Objective To investigate the effect of ATP synthase inhibitory factor 1 (ATPIF1) on the antitumor activity of chimeric antigen receptor (CAR)-NK92 cells. Methods HER2-targeted CAR-NK92 cells with ATPIF1 overexpression or knockdown were constructed. CAR-positive expression rate was detected by flow cytometry. Cell proliferation capacity was measured using CCK-8 assay. Glycolytic capacity was analyzed by Seahorse metabolic analyzer. Mitochondrial membrane potential levels were detected using JC-1 probe. Target cell lysis rate was evaluated by firefly luciferase reporter assay. Expression levels of CD107a, natural-killer group 2 member D (NKG2D), granzyme B (GzmB), perforin, and interleukin 2 (IL-2) were detected via flow cytometry. Quantitative real-time PCR was used to measure the expression of interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), tumor necrosis factor α (TNF-α), ATPIF1, and hexokinase 1 (HK1). The impact of glycolytic inhibition by 2-Deoxy-D-glucose (2-DG) on CAR-NK92 antitumor capacity was examined. Results Successfully generated HER2-targeting control CAR-NK92 cells, as well as ATPIF1-overexpressing and ATPIF1 knockdown CAR-NK92 cells. The ATPIF1-overexpressing CAR-NK92 cells showed significantly enhanced target cell lysis rate, elevated expression levels of NKG2D and CD107a, increased secretion capacities of Granzyme B (GzmB) and IL-2, and upregulated mRNA expression levels of IFIT1 and TNF-α, while ATPIF1-knockdown cells exhibited opposite effects. ATPIF1 overexpression induced metabolic reprogramming in CAR-NK92 cells, manifested by significantly decreased mitochondrial membrane potential (δpsim), markedly upregulated HK1 mRNA expression, and enhanced basal glycolysis and glycolytic capacity. After glycolysis inhibition with 2-DG (5 μmol/L), both ATPIF1-overexpressing and knockdown CAR-NK92 cells showed no significant differences in NKG2D and CD107a expression levels compared to control cells. Conclusion ATPIF1 regulates the antitumor activity of CAR-NK92 cells through modulating glycolytic metabolism. Overexpression of ATPIF1 can enhance the antitumor efficacy of CAR-NK92 cells.
Humans ; Glycolysis ; Killer Cells, Natural/metabolism* ; Receptors, Chimeric Antigen/immunology* ; Granzymes/genetics* ; Hexokinase/metabolism* ; Cell Line, Tumor ; Interleukin-2/genetics* ; Cell Proliferation ; NK Cell Lectin-Like Receptor Subfamily K/genetics* ; Membrane Potential, Mitochondrial

Objective To design and evaluate a dilation incision device capable of facilitating stable support and flexible adjustment during neurosurgical procedures.Methods The dilation incision device was composed of a support plate,an adjustment assembly,a brain support ring,a rotation assembly,an electric motor,an expansion assembly and a neck support ring.The support plate was made of high-strength stainless steel;the adjustment assembly was made up of a first screw,a lifting groove,a slide bar and a nut;the brain support ring was fixed to the adjustment assembly through a support rod,with an outer layer of medical-grade silicone and an inner layer of stainless steel skeleton;the rotation assembly connected the brain support ring with the expansion assembly and consisted of a rotating shaft,a connecting rod and a rotating lug;a high-precision direct current servo motor was selected for the device;the expansion assembly included a spring,an expansion plate and a moving plate,which realized auto expansion or contraction through spring pressure;the neck support ring had its outer layer made of flexible polyurethane foam and inner layer being a stainless steel skeleton.The device had its stability and safety evaluated by static and dynamic tests at different heights(50,100,150 mm)and angles(0°,30°,60°),which was compared with the traditional fixation device to verify its application effect.Results Static and dynamic tests indicated the device showed high stability and safety in different heights and angles,and gained advantages over the traditional device in stability,convenient operation and surgical field visualization.Conclusion The device developed meets the requirements of neurosurgical procedures,and enhances the safety and portability of neurosurgical procedures.[Chinese Medical Equipment Journal,2024,45(10):37-40]

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.