المؤلفون: Ying Gao, Xueping Zheng, Boyang Chang, Yujie Lin, Xiaodan Huang, Wen Wang, Shirong Ding, Weixiang Zhan, Shang Wang, Beibei Xiao, Lanqing Huo, Youhui Yu, Yilin Chen, Run Gong, Yuanzhong Wu, Ruhua Zhang, Li Zhong, Xin Wang, Qiuyan Chen, Song Gao, Zhengfan Jiang, Denghui Wei, Tiebang Kang

المصدر: Cell Research. 32:1086-1104

مصطلحات موضوعية: Mice, Autophagosomes, Autophagy, Tumor Microenvironment, Animals, Membrane Proteins, Humans, Nasopharyngeal Neoplasms, Cell Biology, Lysosomes, Molecular Biology, Immunity, Innate

الوصف: STING, an endoplasmic reticulum (ER) transmembrane protein, mediates innate immune activation upon cGAMP stimulation and is degraded through autophagy. Here, we report that activated STING could be transferred between cells to promote antitumor immunity, a process triggered by RAB22A-mediated non-canonical autophagy. Mechanistically, RAB22A engages PI4K2A to generate PI4P that recruits the Atg12–Atg5–Atg16L1 complex, inducing the formation of ER-derived RAB22A-mediated non-canonical autophagosome, in which STING activated by agonists or chemoradiotherapy is packaged. This RAB22A-induced autophagosome fuses with RAB22A-positive early endosome, generating a new organelle that we name Rafeesome (RAB22A-mediated non-canonical autophagosome fused with early endosome). Meanwhile, RAB22A inactivates RAB7 to suppress the fusion of Rafeesome with lysosome, thereby enabling the secretion of the inner vesicle of the autophagosome bearing activated STING as a new type of extracellular vesicle that we define as R-EV (RAB22A-induced extracellular vesicle). Activated STING-containing R-EVs induce IFNβ release from recipient cells to the tumor microenvironment, promoting antitumor immunity. Consistently, RAB22A enhances the antitumor effect of the STING agonist diABZI in mice, and a high RAB22A level predicts good survival in nasopharyngeal cancer patients treated with chemoradiotherapy. Our findings reveal that Rafeesome regulates the intercellular transfer of activated STING to trigger and spread antitumor immunity, and that the inner vesicle of non-canonical autophagosome originated from ER is secreted as R-EV, providing a new perspective for understanding the intercellular communication of organelle membrane proteins.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::82219cc42773e10bb531492343612681Test
https://doi.org/10.1038/s41422-022-00731-wTest

المؤلفون: Denghui, Wei, Xiaojing, Zhang, Shengnan, Zhang, Jiaqian, Dai, Jianghui, Du, Yu, He, Xiaoyu, Wen

المصدر: Journal of Environmental Science and Health, Part A. 57:510-517

مصطلحات موضوعية: Bioreactors, Environmental Engineering, Sewage, Nitrogen, Sulfates, Ammonium Compounds, Denitrification, Anaerobiosis, General Medicine, Wastewater, Oxidation-Reduction

الوصف: Anaerobic ammonium oxidation (Anammox) was an innovative process for nitrogen removal. In this study, the influence of sulfate in different concentrations (100, 200, 300, and 400 mg L

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c96f099c4febd1e40f03c6a1f78ffbaTest
https://doi.org/10.1080/10934529.2022.2083901Test

المؤلفون: Ya-Qin Wang, Dong-Hong Wu, Denghui Wei, Jia-Yi Shen, Zi-Wei Huang, Xiao-Yu Liang, William C.S. Cho, Jun Ma, Jiawei Lv, Yu-Pei Chen

المصدر: Science Advances. 9

مصطلحات موضوعية: Multidisciplinary

الوصف: The molecular basis underlying nasopharyngeal carcinoma (NPC) remains unclear. Recent progress in transcriptional regulatory network analysis helps identify the master regulator (MR) proteins that transcriptionally define malignant tumor phenotypes. Here, we investigated transcription factor-target interactions and identified TEA domain transcription factor 4 (TEAD4) as an MR of high-risk NPC. Precisely, TEAD4 promoted NPC migration, invasion and cisplatin resistance, depending on its autopalmitoylation. Mechanistically, YTHDF2 (YTH domain family 2) recognized WTAP (Wilms tumor 1–associating protein)–mediated TEAD4 m 6 A methylation to facilitate its stability and led to aberrant up-regulation of TEAD4. Up-regulated TEAD4 further drove NPC progression by transcriptionally activating BZW2 (basic leucine zipper and W2 domains 2) to induce the oncogenic AKT pathway. Moreover, the transcriptional activity of TEAD4 was independent of its canonical coactivators YAP/TAZ. Clinically, TEAD4 serves as an independent predictor of unfavorable prognosis and cisplatin response in NPC. Our data revealed the crucial role of TEAD4 in driving tumor malignancy, thus, may provide therapeutic vulnerability in NPC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::db02c28402ac1f23b5ff6c4e106f5f4bTest
https://doi.org/10.1126/sciadv.add0960Test

المؤلفون: Zi-Qi Zheng, Zhuo-Hui Huang, Ye-Lin Liang, Wei-Hong Zheng, Cheng Xu, Zhi-Xuan Li, Na Liu, Pan-Yang Yang, Ying-Qin Li, Jun Ma, Ying Sun, Ling-Long Tang, Denghui Wei

المصدر: Journal of Biological Chemistry. 299:104677

مصطلحات موضوعية: Cell Biology, Molecular Biology, Biochemistry

الوصف: The N6-methyladenosine (m6A) modification possesses new and essential roles in tumor initiation and progression by regulating mRNA biology. However, the role of aberrant m6A regulation in nasopharyngeal carcinoma (NPC) remains unclear. Here, through comprehensive analyses of NPC cohorts from the GEO database (GES12452, GSE12349, and GSE61218) and our internal cohort, we identified that VIRMA, an m6A writer, is significantly upregulated in NPC and plays an essential role in tumorigenesis and metastasis of NPC, both in vitro and in vivo. High VIRMA expression served as a prognostic biomarker and was associated with poor outcomes in patients with NPC. Mechanistically, VIRMA mediated the m6A methylation of E2F7 3′-UTR, then IGF2BP2 bound and maintained the stability of E2F7 mRNA. An integrative high-throughput sequencing approach revealed that E2F7 drives a unique transcriptome distinct from the classical E2F family in NPC, which functioned as an oncogenic transcriptional activator. E2F7 cooperated with CBFB-recruited RUNX1 in a non-canonical manner to transactivate ITGA2, ITGA5, and NTRK1, strengthening Akt signaling-induced tumor-promoting effect. These results together demonstrate the role of VIRMA as an m6A writer that modulates E2F7 expression to control the transcription program of NPC, unveiling an m6A modulator that is essential for NPC tumorigenesis and metastasis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1cb12fa993feb0b652128b7eff95bb05Test
https://doi.org/10.1016/j.jbc.2023.104677Test

المؤلفون: Wei-Hong Zheng, Zhi-Qing Long, Zi-Qi Zheng, Lu-Lu Zhang, Ye-Lin Liang, Zhi-Xuan Li, Jia-Wei Lv, Jia Kou, Xiao-Hong Hong, Shi-Wei He, Rui Xu, Guan-Qun Zhou, Na Liu, Jun Ma, Ying Sun, Li Lin, Denghui Wei

المصدر: Journal of Biological Chemistry. :104873

مصطلحات موضوعية: Cell Biology, Molecular Biology, Biochemistry

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::6076e86dd59c34b06d46eb2d35589ad1Test
https://doi.org/10.1016/j.jbc.2023.104873Test

المؤلفون: Wang, Ya-Qin, Wu, Dong-Hong, Denghui Wei, Shen, Jia-Yi, Huang, Zi-Wei, Liang, Xiao-Yu, Cho, William C.S., Ma, Jun, Jiawei Lv, Chen, Yu-Pei

الوصف: The Algorithm for the Reconstruction of Accurate Cellular Networks through Adaptive Partitioning (ARACNe-AP) was applied to construct transcriptional interactomes in gene expression profiles from cohorts of patients with nasopharyngeal carcinoma.Then the Virtual Inference of Protein Activity by Enriched Regulon (VIPER) algorithm was applied to prioritize master regulator proteins based on the inferred transcriptional activity. Scripts: · 1-ARACNe-AP.ps1: PowerShell script for the constructof transcriptional interactomes. · 2-VIPER.R:R script for the identification of master regulator proteinsbased on the inferred transcriptional activity. Data: · Expression matrix (GSE12452 and GSE102349): Public nasopharyngeal carcinoma datasets, which can be obtained from GEO database (https://www.ncbi.nlm.nih.gov/geoTest/). · Transcription Factors (TFs) list: List of Human transcription factors, which can be obtained from http://humantfs.ccbr.utoronto.ca/download/v_1.01/TF_names_v_1.01.txtTest Please refer to the following paper for more details: Ya-Qin Wang#, Dong-Hong Wu#, Denghui Wei#, Jia-Yi Shen#, Zi-Wei Huang#, et al., Jiawei Lv*, Yu-Pei Chen*. TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::12eb266b3db53898761f41aae8ecb1aeTest

المؤلفون: Jiawei Lv, Chenfei Wu, Junyan Li, Foping Chen, Shiwei He, Qingmei He, Guanqun Zhou, Jun Ma, Ying Sun, Denghui Wei, Li Lin

المصدر: BMC Medicine. 20

مصطلحات موضوعية: Cohort Studies, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Humans, Nasopharyngeal Neoplasms, General Medicine, Neoplasm Recurrence, Local, Prognosis, Risk Assessment, Circulating Tumor DNA

الوصف: Background Significant intertumoral heterogeneity exists as antitumor treatment is introduced. Heterogeneous therapeutic responses are conventionally evaluated by imaging examinations based on Response Evaluation Criteria in Solid Tumors (RECIST); nevertheless, there are increasing recognitions that they do not fully capture patient clinical benefits. Currently, there is a paucity of data regarding the clinical implication of biological responses assessed by liquid biopsy of on-treatment circulating tumor DNA (ctDNA). Here, we investigated whether biological response evaluated by ctDNA kinetics added critical information to the RECIST, and whether integrating on-treatment biological response information refined risk stratification of cancer patients. Methods In this population-based cohort study, we included 821 patients with Epstein-Barr virus (EBV)-associated nasopharynx of head and neck cancer (NPC) receiving sequential neoadjuvant chemotherapy (NAC) and chemoradiotherapy (CRT), who had pretreatment and on-treatment cfEBV DNA and magnetic resonance imaging (MRI) surveillance. Biological responses evaluated by cfEBV DNA were profiled and compared with conventional MRI-based RECIST evaluation. The inverse probability weighting (IPW)-adjusted survival analysis was performed for major survival endpoints. The Cox proportional hazard regression [CpH]-based model was developed to predict the on-treatment ctDNA-based individualized survival. Results Of 821 patients, 71.4% achieved complete biological response (cBR) upon NAC completion. RECIST-based response evaluations had 25.3% discordance with ctDNA-based evaluations. IPW-adjusted survival analysis revealed that cfEBV DNApost-NAC was a preferential prognosticator for all endpoints, especially for distant metastasis. In contrast, radiological response was more preferentially associated with locoregional recurrence. Intriguingly, cfEBV DNApost-NAC further stratified RECIST-responsive and non-responsive patients; RECIST-based non-responsive patients with cBR still derived substantial clinical benefits. Moreover, detectable cfEBV DNApost-NAC had 83.6% prediction sensitivity for detectable post-treatment ctDNA, which conferred early determination of treatment benefits. Finally, we established individualized risk prediction models and demonstrated that introducing on-treatment ctDNA significantly refined risk stratification. Conclusions Our study helps advance the implementation of ctDNA-based testing in therapeutic response evaluation for a refined risk stratification. The dynamic and refined risk profiling would tailor future liquid biopsy-based risk-adapted personalized therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5bb039ba9f6ce4852bc3ff1801cea050Test
https://doi.org/10.1186/s12916-022-02463-5Test

المؤلفون: Hongli Zhang, Xiaojing Zhang, Denghui Wei, Xiaoyu Wen, Shijie Zhou, Yuqi Li, Yongen Dong, Yaoyao Gong

المصدر: Chemosphere. 313:137468

مصطلحات موضوعية: Environmental Engineering, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Environmental Chemistry, General Medicine, General Chemistry, Pollution

الوصف: Nitrogen and sulfur pollutants coexist in many industrial wastewaters, which may cause serious water pollution issues. In this study, Anammox coupled with sulfide-depending autotrophic denitrification process (coupling process) was established by adding sulfide to an Anammox system in a membrane bioreactor. Variations in nitrogen and sulfur removal performance, extracellular polymeric substances (EPS), key enzyme activities, and microbial components were analyzed. The sulfide in 25.0 mg L

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::647d5938d70bff0e560a4f487ac6e99cTest
https://doi.org/10.1016/j.chemosphere.2022.137468Test

المؤلفون: Denghui Wei, Xiaojing Zhang, Zhao Chen, Yu He, Jiaqian Dai, Shengnan Zhang

المصدر: Water Environment Research. 94

مصطلحات موضوعية: Ecological Modeling, Environmental Chemistry, Waste Management and Disposal, Pollution, Water Science and Technology

الوصف: In this study, three anaerobic digestion reactors using up-flow anaerobic sludge blanket (UASB), anaerobic sequencing batch reactor (AnSBR), and anaerobic membrane bioreactor (AnMBR) were studied. The chemical oxygen demand (COD), gas production, sludge performance, and microbial characteristics of the anaerobic digestion process were assessed. The results showed that the average COD removal efficiencies reached 86%, 83%, and 85%, with corresponding removed rates of 2.49, 0.48, and 0.79 kg COD m

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e60b3396d91d3a1c4348fd58ece07d0Test
https://doi.org/10.1002/wer.10702Test

المؤلفون: Bingbing Ma, Xiaojing Zhang, Denghui Wei, Yongpeng Ma, Qiong Wang, Han Zhang, Jiajie Zhang

المصدر: Journal of Water Process Engineering. 49:103176

مصطلحات موضوعية: Process Chemistry and Technology, Safety, Risk, Reliability and Quality, Waste Management and Disposal, Biotechnology

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::51e468dc4ab88457e8761290a521e073Test
https://doi.org/10.1016/j.jwpe.2022.103176Test