Compound 3k治疗骨关节炎:调控氧化应激通路改善软骨细胞糖酵解的作用机制

背景:骨关节炎现已被认为是一种代谢性疾病,既往研究表明糖酵解在骨关节炎的发生发展中起重要作用。Compound 3k作为一种新型糖酵解小分子抑制剂,具有抗炎及抗肿瘤等功效,因此可靶向糖酵解,有望为骨关节炎治疗提供新的思路。目的:基于缺氧诱导因子1α/活性氧的氧化应激通路探究Compound 3k在糖酵解过度活跃所导致的骨关节炎中的作用机制。方法:取对数生长期的ATDC5成软骨细胞,用10 ng/mL白细胞介素1β作用24 h诱导骨关节炎体外细胞模型,以CCK-8法检测不同浓度(0.25,0.5,1,2.5,5,10,15μmol/L)Compound 3k的细胞毒性,选出合适浓度进行后续实验。将软骨细胞随机分为对照组、模型组、治疗组,模型组以10 ng/mL的白细胞介素1β诱导,治疗组以Compound 3k预刺激2 h后与白细胞介素1β共培养,用CCK-8法检测各组细胞增殖情况;用ELISA试剂盒检测各组细胞炎症水平;用试剂盒检测各组细胞活性氧、细胞外乳酸脱氢酶及葡萄糖含量;qRT-PCR及Western blot检测相关炎症因子白细胞介素6、肿瘤坏死因子α及糖酵解相关基因葡萄糖转运蛋白1、甘油醛3-磷酸脱氢酶、单羧酸转运蛋白1和缺氧诱导因子1α的表达水平。结果与结论:①与对照组相比,模型组细胞增殖活性下降、糖酵解水平活跃,表现为细胞外乳酸脱氢酶含量增加(P<0.001),葡萄糖含量减少(P<0.001),相关炎症因子白细胞介素6(P<0.0001)及肿瘤坏死因子α(P<0.001),糖酵解相关基因葡萄糖转运蛋白1(P<0.001)、甘油醛3-磷酸脱氢酶(P<0.001)、单羧酸转运蛋白1(P<0.001)及缺氧诱导因子1α(P<0.001)的表达水平均上调,并伴随氧化应激,活性氧过量产生。②与模型组相比,Compound 3k的治疗有效提高细胞增殖活性,抑制过度活跃的糖酵解水平的同时,抑制了骨关节炎软骨细胞炎症(P<0.001)及糖酵解相关基因的表达(P<0.001),且抑制氧化应激,缺氧诱导因子1α的表达水平下调(P<0.0001),活性氧水平下降。③上述结果证实,Compound 3k抑制了白细胞介素1β诱导的软骨细胞炎症,其机制可能与糖酵解及缺氧诱导因子1α/活性氧介导的氧化应激有关。

Comparative evaluation of commercial Douchi by different molds:biogenic amines,non-volatile and volatile compounds

To provide new insights into the development and utilization of Douchi artificial starters,three common strains(Aspergillus oryzae,Mucor racemosus,and Rhizopus oligosporus)were used to study their influence on the fermentation of Douchi.The results showed that the biogenic amine contents of the three types of Douchi were all within the safe range and far lower than those of traditional fermented Douchi.Aspergillus-type Douchi produced more free amino acids than the other two types of Douchi,and its umami taste was more prominent in sensory evaluation(P<0.01),while Mucor-type and Rhizopus-type Douchi produced more esters and pyrazines,making the aroma,sauce,and Douchi flavor more abundant.According to the Pearson and PLS analyses results,sweetness was significantly negatively correlated with phenylalanine,cysteine,and acetic acid(P<0.05),bitterness was significantly negatively correlated with malic acid(P<0.05),the sour taste was significantly positively correlated with citric acid and most free amino acids(P<0.05),while astringency was significantly negatively correlated with glucose(P<0.001).Thirteen volatile compounds such as furfuryl alcohol,phenethyl alcohol,and benzaldehyde caused the flavor difference of three types of Douchi.This study provides theoretical basis for the selection of starting strains for commercial Douchi production.

Effect of different drying methods on the amino acids,α-dicarbonyls and volatile compounds of rape bee pollen

The significant demand for high quality food has motivated us to adopt appropriate processing methods to improve the food nutritional quality and flavors.In this study,the effects of five drying methods,namely,pulsed vacuum drying(PVD),freeze drying(FD),infrared drying(IRD),hot-air drying(HAD)and sun drying(SD)on free amino acids(FAAs),α-dicarbonyl compounds(α-DCs)and volatile compounds(VOCs)in rape bee pollen(RBP)were determined.The results showed that FD significantly released the essential amino acids(EAAs)compared with fresh samples while SD caused the highest loss.Glucosone was the dominantα-DCs in RBP and the highest loss was observed after PVD.Aldehydes were the dominant volatiles of RBP and SD samples contained more new volatile substances(especially aldehydes)than the other four drying methods.Comprehensively,FD and PVD would be potential methods to effectively reduce the quality deterioration of RBP in the drying process.

Role of methoxy and C_(α)-based substituents in electrochemical oxidation mechanisms and bond cleavage selectivity of β-O-4 lignin model compounds

In order to better understand the specific substituent effects on the electrochemical oxidation process of β-O-4 bond, a series of methoxyphenyl type β-O-4 dimer model compounds with different localized methoxyl groups, including 2-(2-methoxyphenoxy)-1-phenylethanone, 2-(2-methoxyphenoxy)-1-phenylethanol, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanol, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanol have been selected and their electrochemical properties have been studied experimentally by cyclic voltammetry, and FT-IR spectroelectrochemistry. Combining with electrolysis products distribution analysis and density functional theory calculations, oxidation mechanisms of all six model dimers have been explored. In particular, a total effect from substituents of both para-methoxy(on the aryl ring closing to Cα) and Cα-OH on the oxidation mechanisms has been clearly observed, showing a significant selectivity on the Cα-Cβbond cleavage induced by electrochemical oxidations.

Modern approaches for detection of volatile organic compounds in metabolic studies focusing on pathogenic bacteria:Current state of the art

Pathogenic microorganisms produce numerous metabolites,including volatile organic compounds(VOCs).Monitoring these metabolites in biological matrices(e.g.,urine,blood,or breath)can reveal the presence of specific microorganisms,enabling the early diagnosis of infections and the timely implementation of tar-geted therapy.However,complex matrices only contain trace levels of VOCs,and their constituent com-ponents can hinder determination of these compounds.Therefore,modern analytical techniques enabling the non-invasive identification and precise quantification of microbial VOCs are needed.In this paper,we discuss bacterial VOC analysis under in vitro conditions,in animal models and disease diagnosis in humans,including techniques for offline and online analysis in clinical settings.We also consider the advantages and limitations of novel microextraction techniques used to prepare biological samples for VOC analysis,in addition to reviewing current clinical studies on bacterial volatilomes that address inter-species in-teractions,the kinetics of VOC metabolism,and species-and drug-resistance specificity.

Pressure stimulated current in progressive failure process of combined coal-rock under uniaxial compression:Response and mechanism

Effective monitoring of the structural health of combined coal-rock under complex geological conditions by pressure stimulated currents(PSCs)has great potential for the understanding of dynamic disasters in underground engineering.To reveal the effect of this way,the uniaxial compression experiments with PSC monitoring were conducted on three types of coal-rock combination samples with different strength combinations.The mechanism explanation of PSCs are investigated by resistivity test,atomic force microscopy(AFM)and computed tomography(CT)methods,and a PSC flow model based on progressive failure process is proposed.The influence of strength combinations on PSCs in the progressive failure process are emphasized.The results show the PSC responses between rock part,coal part and the two components are different,which are affected by multi-scale fracture characteristics and electrical properties.As the rock strength decreases,the progressive failure process changes obviously with the influence range of interface constraint effect decreasing,resulting in the different responses of PSC strength and direction in different parts to fracture behaviors.The PSC flow model is initially validated by the relationship between the accumulated charges of different parts.The results are expected to provide a new reference and method for mining design and roadway quality assessment.

Coal-rock gas:Concept,connotation and classification criteria

In recent years,great breakthroughs have been made in the exploration and development of natural gas in deep coal-rock reservoirs in Junggar,Ordos and other basins in China.In view of the inconsistency between the industrial and academic circles on this new type of unconventional natural gas,this paper defines the concept of"coal-rock gas"on the basis of previous studies,and systematically analyzes its characteristics of occurrence state,transport and storage form,differential accumulation,and development law.Coal-rock gas,geologically unlike coalbed methane in the traditional sense,occurs in both free and adsorbed states,with free state in abundance.It is generated and stored in the same set of rocks through short distance migration,occasionally with the accumulation from other sources.Moreover,coal rock develops cleat fractures,and the free gas accumulates differentially.The coal-rock gas reservoirs deeper than 2000 m are high in pressure,temperature,gas content,gas saturation,and free-gas content.In terms of development,similar to shale gas and tight gas,coal-rock gas can be exploited by natural formation energy after the reservoirs connectivity is improved artificially,that is,the adsorbed gas is desorbed due to pressure drop after the high-potential free gas is recovered,so that the free gas and adsorbed gas are produced in succession for a long term without water drainage for pressure drop.According to buried depth,coal rank,pressure coefficient,reserves scale,reserves abundance and gas well production,the classification criteria and reserves/resources estimation method of coal-rock gas are presented.It is preliminarily estimated that the coal-rock gas in place deeper than 2000 m in China exceeds 30×10^(12)m^(3),indicating an important strategic resource for the country.The Ordos,Sichuan,Junggar and Bohai Bay basins are favorable areas for large-scale enrichment of coal-rock gas.The paper summarizes the technical and management challenges and points out the research directions,laying a foundation for the management,exploration,and development of coal-rock gas in China.

Assessment of electrostatic discharge sensitivity of nitrogen-rich heterocyclic energetic compounds and their salts as high energy-density dangerous compounds:A study of structural variables

Nitrogen-rich heterocyclic energetic compounds(NRHECs)and their salts have witnessed widespread synthesis in recent years.The substantial energy-density content within these compounds can lead to potentially dangerous explosive reactions when subjected to external stimuli such as electrical discharge.Therefore,developing a reliable model for predicting their electrostatic discharge sensitivity(ESD)becomes imperative.This study proposes a novel and straightforward model based on the presence of specific groups(-NH_(2) or-NH-,-N=N^(+)-O^(-)and-NNO_(2),-ONO_(2) or-NO_(2))under certain conditions to assess the ESD of NRHECs and their salts,employing interpretable structural parameters.Utilizing a comprehensive dataset comprising 54 ESD measurements of NRHECs and their salts,divided into 49/5 training/test sets,the model achieves promising results.The Root Mean Square Error(RMSE),Mean Absolute Error(MAE),and Maximum Error for the training set are reported as 0.16 J,0.12 J,and 0.5 J,respectively.Notably,the ratios RMSE(training)/RMSE(test),MAE(training)/MAE(test),and Max Error(training)/Max Error(test)are all greater than 1.0,indicating the robust predictive capabilities of the model.The presented model demonstrates its efficacy in providing a reliable assessment of ESD for the targeted NRHECs and their salts,without the need for intricate computer codes or expert involvement.

Organic Compounds Possessing the Plastic Crystalline Phase: Calculation of Their Fusion Enthalpies

For the first time, for different organic and inorganic compounds possessing the plastic crystalline phase, a new semiempirical equation describing dependence of their fusion enthalpies on such physico-chemical quantities as normal melting temperature, surface tension, molar volume and critical molar volume is received on the base of the principle of corresponding states and the energy equipartition theorem. Moreover, the proposed equation allows one to take into account the particularities of one-particle molecular rotation in the plastic crystalline phase.

Nutritional values,bioactive compounds and health benefits of purslane(Portulaca oleracea L.):a comprehensive review

Portulaca oleracea L.,commonly known as purslane,is a worldwide weed species belonging to the family Portulacaceae and has been known as“Global Panacea”.As one of the most widely consumed green vegetables and medicinal plants around the world,it has recently been re-evaluated as a potential“new crop”due to the properties that differentiate it as one of the best vegetable sources of omega-3 fatty acid(α-linolenic acid),as well as a variety of nutrients and phytochemicals.Accordingly,emerging research has found that purslane exhibits health-promoting properties like anti-inflammatory,anti-hyperglycemic,antioxidant,neuroprotective,and immunomodulatory.These findings suggest that this species possesses a potential using as a dietary supplement beyond potherb and traditional medicine.This review systematically summarizes the up-to-date research carried out on purslane,including the nutritional compositions,bioactive compounds,and health benefits it exerts as well as limitations,challenges,and future directions of research.Finally,we hope that this review would provide purslane with a comprehensive reference and future scope as functional and health-promoting food for disease prevention and treatment.

Bioactive compounds in Hericium erinaceus and their biological properties:a review

Hericium erinaceus is a nutritious edible and medicinal fungi,rich in a variety of functional active ingredients,with various physiological functions such as antioxidation,anticancer,and enhancing immunity.It is also effective in protecting the digestive system and preventing neurodegenerative diseases.In this review paper,we summarize the sources,structures and efficacies of the main active components in H.erinaceus fruiting body,mycelium,and culture media,and update the latest research progress on their biological activities and the related molecular mechanisms.Based on this information,we provide detailed challenges in current research,industrialization and information on the active ingredients of H.erinaceus.Perspectives for future studies and new applications of H.erinaceus are proposed.

Antidiabetic Properties of Bidens pilosa and Its Polyacetylenic Compounds for Management of Diabetes: Systematic Review

Bidens pilosa is a member of the Asteraceae family that is widely distributed across the tropics. It has been utilized by different communities both as food and medicinal herb. This plant and its polyacetylenic compounds hold potential as a natural antidiabetic intervention that can be used to combat this global public health problem. Bioactive compounds found in this plant constitute promising interventions for combating obesity which is a major risk factor for the development of type 2 diabetes. These phytocompounds can work independently or synergistically to modulate appetite, lipase activity, adipogenesis and adipocyte apoptosis. However, the efficacy, mode of action and scope of management of diabetes by these compounds remains elusive. The current review aims to summarize data on efficacy in the management of diabetes, an antidiabetic candidate polyacetylenic compound and possible biological activities as an antidiabetic agent from the available literature. Much emphasis has been directed to cytopiloyne as a representative of polyacetylenic compounds extracted from Bidens pilosa and its activity on diabetic animal models. The majority of the studies conducted on animal models described antidiabetic mechanisms that range from hypoglycemic to secretagogue activity of cytopiloyne in a dose-dependent manner. A clinical trial pilot indicated improved glycemic control of Bidens pilosa formulation among diabetic patients in the study. Bidens pilosa and its compounds are highly potent antidiabetic agent(s) that should be graduated to an intervention for management of diabetes through pre-clinical and clinical trials to elucidate its efficacy and safety.

Density functional theory study of B- and Si-doped carbons and their adsorption interactions with sulfur compounds

Understanding the adsorption interactions between carbon materials and sulfur compounds has far-reaching impacts,in addition to their well-known important role in energy storage and conversion,such as lithium-ion batteries.In this paper,properties of intrinsic B or Si single-atom doped,and B-Si codoped graphene(GR)and graphdiyne(GDY)were investigated by using density functional theory-based calculations,in which the optimal doping configurations were explored for potential applications in adsorbing sulfur compounds.Results showed that both B or Si single-atom doping and B-Si codoping could substantially enhance the electron transport properties of GR and GDY,improving their surface activity.Notably,B and Si atoms displayed synergistic effects for the codoped configurations,where B-Si codoped GR/GDY exhibited much better performance in the adsorption of sulfurcontaining chemicals than single-atom doped systems.In addition,results demonstrated that,after B-Si codoping,the adsorption energy and charge transfer amounts of GDY with sulfur compounds were much larger than those of GR,indicating that B-Si codoped GDY might be a favorable material for more effectively interacting with sulfur reagents.

Numerical modeling of fracture propagation of supercritical CO_(2)compound fracturing

The exploitation of shale gas is promising due to depletion of the conventional energy and intensification of the greenhouse effect.In this paper,we proposed a heat-fluid-solid coupling damage model of supercritical CO_(2)(SC-CO_(2))compound fracturing which is expected to be an efficient and environmentally friendly way to develop shale gas.The coupling model is solved by the finite element method,and the results are in good agreement with the analytical solutions and fracturing experiments.Based on this model,the fracture propagation characteristics at the two stages of compound fracturing are studied and the influence of pressurization rate,in situ stress,bedding angle,and other factors are considered.The results show that at the SC-CO_(2)fracturing stage,a lower pressurization rate is conducive to formation of the branches around main fractures,while a higher pressurization rate inhibits formation of the branches around main fractures and promotes formation of the main fractures.Both bedding and in situ stress play a dominant role in the fracture propagation.When the in situ stress ratio(δ_(x)/δ_(y))is 1,the presence of bedding can reduce the initiation pressure and failure pressure.Nevertheless,it will cause the fracture to propagate along the bedding direction,reducing the fracture complexity.In rocks without bedding,hydraulic fracturing has the lengthening and widening effects for SC-CO_(2)induced fracture.In shale,fractures induced at the hydraulic fracturing stage are more likely to be dominated by in situ stresses and have a shorter reorientation radius.Therefore,fracture branches propagating along the maximum principal stress direction may be generated around the main fractures induced by SC-CO_(2)at the hydraulic fracturing stage.When the branches converge with the main fractures,fracture zones are easily formed,and thus the fracture complexity and damage area can be significantly increased.The results are instructive for the design and application of SC-CO_(2)compound fracturing.

Exploring Nutritional Compositions,Volatile Compounds,Health Benefits,Emerging Processing Technologies,and Potential Food Products of Glutinous Rice:A Review

Glutinous rice(Oryza sativa var.glutinosa)stands out as one of the most popular rice varieties globally,amidst thousands of rice cultivars.Its increasing popularity is attributed to its rich nutritional compositions and health benefits.This review aims to summarize the nutritional compositions,volatile compounds,and health benefits of glutinous rice.Further,in-depth studies are necessary to explore the utilization of glutinous rice in enhancing processing technologies and developing new food products.Glutinous rice has been shown to possess numerous health benefits,including antioxidant activity,bioactive compounds,anti-cancer properties,anti-inflammatory effects,anti-diabetic potential,and cholesterol-lowering effects.Besides its nutritional compositions,the major volatile compounds identified in glutinous rice could serve as a functional food for human consumption.Emerging processing technologies related to glutinous rice are elaborated to improve the latest developments for incorporating them into various food products.

Protective mechanism of quercetin compounds against acrylamide-induced hepatotoxicity

Quercetin compounds have antioxidant,anti-inflammatory and anticancer pharmacological functions.Longterm exposure to acrylamide(AA)can cause liver injury and endanger human health.However,whether quercetin compounds can attenuate AA-induced liver injury and the specific mechanism are not clear.Here,we studied the mechanism and structure-activity relationship of quercetin compounds in reducing AA-induced hepatotoxicity in vivo and in vitro.In vivo studies found that quercetin-like compounds protect against AAinduced liver injury by reducing oxidative stress levels,activating the Akt/m TOR signaling pathway to attenuate autophagy,and improving mitochondrial apoptosis and endoplasmic reticulum stress-mediated apoptosis.In vitro studies found that quercetin compounds protected Hep G2 cells from AA by attenuating the activation of AA-induced autophagy,lowering reactive oxygen species(ROS)levels by exerting antioxidant effects and thus attenuating oxidative stress,increasing mitochondrial membrane potential(MMP),and improving apoptosis-related proteins,thus attenuating AA-induced apoptosis.Furthermore,the conformational differences between quercetin compounds correlated with their protective capacity against AA-induced hepatotoxicity,with quercetin showing the best protective capacity due to its strongest antioxidant activity.In conclusion,quercetin compounds can protect against AA-induced liver injury through multiple pathways of oxidative stress,autophagy and apoptosis,and their protective capacity correlates with antioxidant activity.

Comparative Analysis of Organic and Compound Fertilizers on the Yield and Metabolites of Platostoma palustre

To explore the effect of fertilizers on the yield and quality of Platostoma palustre,in this study,P.palustre was utilized as the research material,and field experiments were conducted with different application rates of compound fertilizer and organic fertilizer and non-targeted metabolomics analysis was further employed to compare and analyze the differences in the metabolic components between the compound fertilizer and organic fertilizer treatments.The results of field experiments demonstrated that both compound and organic fertilizers could promote the fresh weight,shade dry weight,and dry weight of P.palustre,with 450 kg hm−2 compound fertilizer and 4500 kg hm−2 organic fertilizer presenting the optimum effects.Non-targeted metabolomics revealed that 1096 metabolites were identified in 450 kg hm−2 compound fertilizer and 4500 kg hm−2 organic fertilizer,and 885 metabolites were annotated in the Human Metabolome Database(HMDB).There were 318 differential metabolites(DMs)found between the two treatments,and 263 metabolites were annotated in HMDB.The abundance of 2 phenolic compounds and 12 organic oxygen compounds in the treatment of 4500 kg hm−2 organic fertilizer was significantly higher than that of the 450 kg hm−2 compound fertilizer,while the abundance of 21 organic oxygen compounds,14 flavonoids,3 phenolic compounds,and 5 cinnamic acids and their derivatives was significantly up-regulated in 450 kg hm−2 compound fertilizer treatment.In addition,5 metabolic pathways were significantly enriched,and the flavone and flavonol biosynthesis was the most significantly differential metabolic pathway.These results suggested that the application of both compound fertilizers and organic fertilizers can increase the yield of P.palustre,but their effects on metabolites were different.This study has considerable implications for the planting and cultivation of P.palustre,furnishing a scientific foundation for an efficient and rational application of fertilizer.

Analytical Determination of Size and Location of Roadside Horizontal Sightline Offsets for Compound Curves

AASHTO’s guideline for geometric design of highways and similar guidelines require that roadside areas on the inside of horizontal curves be cleared of high objects to provide stopping sight distance. The guidelines have analytical models for determining the extent of clearance, known as the horizontal sightline offset or clearance offset, for simple curves. Researchers in the past have developed analytical models for clearance offsets for spiraled and reverse curves. Very few researchers developed analytical models for available sight distances for compound curves. Still missing are models for horizontal sightline offsets and locations of the offsets for compound curves. The objective of this paper is to present development of analytical models and charts for determining horizontal sightline offsets and their locations for compound curves. The paper considers curves whose component arcs are individually shorter than stopping sight distance. The resulting models and the charts have been verified with accurate values determined using graphical methods. The models and the charts will find application in geometric design of highway compound curves.

New recessive compound heterozygous variants of RP1L1 in RP1L1 maculopathy

AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.

Identification of breath volatile organic compounds to distinguish pancreatic adenocarcinoma,pancreatic cystic neoplasm,and patients without pancreatic lesions

BACKGROUND Volatile organic compounds(VOCs)are a promising potential biomarker that may be able to identify the presence of cancers.AIM To identify exhaled breath VOCs that distinguish pancreatic ductal adenocar-cinoma(PDAC)from intraductal papillary mucinous neoplasm(IPMN)and healthy volunteers.METHODS We collected exhaled breath from histologically proven PDAC patients,radiological diagnosis IPMN,and healthy volunteers using the ReCIVA®device between 10/2021-11/2022.VOCs were identified by thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry and compared between groups.RESULTS A total of 156 participants(44%male,mean age 62.6±10.6)were enrolled(54 PDAC,42 IPMN,and 60 controls).Among the nine VOCs identified,two VOCs that showed differences between groups were dimethyl sulfide[0.73 vs 0.74 vs 0.94 arbitrary units(AU),respectively;P=0.008]and acetone dimers(3.95 vs 4.49 vs 5.19 AU,respectively;P<0.001).After adjusting for the imbalance parameters,PDAC showed higher dimethyl sulfide levels than the control and IPMN groups,with adjusted odds ratio(aOR)of 6.98(95%CI:1.15-42.17)and 4.56(1.03-20.20),respectively(P<0.05 both).Acetone dimer levels were also higher in PDAC compared to controls and IPMN(aOR:5.12(1.80-14.57)and aOR:3.35(1.47-7.63),respectively(P<0.05 both).Acetone dimer,but not dimethyl sulfide,performed better than CA19-9 in PDAC diagnosis(AUROC 0.910 vs 0.796).The AUROC of acetone dimer increased to 0.936 when combined with CA19-9,which was better than CA19-9 alone(P<0.05).CONCLUSION Dimethyl sulfide and acetone dimer are VOCs that potentially distinguish PDAC from IPMN and healthy participants.Additional prospective studies are required to validate these findings.