Nucleolin Malonylation as a Nuclear-Cytosol Signal Exchange Mechanism to Drive Cell Proliferation in Hepatocarcinoma by Enhancing AKT Translation.

Cancer cells undergo metabolic reprogramming that is intricately linked to malignancy. Protein acylations are especially responsive to metabolic changes, influencing signal transduction pathways and fostering cell proliferation. However, as a novel type of acylations, the involvement of malonylation in cancer remains poorly understood. In this study, we observed a significant reduction in malonyl-CoA levels in hepatocellular carcinoma (HCC), which correlated with a global decrease in malonylation. Subsequent nuclear malonylome analysis unveiled nucleolin (NCL) malonylation, which was notably enhanced in HCC biopsies. we demonstrated that NCL undergoes malonylation at lysine residues 124 and 398. This modification triggers the translocation of NCL from the nucleolus to nucleoplasm and cytoplasm, binding to AKT mRNA, and promoting AKT translation in HCC. Silencing AKT expression markedly attenuated HCC cell proliferation driven by NCL malonylation. These findings collectively highlight nuclear signaling in modulating AKT expression, suggesting NCL malonylation as a novel mechanism through which cancer cells drive cell proliferation.

Plasma-based ambient mass spectrometry: Recent progress and applications.

Ambient mass spectrometry (AMS) has grown as a group of advanced analytical techniques that allow for the direct sampling and ionization of the analytes in different statuses from their native environment without or with minimum sample pretreatments. As a significant category of AMS, plasma-based AMS has gained a lot of attention due to its features that allow rapid, real-time, high-throughput, in vivo, and in situ analysis in various fields, including bioanalysis, pharmaceuticals, forensics, food safety, and mass spectrometry imaging. Tens of new methods have been developed since the introduction of the first plasma-based AMS technique direct analysis in real-time. This review first provides a comprehensive overview of the established plasma-based AMS techniques from their ion source configurations, mechanisms, and developments. Then, the progress of the representative applications in various scientific fields in the past 4 years (January 2017 to January 2021) has been summarized. Finally, we discuss the current challenges and propose the future directions of plasma-based AMS from our perspective.

Identification of a small-molecule RPL11 mimetic that inhibits tumor growth by targeting MDM2-p53 pathway.

BACKGROUND: Targeting ribosome biogenesis to activate p53 has recently emerged as a therapeutic strategy in human cancer. Among various ribosomal proteins, RPL11 centralizes the nucleolar stress-sensing pathway by binding MDM2, leading to MDM2 inactivation and p53 activation. Therefore, the identification of MDM2-binding RPL11-mimetics would be valuable for anti-cancer therapeutics. METHODS: Based on the crystal structure of the interface between RPL11 and MDM2, we have identified 15 potential allosteric modulators of MDM2 through the virtual screening. RESULTS: One of these compounds, named S9, directly binds MDM2 and competitively inhibits the interaction between RPL11 and MDM2, leading to p53 stabilization and activation. Moreover, S9 inhibits cancer cell proliferation in vitro and in vivo. Mechanistic study reveals that MDM2 is required for S9-induced G2 cell cycle arrest and apoptosis, whereas p53 contributes to S9-induced apoptosis. CONCLUSIONS: Putting together, S9 may serve as a lead compound for the development of an anticancer drug that specifically targets RPL11-MDM2-p53 pathway.

Ultrasensitive and Simultaneous Detection of Multielements in Aqueous Samples Based on Biomimetic Array Combined with Laser-Induced Breakdown Spectroscopy.

Ultrasensitive detection of metallic elements in liquids has attracted considerable attention in fields such as environmental pollution monitoring and drinking water quality control. Hence, it is of great significance to develop a sensitive and simultaneous detection strategy for multiple metal elements in liquid. Laser-induced breakdown spectroscopy (LIBS) technology shows unique advantages because of its simple, rapid, and real-time in situ detection, but the laser energy will be greatly attenuated in the liquids; thus, the sensitivity of LIBS for direct detection of metal elements in liquid samples will decrease sharply. In this study, inspired by the structure of Stenocara beetle's back, a superhydrophobic biomimetic interface with hydrophilic array was prepared for enriching low-concentration targets into detection regions, and the biomimetic array LIBS (BA-LIBS) was successfully established. The ultrasensitive and simultaneous detection of nine metal elements in drinking water was realized based on the effective enrichment method. The limits of detection of the nine metal elements in mixed solution ranged from 8.3 ppt to 13.49 ppb. With these excellent properties, this facile and ultrasensitive BA-LIBS strategy might provide a new idea for the prevention and control of metal hazards in the liquid environment.

Exploration and performance evaluation of microwave-induced plasma with different discharge gases for ambient desorption/ionization mass spectrometry.

RATIONALE: Microwave-induced plasma (MIP) with different discharge gases of argon or helium provides significant plasma-based ambient desorption/ionization sources, which have potential applicability in direct analysis of complex samples without any sample pre-treatment. In this study, experiments were conducted to better understand microwave-induced plasma desorption/ionization (MIPDI) sources and the corresponding ionization mechanisms. METHODS: Emission spectra of microwave-induced argon (MIP-Ar) and helium (MIP-He) plasmas were obtained from the plasma tail flame of a MIP source. Compounds including L-phenylalanine, L-serine, L-valine, urea, 4-acetaminophen, gallic acid and L-ascorbic acid were analyzed using both sources. Polyethylene glycol 400 (PEG400) oligomers were detected by MIP-Ar and MIP-He mass spectrometry at different microwave powers. Mass spectra of higher molecular weight PEGs (including PEG800, PEG1000 and PEG2000) were also acquired using both sources. RESULTS: In the emission spectra, N2 , H-I and O-I species were observed by MIP-Ar/He. In addition, SiO2 , Na-I, Si-I and Si-II species were generated by MIP-He. In the mass spectra of compounds, [M+H]+ , [2M+H]+ , [M+O+H]+ , [M+2O-H]+ and fragment ions were observed. In the mass spectra of PEG400 obtained by MIP-Ar/He at different microwave powers, higher molecular weight oligomers could only be observed with higher microwave power. PEGs with molecular weights as high as 1000 Da were also successfully analyzed by MIPDI. CONCLUSIONS: According to the different natures of the samples, either MIP-Ar or MIP-He can be chosen as a working ion source for mass spectrometry. The MIPDI source is potentially applicable to the analysis of compounds with high molecular weights, especially polymers with high degree of polymerization (such as PEG2000), which is a challenging issue for the traditional ambient ionization sources. Copyright © 2017 John Wiley & Sons, Ltd.

Exploration of Microplasma Probe Desorption/Ionization Mass Spectrometry (MPPDI-MS) for Biologically Related Analysis.

To expand the applications of glow discharge microplasma into biological analysis, an innovative ambient ion source for mass spectrometry, microplasma probe desorption/ionization mass spectrometry (MPPDI-MS), has been developed and demonstrated. Electrodes and a sampling tube were creatively combined using a stainless steel syringe needle, and efficient methods of introduction for biological samples in solid, liquid, and gaseous phases like phospholipid and amino acids were specially designed. Based on the active species generated by glow discharge plasma, simplified protonated spectra were obtained without extra solvent spray assistance. The method is easy to operate and versatile and especially has the ability to distinguish the isomeric compounds of ketone and aldehyde. Quantitative results of this method for different biological samples in different phases were also performed well. It was proved that with further improvement, this sensitive and selective analysis using MPPDI-MS with minimal invasiveness will be an ingenious tool in disease diagnosis and single-cell detections in the future.

A Novel Accurate Peak Extraction Algorithm of Mass Spectrometry Based on Iterative Adaptive Curve Fitting.

In the analysis of mass spectrometry, the peak identification from the overlapped region is necessary yet difficult. Although various methods have been developed to identify these peaks, especially the continuous wavelet transformation, their applications are still limited and it is hard to deal with the complex overlapped peaks. In this study, a novel peak extraction algorithm of mass spectrometry based on iterative adaptive curve fitting is proposed to address these challenges. It fully utilizes the global optimization characteristics of adaptive curve fitting. Initial peak parameters are obtained using a window searching method, and the residuals between the adaptive fitting peak and the original data indicate the fit's effectiveness and provide information about the peaks in overlap. Using this information, we performed iterative adaptive fitting, continuously updating the overlapped peaks until the residuals met the completion criteria. All of the peaks within the overlapped region can be successfully extracted by the final fitting. The proposed method is evaluated by the simulated data, the real signal from a public data set, and the spectra of two different mass spectrometry instruments. The results demonstrate that this method can more effectively extract peaks with severe overlap and multiple overlapped peaks, resist noise interference, and offer the potential to process peaks with a high dynamic range. More importantly, the proposed method accurately identifies overlapped peaks in the actual spectra from various mass spectrometry instruments, which helps the qualitative and quantitative analyses to a great extent.

The High-Efficiency Calculation and Analysis of Different Quadrupole Fields Based on the Method of Fundamental Solution.

The calculation and analysis of electric fields are indispensable steps in the design of mass spectrometry. In this work, an approach for this calculation was established based on the method of fundamental solution (MFS). It was proved to be much faster and more accurate than the other popular methods, and its optimum parameters were found for the calculation of different quadrupole fields. After this, quadrupole fields with round rods and different shielding covers were computed to investigate the impact of shielding covers, and a strategy of nonequilibrium allocation in the MFS was proposed to further improve the calculational efficiency. Moreover, through field calculation and mass analysis, the performances of the quadrupole fields with rectangular rods and different electrode cross section lengths were demonstrated, and their optimum sizes were also found. The proposed method and results of analysis in this work provided a highly efficient calculational approach and useful instruction for the design of a quadrupole mass filter.

Exhaled breath is found to be better than blood samples for determining propofol concentrations in the brain tissues of rats.

The correlation between propofol concentration in exhaled breath (CE) and plasma (CP) has been well-established, but its applicability for estimating the concentration in brain tissues (CB) remains unknown. Given the impracticality of directly sampling human brain tissues, rats are commonly used as a pharmacokinetic model due to their similar drug-metabolizing processes to humans. In this study, we measuredCE,CP, andCBin mechanically ventilated rats injected with propofol. Exhaled breath samples from the rats were collected every 20 s and analyzed using our team's developed vacuum ultraviolet time-of-flight mass spectrometry. Additionally, femoral artery blood samples and brain tissue samples at different time points were collected and measured using high-performance liquid chromatography mass spectrometry. The results demonstrated that propofol concentration in exhaled breath exhibited stronger correlations with that in brain tissues compared to plasma levels, suggesting its potential suitability for reflecting anesthetic action sites' concentrations and anesthesia titration. Our study provides valuable animal data supporting future clinical applications.

A study of the transient gas flow affected ion transmission in atmospheric pressure interfaces based on large eddy simulation for electrospray ionization mass spectrometry.

Modern atmosphere pressure interface (API) enables high-efficiency coupling between mass analyzers in high vacuum and atmosphere ionization sources such as electrospray ionization (ESI) source. The transient gas flow entering API possesses strong compressibility and turbulent characteristics, which exerts a huge impact on ion transmission. However, the instantaneous nature and vortical morphology of the turbulence in API and its affection in ion transmission were hardly covered in the reported research. Here we conduct a transient turbulent flow-affected ion transmission evaluation for two typical APIs, the ion funnel and the S-lens, based on scale-resolving large eddy simulation and electro-hydrodynamical ion tracing simulation. In our simulation, the transient properties of the gas flow in the two APIs are illustrated and analyzed in-depth. After experimentally validated on a homemade ESI-TOF-MS platform, the results suggest that the ion funnel can achieve a higher droplet desolvation rate by introducing a unique droplet recirculation mechanism. Meanwhile, the less-dispersed gas flow in S-lens is beneficial in actuating ions axially. In conclusion, the application of the scale-resolving turbulence model helps us to understand the complicated fluid-ion interaction mechanism in APIs and is promising in the development of mass spectrometry instruments of higher performance.

Microfabricated glow discharge plasma (MFGDP) for ambient desorption/ionization mass spectrometry.

A novel ambient ionization technique for mass spectrometry, microfabricated glow discharge plasma (MFGDP), is reported. This device is made of a millimeter-sized ceramic cavity with two platinum electrodes positioned face-to-face. He or Ar plasma can be generated by a direct current voltage of several hundreds of volts requiring a total power below 4 W. The thermal plume temperature of the He plasma was measured and found to be between 25 and 80 °C at a normal discharge current. Gaseous, liquid, creamy, and solid samples with molecular weights up to 1.5 kDa could be examined in both positive and negative mode, giving limits of detection (LOD) at or below the fg/mm(2) level. The relative standard deviation (RSD) of manual sampling ranged from 10% to ~20%, while correlation coefficients of the working curve (R(2)) are all above 0.98 with the addition of internal standards. The ionization mechanisms are examed via both optical and mass spectrometry. Due to the low temperature characteristics of the microplasma, nonthermal momentum desorption is considered to dominate the desorption process.

Microwave-induced plasma desorption/ionization source for ambient mass spectrometry.

A new ionization source based on microwave induced plasma was developed for ambient desorption/ionization. The microwave-induced plasma desorption/ionization source (MIPDI) was composed of a copper Surfatron microwave cavity where a fused-silica tube was centered axially. Stable nonlocal thermodynamic equilibrium plasma was generated in the quartz discharge tube when a microwave at a frequency of 2450 MHz was coupled to the microwave cavity. Analytes deposited on the surface of poly(tetrafluoroethylene) (PTFE) or quartz slide after hydrofluoric acid (HF) etching were desorbed and ionized by the plasma. The performance of the MIPDI technique was validated by the analysis of a variety of chemical substances, polymer compounds, and pharmaceutical drugs using argon or helium as the discharge gas. Protonated [M + H](+) or deprotonated [M - H](-) ions were observed in the positive or negative mode. MIPDI was also used for the analysis of compounds in a complex matrix without any sample preparation. MIPDI was also capable of analyzing liquid samples. The signal-to-noise ratio was 463 in the analysis of 9.2 ng of phenylalanine, and the limit of detection was 60 pg for phenylalanine. MIPDI could desorb and ionize analytes with a molecular weight of up to 1200, which was demonstrated by the analysis of polyethylene glycol 800 (PEG800). MIPDI has advantages of simple instrumentation, relatively high temperature, stability, and reproducibility.

Development of mass spectrometry imaging techniques and its latest applications.

Mass spectrometry imaging (MSI) is a novel molecular imaging technology that collects molecular information from the surface of samples in situ. The spatial distribution and relative content of various compounds can be visualized simultaneously with high spatial resolution. The prominent advantages of MSI promote the active development of ionization technology and its broader applications in diverse fields. This article first gives a brief introduction to the vital parts of the processes during MSI. On this basis, provides a comprehensive overview of the most relevant MS-based imaging techniques from their mechanisms, pros and cons, and applications. In addition, a critical issue in MSI, matrix effects is also discussed. Then, the representative applications of MSI in biological, forensic, and environmental fields in the past 5 years have been summarized, with a focus on various types of analytes (e.g., proteins, lipids, polymers, etc.) Finally, the challenges and further perspectives of MSI are proposed and concluded.

Calibration and validation of ultraviolet time-of-flight mass spectrometry for online measurement of exhaled ciprofol.

Ciprofol (HSK 3486, C14H20O), a novel 2,6-disubstituted phenol derivative similar to propofol, is a new type of intravenous general anaesthetic. We found that the exhaled ciprofol concentration could be measured online by ultraviolet time-of-flight mass spectrometry (UV-TOFMS), which could be used to predict the plasma concentration and anaesthetic effects of ciprofol. In this study, we present the calibration method and validation results of UV-TOFMS for the quantification of ciprofol gas. Using a self-developed gas generator to prepare different concentrations of ciprofol calibration gas, we found a linear correlation between the concentration and intensity of ciprofol from 0 parts per trillion by level (pptv) to 485.85 pptv (R2 = 0.9987). The limit of quantification was 48.59 pptv and the limit of detection was 7.83 pptv. The imprecision was 12.44% at 97.17 pptv and was 8.96% at 485.85 pptv. The carry-over duration was 120 seconds. In addition, we performed a continuous infusion of ciprofol in beagles, measured the exhaled concentration of ciprofol by UV-TOFMS, determined the plasma concentration by high-performance liquid chromatography, and monitored the anaesthetic effects as reflected by the bispectral index value. The results showed that the exhaled and plasma concentrations of ciprofol were linearly correlated. The exhaled ciprofol concentration correlated well with the anaesthetic effect. The study showed that we could use UV-TOFMS to provide a continuous measurement of gaseous ciprofol concentration at 20 second intervals.

Sandwiched composite electrolyte with excellent interfacial contact for high-performance solid-state sodium-ion batteries.

Solid-state sodium-ion batteries have attracted significant attention due to their rich resources, high safety, and high energy density. However, the lower ionic conductivity and inferior interfacial contact between solid-state electrolytes (SSEs) and electrodes limit their practical applications. Herein, polyvinylideneuoride-co-hexauoropropylene (PVDF-HFP) membrane is selected and a novel sandwiched composite PVDF-HFP/Na2.5Zr1.95Ce0.05Si2.2P0.8O11.3F0.7/PVDF-HFP (G-NZC0.05SPF0.7-G) SSEs is well designed. The ionic conductivity of Na3Zr2Si2PO12 is enhanced by Ce4+/F- co-doping. The effects of Ce4+ and F- doping on the crystal structure, density, and ionic conductivity for Na3Zr2Si2PO12 are well investigated. The optimal NZC0.05SPF0.7 delivers a high ionic conductivity of 1.39 × 10-3 S cm-1 at 25 â„ƒ. Moreover, the PVDF-HFP membrane can significantly enhance the interface compatibility between NZC0.05SPF0.7 and electrodes. The as-prepared G-NZC0.05SPF0.7-G exhibits a large ionic conductivity of 1.07 × 10-3 S cm-1 at 25 â„ƒ, wide electrochemical stability window up to 4.5 V, high critical current density of 1.2 A cm-2, and stable Na plating/stripping over 600 h at 0.3 A cm-2. The solid-state Na0.67Mn0.47Ni0.33Ti0.2O2/G-NZC0.05SPF0.7-G/Na battery delivers a remarkable cycling stability and rate capability at 25 â„ƒ, indicating that the as-prepared G-NZC0.05SPF0.7-G has a promising application for solid-state SIBs. This study demonstrates an effective strategy to develop advanced solid-state electrolytes for solid-state SIBs.

Rapid and Online Detection of Foodborne Bacteria via a Novel Ultraviolet Photoionization Time-of-Flight Mass Spectrometry.

Foodborne bacteria are widespread contaminated sources of food; hence, the real-time monitoring of pathogenic bacteria in food production is important for the food industry. In this study, a novel rapid detection method based on microbial volatile organic compounds (MVOCs) emitted from foodborne bacteria was established by using ultraviolet photoionization time-of-flight mass spectrometry (UVP-TOF-MS). The results showed obvious differences of MVOCs among the five species of bacteria, and the characteristic MVOCs for each bacterium were selected by a feature selection algorithm. Online monitoring of MVOCs during bacterial growth displayed distinct metabolomic patterns of the five species. MVOCs were most abundant and varied among species during the logarithmic phase. Finally, MVOC production by bacteria in different food matrixes was explored. The machine learning models for bacteria cultured in different matrixes showed a good classification performance for the five species with an accuracy of over 0.95. This work based on MVOC analysis by online UVP-TOF-MS achieved effective rapid detection of bacteria and showed its great application potential in the food industry for bacterial monitoring.

Reaching the initial coulombic efficiency and structural stability limit of P2/O3 biphasic layered cathode for sodium-ion batteries.

The P2/O3 biphasic layered oxide (NaxMn1-yMyO2, M: doping elements) is a cathode family with great promise for sodium-ion batteries (SIBs) because of their tunable electrochemical performance and low cost. However, the ultrahigh initial coulombic efficiency (ICE) and inferior cycling performance of P2/O3-NaxMn1-yMyO2 need to be improved for practical application. Herein, Ni/Cu co-doped P2/O3-Na0.75Mn1-yNiy-zCuzO2 materials are well-designed. The ultrahigh ICE can be restrained by altering the ratio of P2/O3 via adjusting Ni content, and the structural stability can be improved by Cu doping via enlarging parameter c of O3 phase and suppressing irreversible P2-O2 phase transformation. The optimal P2/O3-Na0.75Mn0.6Ni0.3Cu0.1O2 delivers a capacity of 142.4 with ICE of 107.8%, superior capacity retention in the temperature range of -40 âˆ¼ 30 °C, and rate performance of 95.9 mAh g-1 at 1.2 A g-1. The overall storage mechanism of P2/O3-Na0.75Mn0.6Ni0.3Cu0.1O2 is revealed by the combination of electrochemical profiles, in situ X-ray diffraction, and first-principles calculations. The Na-ion full battery based on P2/O3-Na0.75Mn0.6Ni0.3Cu0.1O2 cathode can achieve a remarkable energy density of 306.9 Wh kg-1 with a power density of 695.5 W kg-1 at 200 mA g-1. This work may shed light on the rational design of high-performance P2/O3 biphasic layered cathode for SIBs.

CPEB2 inhibit cell proliferation through upregulating p21 mRNA stability in glioma.

Glioma is the most common primary malignant brain tumor in adults and remains an incurable disease at present. Thus, there is an urgent need for progress in finding novel molecular mechanisms that control the progression of glioma which could be used as therapeutic targets for glioma patients. The RNA binding protein cytoplasmic polyadenylate element-binding protein 2 (CPEB2) is involved in the pathogenesis of several tumors. However, the role of CPEB2 in glioma progression is unknown. In this study, the functional characterization of the role and molecular mechanism of CPEB2 in glioma were examined using a series of biological and cellular approaches in vitro and in vivo. Our work shows CPEB2 is significantly downregulated in various glioma patient cohorts. Functional characterization of CPEB2 by overexpression and knockdown revealed that it inhibits glioma cell proliferation and promotes apoptosis. CPEB2 exerts an anti-tumor effect by increasing p21 mRNA stability and inducing G1 cell cycle arrest in glioma. Overall, this work stands as the first report of CPEB2 downregulation and involvement in glioma pathogenesis, and identifies CPEB2 as an important tumor suppressor gene through targeting p21 in glioma, which revealed that CPEB2 may become a promising predictive biomarker for prognosis in glioma patients.

A new Mn-based layered cathode with enlarged interlayer spacing for potassium ion batteries.

Layered Mn-based cathode (KxMnO2) has attracted wide attention for potassium ion batteries (PIBs) because of its high specific capacity and energy density. However, the structure and capacity of KxMnO2 cathode are constantly degraded during the cycling due to the strong Jahn-Teller effect of Mn3+ and huge ionic radius of K+. In this work, lithium ion and interlayer water were introduced into Mn layer and K layer in order to suppress the Jahn-Teller effect and expand interlayer spacing, respectively, thus obtaining new types of K0.4Mn1-xLixO2·0.33H2O cathode materials. The interlayer spacing of the K0.4MnO2 increased from 6.34 to 6.93 Å after the interlayer water insertion. X-ray photoelectron spectroscopy studies demonstrated that proper lithium doping can effectively control the ratio of Mn3+/Mn4+ and inhibit the Jahn-Teller effect. In-situ X-ray diffraction exhibited that lithium doping can inhibit the irreversible phase transition and improve the structural stability of materials during cycling. As a result, the optimal K0.4Mn0.9Li0.1O2·0.33H2O not only delivered a higher capacity retention of 84.04 % compared to the value of 28.09 % for K0.4MnO2·0.33H2O, but also maintained a greatly enhanced rate capability. This study provides a new opportunity for designing layered manganese-based cathode materials with high performance for PIBs.

A preclinical study on online monitoring of exhaled ciprofol concentration by the ultraviolet time-of-flight spectrometer and prediction of anesthesia depth in beagles.

BACKGROUND: Exhaled air has been demonstrated as a reliable medium for monitoring propofol concentration. However, online monitoring of exhaled ciprofol have not been reported. METHODS: Thirty-six beagles undergoing mechanical ventilation were divided into 6 groups, including bolus injection of low (Group BL, n = 6), medium (Group BM, n = 6), and high dose of ciprofol (Group BH, n = 6) groups; as well as 1 h continuous infusion of low (Group IL, n = 6), medium (Group IM, n = 6), and high dose of ciprofol (Group IH, n = 6) groups. The ciprofol concentration in exhaled air (CE) was determined by the ultraviolet time-of-flight mass spectrometer (UV-TOFMS). The correlations of CE and plasma concentration (Cp), CE and the bispectral index (BIS) were explored. Additionally, the pharmacokinetics (PK) models of CE and Cp, the pharmacodynamics (PD) models of CE and BIS were also established. RESULTS: Online monitoring of exhaled ciprofol can be achieved with the UV-TOFMS instrument. The CE of ciprofol in beagles was found at parts per billion by volume (ppbv) level. The linear correlation of CE and Cp was weak in bolus injection groups (R2 = 0.01) nonetheless moderate in continuous infusion groups (R2 = 0.53). The i.v. bolus PK model of CE and Cp can be fitted with the non-compartment models. Additionally, the the PD models of CE and BIS can be well fitted with the inhibitory sigmoid Emax model with the estimate values of IC50 = 0.05 ± 0.01 ppbv, γ = 4.74 ± 1.51, E0 = 81.40 ± 3.75, Imax = 16.35 ± 4.27 in bolus injection groups; and IC50 = 0.05 ± 0.01 ppbv, γ = 6.92 ± 1.30, E0 = 83.08 ± 1.62, Imax = 12.58 ± 1.65 in continuous infusion groups. CONCLUSIONS: Online monitoring of exhaled ciprofol concentration in beagles can be achieved with the UV-TOFMS instrument. Good correlations can be observed between exhaled ciprofol concentration and its cerebral effects reflected by the BIS value, demonstrating the potential of exhaled ciprofol monitoring for titrating depth of anesthesia in future clinical setting.