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Supplemental Table S1. qRT-PCR primers used in this study Supplemental Table S2. siRNA sequence used in this study Supplemental Table S3. Primers used for shRNA plasmid construction Supplemental Table S4. Primers used for truncation variants plasmid construction Supplemental Table S5. Primers sequence used for ChIP-PCR assay Supplemental Table S6. Probe sequence of TINCR in situ hybridization (ISH) Supplemental Table S7. Clinical characteristics of nasopharyngeal carcinoma patients according to the high and low expression of TINCR Supplemental Table S8. Univariate and multivariable Cox regression analysis of TINCR expression level and survival Supplemental Table S9. The top10 proteins found by mass spectrometry analysis in the antisense-TINCR group (negative control). Supplemental Table S10. The top10 proteins found by mass spectrometry analysis in the TINCR group. The bold portion shows the proteins that overlap antisense-TINCR

Frontier evidence suggests that dysregulation of long noncoding RNAs (lncRNA) is ubiquitous in all human tumors, indicating that lncRNAs might have essential roles in tumorigenesis. Therefore, an in-depth study of the roles of lncRNA in nasopharyngeal carcinoma (NPC) carcinogenesis might be helpful to provide novel therapeutic targets. Here we report that lncRNA TINCR was significantly upregulated in NPC and was associated positively with poor survival. Silencing TINCR inhibited NPC progression and cisplatin resistance. Mechanistically, TINCR bound ACLY and protected it from ubiquitin degradation to maintain total cellular acetyl-CoA levels. Accumulation of cellular acetyl-CoA promoted de novo lipid biosynthesis and histone H3K27 acetylation, which ultimately regulated the peptidyl arginine deiminase 1 (PADI1)–MAPK–MMP2/9 pathway. In addition, insulin-like growth factor 2 mRNA-binding protein 3 interacted with TINCR and slowed its decay, which partially accounted for TINCR upregulation in NPC. These findings demonstrate that TINCR acts as a crucial driver of NPC progression and chemoresistance and highlights the newly identified TINCR–ACLY–PADI1–MAPK–MMP2/9 axis as a potential therapeutic target in NPC.Significance:TINCR-mediated regulation of a PADI1–MAPK–MMP2/9 signaling pathway plays a critical role in NPC progression and chemoresistance, marking TINCR as a viable therapeutic target in this disease.

Supplemental Figure S1. TINCR is upregulated in six other cancer types. Supplemental Figure S2. GSEA analyses results of TINCR silencing. Supplemental Figure S3. Overexpression of TINCR promotes NPC cell proliferation, metastasis and cisplatin resistance in vitro. Supplemental Figure S4. Overexpression of TINCR reverses the suppressive effects of TINCR knockdown on cell proliferation, cisplatin resistance and metastasis. Supplemental Figure S5. TINCR targets ACLY and impairs its ubiquitination degradation. Supplemental Figure S6. Silencing TINCR has no effects on the expressions of KAT3A and KAT3B. Supplemental Figure S7. The ACLY-binding motif CUGKR is critical for the role of TINCR in maintaining ACLY protein stability and lipid synthesis levels. Supplemental Figure S8. Acetyl-CoA is responsible for TINCR-mediated NPC progression and chemoresistance. Supplemental Figure S9. Correlation between TINCR and PADI1 expression in 16 other cancer types from the TCGA database. Supplemental Figure S10. Silencing TINCR decreases the proteolytic activities of MMP2/9, but had no effects on H3K27ac levels at MMP2/9 promoters. Supplemental Figure S11. IGFBP3 is overexpressed in NPC

Frontier evidence suggests that dysregulation of long noncoding RNAs (lncRNA) is ubiquitous in all human tumors, indicating that lncRNAs might have essential roles in tumorigenesis. Therefore, an in-depth study of the roles of lncRNA in nasopharyngeal carcinoma (NPC) carcinogenesis might be helpful to provide novel therapeutic targets. Here we report that lncRNA TINCR was significantly upregulated in NPC and was associated positively with poor survival. Silencing TINCR inhibited NPC progression and cisplatin resistance. Mechanistically, TINCR bound ACLY and protected it from ubiquitin degradation to maintain total cellular acetyl-CoA levels. Accumulation of cellular acetyl-CoA promoted de novo lipid biosynthesis and histone H3K27 acetylation, which ultimately regulated the peptidyl arginine deiminase 1 (PADI1)–MAPK–MMP2/9 pathway. In addition, insulin-like growth factor 2 mRNA-binding protein 3 interacted with TINCR and slowed its decay, which partially accounted for TINCR upregulation in NPC. These findings demonstrate that TINCR acts as a crucial driver of NPC progression and chemoresistance and highlights the newly identified TINCR–ACLY–PADI1–MAPK–MMP2/9 axis as a potential therapeutic target in NPC. Significance: TINCR-mediated regulation of a PADI1–MAPK–MMP2/9 signaling pathway plays a critical role in NPC progression and chemoresistance, marking TINCR as a viable therapeutic target in this disease.

This article aims to identify four commonly applied herbs from Curcuma genus of Zingiberaceae family,namely Curcumae Radix( Yujin),Curcumae Rhizoma( Ezhu),Curcumae Longae Rhizoma( Jianghuang) and Wenyujin Rhizoma Concisum( Pianjianghuang). The odor fingerprints of those four herbal medicines were collected by electronic nose,respectively. Meanwhile,XGBoost algorithm was introduced to data analysis and discriminant model establishment,with four indexes for performance evaluation,including accuracy,precision,recall,and F-measure. The discriminant model was established by XGBoost with positive rate of returning to 166 samples in the training set and 69 samples in the test set were 99. 39% and 95. 65%,respectively. The top four of the contribution to the discriminant model were LY2/g CT,P40/1,LY2/Gh and LY2/LG,the least contributing sensor was T70/2. Compared with support vector machine,random forest and artificial neural network,XGBoost algorithms shows better identification capacity with higher recognition efficiency. The accuracy,precision,recall and F-measure of the XGBoost discriminant model forecast set were 95. 65%,95. 25%,93. 07%,93. 75%,respectively. The superiority of XGBoost in the identification of Curcuma herbs was verified. Obviously,this new method could not only be suitable for digitization and objectification of traditional Chinese medicine( TCM) odor indicators,but also achieve the identification of different TCM based on their odor fingerprint in electronic nose system. The introduction of XGBoost algorithm and more excellent algorithms provide more ideas for the application of electronic nose in data mining for TCM studies.

Alternative splicing (AS) has emerged as a key event in tumor development and microenvironment formation. However, comprehensive analysis of AS and its clinical significance in head and neck squamous cell carcinoma (HNSC) is urgently required. Methods: Genome-wide profiling of AS events using RNA-Seq data from The Cancer Genome Atlas (TCGA) program was performed in a cohort of 464 patients with HNSC. Cancer-associated AS events (CASEs) were identified between paired HNSC and adjacent normal tissues and evaluated in functional enrichment analysis. Splicing networks and prognostic models were constructed using bioinformatics tools. Unsupervised clustering of the CASEs identified was conducted and associations with clinical, molecular and immune features were analyzed. Results: We detected a total of 32,309 AS events and identified 473 CASEs in HNSC; among these, 91 were validated in an independent cohort (n = 15). Functional protein domains were frequently altered, especially by CASEs affecting cancer drivers, such as PCSK5. CASE parent genes were significantly enriched in pathways related to HNSC and the tumor immune microenvironment, such as the viral carcinogenesis (FDR < 0.001), Human Papillomavirus infection (FDR < 0.001), chemokine (FDR < 0.001) and T cell receptor (FDR

Using split plot design, a pot experiment with sand culture was conducted to investigate the effects ofnitrogen and sulfur combined application on nutritional components and active component of Isatis indigotica at seedling stage under different N (5，15，25 mmol·L⁻¹)and S(0.00，1.25，2.50，5.00，7.50 mmol·L⁻¹) levels. The results showed thatthe two elements had obvious effects and the leaf and root dry weights of I. indigotica seedlings increased greatly at N₂ level. Under the same nitrogen concentration, the leaf and root dry weights increased firstly and decreased with the rising of sulfur concentrations in which S₂ was conducive to the growth and biomass accumulation. Soluble sugar, soluble protein, soluble amino acids contents were the highest in N₁, N₂ and N₃ treatments, respectively. The influence of sulfur concentrations on nutritional components was same as biomass, but the peak of different nutritional components was diversity in different nitrogen levels. The effects on secondary metabolites (total flavones, indigo, indriubin, epigotrin contents) were not obvious significantly, in which these indexes by N₁S₃，N₁S₂，N₃S₀，N₃S₁were the highest, respectively. In conclusion, the combination of nitrogen and sulfur of N₂S₂(N 15 mmol·L⁻¹ and S 2.5 mmol·L⁻¹) was beneficial to the growth and secondary metabolites accumulation of I. indigotica. These results could provide a theoretical basis for rational fertilization and cultivation of I. indigotica seedling.

Lysine doped polypeptide modified particles were chemically synthesized in different weight ratios of polypeptide to Py feed. The microstructures of these PPys were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier Transform Infrared (FTIR). Semiconductor parameter analyzer, ubbelohde viscometer and rotation viscometer were used to characterize the electrical property, viscosity and solubility of these PPys. The results show that the polypeptide has the function as the template in the Py polymerization. The lysine doped PPys form many rings with diameters of about several micrometers, with the weight ratio increase, the ring structure become more obvious and the diameters of the rings decrease to about 200 nm. The conductivity of lysine doped polypeptide modified PPys synthesized with the weight ratio of 3:1 is about 1.73 × 10-3S/cm. It is mostly soluble in acetic acid, good soluble in the mixture of acetic acid and HFIP with a volume ratio of 2:1. Moreover, the solubility in the mixture of acetic acid and HFIP is little affected by weight ratio and maintain about 93.8%, indicating its good solubility in no toxicity solvent or very low toxicity solvent.

Dodecylbenzenesulfonic acid (DBSA) doped polypanilines (PANIs) were chemically synthesized in different molar ratios of aniline (An) to ammonium persulfate (APS) and An to DBSA. The microstructures of these PANIs were investigated by means of scanning electron microscope (SEM), X-ray diffraction (XRD), and Fourier Transform Infrared (FTIR). UV-Vis spectrometer, semiconductor parameter analyzer, ubbelohde viscometer and electrospinning technique were used to characterize the optical, electrical properties, viscosity and solubility of these PANIs. The results show that the molar rations of An to APS and An to DBSA had strong effect on the microstructure, molecular weight, degree of crystallinity, optical property, solubility and conductivity of obtained DBSA doped PANI. With the increase of the molar ratios of An to APS and An to DBSA, the conductivities and molecular weight of DBSA doped PANIs decreased, while the degree of crystallinity and solubility of DBSA doped PANIs increased. The DBSA doped PANI could dissolve in dichloromethane or HFIP and could be fabricated short fibers by electrospinning. Moreover, the solution of DBSA doped PANIs in concentrated sulphuric acid showed liquid crystal property.