Theoretical investigation of the reaction mechanism of THP oxidative rearrangement catalysed by BBOX.

γ-Butyrobetaine hydroxylase (BBOX) is a non-heme FeII/2OG dependent enzyme that is able to perform two different kinds of catalytic reactions on 3-(2,2,2-trimethylhydrazinium) propionate (THP) to produce distinct catalytic products. Although the structure of BBOX complexed with THP has been resolved, the details of its catalytic mechanism are still elusive. In this study, by employing molecular dynamics (MD) simulations and density functional theory (DFT) calculations, the mechanism of the THP oxidative rearrangement reactions catalysed by BBOX was investigated. Our calculations revealed how the enzyme undergoes a conformational conversion to initiate the catalytic reactions. In the first catalytic step, BBOX performs hydrogen abstraction from the substrate THP as a common non-heme iron enzyme. Due to the structure of the substrate stabilizing the radical species and polarizing the adjacent N-N bond, in the next step, THP takes the pathway for N-N bond homolysis but not regular hydroxyl rebounding. The cleaved ammonium radical could either react with the hydroxyl group on the iron centre of the enzyme or recombine with the other cleaved fragment of the substrate to generate the rearranged product. This study revealed the catalytic mechanism of BBOX, detailing how the enzyme and the substrate regulated the hydroxyl rebound process to generate various products.

[An in vitro experiment on the stability and irritant of hypochlorous acid in oral cavity].

PURPOSE: To study the stability of physicochemical properties and sterilizing effect about two commercially available hypochlorous acid (HClO) products under simulated clinical conditions, and to evaluate the compatibility of HClO on soft and hard tissues and cells in oral cavity. METHODS: Samples of HClO solution with different production processes were prepared, to detect the changes of physicochemical indexes of each sample over time under simulated clinical conditions (shielded from light at 20-25 ℃, open the cover for 5 minutes every day), including free available chlorine, oxidation-reduction potential and pH. Through suspension quantitative germicidal test, the antibiosis-concentration curve of HClO solution was made, so as to calibrate the change of antibacterial ability of disinfectant with the decrease of available chlorine content during storage. Pulp, tongue and dentine were immersed in PBS, 100 ppm HClO, 200 ppm HClO and 3% NaClO. The influence on soft and hard tissues was evaluated by weighing method and microhardness test. The toxic effects of HClO, NaClO and their 10-fold diluent on human gingival fibroblasts were determined by CCK-8 cytotoxicity assay. GraphPad PRIS 8.0 software was used to analyze the data. RESULTS: Under simulated conditions, the free available chlorine (FAC) of HClO solution decayed with time, and the attenuation degree was less than 20 ppm within 1 month. The bactericidal effect of each HClO sample was still higher than 5log after concentration decay. There was no obvious dissolution and destruction to soft and hard tissues for HClO(P＞0.05). The cell viability of HClO to human gingival fibroblast cells (HGFC) was greater than 80%, which was much higher than 3% NaClO (P＜0.001). CONCLUSIONS: The bactericidal effect and stability of HClO solution can meet clinical needs, which has low cytotoxicity and good histocompatibility. It is expected to become a safe and efficient disinfection product in the field of living pulp preservation and dental pulp regeneration.

Unraveling the role of hepatitis B virus DNA integration in B-cell lymphomagenesis.

BACKGROUND: Studies have shown that hepatitis B virus (HBV)-associated B-cell non-Hodgkin lymphoma (NHL) constitutes a unique subgroup with distinct clinical features. It still leaves open the question of whether the integration of HBV DNA into the B-cell genome is a causal mechanism in the development of lymphoma. METHODS: Using the hybridisation capture-based next generation sequencing and RNA sequencing, we characterised the HBV integration pattern in 45 HBV-associated B-cell NHL tumour tissues. RESULTS: A total of 354 HBV integration sites were identified in 13 (28.9%) samples, indicating the relatively low integration frequency in B-cell NHLs. High plasma HBV DNA loads were not associated with the existence of HBV integration. The insertion sites distributed randomly across all the lymphoma genome without any preferential hotspot neither at the chromosomal level nor at the genetic level. Intriguingly, most HBV integrations were nonclonal in B-cell NHLs, implying that they did not confer a survival advantage. Analysis of the paired diagnosis-relapse samples showed the unstable status of HBV integrations during disease progression. Furthermore, transcriptomic analysis revealed the limited biological impact of HBV integration. CONCLUSION: Our study provides an unbiased HBV integration map in B-cell NHLs, revealing the insignificant role of HBV DNA integration in B-cell lymphomagenesis.

Clinical characteristics and survival of esophageal cancer patients: annual report of the surgical treatment in Shanghai Chest Hospital, 2017.

Background: Esophageal cancer remains a significant burden of lethal cancers worldwide, particularly in China. This is an annual report of Shanghai Chest Hospital (SCH) on surgical treatment for esophageal cancer patients in 2017. Methods: All patients who received surgical treatment for esophageal cancer at SCH in 2017 were given a detailed summary of clinical information based on the database of SCH. Kaplan-Meier method was used to present their survival, subgroup analyses, and multivariate Cox regression analysis were used to estimate the potential risk factors for prognosis. Results: In 2017, a total of 663 patients received surgical treatment (628 esophagectomies and 35 endoscopic resections) for esophageal cancer at SCH. Of the patients who underwent esophagectomy, 292 patients received perioperative treatment, majority of which was postoperative treatment (47.9%). Only 69 (10.4%) patients received preoperative treatment. Minimally invasive techniques were used in 444 (70.7%) patients and robotic-assisted esophagectomies were used in 130 (20.7%) patients. Complete resection (R0) was achieved in 90.3% of esophagectomy patients. The 5-year overall survival (OS) rate after esophagectomy was 52.5%. Conclusions: The 5-year OS of patients with esophageal cancer can reach 52.5% after surgical treatment in 2017 at SCH. The exact beneficiaries of neoadjuvant therapy are still unclear in the 2017 cohort.

Gut microbiota dysbiosis-related susceptibility to nontuberculous mycobacterial lung disease.

The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota dysbiosis in patients with NTM-LD. Reduced abundance of Prevotella copri was significantly associated with NTM-LD and its disease severity. Compromised TLR2 activation activity in feces and plasma in the NTM-LD patients was highlighted. In the antibiotics-treated mice as a study model, gut microbiota dysbiosis with reduction of TLR2 activation activity in feces, sera, and lung tissue occurred. Transcriptomic analysis demonstrated immunocompromised in lung which were closely associated with increased NTM-LD susceptibility. Oral administration of P. copri or its capsular polysaccharides enhanced TLR2 signaling, restored immune response, and ameliorated NTM-LD susceptibility. Our data highlighted the association of gut microbiota dysbiosis, systematically compromised immunity and NTM-LD development. TLR2 activation by P. copri or its capsular polysaccharides might help prevent NTM-LD.

Intersubject correlations in reward and mentalizing brain circuits separately predict persuasiveness of two types of ISIS video propaganda.

The Islamist group ISIS has been particularly successful at recruiting Westerners as terrorists. A hypothesized explanation is their simultaneous use of two types of propaganda: Heroic narratives, emphasizing individual glory, alongside Social narratives, which emphasize oppression against Islamic communities. In the current study, functional MRI was used to measure brain responses to short ISIS propaganda videos distributed online. Participants were shown 4 Heroic and 4 Social videos categorized as such by another independent group of subjects. Persuasiveness was measured using post-scan predictions of recruitment effectiveness. Inter-subject correlation (ISC) was used to measure commonality of brain activity time courses across individuals. ISCs in ventral striatum predicted rated persuasiveness for Heroic videos, while ISCs in mentalizing and default networks, especially in dmPFC, predicted rated persuasiveness for Social videos. This work builds on past findings that engagement of the reward circuit and of mentalizing brain regions predicts preferences and persuasion. The observed dissociation as a function of stimulus type is novel, as is the finding that intersubject synchrony in ventral striatum predicts rated persuasiveness. These exploratory results identify possible neural mechanisms by which political extremists successfully recruit prospective members and specifically support the hypothesized distinction between Heroic and Social narratives for ISIS propaganda.

Comparative physiological, biochemical and transcriptomic analyses to reveal potential regulatory mechanisms in response to starvation stress in Cipangopaludina chinensis.

Cipangopaludina chinensis, as a financially significant species in China, represents a gastropod in nature which frequently encounters starvation stress owing to its limited prey options. However, the underlying response mechanisms to combat starvation have not been investigated in depth. We collected C. chinensis under several times of starvation stress (0, 7, 30, and 60 days) for nutrient, biochemical characteristics and transcriptome analyses. The results showed that prolonged starvation stress (> 30 days) caused obvious fluctuations in the nutrient composition of snails, with dramatic reductions in body weight, survival and digestive enzyme activity (amylase, protease, and lipase), and markedly enhanced the antioxidant enzyme activities of the snails. Comparative transcriptome analyses revealed 3538 differentially expressed genes (DEGs), which were significantly associated with specific starvation stress-responsive pathways, including oxidative phosphorylation and alanine, aspartate, and glutamate metabolism. Then, we identified 40 candidate genes (e.g., HACD2, Cp1, CYP1A2, and GPX1) response to starvation stress through STEM and WGCNA analyses. RT-qPCR verified the accuracy and reliability of the high-throughput sequencing results. This study provides insights into snail overwintering survival and the potential regulatory mechanisms of snail adaptation to starvation stress.

Genetic diversity and population structure of Bellamya purificata in Guangxi.

Bellamya purificata is an important medicinal value and economically farmed species in China. However, because little is known about the genetic characteristics of this species, the utilization of high-quality germplasm resources is hindered. The study examined the genetic differentiation between, and the structure of 12 B. purificata populations in Guangxi using 7 microsatellite DNA markers. High genetic diversity occurred in each population, with mean observed heterozygosity 0.655 and a mean expected heterozygosity 0.832. Analysis of molecular variance reveals genetic diversity to be greater within (95.2%) than among populations (4.8%). Genetic differentiation between populations is weak (Fst = 0.048, P < 0.001), with mixing of genetic clusters prevalent at the level of the individual. Genetic flow exists between populations (Nm = 3.084-11.778), with Longshui and Guilin populations exchanging frequently. A Mantel test reveals a low correlation between geographic and genetic distances (r = 0.2482, P < 0.071), suggesting that dispersal between neighboring populations facilitates population exchange. No significant heterozygosity excess was observed for any population (P > 0.05), indicating a lack of recent genetic bottlenecks. The results provide important genetic information for B. purificata, and data for potential germplasm discovery and aquaculture development.

Suppressing Organic Bromine but Promoting Bromate: Is the Ultraviolet/Ozone Process a Double-Edged Sword for the Toxicity of Wastewater to Mammalian Cells?

Brominated byproducts and toxicity generation are critical issues for ozone application to wastewater containing bromide. This study demonstrated that ultraviolet/ozone (UV/O3, 100 mJ/cm2, 1 mg-O3/mg-DOC) reduced the cytotoxicity of wastewater from 14.2 mg of pentol/L produced by ozonation to 4.3 mg of pentol/L (1 mg/L bromide, pH 7.0). The genotoxicity was also reduced from 1.65 to 0.17 µg-4-NQO/L by UV/O3. Compared with that of O3 alone, adsorbable organic bromine was reduced from 25.8 to 5.3 µg/L by UV/O3, but bromate increased from 32.9 to 71.4 µg/L. The UV/O3 process enhanced the removal of pre-existing precursors (highly unsaturated and phenolic compounds and poly aromatic hydrocarbons), while new precursors were generated, yet the combined effect of UV/O3 on precursors did not result in a significant change in toxicity. Instead, UV radiation inhibited HOBr concentration through both rapid O3 decomposition to reduce HOBr production and decomposition of the formed HOBr, thus suppressing the AOBr formation. However, the hydroxyl radical-dominated pathway in UV/O3 led to a significant increase of bromate. Considering both organic bromine and bromate, the UV/O3 process effectively controlled both cytotoxicity and genotoxicity of wastewater to mammalian cells, even though an emphasis should be also placed on managing elevated bromate. Futhermore, other end points are needed to evaluate the toxicity outcomes of the UV/O3 process.

Comparison of the 2022 world health organization classification and international consensus classification in myelodysplastic syndromes/neoplasms.

In 2022, two novel classification systems for myelodysplastic syndromes/neoplasms (MDS) have been proposed: the International Consensus Classification (ICC) and the 2022 World Health Organization (WHO-2022) classification. These two contemporary systems exhibit numerous shared features but also diverge significantly in terminology and the definition of new entities. Thus, we retrospectively validated the ICC and WHO-2022 classification and found that both systems promoted efficient segregation of this heterogeneous disease. After examining the distinction between the two systems, we showed that a peripheral blood blast percentage ≥ 5% indicates adverse survival. Identifying MDS/acute myeloid leukemia with MDS-related gene mutations or cytogenetic abnormalities helps differentiate survival outcomes. In MDS, not otherwise specified patients, those diagnosed with hypoplastic MDS and single lineage dysplasia displayed a trend of superior survival compared to other low-risk MDS patients. Furthermore, the impact of bone marrow fibrosis on survival was less pronounced within the ICC framework. Allogeneic transplantation appears to improve outcomes for patients diagnosed with MDS with excess blasts in the ICC. Therefore, we proposed an integrated system that may lead to the accurate diagnosis and advancement of future research for MDS. Prospective studies are warranted to validate this refined classification.

Impact of operative time on textbook outcome after minimally invasive esophagectomy, a risk-adjusted analysis from a high-volume center.

BACKGROUND: We aimed to study the impact of operative time on textbook outcome (TO), especially postoperative complications and length of postoperative stay in minimally invasive esophagectomy. METHODS: Patients undergoing esophagectomy for curative intent within a prospectively maintained database from 2016 to 2022 were retrieved. Relationships between operative time and outcomes were quantified using multivariable mixed-effects models with medical teams random effects. A restricted cubic spline (RCS) plotting was used to characterize correlation between operative time and the odds for achieving TO. RESULTS: Data of 2210 patients were examined. Median operative time was 270 mins (interquartile range, 233-313) for all cases. Overall, 902 patients (40.8%) achieved TO. Among non-TO patients, 226 patients (10.2%) had a major complication (grade ≥ III), 433 patients (19.6%) stayed postoperatively longer than 14 days. Multivariable analysis revealed operative time was associated with higher odds of major complications (odds ratio 1.005, P < 0.001) and prolonged postoperative stay (≥ 14 days) (odds ratio 1.003, P = 0.006). The relationship between operative time and TO exhibited an inverse-U shape, with 298 mins identified as the tipping point for the highest odds of achieving TO. CONCLUSIONS: Longer operative time displayed an adverse influence on postoperative morbidity and increased lengths of postoperative stay. In the present study, the TO displayed an inverse U-shaped correlation with operative time, with a significant peak at 298 mins. Potential factors contributing to prolonged operative time may potentiate targets for quality metrics and risk-adjustment process.

Novel method for identifying the heaviest QED atom.

QED atoms are composed of unstructured and point-like lepton pairs bound together by the electromagnetic force. The smallest and heaviest QED atom is formed by a τ+τ- pair. Currently, the only known atoms of this type are the e+e- and µ+e- atoms, which were discovered 64 years ago and remain the sole examples found thus far. We demonstrate that the Jτ (τ+τ- atom with JPC=1--) atom signal can be observed with a significance larger than 5σ including both statistical and systematic uncertainties, via. the process e+e-→X+Y-Ɇ (X,Y=e,µ,π,K, or ρ, and Ɇ is the missing energy due to unobserved neutrinos) with 1.5ab-1 data taken around the τ pair production threshold. The τ lepton mass can be measured with a precision of 1 keV with the same data sample. This is within one year's running time of the proposed super tau-charm facility in China or super charm-tau factory in Russia.

Glutathione ligand self-assembly enables luminescence from Au15 nanoclusters for highly sensitive and selective monitoring of blood Pb(II) ions.

Lead Pb(II) ions is a cumulative toxicant that impacts several biological systems and poses severe harm to young children. Accurate Pb(II) ions monitoring is thus of paramount importance. Here, we present the synthesis and application of glutathione-capped Au15 nanoclusters (Au15(SG)13) as a luminescence probe for the accurate and selective monitoring of blood Pb(II). The introduction of Pb(II) ions triggers orderly self-assembly of Au15 nanoclusters, resulting in the formation of rigid shell around Au nuclei. This limits the localized vibration of the glutathione ligands and their interaction with water molecules, greatly reducing non-radiative energy loss, and thereby enhancing the photoluminescence signal. Consequently, Au15(SG)13 nanoclusters exhibit high sensitivity for Pb(II) detection. The detection signal displays a linear relationship with Pb(II) over a wide detection range (0-800 µg/L), demonstrating a substantial sensitivity of 35.29 µg/L. Moreover, the developed nanoclusters show superior selectivity for Pb(II) ions, distinguishing them from other prevalent heavy metals. This work pave the way for the development of advanced Pb(II) sensors with high sensitivity and selectivity.

Mechanistic insight into the competition between interfacial and bulk reactions in microdroplets through N2O5 ammonolysis and hydrolysis.

Reactive uptake of dinitrogen pentaoxide (N2O5) into aqueous aerosols is a major loss channel for NOx in the troposphere; however, a quantitative understanding of the uptake mechanism is lacking. Herein, a computational chemistry strategy is developed employing high-level quantum chemical methods; the method offers detailed molecular insight into the hydrolysis and ammonolysis mechanisms of N2O5 in microdroplets. Specifically, our calculations estimate the bulk and interfacial hydrolysis rates to be (2.3 ± 1.6) × 10-3 and (6.3 ± 4.2) × 10-7 ns-1, respectively, and ammonolysis competes with hydrolysis at NH3 concentrations above 1.9 × 10-4 mol L-1. The slow interfacial hydrolysis rate suggests that interfacial processes have negligible effect on the hydrolysis of N2O5 in liquid water. In contrast, N2O5 ammonolysis in liquid water is dominated by interfacial processes due to the high interfacial ammonolysis rate. Our findings and strategy are applicable to high-chemical complexity microdroplets.

H-ferritin-nanocaged gadolinium nanoparticles for ultra-sensitive MR molecular imaging.

Rationale: Magnetic resonance imaging (MRI) is a powerful diagnostic technology by providing high-resolution imaging. Although MRI is sufficiently valued in its resolving morphology, it has poor sensitivity for tracking biomarkers. Therefore, contrast agents are often used to improve MRI diagnostic sensitivity. However, the clinically used Gd chelates are limited in improving MRI sensitivity owing to their low relaxivity. The objective of this study is to develop a novel contrast agent to achieve a highly sensitive tracking of biomarkers in vivo. Methods: A Gd-based nanoprobe composed of a gadolinium nanoparticle encapsulated within a human H-ferritin nanocage (Gd-HFn) has been developed. The specificity and sensitivity of Gd-HFn were evaluated in vivo in tumor-bearing mice and apolipoprotein E-deficient mice (Apoe-/-) by MRI. Results: The Gd-HFn probe shows extremely high relaxivity values (r1 = 549 s-1mM-1, r2 = 1555 s-1mM-1 under a 1.5-T magnetic field; and r1 = 428 s-1mM-1 and r2 = 1286 s-1mM-1 under a 3.0-T magnetic field), which is 175-fold higher than that of the clinically standard Dotarem (Gd-DOTA, r1 =3.13 s-1mM-1) under a 1.5-T magnetic field, and 150-fold higher under a 3.0-T magnetic field. Owing to the substantially enhanced relaxivity values, Gd-HFn achieved a highly sensitive tracking for the tumor targeting receptor of TfR1 and enabled the in vivo MRI visualization of tumors approaching the angiogenic switch. Conclusions: The developed Gd-HFn contrast agent makes MRI a more powerful tool by simultaneously providing functional and morphological imaging information, which paves the way for a new perspective in molecular imaging.

Datasets of various geotechnical surveys in several arrays in the Taipei Basin.

The standard penetration test (SPT), seismic cone penetration test (SCPT), and various in-situ seismic tests are commonly utilized for geotechnical site investigations. The investigated data via these tests are widely adopted to capture site characteristics for geotechnical engineering design. However, site characterizations vary in the above in-situ tests, which leads to uncertainties in the corresponding engineering analysis and design. To address these variabilities, this paper meticulously carried out the above-mentioned geotechnical in-situ tests with rigorous supervision at 13 selected sites in the Taipei Basin, yielding several valuable datasets. The datasets consist of digital investigation data including SPT-N, soil classification, CPT-qc and -fs, and the shear wave velocities (Vs) obtained from different measurements. We believe that these datasets will be beneficial for conducting various calibration studies for different geotechnical investigation methods and the corresponding geotechnical parameters.

The Role of the ADAMTS18 Gene-Induced Immune Microenvironment in Mouse Kidney Development.

The aim of this study is to investigate the role of the ADAMTS18 gene in regulating the renal development of mice. PAS staining was used to observe the kidney development of E12.5-E17.5 mice, while immunofluorescence staining and RT-PCR were used to observe the expression of ADAMTS18. Ureteric bud (UB) branches were observed using immunofluorescence staining using the UB marker E-cadherin, and the apoptosis and proliferation of posterior renal mesenchymal cells were analyzed using TUNEL and PH3 fluorescence staining. Flow cytometry was used to analyze the immune cell infiltration, and western blotting (WB) was used to analyze the expression of PD-1/PD-L1 and CTLA-4. As a result, the ADAMTS18 gene expression gradually increased as the kidney continued to mature during embryonic development. Compared with that in the control and vector groups, UB branching was significantly reduced in the ADAMTS18 deletion group (p < 0.05), but that deletion of ADAMTS18 did not affect posterior renal mesenchymal cell proliferation or apoptosis (p > 0.05). Compared with those in the control and vector groups, the proportion of embryonic kidney B cells and the proportion of CD8+ cells were significantly greater after ADAMTS18 was knocked down (p < 0.05), but the difference in neutrophil counts was not significant (p > 0.05). The WB analysis revealed that the PD-1/PD-L1 and CTLA-4 expression was significantly increased after ADAMTS18 was knocked down (p < 0.05). In conclusion, the ADAMTS18 gene may be involved in mice kidney development by regulating the immune microenvironment and activating immune checkpoints. Deletion of the ADAMTS18 gene may be unfavorable for kidney development.

Hostile Attribution Bias Shapes Neural Synchrony in the Left Ventromedial Prefrontal Cortex during Ambiguous Social Narratives.

Hostile attribution bias refers to the tendency to interpret social situations as intentionally hostile. While previous research has focused on its developmental origins and behavioral consequences, the underlying neural mechanisms remain underexplored. Here, we employed functional near-infrared spectroscopy (fNIRS) to investigate the neural correlates of hostile attribution bias. While undergoing fNIRS, male and female participants listened to and provided attribution ratings for 21 hypothetical scenarios where a character's actions resulted in a negative outcome for the listener. Ratings of hostile intentions were averaged to measure hostile attribution bias. Using intersubject representational similarity analysis, we found that participants with similar levels of hostile attribution bias exhibited higher levels of neural synchrony during narrative listening, suggesting shared interpretations of the scenarios. This effect was localized to the left ventromedial prefrontal cortex (VMPFC) and was particularly prominent in scenarios where the character's intentions were highly ambiguous. We then grouped participants into high and low bias groups based on a median split of their hostile attribution bias scores. A similarity-based classifier trained on the neural data classified participants as having high or low bias with 75% accuracy, indicating that the neural time courses during narrative listening was systematically different between the two groups. Furthermore, hostile attribution bias correlated negatively with attributional complexity, a measure of one's tendency to consider multifaceted causes when explaining behavior. Our study sheds light on the neural mechanisms underlying hostile attribution bias and highlights the potential of using fNIRS to develop nonintrusive and cost-effective neural markers of this sociocognitive bias.

Phenotypic and metabolomic characteristics of mouse models of metabolic associated steatohepatitis.

BACKGROUND: Metabolic associated steatohepatitis (MASH) is metabolic disease that may progress to cirrhosis and hepatocellular carcinoma. Mouse models of diet-induced MASH, which is characterized by the high levels of fats, sugars, and cholesterol in diets, are commonly used in research. However, mouse models accurately reflecting the progression of MASH in humans remain to be established. Studies have explored the potential use of serological metabolites as biomarkers of MASH severity in relation to human MASH. METHODS: We performed a comparative analysis of three mouse models of diet-induced MASH in terms of phenotypic and metabolomic characteristics; MASH was induced using different diets: a high-fat diet; a Western diet; and a high-fat, high-cholesterol diet. Liver cirrhosis was diagnosed using standard clinical approaches (e.g., METAVIR score, hyaluronan level, and collagen deposition level). Mouse serum samples were subjected to nuclear magnetic resonance spectroscopy-based metabolomic profiling followed by bioinformatic analyses. Metabolomic analysis of a retrospective cohort of patients with hepatocellular carcinoma was performed; the corresponding cirrhosis scores were also evaluated. RESULTS: Using clinically relevant quantitative diagnostic methods, the severity of MASH was evaluated. Regarding metabolomics, the number of lipoprotein metabolites increased with both diet and MASH progression. Notably, the levels of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) significantly increased with fibrosis progression. During the development of diet-induced MASH in mice, the strongest upregulation of expression was noted for VLDL receptor. Metabolomic analysis of a retrospective cohort of patients with cirrhosis indicated lipoproteins (e.g., VLDL and LDL) as predominant biomarkers of cirrhosis. CONCLUSIONS: Our findings provide insight into the pathophysiology and metabolomics of experimental MASH and its relevance to human MASH. The observed upregulation of lipoprotein expression reveals a feedforward mechanism for MASH development that may be targeted for the development of noninvasive diagnosis.