Prediction of protein N-terminal acetylation modification sites based on CNN-BiLSTM-attention model.

N-terminal acetylation is one of the most common and important post-translational modifications (PTM) of eukaryotic proteins. PTM plays a crucial role in various cellular processes and disease pathogenesis. Thus, the accurate identification of N-terminal acetylation modifications is important to gain insight into cellular processes and other possible functional mechanisms. Although some algorithmic models have been proposed, most have been developed based on traditional machine learning algorithms and small training datasets. Their practical applications are limited. Nevertheless, deep learning algorithmic models are better at handling high-throughput and complex data. In this study, DeepCBA, a model based on the hybrid framework of convolutional neural network (CNN), bidirectional long short-term memory network (BiLSTM), and attention mechanism deep learning, was constructed to detect the N-terminal acetylation sites. The DeepCBA was built as follows: First, a benchmark dataset was generated by selecting low-redundant protein sequences from the Uniport database and further reducing the redundancy of the protein sequences using the CD-HIT tool. Subsequently, based on the skip-gram model in the word2vec algorithm, tripeptide word vector features were generated on the benchmark dataset. Finally, the CNN, BiLSTM, and attention mechanism were combined, and the tripeptide word vector features were fed into the stacked model for multiple rounds of training. The model performed excellently on independent dataset test, with accuracy and area under the curve of 80.51% and 87.36%, respectively. Altogether, DeepCBA achieved superior performance compared with the baseline model, and significantly outperformed most existing predictors. Additionally, our model can be used to identify disease loci and drug targets.

Stem cell therapy with CRISPR/Cas9-mediated MALAT1 delivery modulates miR-142 and rescues wound healing in rats with age-associated diabetic foot ulcers.

BACKGROUND: Diabetic foot ulcer (DFU) is a serious diabetes complication, significantly impacting the quality of life, particularly in the elderly. Age-associated DFUs pose additional challenges due to impaired healing mechanisms. Our study aims to explore the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) as a miR-142 sponge in repairing diabetic rat foot ulcer tissue under age-associated diabetes, offering a new theoretical basis and therapeutic target for preventing and treating diabetic vascular disease in the elderly. METHODS: Using qPCR, we analyzed MALAT1 and miR-142 expression in EPCs and hUC-MSCs. Targetscan predicted potential interaction targets for MALAT1 and miR-142, confirmed by dual luciferase reporter gene assay. An age-associated diabetic rat model was established using Streptozotocin (STZ) injection. Hypoxia, apoptosis, and angiogenesis-related proteins were assessed through Western Blot. In vitro, miR-142 inhibition and MALAT1 overexpression promoted foot ulcer healing in diabetic rats. RESULTS: MALAT1 acted as a miR-142 sponge, downregulated in hUC-MSCs under high glucose, relevant to age-associated diabetic foot ulcers. MiR-142 negatively regulated SIRT1 and Nrf2. In vitro experiments demonstrated potential significance for age-related DFU treatment. CONCLUSIONS: MALAT1 in human umbilical cord mesenchymal stem cells expedited foot ulcer healing in diabetic rats, particularly in age-associated diabetes, through miR-142 sponge activity. These findings offer insights for novel therapeutic strategies targeting elderly diabetic foot ulcers, emphasizing exogenous stem cell transplantation's potential in effective DFU treatment for the elderly.

FGF19 promotes nasopharyngeal carcinoma progression by inducing angiogenesis via inhibiting TRIM21-mediated ANXA2 ubiquitination.

PURPOSE: Nasopharyngeal carcinoma (NPC) has characteristics of high invasion and early metastasis. Most NPC patients present with locoregionally advanced illness when first diagnosed. Therefore, it is urgent to discover NPC biomarkers. Fibroblast growth Factor 19 (FGF19) plays a role in various physiological or pathological processes, including cancer. In this research, we discovered the importance of FGF19 in NPC, and clarified its role in tumour angiogenesis. METHODS: Western blotting, immunohistochemistry and ELISA were used to investigate FGF19 expression in NPC. Then we took CCK8, colony formation, Transwell and wound healing assays to identify the influence of FGF19 on NPC malignant behaviours. The proliferative and metastatic capacity of FGF19 were evaluated in nude mice and zebrafish. The role of FGF19 in angiogenesis was investigated by tube formation and Matrigel plug angiogenesis assays. We then evaluated the variation in Annexin A2(ANXA2) levels with the treatment of FGF19. Lastly, co-immunoprecipitation and ubiquitination assays were performed to identify the mechanisms involved. RESULTS: FGF19 levels were elevated in tissues and serum of NPC patients and were associated with poor clinical stages. High expression of FGF19 promoted NPC malignant behaviours. In particular, FGF19 expression was correlated with microvessel density in tissues and NPC-derived FGF19 could accelerate angiogenesis in vitro and in vivo. Mechanistically, FGF19 influenced ANXA2 expression to promote angiogenesis. Moreover, tripartite motif-containing 21(TRIM21) interacted with ANXA2 and was responsible for ANXA2 ubiquitination. CONCLUSION: FGF19 promoted NPC angiogenesis by inhibiting TRIM21-mediated ANXA2 ubiquitination. It may serve as a noninvasive biomarker for NPC and provides new insights for therapy.

Quantitative Risk Assessment of Salmonella in Breaded Pork Products in China.

Pork products were the most common media of Salmonella in China, breaded pork products as a very popular meat presently, whose Salmonella risk should be drawn to attention. Given that quantitative risk assessment is a more scientific method for risk evaluation, a quantitative risk assessment model of Salmonella in breaded pork products was first constructed from processing to consumption, and was used for assessing the risk and the effective interventions in this study. The data of Salmonella contamination in breaded pork products during processing were obtained from the actual detection data of samples from a representative meat processing plant. With combining the predictive microbial modeling and dose-response relationship, the risk of Salmonella in breaded pork products was charactered, and the probability of Salmonella infection per meal was found to be 5.585 × 10-9. Based on the results of sensitivity analysis, the curing and seasoning process was found to be the key control point for Salmonella contamination during the processing, and consumer behavior was the key control point affecting the probability of Salmonella infection from processing to consumption. The model was also applied for assessing the effectiveness of risk interventions, and among the nine interventions given, control of thawing temperature before cooking such as microwave thawing could reduce the risk of infection by 30.969-fold, while cooking the products thoroughly, Salmonella would not pose a pathogenic hazard to consumers. The model and the assessed results in this study may provide guidance on microbial control in producing process and safety consumption of breaded pork products.

Molecular epidemiological characteristics and genetic evolutionary relationships of methicillin-resistant Staphylococcus aureus of different avian origins in Qingdao, China, using whole-genome sequencing.

Introduction: To understand the prevalence of avian methicillin-resistant Staphylococcus aureus (MRSA) and the current status of drug resistance in Qingdao, a comprehensive molecular epidemiological investigation and analysis of evolutionary relationships of MRSA isolates from broiler and layer chickens and waterfowl was conducted. Material and Methods: One hundred and two avian MRSA strains were identified by multi-locus sequence typing, staphylococcal protein A (spa) and staphylococcal cassette chromosome mec (SCCmec) typing, and whole-genome sequencing. Results: The sequence type (ST) 9-t899-SCCmec IVb type represented the highest proportion of avian-derived MRSA strains (71.57%), with ST398 type strains occasionally observed in broilers and waterfowl. The poultry-derived MRSA strains were all resistant to eight or more antimicrobials. Avian-derived MRSA strains carried 20 resistance genes, 109 virulence genes and 10 plasmids. Strains carrying the cfr oxazolidinone resistance gene were occasionally seen in broiler- and layer-derived MRSA. Single nucleotide polymorphism (SNP) core genome evolution and locus difference analysis showed that the closest strains were all of ST9-t899 type (to which also affiliated the highest number of strains) and this type occurred on all three kinds of poultry farm, but the SNP difference loci between strains of the same type ranged from 0 to 1472. Conclusion: The dominant type of MRSA from different poultry sources in Qingdao is ST9-t899-SCCmec IVb, which is commonly resistant to a variety of antimicrobial drugs and carries a variety of resistance genes and a large number of virulence genes. Sequence type 9-t899 type is widely spread among the three kinds of poultry investigated, but there are differences in affiliations.

Human Umbilical Cord Mesenchymal Stem Cells Repair Endothelial Injury and Dysfunction by Regulating NLRP3 to Inhibit Endothelial Cell Pyroptosis in Kawasaki Disease.

Vascular endothelial inflammation and endothelial dysfunction are the main causes of endothelial injury in Kawasaki disease (KD). Human umbilical cord-derived mesenchymal stem cells (Huc-MSCs) have multiple functions in immune regulation. This study examined whether Huc-MSCs inhibited endothelial inflammation and improved endothelial function in KD through constructing cell and in vivo animal KD vasculitis models. The pyroptosis factor NOD-like receptor protein 3 (NLRP3) was involved in the inflammatory process in the acute phase of KD. After tail vein injection of Huc-MSCs, inflammatory cell infiltration and the expression of pyroptosis-related proteins in the LCWE-induced KD mouse vasculitis model were significantly reduced. In vitro, NLRP3-dependent pyroptosis successfully induced human umbilical vein endothelial cell (HUVEC) damage. Huc-MSCs effectively increased the abilities of impaired HUVECs to proliferate, migrate, invade, and form vessel-like tubes, while inhibiting their apoptosis, suggesting that Huc-MSCs can reduce inflammation and improve vascular endothelial function by inhibiting the NLRP3-dependent pyroptosis pathway in KD, providing a possibility and novel target for KD endothelial injury and dysfunction.

UBE2V2 promotes metastasis by regulating EMT and predicts a poor prognosis in lung adenocarcinoma.

PURPOSE: As a member of the ubiquitin-conjugating enzyme (E2) family, UBE2V2 demonstrates significant tumorigenicity in many cancers. However, the relationship between UBE2V2 expression and the morbidity of lung adenocarcinoma (LUAD) is still unknown. METHODS: We detected the mRNA and protein expression of UBE2V2 and analyzed its relationship with clinical parameters as well as survival prognosis based on bioinformatic and immunohistochemistry (IHC) in LUAD. The signaling pathway of UBE2V2 in the development of LUAD was obtained by GSEA. The TIMER database was used to investigate the association between UBE2V2 expression and the level of infiltration of different immune cells. Finally, we explored the effects of UBE2V2 knockdown on the proliferation, apoptosis, and migration of LUAD cells. RESULTS: The results showed that UBE2V2 was a potential oncogene and might be considered an independent prognostic molecule for LUAD patients based on TCGA prediction (HR: 1.497 p = 0.012) and IHC (HR:1.864 p = 0.044). IHC showed that UBE2V2 was related to the following clinicopathological factors: gender (p = 0.043), stage (p = 0.042), and lymph node metastasis (p = 0.002). Finally, knockdown of UBE2V2 reduced the migration of LUAD cells by regulating EMT-related proteins. Knockdown of UBE2V2 induced LUAD cells to arrest in the G1 phase. Knockdown of UBE2V2 increased LUAD cell apoptosis and decreased proliferation, which might be related to the downregulation of PCNA and upregulation of P53 and ƳH2AX expression. Interestingly, UBE2V2 is negatively correlated with B cells, CD4+ T cells, macrophages, and dendritic cells. CONCLUSION: UBE2V2 may be a valuable therapeutic target for lung cancer.

[Role and mechanism of platelet-derived growth factor BB in thrombocytosis in Kawasaki disease]. / è¡€å°æ¿è¡ç”Ÿç”Ÿé•¿å› å­BBåœ¨å·å´Žç— è¡€å°æ¿å¢žå¤šä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To study the role and mechanism of platelet-derived growth factor BB (PDGF-BB) on platelet production in Kawasaki disease (KD) mice and human megakaryocytic Dami cells through in vitro and invivo experiments. METHODS: ELISA was used to measure the expression of PDGF in the serum of 40 children with KD and 40 healthy children. C57BL/6 mice were used to establish a model of KD and were then randomly divided into a normal group, a KD group, and an imatinib group (30 mice in each group). Routine blood test was performed for each group, and the expression of PDGF-BB, megakaryocyte colony forming unit (CFU-MK), and the megakaryocyte marker CD41 were measured. CCK-8, flow cytometry, quantitative real-time PCR, and Western blot were used to analyze the role and mechanism of PDGF-BB in platelet production in Dami cells. RESULTS: PDGF-BB was highly expressed in the serum of KD children (P<0.001). The KD group had a higher expression level of PDGF-BB in serum (P<0.05) and significant increases in the expression of CFU-MK and CD41 (P<0.001), and the imatinib group had significant reductions in the expression of CFU-MK and CD41 (P<0.001). In vitro experiments showed that PDGF-BB promoted Dami cell proliferation, platelet production, mRNA expression of PDGFR-ß, and protein expression of p-Akt (P<0.05). Compared with the PDGF-BB group, the combination group (PDGF-BB 25 ng/mL + imatinib 20 µmol/L) had significantly lower levels of platelet production, mRNA expression of PDGFR-ß, and protein expression of p-Akt (P<0.05). CONCLUSIONS: PDGF-BB may promote megakaryocyte proliferation, differentiation, and platelet production by binding to PDGFR-ß and activating the PI3K/Akt pathway, and the PDGFR-ß inhibitor imatinib can reduce platelet production, which provides a new strategy for the treatment of thrombocytosis in KD.

CanMethdb: a database for genome-wide DNA methylation annotation in cancers.

MOTIVATION: DNA methylation within gene body and promoters in cancer cells is well documented. An increasing number of studies showed that cytosine-phosphate-guanine (CpG) sites falling within other regulatory elements could also regulate target gene activation, mainly by affecting transcription factors (TFs) binding in human cancers. This led to the urgent need for comprehensively and effectively collecting distinct cis-regulatory elements and TF-binding sites (TFBS) to annotate DNA methylation regulation. RESULTS: We developed a database (CanMethdb, http://meth.liclab.net/CanMethdb/) that focused on the upstream and downstream annotations for CpG-genes in cancers. This included upstream cis-regulatory elements, especially those involving distal regions to genes, and TFBS annotations for the CpGs and downstream functional annotations for the target genes, computed through integrating abundant DNA methylation and gene expression profiles in diverse cancers. Users could inquire CpG-target gene pairs for a cancer type through inputting a genomic region, a CpG, a gene name, or select hypo/hypermethylated CpG sets. The current version of CanMethdb documented a total of 38 986 060 CpG-target gene pairs (with 6 769 130 unique pairs), involving 385 217 CpGs and 18 044 target genes, abundant cis-regulatory elements and TFs for 33 TCGA cancer types. CanMethdb might help biologists perform in-depth studies of target gene regulations based on DNA methylations in cancer. AVAILABILITY AND IMPLEMENTATION: The main program is available at https://github.com/chunquanlipathway/CanMethdb. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Establishment and Application of a Predictive Growth Kinetic Model of Salmonella with the Appearance of Two Other Dominant Background Bacteria in Fresh Pork.

To better guide microbial risk management and control, growth kinetic models of Salmonella with the coexistence of two other dominant background bacteria in pork were constructed. Sterilized pork cutlets were inoculated with a cocktail of Salmonella Derby (S. Derby), Pseudomonas aeruginosa (P. aeruginosa), and Escherichia coli (E. coli), and incubated at various temperatures (4-37 °C). The predictive growth models were developed based on the observed growth data. By comparing R2 of primary models, Baranyi models were preferred to fit the growth curves of S. Derby and P. aeruginosa, while the Huang model was preferred for E. coli (all R2 ≥ 0.997). The secondary Ratkowsky square root model can well describe the relationship between temperature and µmax (all R2 ≥ 0.97) or Lag (all R2 ≥ 0.98). Growth models were validated by the actual test values, with Bf and Af close to 1, and MSE around 0.001. The time for S. Derby to reach a pathogenic dose (105 CFU/g) at each temperature in pork was predicted accordingly and found to be earlier than the time when the pork began to be judged nearly fresh according to the sensory indicators. Therefore, the predictive microbiology model can be applied to more accurately predict the shelf life of pork to secure its quality and safety.

Analysis of Key Control Points of Microbial Contamination Risk in Pork Production Processes Using a Quantitative Exposure Assessment Model.

Pork is one of the most common foods causing microbial foodborne diseases. Since pork directly enters the market after slaughtering, the control of microbial contamination in the slaughtering processes is the key to ensuring the quality and safety of pork. The contamination level of Escherichia coli, a health-indicator bacterium, can reflect the risk level of potential pathogens. In order to assess the E. coli exposure risk of pork during slaughtering and to identify the key control points, we established an E. coli quantitative exposure assessment model for swine-slaughtering processes in slaughterhouses of different sizes. The model simulation data indicated the E. coli contamination pattern on the surfaces of swine carcasses during slaughtering. The changes in E. coli contamination were analyzed according to the simulation data of each slaughtering process. It was found that the number of E. coli after trimming in big and small slaughterhouses increased to the maximum values for the whole processes, which were 3.63 and 3.52 log10 CFU/100 cm2, respectively. The risk contribution of each slaughtering process to the E. coli contamination on the surface of terminal swine carcasses can be determined by correlation analysis. Because the absolute value of correlation coefficient during the trimming process was maximum (0.49), it was regarded as the most important key control point. This result can be further proved via the multilocus sequence typing of E. coli. The dominant sequence type before trimming processes was ST10. ST1434 began to appear in the trimming process and then became the dominant sequence type in the trimming and pre-cooling processes. The model can provide a theoretical basis for microbial hygiene supervision and risk control in swine-slaughtering processes.

Grandparental care and childhood obesity in China.

Ongoing increases in childhood obesity have become a serious public health concern. Meanwhile, caregiving by grandparents becomes a worldwide social phenomenon. This study estimates the effect of grandparental care on childhood obesity and explores its pathways. Utilizing five waves of panel data from the China Family Panel Studies, we found that grandparental care significantly increases the probability of childhood obesity, adding 3.6 percentage points. The effect is heterogeneous between boys and girls and between grandparents with different education attainments. The channels through which grandparents contribute to childhood obesity include inappropriate dietary patterns and insufficient physical activities. Additionally, we found that grandparents' famine experience generates a long-term fear of hunger, which translates into overfeeding their grandchildren, thus aggravating childhood obesity in China.

Effect of humic acid as a photosensitizer combined with low-energy laser on orthodontic tooth movement in rats.

BACKGROUND/PURPOSE: Humic acid (HA) could promote light conversion reaction, and lasers accelerate orthodontic tooth movement. We investigated the effect of HA, as a photosensitizer, combined with low-energy laser on orthodontic tooth movement in rats. MATERIALS AND METHODS: An orthodontic tooth movement model was established, and the upper left first molar was moved mesially by a nickel-titanium tension spring with a 50-g force. HA was injected into the rats' abdominal cavity (80 mg/kg once daily). The periodontal tissue of the upper left upper first molar on the pressure side was irradiated (50 s once every 2 days) using a semiconductor laser (wavelength, 650 nm; power, 50 mV). Distance moved by the upper left first molar was measured at different time points, and the tissue of the first molar was sectioned and scanned by micro-computed tomography to evaluate the alveolar bone density. Tartrate-resistant acidic phosphatase staining was used to observe the osteoclast number, alveolar bone, and periodontal tissue. RESULTS: HA alone did not significantly affect orthodontic tooth movement, alveolar structure density, or periodontal tissue remodeling (P > 0.05). HA combined with a low-energy laser accelerated orthodontic tooth movement. The number of bone absorption lacunae and osteoclasts on the alveolar bone's pressure side increased significantly (P < 0.05), while the density decreased significantly (P < 0.05); however, no root absorption was observed. CONCLUSION: HA can improve the conversion rate of low-energy lasers, enhance the low-energy laser effect, and promote orthodontic tooth movement and periodontal tissue reconstruction on the pressure side in rats, without causing root resorption.

Human umbilical cord mesenchymal stem cells regulate CD54 and CD105 in vascular endothelial cells and suppress inflammation in Kawasaki disease.

OBJECTIVE: The objective was to evaluate the expression levels of CD31+CD54+ and CD31+CD105+ endothelial microparticles (EMPs) before and after intravenous immunoglobulin (IVIG) treatment of Kawasaki disease (KD). To explore the role of human umbilical cord mesenchymal stem cells (hucMSCs) in inhibiting endothelial inflammation in KD, the effects of hucMSCs on the expression of CD54 and CD105 in endothelial cells in KD were analyzed in vivo and in vitro. METHODS: The concentrations of IL-1ß and VEGF in the peripheral blood of KD or healthy children were detected, and the distributions of CD31+CD54+ and CD31+CD105+ EMPs in platelet-poor plasma (PPP) were analyzed by flow cytometry. Human umbilical vein endothelial cells (HUVECs) were first cocultured with the patients' peripheral blood mononuclear cells (PBMCs). Next, HUVECs were cocultured with hucMSCs after stimulation with inactivated serum from patients. Cell proliferation and migration activities were assessed, and the expression of CD54, CD105 and IL-1ß was analyzed. In an in vivo study, hucMSCs were transplanted into KD mice. The locations and expression levels of CD54, CD105 and IL-1ß in the heart tissues of mice were analyzed. RESULTS: The levels of IL-1ß and CD31+CD54+ EMPs were significantly higher before IVIG treatment and 2 weeks after treatment in KD patients (P < 0.01). However, the levels of VEGF and CD31+CD105+ EMPs increased significantly in KD only after IVIG treatment (P < 0.01). KD-inactivated serum stimulation combined with cocultivation of PBMCs can activate inflammation in HUVECs, leading to reduced cell proliferation and migration activities. Cocultivation also increased the expression of CD54 and decreased the expression of CD105 (P < 0.001). Cocultivation with hucMSCs can reverse these changes. Additionally, hucMSC transplantation downregulated the expression of IL-1ß and CD54 and significantly upregulated the expression of CD105 in KD mice. CONCLUSION: The expression levels of CD31+CD54+ and CD31+CD105+ EMPs showed inconsistent changes at different KD statuses, providing potential markers for clinical application. HucMSCs suppress inflammation and regulate the expression levels of CD54 and CD105 in vascular endothelial cells in KD, possibly providing a new basis for stem cell therapy for KD.

Surveillance and Reduction Control of Escherichia coli and Diarrheagenic E. coli During the Pig Slaughtering Process in China.

The microbial contamination of pork during the slaughter process, especially that of the hygiene indicator bacteria, Escherichia coli, is closely related to the safety and quality of the meat. Some diarrheagenic E. coli can cause serious foodborne diseases, and pose a significant threat to human life and health. In order to ascertain the current status of E. coli and diarrheagenic E. coli contamination during the pig slaughter process in China, we conducted thorough monitoring of large-sized slaughterhouses, as well as small- or medium-sized slaughterhouses, in different provinces of China from 2019 to 2020. The overall positive rate of E. coli on the pork surface after slaughter was very high (97.07%). Both the amount of E. coli contamination and the positive ratio of diarrheagenic E. coli in large-sized slaughterhouses (7.50-13.33 CFU/cm2, 3.44%) were lower than those in small- or medium-sized slaughterhouses (74.99-133.35 CFU/cm2, 5.71%). Combined with the current status of sanitary control in slaughterhouses, we determined that pre-cooling treatment significantly reduced E. coli and diarrheagenic E. coli in pork after slaughter, while microbiological testing reduced E. coli. Based on our monitoring data, China urgently needs to establish relevant standards to better control microbial contamination during pig slaughtering progress. This study provided a theoretical basis for the hygiene quality management of the pig slaughter industry in China.

The Application of Skin Care Product in Melasma Treatment.

Melasma is an acquired and chronic hyperpigmentation disorder which is recognized as one of the most psychologically distressing and difficult to cure forms of skin hyperpigmentation. It is associated with substantial quality of life impairments. Treatments of melasma include local application, oral medication, physical laser therapy and program combination therapy. However, routine treatment usually leads to the damage of skin barrier function, resulting in adverse reactions such as erythema, pruritus, post-inflammatory pigmentation and even scar. Skin care products contain a variety of active ingredients, which are widely concerned by cosmetic dermatologists because of high safety, good tolerance and the effect of improving the damaged skin barrier. Using skin care products alone or in combination with routine treatment not only can improve the curative effect for melasma, reduce side effects and recurrence rate, but also improve patient satisfaction. This article mainly describes the application of skin care products in the treatment of melasma.

Nuclear exosome HMGB3 secreted by nasopharyngeal carcinoma cells promotes tumour metastasis by inducing angiogenesis.

Distant metastasis accompanied by angiogenesis is the main cause of nasopharyngeal carcinoma (NPC)-related death. Nuclear exosomes (nEXOs) are potential tumour biomarkers. High mobility group box 3 (HMGB3), a nuclear protein, is known to be overexpressed in cancers. However, its role in NPC has not been elucidated. Here, we explore for the first time the function of nEXO HMGB3 in tumour angiogenesis involved in NPC metastasis using a series of in vitro experiments with NPC cell lines and clinical specimens and in vivo experiments with tumour xenograft zebrafish angiogenesis model. We found a high expression of HMGB3 in NPC, accompanied by the formation of micronuclei, to be associated with metastasis. Furthermore, the NPC-secreted HMGB3 expression was associated with tumour angiogenesis. Moreover, HMGB3-containing nEXOs, derived from the micronuclei of NPC cells, were ingested by the human umbilical vein endothelial cells (HUVECs), and accelerated angiogenesis in vitro and in vivo. Importantly, western blotting and flow cytometry analysis showed that circulating nEXO HMGB3 positively correlated with NPC metastasis. In summary, nEXO HMGB3 can be a significant biomarker of NPC metastasis and provide a novel basis for anti-angiogenesis therapy in clinical metastasis.

HIF-1α downregulation of miR-433-3p in adipocyte-derived exosomes contributes to NPC progression via targeting SCD1.

Resident adipocytes under a hypoxic tumor microenvironment exert an increasingly important role in cell growth, proliferation, and invasion in cancers. However, the communication between adipocytes and cancer cells during nasopharyngeal carcinoma (NPC) progression is poorly understood. Here, we demonstrate that hypoxic adipocyte-derived exosomes are key information carriers that transfer low expression of miR-433-3p into NPC cells. In addition, luciferase reporter assays detected that hypoxia inducible factor-1α (HIF-1α) induced miR-433-3p transcription through five binding sites at its promoter region. Concordantly, the low expression of miR-433-3p promoted proliferation, migration, and lipid accumulation in NPC cells via targeting stearoyl-CoA desaturase 1 (SCD1) are suggested by functional studies. Consistent with these findings, in tumor-bearing mice, NPC cells with low HIF-1α expression, high miR-433-3p expression, and low SCD1 expression were equally endowed with remarkably reduced potential of tumorigenesis. Collectively, our study highlights the critical role of the HIF-1α-miR-433-3p-SCD1 axis in NPC progression, which can serve as a mechanism-based potential therapeutic approach.

TRlnc: a comprehensive database for human transcriptional regulatory information of lncRNAs.

Long noncoding RNAs (lncRNAs) have been proven to play important roles in transcriptional processes and biological functions. With the increasing study of human diseases and biological processes, information in human H3K27ac ChIP-seq, ATAC-seq and DNase-seq datasets is accumulating rapidly, resulting in an urgent need to collect and process data to identify transcriptional regulatory regions of lncRNAs. We therefore developed a comprehensive database for human regulatory information of lncRNAs (TRlnc, http://bio.licpathway.net/TRlnc), which aimed to collect available resources of transcriptional regulatory regions of lncRNAs and to annotate and illustrate their potential roles in the regulation of lncRNAs in a cell type-specific manner. The current version of TRlnc contains 8 683 028 typical enhancers/super-enhancers and 32 348 244 chromatin accessibility regions associated with 91 906 human lncRNAs. These regions are identified from over 900 human H3K27ac ChIP-seq, ATAC-seq and DNase-seq samples. Furthermore, TRlnc provides the detailed genetic and epigenetic annotation information within transcriptional regulatory regions (promoter, enhancer/super-enhancer and chromatin accessibility regions) of lncRNAs, including common SNPs, risk SNPs, eQTLs, linkage disequilibrium SNPs, transcription factors, methylation sites, histone modifications and 3D chromatin interactions. It is anticipated that the use of TRlnc will help users to gain in-depth and useful insights into the transcriptional regulatory mechanisms of lncRNAs.

LncSEA: a platform for long non-coding RNA related sets and enrichment analysis.

Long non-coding RNAs (lncRNAs) have been proven to play important roles in transcriptional processes and various biological functions. Establishing a comprehensive collection of human lncRNA sets is urgent work at present. Using reference lncRNA sets, enrichment analyses will be useful for analyzing lncRNA lists of interest submitted by users. Therefore, we developed a human lncRNA sets database, called LncSEA, which aimed to document a large number of available resources for human lncRNA sets and provide annotation and enrichment analyses for lncRNAs. LncSEA supports >40 000 lncRNA reference sets across 18 categories and 66 sub-categories, and covers over 50 000 lncRNAs. We not only collected lncRNA sets based on downstream regulatory data sources, but also identified a large number of lncRNA sets regulated by upstream transcription factors (TFs) and DNA regulatory elements by integrating TF ChIP-seq, DNase-seq, ATAC-seq and H3K27ac ChIP-seq data. Importantly, LncSEA provides annotation and enrichment analyses of lncRNA sets associated with upstream regulators and downstream targets. In summary, LncSEA is a powerful platform that provides a variety of types of lncRNA sets for users, and supports lncRNA annotations and enrichment analyses. The LncSEA database is freely accessible at http://bio.liclab.net/LncSEA/index.php.