Digested wastewater contains pathogenic microorganisms and high ammonia concentrations,which can pose a potential risk to public health.Effective removal of pathogens and nitrogen is crucial for the post-treatment of ...Digested wastewater contains pathogenic microorganisms and high ammonia concentrations,which can pose a potential risk to public health.Effective removal of pathogens and nitrogen is crucial for the post-treatment of digested wastewater.Partial nitrification-anammox is an energy-saving nitrogen removal process.Free nitrous acid(FNA),an intermediate product of partial nitrification,has the potential to inactivate microorganisms.However,the efficiency and mechanisms of FNA-related inactivation in pathogens during partial nitrification remains unclear.In this study,Enterococcus and Escherichia coli(E.coli)were selected to investigate the efficiency and mechanisms of FNA-related inactivation in partial nitrification process.The results revealed that 83%±13%and 59%±27%of E.coli and Enterococcus were removed,respectively,in partial nitrification process at FNA concentrations of 0.023−0.028 mg/L.When the concentration of FNA increased from 0 to 0.5 mg/L,the inactivation efficiencies of E.coli and Enterococcus increased from 0 to 99.9%and 89.9%,respectively.Enterococcus exhibited a higher resistance to FNA attack compared to E.coli.3D-laser scanning microscopy(3D-LSM)and scanning electron microscopy(SEM)revealed that FNA exposure caused the surface collapse of E.coli and Enterococcus,as well as visible pore formation on the surface of E.coli cells.4',6-Diamidino-2-phenylindole dihydrochloride n-hydrate(DAPI)/propidium iodide(PI)and biomolecule leakage confirmed that inactivation of E.coli and Enterococcus occurred due to breakdown of cell walls and cell membranes.These findings indicate that partial nitrification process can be used for the removal of residual pathogenic microorganisms.展开更多
Cancer vaccines represent a promising immunotherapeutic treatment modality.The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex(MHC) class I molecules ...Cancer vaccines represent a promising immunotherapeutic treatment modality.The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex(MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects.Current vaccination strategies,however,are not able to achieve the spatiotemporal control of antigen cross-presentation.Here,we report a liposomal vaccine loading the second near-infrared window(NIR-II,1000—1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance.The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes(DLNs).Moreover,the photothermally induced endolysosomal rupture initiates autophagy.We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/m TOR pathway.The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation.This study presents a paradigm of NIR-II image-guided light-triggered vaccination.The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.展开更多
Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer,but its function and regulatory network in metastasis remain unclear.A comprehensive investigation of key regulators in can...Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer,but its function and regulatory network in metastasis remain unclear.A comprehensive investigation of key regulators in cancer metastasis is urgently needed.Transcriptome sequencing(RNA-seq)of primary esophageal squamous cell carcinoma(ESCC)and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4(KCTD4)as a driver of cancer metastasis.KCTD4 expression was found upregulated in metastatic ESCC.High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo.Mechanistically,KCTD4 binds to CLIC1 and disrupts its dimerization,thus increasing intracellular Ca^(2+)level to enhance NFATc1-dependent fibronectin transcription.KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner,which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback.Furthermore,a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4-CLIC1 interaction,providing a potential therapeutic strategy.Taken together,our study not only uncovers KCTD4 as a regulator of calcium homeostasis,but also reveals KCTD4/CLIC1-Ca^(2+)-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis.These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.展开更多
基金supported by the Natural Science Foundation of Anhui Province(China)(No.2208085ME145)the Key Project of Science and Technology in Anhui Province(China)(No.1801041130)the National Key R&D Program of China(No.2019YFC0408502).
文摘Digested wastewater contains pathogenic microorganisms and high ammonia concentrations,which can pose a potential risk to public health.Effective removal of pathogens and nitrogen is crucial for the post-treatment of digested wastewater.Partial nitrification-anammox is an energy-saving nitrogen removal process.Free nitrous acid(FNA),an intermediate product of partial nitrification,has the potential to inactivate microorganisms.However,the efficiency and mechanisms of FNA-related inactivation in pathogens during partial nitrification remains unclear.In this study,Enterococcus and Escherichia coli(E.coli)were selected to investigate the efficiency and mechanisms of FNA-related inactivation in partial nitrification process.The results revealed that 83%±13%and 59%±27%of E.coli and Enterococcus were removed,respectively,in partial nitrification process at FNA concentrations of 0.023−0.028 mg/L.When the concentration of FNA increased from 0 to 0.5 mg/L,the inactivation efficiencies of E.coli and Enterococcus increased from 0 to 99.9%and 89.9%,respectively.Enterococcus exhibited a higher resistance to FNA attack compared to E.coli.3D-laser scanning microscopy(3D-LSM)and scanning electron microscopy(SEM)revealed that FNA exposure caused the surface collapse of E.coli and Enterococcus,as well as visible pore formation on the surface of E.coli cells.4',6-Diamidino-2-phenylindole dihydrochloride n-hydrate(DAPI)/propidium iodide(PI)and biomolecule leakage confirmed that inactivation of E.coli and Enterococcus occurred due to breakdown of cell walls and cell membranes.These findings indicate that partial nitrification process can be used for the removal of residual pathogenic microorganisms.
基金supported in part by grants from National Natural Science Foundation of China(No.81991493,China)Shanghai Municipal Health Commission(No.2022XD045,China)。
文摘Cancer vaccines represent a promising immunotherapeutic treatment modality.The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex(MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects.Current vaccination strategies,however,are not able to achieve the spatiotemporal control of antigen cross-presentation.Here,we report a liposomal vaccine loading the second near-infrared window(NIR-II,1000—1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance.The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes(DLNs).Moreover,the photothermally induced endolysosomal rupture initiates autophagy.We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/m TOR pathway.The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation.This study presents a paradigm of NIR-II image-guided light-triggered vaccination.The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.
基金supported by National Natural Science Foundation of China(82273368,82073196,82204455)the National Key Research and Development Program of China(2021YFC2501900)+4 种基金Natural Science foundation of Guangdong Province(2021A1515011158,2021A0505030035,China)Guangdong Basic and Applied Basic Research Foundation Outstanding Youth Project(2023B1515020012,China)Guangzhou Science and Technology Project(202201020032,China)Key Laboratory of Guangdong Higher Education Institutes(2021KSY009,China)Open Project funded by the MOE Key Laboratory of Tumor Molecular Biology(2023 Open Project-50411651-2020-1,China)。
文摘Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer,but its function and regulatory network in metastasis remain unclear.A comprehensive investigation of key regulators in cancer metastasis is urgently needed.Transcriptome sequencing(RNA-seq)of primary esophageal squamous cell carcinoma(ESCC)and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4(KCTD4)as a driver of cancer metastasis.KCTD4 expression was found upregulated in metastatic ESCC.High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo.Mechanistically,KCTD4 binds to CLIC1 and disrupts its dimerization,thus increasing intracellular Ca^(2+)level to enhance NFATc1-dependent fibronectin transcription.KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner,which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback.Furthermore,a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4-CLIC1 interaction,providing a potential therapeutic strategy.Taken together,our study not only uncovers KCTD4 as a regulator of calcium homeostasis,but also reveals KCTD4/CLIC1-Ca^(2+)-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis.These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.