MTA3 Represses Cancer Stemness by Targeting the SOX2OT/SOX2 Axis

Cancer cell stemness (CCS) plays critical roles in both malignancy maintenance and metastasis, yet the underlying molecular mechanisms are far from complete. Although the importance of SOX2 in cancer development and CCS are well recognized, the role of MTA3 in these processes is unknown. In this study, we used esophageal squamous cell carcinoma (ESCC) as a model system to demonstrate that MTA3 can repress both CCS and metastasis in vitro and in vivo. Mechanistically, by forming a repressive complex with GATA3, MTA3 downregulates SOX2OT, subsequently suppresses the SOX2OT/SOX2 axis, and ultimately represses CCS and metastasis. More importantly, MTA

MTA3 Represses Cancer Stemness by Targeting the SOX2OT/SOX2 Axis

Cancer cell stemness (CCS) plays critical roles in both malignancy maintenance and metastasis, yet the underlying molecular mechanisms are far from complete. Although the importance of SOX2 in cancer development and CCS are well recognized, the role of MTA3 in these processes is unknown. In this study, we used esophageal squamous cell carcinoma (ESCC) as a model system to demonstrate that MTA3 can repress both CCS and metastasis in vitro and in vivo. Mechanistically, by forming a repressive complex with GATA3, MTA3 downregulates SOX2OT, subsequently suppresses the SOX2OT/SOX2 axis, and ultimately represses CCS and metastasis. More importantly, MTA

Metabolic Labeling of Peptidoglycan with NIR-II Dye Enables in vivo Imaging of Gut Microbiota.

Deepening our understanding of mammalian gut microbiota has been greatly hampered by the lack of a facile, real-time and in vivo bacterial imaging method. To address this unmet need in microbial visualization, we herein report the development of a second near-infrared (NIR-II)-based method for in vivo imaging of gut bacteria. Using D-propargylglycine in gavage and then click reaction with an azide-containing NIR-II dye, gut microbiota of a donor mouse was strongly labeled with NIR-II fluorescence on their peptidoglycan. The bacteria could be readily visualized in recipient mouse gut with high spatial resolution and deep tissue penetration under NIR irradiation. We then adopted this chemical strategy to image different bacterial species, which expanded its applicability in microbiology. Moreover, by employing this method, we found that the biogeography of gut microbiota was dramatically affected by host’s gastrointestinal motilities. The NIR-II-based metabolic labeling strategy reported here, to our knowledge, provides the first protocol for facile in vivo visualization of gut microbiota within deep tissues, and offers an instrumental tool for deciphering the complex biology of these gut "dark matters"

Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling

Smoking is one of the most impactful lifestyle-related risk factors in many cancer types including esophageal squamous cell carcinoma (ESCC). As the major component of tobacco and e-cigarettes, nicotine is not only responsible for addiction to smoking but also a carcinogen. Here we report that nicotine enhances ESCC cancer malignancy and tumor-initiating capacity by interacting with cholinergic receptor nicotinic alpha 7 subunit (CHRNA7) and subsequently activating the JAK2/STAT3 signaling pathway. We found that aberrant CHRNA7 expression can serve as an independent prognostic factor for ESCC patients. In multiple ESCC mouse models, dextromethorphan and metformin synergistically repressed nicotine-enhanced cancer-initiating cells (CIC) properties and inhibited ESCC progression. Mechanistically, dextromethorphan non-competitively inhibited nicotine binding to CHRNA7 while metformin downregulated CHRNA7 expression by antagonizing nicotine-induced promoter DNA hypomethylation of CHRNA7. Since dextromethorphan and metformin are two safe FDA-approved drugs with minimal undesirable side-effects, the combination of these drugs has a high potential as either a preventive and/or a therapeutic strategy against nicotine-promoted ESCC and perhaps other nicotine-sensitive cancer types as well

Correction:Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling (Oncogene, (2021), 40, 11, (1974-1987), 10.1038/s41388-021-01682-z)

Only after the article was published online did the authors notice the misspelling of the second author’s name. It should be “Liang Du” instead of “Du Liang”. The authors sincerely apologize for any inconvenience this might have caused. The original article has been corrected

Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling

Smoking is one of the most impactful lifestyle-related risk factors in many cancer types including esophageal squamous cell carcinoma (ESCC). As the major component of tobacco and e-cigarettes, nicotine is not only responsible for addiction to smoking but also a carcinogen. Here we report that nicotine enhances ESCC cancer malignancy and tumor-initiating capacity by interacting with cholinergic receptor nicotinic alpha 7 subunit (CHRNA7) and subsequently activating the JAK2/STAT3 signaling pathway. We found that aberrant CHRNA7 expression can serve as an independent prognostic factor for ESCC patients. In multiple ESCC mouse models, dextromethorphan and metformin synergistically repressed nicotine-enhanced cancer-initiating cells (CIC) properties and inhibited ESCC progression. Mechanistically, dextromethorphan non-competitively inhibited nicotine binding to CHRNA7 while metformin downregulated CHRNA7 expression by antagonizing nicotine-induced promoter DNA hypomethylation of CHRNA7. Since dextromethorphan and metformin are two safe FDA-approved drugs with minimal undesirable side-effects, the combination of these drugs has a high potential as either a preventive and/or a therapeutic strategy against nicotine-promoted ESCC and perhaps other nicotine-sensitive cancer types as well

Combination of dynamic pH junction with capillary electrophoresis-mass spectrometry for the determination of systemins in plant samples

Systemin is an important group of plant peptide hormones participating in the regulation of plant defensive responses. An improved method, based on dynamic pH junction and capillary electrophoresis-quadrupole time-of-flight mass spectrometry, was developed for online enrichment and sensitive determination of trace systemins in plants. After optimization, the online enrichment factors for six target systemins ranged from 90- to 127-fold. The detection limits reached lower than 0.5 nM, which were comparable with the sensitivity of LC-MS method. Satisfactory quantitative results were obtained in terms of linearity (R-2 >= 0.993), dynamic range (3-120 ng/mL), and reproducibility (<= 6.7%). For the analysis of real plant samples, a rapid sample preparation method was developed, using two steps of SPE purification with different retention and separation mechanisms. Finally, this method realized the successful detection of tomato systemin and tobacco hydroxyproline-rich systemin I from plant leaves with shorter analysis time

Simultaneous discrimination of jasmonic acid stereoisomers by CE-QTOF-MS employing the partial filling technique

Jasmonic acid (JA), an essential plant hormone controlling the plant defense signaling system and developmental processes, has stereospecific bioactivities that have not been well understood mainly due to the limitation in separation and detection methodologies. In this work, a fast CE-UV method based on short-end injection technique and a sensitive CE-QTOF-MS method based on partial filling technique were successfully developed for the enantioseparation of racemic JA. The successive coating technique was also involved by modifying the capillary with multiple ionic polymer layers of polybrene-dextran sulfate-polybrene. This was the first report on the direct resolution of both pairs of JA enantiomers, including two naturally occurring JA stereoisomers. Although no pure JA stereoisomers were commercially available, all the separated JA stereoisomers were identified indirectly by comparing the difference between the racemic standard and plant samples based on the presence and the ratio of each stereoisomer. Satisfactory results were obtained in terms of sensitivity (LOD, 24 ng/mL or 0.7 fmol for single JA stereoisomer) using 45 mmol/L ammonium acetate at pH 4.5 containing 70 mmol/L alpha-CD as the buffer system. This established CE-QTOF-MS method was later successfully applied for the study of the naturally occurring JA stereoisomers in wounded tobacco leaves

Reduced Graphene Oxide-Hybridized Polymeric High-Internal Phase Emulsions for Highly Efficient Removal of Polycyclic Aromatic Hydrocarbons from Water Matrix

Reduced graphene oxide (RGO)-hybridized polymeric high-internal phase emulsions (RGO/polyHIPEs) with an open-cell structure and hydrophobicity have been successfully prepared using 2-ethylhexyl acrylate and ethylene glycol dimethacrylate as the monomer and the cross-linker, respectively. The adsorption mechanism and performance of this RGO/polyHIPEs to polycyclic aromatic hydrocarbons (PAHs) were investigated. Adsorption isotherms of PAHs on RGO/polyHIPEs show that the saturated adsorption capacity is 47.5 mg/g and the equilibrium time is 8 h. Cycling tests show that the adsorption capacity of RGO/polyHIPEs remains stable in 10 adsorption–desorption cycles without observable structure change in RGO/polyHIPEs. Moreover, the PAH residues in water samples after being purified by RGO/polyHIPEs are lower than the limit values in drinking water set by the European Food Safety Authority. These results demonstrate that the RGO/polyHIPEs have great potentiality in PAH removal and water purification