Clonal evolution of hematopoietic stem cells after cancer chemotherapy.

Normal hematopoietic stem and progenitor cells (HSPCs) inherently accumulate somatic mutations and lose clonal diversity with age, processes implicated in the development of myeloid malignancies 1 . The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal HSPCs is not well defined. We conducted whole-genome sequencing on 1,032 single-cell-derived HSPC colonies from 10 patients with multiple myeloma (MM), who had undergone various chemotherapy regimens. Our findings reveal that melphalan treatment distinctly increases mutational burden with a unique mutation signature, whereas other MM chemotherapies do not significantly affect the normal mutation rate of HSPCs. Among these therapy-induced mutations were several oncogenic drivers such as TET2 and PPM1D . Phylogenetic analysis showed a clonal architecture in post-treatment HSPCs characterized by extensive convergent evolution of mutations in genes such as TP53 and PPM1D . Consequently, the clonal diversity and structure of post-treatment HSPCs mirror those observed in normal elderly individuals, suggesting an accelerated clonal aging due to chemotherapy. Furthermore, analysis of matched therapy-related myeloid neoplasm (t-MN) samples, which occurred 1-8 years later, enabled us to trace the clonal origin of t-MNs to a single HSPC clone among a group of clones with competing malignant potential, indicating the critical role of secondary mutations in dictating clonal dominance and malignant transformation. Our findings suggest that cancer chemotherapy promotes an oligoclonal architecture with multiple HSPC clones possessing competing leukemic potentials, setting the stage for the selective emergence of a singular clone that evolves into t-MNs after acquiring secondary mutations. These results underscore the importance of further systematic research to elucidate the long-term hematological consequences of cancer chemotherapy.

Evaluation of pharmaceutical consumption between urban and suburban catchments in China by wastewater-based epidemiology.

Wastewater-based epidemiology (WBE) is amply used for estimating human consumption of chemicals, yet information on regional variation of pharmaceuticals and their environmental fate are scarce. Thus, this study aims to estimate the consumption of three cardiovascular, four non-steroidal anti-inflammatory pharmaceuticals (NSAIDs), and four psychoactive pharmaceuticals between urban and suburban catchments in China by WBE, and to explore their removal efficiencies and ecological risks. Eleven analytes were detected in both influent and effluent samples. The estimated consumptions ranged from

Linc-ROR inhibits NK cell-killing activity by promoting RXRA ubiquitination and reducing MICB expression in gastric cancer patients.

Linc-ROR plays an important role in gastric cancer (GC) development and progression. This study sought to determine how the aberrant expression of Linc-ROR impacts GC progression and immune evasion, and to identify new targets for GC therapy. GC cells overexpressing Linc-ROR and GSAGS cells were cocultured with NK-92 cells, respectively, and Linc-ROR expression was determined using reverse transcription polymerase chain reaction. Linc-ROR overexpression experiments were used to measure the expression of MICB, a tumor protein that is recognized by natural killer (NK) cells. Bioinformatics analysis identified retinoid X receptor α (RXRA) and YY1 as MICB-specific transcription factors. Cotransfection and ubiquitinated drug experiments found that Linc-ROR promoted the ubiquitination and degradation of RXRA. Linc-ROR was upregulated in GC tissue and high expression was associated with tumor escape from NK-92 cell-mediated immunity. Linc-ROR overexpression inhibited the expression of MICB on the cell surface by degrading RXRA. These findings indicate that Linc-ROR promotes the binding of RXRA and E3 ligase UBE4B, reducing RXRA and MICB expression, and limiting NK cell-killing activity. Linc-ROR is a critical long noncoding RNA with a tumor-promoting function in GC and thus may serve as a potential therapeutic target.

Perturbation of lipid metabolism in 3T3-L1 at different stages of preadipocyte differentiation and new insights into the association between changed metabolites and adipogenesis promoted by TBBPA or TBBPS.

Tetrabromobisphenol A (TBBPA) and tetrabromobisphenol S (TBBPS) are widely distributed brominated flame retardants. While TBBPA has been demonstrated to stimulate adipogenesis, TBBPS is also under suspicion for potentially inducing comparable effects. In this study, we conducted a non-targeted metabolomics to examine the metabolic changes in 3T3-L1 cells exposed to an environmentally relevant dose of TBBPA or TBBPS. Our findings revealed that 0.1 µM of both TBBPA and TBBPS promoted the adipogenesis of 3T3-L1 preadipocytes. Multivariate analysis showed significant increases in glycerophospholipids, sphingolipids, and steroids relative levels in 3T3-L1 cells exposed to TBBPA or TBBPS at the final stage of preadipocyte differentiation. Metabolites set composed of glycerophospholipids was found to be highly effective predictors of adipogenesis in 3T3-L1 cells exposed to TBBPA or TBBPS (revealed from the receiver operating characteristic curve with an area under curve > 0.90). The results from metabolite set enrichment analysis suggested both TBBPA and TBBPS exposures significantly perturbed steroid biosynthesis in adipocytes. Moreover, TBBPS additionally disrupted the sphingolipid metabolism in the adipocytes. Our study presents new insights into the obesogenic effects of TBBPS and provides valuable information about the metabolites associated with adipogenesis induced by TBBPA or TBBPS.

Influence of tumor mycobiome on cancer pathogenesis (Review).

Cancer tissues harbor a large microbiome. There is growing evidence that the tumor microbiome is significantly correlated with the prognosis of cancer patients, but the exact underlying mechanisms have remained elusive. Although the tumor mycobiome is less abundant than the biome of bacteria, it is prevalent in most cancers in humans. The present review describes in detail the impact of the tumor mycobiome on cancer pathogenesis. The tumor mycobiome promotes tumor progression and metastasis by affecting the human immune system, maintaining a pro-inflammatory environment, producing aflatoxins, attenuating cell adhesion mechanisms and fungal-bacterial interactions. Furthermore, the tumor mycobiome likewise has great potential for cancer prevention, diagnosis and treatment.

A High Performance Wheat Disease Detection Based on Position Information.

Protecting wheat yield is a top priority in agricultural production, and one of the important measures to preserve yield is the control of wheat diseases. With the maturity of computer vision technology, more possibilities have been provided to achieve plant disease detection. In this study, we propose the position attention block, which can effectively extract the position information from the feature map and construct the attention map to improve the feature extraction ability of the model for the region of interest. For training, we use transfer learning to improve the training speed of the model. In the experiment, ResNet built on positional attention blocks achieves 96.4% accuracy, which is much higher compared to other comparable models. Afterward, we optimized the undesirable detection class and validated its generalization performance on an open-source dataset.

Microcystin bound on microplastics in eutrophic waters: A potential threat to zooplankton revealed by adsorption-desorption processes.

The presence of microplastics (MPs) in eutrophic waters (both freshwaters and coastal waters) is increasingly reported globally, as has the occurrence of cyanotoxins, including microcystins (MCs). MPs have the potential to act as vectors for MCs in freshwater environments, but the transportation mechanisms and associated risks remain poorly understood. In this study, we investigated how aging process and water conditions influenced the adsorption behavior of the microcystin-leucine-arginine (MC-LR) onto polyethylene (PE) and polypropylene (PP). Adsorption kinetics and isotherms showed that the MC-LR sorption capacity in descending order was aged PP > pristine PP > aged PE > pristine PE. The aging process increased the MC-LR sorption amount by 25.1% and 6.5% for PP and PE, respectively. The increase in sorption affinity of aged MPs may be attributed to the significant surface oxidation and the formation of the hydrogen bonding between MPs and MC-LR. Furthermore, MC-LR sorption can be largely influenced by the aqueous conditions. MC-LR preferred to be much adsorbed onto different MPs in brackish water than in freshwater owing to the cation bridging effect and complexation of high levels of cations. The usual alkalescent pH in eutrophic waters did not favor MC-LR sorption to MPs. Finally, based on the desorption results, assuming a worst-case scenario, MC-LR bound on MPs may have a high risk to daphnids. The findings obtained in this study have improved our knowledge in the interaction of MPs with hydrophilic cyanotoxins in aqueous ecosystems, as well as the risks associated with their coexistence.

Is e-waste a source of phthalate and novel non-phthalate plasticizers? A comparison study on indoor dust.

Nine traditional phthalate plasticizers and 33 novel non-phthalate plasticizers were determined in indoor dust from a typical e-waste recycling area. The median concentrations ranged from Dakeng > Baihetang > Shiding > Jieyang, which was consistent with the local e-waste dismantling activities and supported by polybrominated diphenyl ethers (PBDEs) levels. The correlations between chemical levels and the indicators indicated that most phthalates and non-phthalate plasticizers in the dust, might not be primarily influenced by e-waste emission sources. Additionally, the estimated median human exposures of phthalates and non-phthalates via dust ingestion were 30.6 and 1.82 ng/kg/day for adults, and 299 and 17.8 ng/kg/day for toddlers respectively, indicating negligible health risks.

Occurrence and ecological risks of brominated flame retardants and dechlorane plus in sediments from the Pearl River Estuary and Daya Bay, South China.

Considering the phasing-out of polybrominated diphenyl ethers (PBDEs), environmental concerns of PBDE alternatives and dechlorane plus (DP) are rising. Accordingly, this study investigates occurrence and ecological risks of PBDEs, PBDE alternatives and DPs in sediments of two littoral regions, the Pearl River Estuary (PRE) and Daya Bay (DYB), in southern China. Total PBDEs concentrations in surface sediments of the PRE and DYB were in the range (mean) of 0.30-28.7 (8.71) and 0.29-43.4 (6.05) ng/g dw, respectively. DP levels in surface sediments of the PRE (0.004-0.27 ng/g dw) were significantly higher than those in the DYB (0.005-0.24 ng/g dw) (p < 0.05). BDE 209 was the predominant component, followed by DBDPE, exhibiting regional variations in BFRs usage. Vertical profiles of BFRs and DP in the PRE and DYB sediment cores exhibited clear anthropogenic influences. Risk quotients suggest critical ecological risks of tetra-, penta- and deca-BDE congeners in all the surface sediments.

GPM6A expression is suppressed in hepatocellular carcinoma through miRNA-96 production.

GPM6A is a glycoprotein in endothelial cells, and its biological function in the development of hepatocellular carcinoma (HCC) is unknown. Through Affymetrix gene expression microarray and bioinformatic analysis, very low GPM6A expression was found in HCC tissue. The present study aims to explore the function and regulatory mechanism of GPM6A in HCC development and progression. Levels of GPM6A expression in HCC specimens from different disorders and various hepatoma cell lines were determined, and its role on cell proliferation was evaluated in hepatoma cells stably overexpressing GPM6A. Modulation of a specific microRNA (miRNA) on its expression and function was evaluated with miRNA mimetic transfection. Herein, it is reported that much lower GPM6A levels were found in HCC tissues than pericancerous liver tissues and correlated to a poor prognosis. GPM6A overexpression inhibited cell proliferation, suppressed colony formation, migration and invasion in two hepatoma cell types. Available evidence does not support that genetic and epigenetic dysregulation contributes significantly to GPM6A inactivation in HCC. Additional findings demonstrated that miR-96-5p acted directly on the 3'-UTR of the GPM6A gene and significantly decreased its mRNA and protein levels. MiR-96-5p transfection promoted proliferation, migration and invasion of SMMC-7721 and MHCC-97H hepatoma cells; whereas the function of oncogenic microRNA-96 was significantly inhibited in GPM6A-overexpressed hepatoma cells. In conclusion, GPM6A expression in HCC is commonly suppressed regardless its base disease types, and its low expression in HCC tissues is most likely attributed to upregulated miR-96-5p. GPM6A may function as a valuable biomarker for HCC progression and prognosis.

Legacy and alternative flame retardants in indoor dust from e-waste industrial parks and adjacent residential houses in South China: Variations, sources, and health implications.

Many studies have elucidated health concerns of informal e-waste recycling activities, yet few has evaluated the effectiveness of the regulations as well as the human exposure risks to adjacent residents. Herein, legacy polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCDs), and alternative organophosphate esters (OPEs) were investigated in indoor dust collected from three e-waste industrial parks and five adjacent villages located in south China. The levels and composition patterns varied significantly between workshop and home dust. BDE209 showed much higher (p < 0.01) concentrations in workshop dust versus home dust, while relatively comparable levels were found for OPEs and HBCDs. Principal component analysis revealed that OPEs and PBDEs were mainly related to home and workshop dust, respectively. Results strongly indicated that e-waste dismantling activities still contribute to a high burden of BDE209 to surrounding residents, whilst the sources of OPEs may also originated from household products, especially for TCEP. The estimated daily intakes (EDIs) via dust ingestion and dermal absorption for occupational worker and nearby toddlers were below available reference dose (RfD) values even at worst case scenario. This study highlights the significance of deca-BDEs rather than alternative OPEs in e-waste generated in China, which could provide scientific suggestions for policy formulation.

Exploring antibiotic consumption between urban and sub-urban catchments using both parent drugs and related metabolites in wastewater-based epidemiology.

Consumption of antibiotics leads to the dissemination of antimicrobial resistance worldwide. Better knowledge of temporal and spatial consumption of antibiotics helps public health authorities to control their usage and combat antimicrobial resistance. However, measuring antibiotic consumption with population surveys, sales data, and production statistics remains challenging due to the complexity of prescription preference, patient compliance, and direct disposal of unused drugs. With the approach of wastewater-based epidemiology (WBE), this study aims to evaluate the consumption of eight commonly-used antibiotics between developed urban and developing sub-urban catchments in China and to characterise the ratios of parent drugs to metabolites in studying the consumption. Seven parent antibiotics were detected in all the wastewater samples (n = 56), whereas some metabolites were detected sporadically. The ratios of parent chemicals to metabolites varied among locations and were often higher than the ratios in pharmacokinetic studies. Estimated consumption of antibiotics ranged from 3.2 ± 2.0 mg/day/1000 inhabitants for trimethoprim to 28,400 ± 7800 mg/day/1000 inhabitants for roxithromycin in the studied catchments. Higher consumption of sulfapyridine, sulfadiazine and roxithromycin was observed in urban than suburban catchments, while consumption of sulfamethoxazole, norfloxacin, and trimethoprim was higher in suburban than in urban catchments. Using the literature data, we found more than 95% reduction of antibiotic use in an urban catchment. Our study revealed the geographical pattern in antibiotic use across different urban and suburban catchments via WBE, and the potential of monitoring parent-to-metabolite ratios for WBE in estimating antibiotic use. These results provide a basis for health authorities to plan different drug-specific control policies between urban and suburban catchments, and for future WBE studies to be aware of other sources, such as animal husbandry and disposals of unused drugs, that can influence the estimated consumption.

Spatiotemporal distribution, partitioning behavior and flux of per- and polyfluoroalkyl substances in surface water and sediment from Poyang Lake, China.

Thirty-five legacy and emerging per- and polyfluoroalkyl substances (PFAS) were analyzed in surface water and sediments collected from Poyang Lake, the largest freshwater lake in China. The Æ©PFAS concentrations ranged from 23 to 1000 ng/L in water dissolved phase, 1.3-9.8 ng/L in suspended particulate matters, and 0.26-2.9 ng/g dry weight in sediments. Short-chain and emerging PFAS were predominant in surface water and sediments, rather than legacy perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Hexafluoropropylene oxide dimer/trimer acid (HFPO-DA/TA), 6:2 and 8:2 chlorinated polyfluorinated ether sulfonic acids (6:2 and 8:2 Cl-PFESAs), 6:2 fluorotelomer sulfonate (6:2 FTS), and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) were detected in all samples, indicating that these emerging PFAS have been widely produced and used in this region. The high concentrations of HFPO-DA/TA, 6:2 FTS, 6:2, 8:2 Cl-PFESAs, and OBS in sediments and their higher water-sediment distribution coefficients than those of predecessors (PFOA or PFOS) suggest that lake sediments could be an important long-term sink for these emerging alternatives. The positive matrix factorization model demonstrated that food packaging and textile treatments (50%) and fluoropolymer manufacturing (26% for alternative sources and 8.2% for legacy sources) were the two major sources of PFAS in Poyang Lake. The influx and outflux of total PFAS in Poyang Lake were 9.0 and 12.8 ton/year, respectively, and the OBS flux was estimated for the first time. The results provide insights into the environmental behavior and fate of emerging PFAS in freshwater ecosystems.

Interaction of tetrabromobisphenol A (TBBPA) with microplastics-sediment (MPs-S) complexes: A comparison between binary and simple systems.

The presence of microplastics (MPs) and the associated organic pollutants in the aquatic environment has attracted growing concern in recent years. MPs could compete with chemicals for adsorption sites on the surface of sediment, affecting the sorption processes of pollutants on sediment. However, few studies focused on the binary system of microplastics-sediment (MPs-S), which appear much common in aquatic environment. Herein, we investigated the interactions between a continuously used flame retardant tetrabromobisphenol A (TBBPA) and four MPs-S complexes (PVC-S, PE-S, PP-S and PS-S). The equilibrium adsorption capacities were 17.1, 15.6, 15.4, and 14.0 mg/kg for PVC-S, PS-S, PE-S, and PP-S, respectively. Kinetics suggest that adsorption behavior of TBBPA was fitted by pseudo-second-order model. Co-adsorption of TBBPA in binary systems were much lower than the sum of each simple system, which may be due to the mutually occupied adsorption sites. Higher ionic strength and lower dissolved organic matter strengthened the sorption of TBBPA onto MPs-S complexes. The enhanced sorption capacities for TBBPA were observed with elevated proportion and small particle size of MPs in the MPs-S complexes. This study contributes to the knowledge on the impact of MPs in partitioning of organic pollutants in-between solid and aqueous phases in the aquatic environment.

Significance of biotransformation and excretion on the enantioselective bioaccumulation of hexabromocyclododecane (HBCDD) in laying hens and developing chicken embryos.

Although (-)-α-hexabromocyclododecane (HBCDD) and (+)-γ-HBCDD are preferentially enriched in chickens, the key factors contributing to their selective bioaccumulation in hens and their potential biotransformation in developing chicken embryos remain unclear. Herein, in vivo and in ovo exposure experiments using hens and fertilized eggs were conducted to investigate the absorption, excretion, and biotransformation of HBCDDs in chickens. γ-HBCDD (76%) exhibited a higher absorption efficiency than α- (22%) and ß- (69%) HBCDDs. However, α-HBCDD was dominant in hen tissues, although γ-HBCDD accounted for >75% in the spiked feed. Moreover, chicken embryos biotransformed approximately 9.5% and 11.7% of absorbed α- and γ-HBCDDs, respectively, implying that diastereomer-selective elimination causes the predominance of α-HBCDD in hens. The concentration and enantiomer fraction (EF) of α-HBCDD in laid eggs were significantly positively correlated, suggesting enantioselective elimination. The EFs of α- and γ-HBCDDs varied between feces from the exposure and depuration periods, indicating the preferred excretion of (+)-α- and (-)-γ-HBCDDs. Furthermore, the enantioselective biotransformation of (-)-γ-HBCDD was confirmed in developing chicken embryos. These results show that excretion and biotransformation contribute to the diastereomer- and enantiomer-selective bioaccumulation of HBCDDs in chickens; The results may improve our understanding of the environmental fate and ecological risks of HBCDDs in biota.

A review of measurement techniques for aerosol effective density.

Density (ρ) is one of the most important physical properties of aerosol particles. Owing to the complex nature of aerosols and the challenges of measuring them, effective density (ρe) is generally used as an alternative measure. Various methods have been developed to quantify the ρe of aerosols, which provide powerful technical support and understanding of their physical properties. Here, we present a comprehensive review of the characterisation techniques of ρe currently used in the literature. Overall, six categories of measurement are identified, and the typical configuration, measurement principles, errors and field applications of each are demonstrated. Their respective advantages and disadvantages are also discussed to improve their application. Finally, we outline future directions for further technical improvement in, and instrumental development for, ρe measurement.

Exposure of adult zebrafish (Danio rerio) to Tetrabromobisphenol A causes neurotoxicity in larval offspring, an adverse transgenerational effect.

Tetrabromobisphenol A (TBBPA) is one of the most extensively used brominated flame retardants and is universally detected in the environment. However, information related to its transgenerational toxicity is sparse. Using zebrafish as a study model, adult fish were exposed to TBBPA at different concentrations (0, 3, 30, or 300 µg/L) for 42 d and then, the exposed adults were spawned in TBBPA-free water. The neurobehavior of adults and larval offspring was evaluated, and the levels of thyroxine (T4), triiodothyronine (T3) and neurotransmitters (acetylcholine, dopamine and gamma-aminobutyric acid) were quantified in larvae and embryos. Our results showed that TBBPA was detected in embryo and the locomotor activity of larval offspring was significantly reduced, suggesting that TBBPA can transfer to offspring and result in neurotoxicity in larval offspring. Furthermore, a reduction in T3 levels was observed in both the larvae and embryos. We also found a significantly decreased content of dopamine in larval offspring, accompanied by downregulated mRNA expression of rdr2b and drd3. Our results demonstrated that TBBPA can be transferred to offspring embryos, and subsequently induce neurotoxicity in larval offspring by affecting the amount of T3 transferred from the parents to embryos and the production of dopamine in larvae.

NLRP3 deficiency did not attenuate NASH development under high fat calorie diet plus high fructose and glucose in drinking water.

NOD-like receptor protein 3 (NLRP3) promotes the inflammatory response during progression of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). This study aimed to further delineate the role of NLRP3 in NASH development by abolishing its expression in mice. A high-fat and calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) was used to establish NASH in both wild-type (WT) and NLRP3 knock-out (KO) mice. Hepatocellular injury, hepatic steatosis and fibrosis, as well as inflammatory response and insulin resistance in the liver and epidydimal white adipose tissue (eWAT) were determined. Elevated body weight, liver weight and serum alanine transaminase level, increased hepatic triglyceride accumulation and collagen deposition, and worsened systemic insulin resistance were observed in Nlrp3-/- mice compared to WT mice under HFCD-HF/G feeding. Upregulated hepatic transcription of tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1), and enhanced infiltration of inducible nitric oxide synthase-positive (iNOS+) M1 macrophages were also documented in HFCD-HF/G-fed Nlrp3-/- mice in comparison to HFCD-HF/G-fed WT mice. Moreover, transcription of TNF-α and MCP-1 and infiltration of iNOS+ M1 macrophages were increased in the liver of Nlrp3-/- mice under control diet. NLRP3 deficiency did not attenuate, but instead aggravated NASH development under HFCD-HF/G feeding. The worsened extent of NASH might be attributed to enhanced hepatic MCP-1 expression and M1 macrophage infiltration in Nlrp3-/- mice. Our study points to additional caution when NLRP3 blockade is considered as a therapeutic strategy in the treatment of human NASH.

Sorption of tetrabromobisphenol A onto microplastics: Behavior, mechanisms, and the effects of sorbent and environmental factors.

Microplastics (MPs) and halogenated organic pollutants coexist in ambient water and MPs tend to sorb organic pollutants from surrounding environments. Herein, a study on the sorption behavior of tetrabromobisphenol-A (TBBPA) onto four different MPs, namely, polyethylene (PE), polypropylene (PP), polystyrene (PS), and polyvinyl chloride (PVC) was carried out. Effects of MPs properties and environmental factors, including the type, surface charge and pore volume as well as the ionic strength (Ca2+) and humic acid (HA) on the sorption of TBBPA were discussed. Results showed that the sorption of TBBPA onto the MPs could reached an equilibrium within 24 h, and the sorption capacities decreased in the following order -PVC (101.85 mg kg-1) >PS (78.95 mg kg-1) >PP (58.57 mg kg-1) >PE (49.43 mg kg-1). Adsorption kinetics data fitted by intraparticle diffusion model revealed both surface sorption and intraparticle diffusion contributed, in the interfacial diffusion stage approximately 11-29% of TBBPA slowly diffused onto the surface of the MPs, and finally, in the intraparticle diffusion stage. The increase of Ca2+ concentration could promote the sorption of TBBPA by PE, PP, and PS, but no significant alteration for PVC. For all the four MPs, HA was found to exert a negative effect on TBBPA sorption. The adsorption was mainly driven by hydrophobic partition and electrostatic interactions.

Serum lipocalin-2 is a potential biomarker for the clinical diagnosis of nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. We aimed to investigate the usefulness of a key biomarker, lipocalin-2 (LCN2), for the detection of NASH progression. METHODS: A mouse NASH model was established using a high-fat diet and a high-sugar drinking water. Gene expression profile of the NASH model was analyzed using RNA sequencing. Moreover, 360 NAFLD patients (steatosis, 83; NASH, 277), 40 healthy individuals, and 87 patients with alcoholic fatty liver disease were recruited. RESULTS: Inflammatory infiltration, focal necrosis in the leaflets, steatosis, and fibrosis were documented in the mouse liver. In total, 504 genes were differentially expressed in the livers of NASH mice, and showed significant functional enrichment in the inflammation-related category. Upregulated liver LCN2 was found to be significantly interactive with various interleukins and toll-like receptors. Serum LCN2 levels were significantly increased in NAFLD patients. Serum LCN2 levels were correlated with steatosis, intralobular inflammation, semiquantitative fibrosis score, and nonalcoholic fatty liver disease activity score. The area under the curve of serum LCN2 was 0.987 with a specificity of 100% and a sensitivity of 93.5% for NASH diagnosis, and 0.977 with almost the same specificity and sensitivity for steatosis. CONCLUSION: LCN2 might be involved in the transition from NAFL to NASH by mediating inflammation. Serum LCN2 levels might be a novel biomarker for the diagnosis of NASH.