection fraction than inflammation. Notably, our mice experiment indicated that long-term treatment with recombinant PGLYRP1 could significantly impair the cardiovascular system as reflected from both increased atherogenic lesions and reduced fractional shortening of the left ventricle. Our findings, therefore, supported the circulating levels of PGLYRP1 as a valuable biomarker for both CAD and HF.

Cyclin-Dependent Kinase Inhibitor 2b Controls Fibrosis and Functional Changes in Ischemia-Induced Heart Failure via the BMI1-p15-Rb Signalling Pathway.

BACKGROUND: Cardiac fibrosis is an important cause of heart failure (HF) after myocardial infarction (MI). Cyclin-dependent kinase inhibitor 2b (CDKN2b) regulates the cell cycle by encoding the p15 protein and participates in the development of various tumours. However, the role of CDKN2b/p15 in cardiac fibrosis and HF after MI remains unclear. METHODS: Lentivirus was used to induce the silence and overexpression of CDKN2b. Cardiac function was detected with the use of echocardiography. Immunohistochemistry, immunofluorescence, Western blotting, Cell Counting Kit 8, and wound healing assay were used to illustrate the potential mechanism associated with CDKN2b. RESULTS: The p15 protein expression was significantly down-regulated in both human and mouse failing hearts. Cardiac down-regulation of CDKN2b promoted myocardial fibrosis and worsened cardiac function in MI mice, while systemic CDKN2b silencing induced diastolic dysfunction in vivo. In addition, cardiac overexpression of CDKN2b ameliorated cardiac fibrosis and improved cardiac function in MI mice. Mechanistically, silencing CDKN2b gene enhanced the phosphorylation of retinoblastoma (Rb) protein and reinforced the migration and proliferation capabilities of cardiac fibroblasts. B Lymphoma Mo-MLV insertion region 1 homolog (BMI1) was up-regulated in failing heart and inversely regulated the expression of CDKN2b/p15 and the phosphorylation of Rb protein. The BMI1-p15-Rb signalling pathway is a potential mechanism of ischemia-induced cardiac fibrosis and HF. CONCLUSIONS: Cardiac fibrosis and heart function could be worsened by the down-regulation and relieved by the up-regulation of CDKN2b/p15 in ischemia-induced HF via regulating the proliferation and migration capabilities of cardiac fibroblasts. These effects could be partially explained by the regulation of the BMI1-p15-Rb signalling pathway.

Downregulation of SLC27A6 by DNA Hypermethylation Promotes Proliferation but Suppresses Metastasis of Nasopharyngeal Carcinoma Through Modulating Lipid Metabolism.

Lipid is the building block and an important source of energy, contributing to the malignant behavior of tumor cells. Recent studies suggested that lipid droplets (LDs) accumulations were associated with nasopharyngeal carcinoma (NPC) progression. Solute carrier family 27 member 6 (SLC27A6) mediates the cellular uptake of long-chain fatty acid (LCFA), a necessary lipid component. However, the functions of SLC27A6 in NPC remain unknown. Here, we found a significant reduction of SLC27A6 mRNA in NPC tissues compared with normal nasopharyngeal epithelia (NNE). The promoter methylation ratio of SLC27A6 was greater in NPC than in non-cancerous tissues. The demethylation reagent 5-aza-2'-deoxycytidine (5-aza-dC) remarkably restored the mRNA expression of SLC27A6, suggesting that this gene was downregulated in NPC owing to DNA promoter hypermethylation. Furthermore, SLC27A6 overexpression level in NPC cell lines led to significant suppression of cell proliferation, clonogenicity in vitro, and tumorigenesis in vivo. Higher SLC27A6 expression, on the other hand, promoted NPC cell migration and invasion. In particular, re-expression of SLC27A6 faciliated epithelial-mesenchymal transition (EMT) signals in xenograft tumors. Furthermore, we observed that SLC27A6 enhanced the intracellular amount of triglyceride (TG) and total cholesterol (T-CHO) in NPC cells, contributing to lipid biosynthesis and increasing metastatic potential. Notably, the mRNA level of SLC27A6 was positively correlated with cancer stem cell (CSC) markers, CD24 and CD44. In summary, DNA promoter hypermethylation downregulated the expression of SLC27A6. Furthermore, re-expression of SLC27A6 inhibited the growth capacity of NPC cells but strengthened the CSC markers. Our findings revealed the dual role of SLC27A6 in NPC and shed novel light on the link between lipid metabolism and CSC maintenance.

Effects of Cardiomyocyte-Specific Deletion of STAT3-A Murine Model of Heart Failure With Preserved Ejection Fraction.

Aims: There is a high incidence of heart failure with preserved ejection fraction (HFpEF), but the options of treatment are limited. A new animal model of HFpEF is urgently needed for in-depth research on HFpEF. Signal transducer and activator of transcription 3 (STAT3) may affect the passive stiffness of myocardium, which determines cardiac diastolic function. We hypothesized that cardiomyocyte-specific deletion of STAT3 increases cardiac passive stiffness, which results the murine features of HFpEF. Methods and Results: Cardiomyocyte-specific deletion of STAT3 (STAT3cKO) mice was generated by the Cre/FLOXp method. The STAT3cKO mice showed heavier cardiac fibrosis and cardiac hypertrophy comparing with wild-type (WT) mice. Furthermore, STAT3cKO mice showed increased serum brain natriuretic peptide (BNP) level, and growth stimulation expressed gene 2 (ST2) level. Other indicators reflecting cardiac passive stiffness and diastolic function, including end diastolic pressure volume relation, MV A value, MV E value, E/A and E/E' had different fold changes. All these changes were accompanied by decreasing levels of protein kinase G (PKG). Bioinformatic analysis of STAT3cKO mice hearts suggested cGMP-PKG signaling pathway might participate in the pathogenesis of HFpEF by means of adjusting different biological functions. Conclusions: Cardiomyocyte-specific deletion of STAT3 results in a murine HFpEF model which imitates the clinical characteristics partly by affecting cardiac PKG levels. Better understanding of the factors influencing HFpEF may finally provided innovative therapies.

Tunable multicolour S/N co-doped carbon quantum dots synthesized from waste foam and application to detection of Cr3+ ions.

In this study, by adjusting sulfuric acid concentrations, tunable multicolour S/N-carbon quantum dots (CQDs) were synthesized from waste foam as the raw material. The S/N-CQDs presented blue, blue-green, green, green-yellow and yellow emission with an emission peak shifting from 475 to 589 nm and with optimum excitation wavelengths of 385, 405, 440, 450, and 500 nm, respectively. Using transmission electron microscopy, the S/N-CQDs were seen to be spherical in morphology with a size around 6-8 nm. Fourier transform infrared spectra and X-ray photoelectron spectroscopy indicated that the surface of the S/N-CQDs was highly oxidized and sulfur doped. The fluorescence mechanism of multicolour S/N-CQDs emission was mainly related to a band gap change caused by the surface state. Blue-emitting S/N-CQDs were used as a fluorescent probe that was highly selective and sensitive to Cr3+ ions, with a low detection limit of 6 µM. The waste foam-derived S/N-CQDs exhibited promising potential for ion detection in real water samples due to its excellent fluorescence activity.

Combination of RERG and ZNF671 methylation rates in circulating cell-free DNA: A novel biomarker for screening of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia, hence, identifying easily detectable biomarkers for NPC screening is essential for better diagnosis and prognosis. Using genome-wide and targeted analyses based on next-generation sequencing approaches, we previously showed that gene promoters are hypermethylated in NPC tissues. To confirm whether DNA methylation rates of genes could be used as biomarkers for NPC screening, 79 histologically diagnosed NPC patients and 29 noncancer patients were recruited. A convenient quantitative analysis of DNA methylation using real-time PCR (qAMP) was carried out, involving pretreatment of tissue DNA, and circulating cell-free DNA (ccfDNA) from nonhemolytic plasma, with methylation-sensitive and/or methylation-dependent restriction enzymes. The qAMP analyses revealed that methylation rates of RERG, ZNF671, ITGA4, and SHISA3 were significantly higher in NPC primary tumor tissues compared to noncancerous tissues, with sufficient diagnostic accuracy of the area under receiver operating characteristic curves (AUC). Interestingly, higher methylation rates of RERG in ccfDNA were statistically significant and yielded a very good AUC; however, those of ZNF671, ITGA4, and SHISA3 were not significant. Furthermore, the combination of methylation rates of RERG and ZNF671 in ccfDNA showed higher diagnostic accuracy than either of them individually. In conclusion, the methylation rates of specific genes in ccfDNA can serve as novel biomarkers for early detection and screening of NPC.