Rapid determination and risk evaluation of multi-class antibiotics in aquatic products by one-step purification process coupled with ultra-high performance liquid chromatography-tandem mass spectrometry.

A sensitive and robust multiclass analytical method was established to simultaneously determine 55 antibiotics in aquatic products through liquid chromatography-tandem mass spectrometry. A simple one-step purification process was successfully developed, which combined post-acidic acetonitrile extraction directly by an enhanced matrix removal cartridge. This approach eliminated the need for solvent transition. The established method for 55 antibiotics achieved an excellent linear relationship with R2 values ≥ 0.9921 in the range of 0.05-200 µg/L. The quantitation limits ranged within 0.04-5.0 µg/kg. Satisfactory recoveries (76.2%-99.7 %) were achieved with the relative standard deviations below 13.9 %. Furthermore, the antibiotic residues in aquatic products were analyzed, and the health and antibiotic resistance risk assessments were conducted. Although the health risks of target antibiotics were acceptable, a resistance risk was observed. Therefore, monitoring antibiotic residue levels in aquatic products requires considerable attention and further research to ensure the quality of marine products and consumer safety.

FGF10 protects against particulate matter-induced lung injury by inhibiting ferroptosis via Nrf2-dependent signaling.

Particulate matter (PM) is considered the fundamental component of atmospheric pollutants and is associated with the pathogenesis of many respiratory diseases. Fibroblast growth factor 10 (FGF10) mediates mesenchymal-epithelial signaling and has been linked with the repair process of PM-induced lung injury (PMLI). However, the pathogenic mechanism of PMLI and the specific FGF10 protective mechanism against this injury are still undetermined. PM was administered in vivo into murine airways or in vitro to human bronchial epithelial cells (HBECs), and the inflammatory response and ferroptosis-related proteins SLC7A11 and GPX4 were assessed. The present research investigates the FGF10-mediated regulation of ferroptosis in PMLI mice models in vivo and HBECs in vitro. The results showed that FGF10 pretreatment reduced PM-mediated oxidative damage and ferroptosis in vivo and in vitro. Furthermore, FGF10 pretreatment led to reduced oxidative stress, decreased secretion of inflammatory mediators, and activation of the Nrf2-dependent antioxidant signaling. Additionally, silencing of Nrf2 using siRNA in the context of FGF10 treatment attenuated the effect on ferroptosis. Altogether, both in vivo and in vitro assessments confirmed that FGF10 protects against PMLI by inhibiting ferroptosis via the Nrf2 signaling. Thus, FGF10 can be used as a novel ferroptosis suppressor and a potential treatment target in PMLI.

High-throughput analytical methodology of monoalkyl phthalate esters and the composite risk assessment with their parent phthalate esters in aquatic organisms and seawater.

A sensitive, robust, and highly efficient analytical methodology involving solid phase extraction coupled to ultra-high performance liquid chromatography tandem mass spectrometry was successfully established to detect 13 monoalkyl phthalate esters (MPAEs) in aquatic organisms and seawater. After the organisms were preprocessed using enzymatic deconjugation with ß-glucuronidase, extraction, purification, and qualitative and quantitative optimization procedures were performed. Under optimal conditions, the limits of detection varied from 0.07 to 0.88 µg/kg (wet weight) and 0.04-1.96 ng/L in organisms and seawater, respectively. Collectively, MPAEs achieved acceptable recovery values (91.0-102.7%) with relative standard deviations less than 10.4% and matrix effects ranging from 0.93 to 1.07 in the above matrix. Furthermore, MPAEs and phthalate esters were detected by the developed methodology and gas chromatography-triple quadrupole tandem mass spectrometer in practical samples, respectively. Mono-n-butyl phthalate and mono-iso-butyl phthalate were the most predominant congeners, accounting for 24.8-35.2% in aquatic organisms and seawater. Comprehensive health and ecological risks were higher after the MPAEs were incorporated than when phthalate esters were considered separately, and greater than their risk threshold. Therefore, the risks caused by substances and their metabolites in multiple media, with analogous structure-activity relationships, should be considered to ensure the safety of aquatic organisms and consumers.

Precision Sequence-Defined Polymers: From Sequencing to Biological Functions.

Precise sequence-defined polymers (SDPs) with uniform chain-to-chain structure including chain length, unit sequence, and end functionalities represent the pinnacle of sophistication in the realm of polymer science. For example, the absolute control over the unit sequence of SDPs allows for the bottom-up design of polymers with hierarchical microstructures and functions. Accompanied with the development of synthetic techniques towards precision SDPs, the decoding of SDP sequences and construction of advanced functions irreplaceable by other synthetic materials is of central importance. In this Minireview, we focus on recent advances in SDP sequencing techniques including tandem mass spectrometry (MS), chemically assisted primary MS, as well as other non-destructive sequencing methods such as nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD), and nanopore sequencing. Additionally, we delve into the promising prospects of SDP functions in the area of cutting-edge biological research. Topics of exploration include gene delivery systems, the development of hybrid materials combining SDPs and nucleic acids, protein recognition and regulation, as well as the interplay between chirality and biological functions. A brief outlook towards the future directions of SDPs is also presented.

Label-Free Quantification of Digital Nanorods Assembled from Discrete Oligourethane Amphiphiles.

Polymeric nanoparticles (NPs) have been extensively designed for theranostic agent delivery. Previous methods for tracking their biological behavior and assessing theranostic efficacy heavily rely on fluorescence or isotope labeling. However, these labeling techniques may alter the physicochemical properties of the labeled NPs, leading to inaccurate biodistribution information. Therefore, it is highly desirable to develop label-free techniques for accurately assessing the biological fate of polymeric NPs. Here, we create discrete oligourethane amphiphiles (DOAs) with methoxy (OMe), hydroxyl (OH), and maleimide (MI) moieties at the dendritic oligo(ethylene glycol) (dOEG) ends. We obtained four types of digital nanorods (NRs) with distinct surface functional groups through self-assembly of a single DOA (OMe and OH NRs) or coassembly of two DOAs (OMe-MI and OH-MI NRs). These unique NRs can be directly quantified in a label-free manner by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Specifically, OMe-MI NRs exhibited the best blood circulation, and OH-MI showed the highest area under the curve (AUC) value after intravenous injection. Biodistribution studies demonstrated that MI-containing NRs generally had lower accumulation in the liver and spleen compared to that of MI-free NRs, except for the comparison between OMe and OMe-MI NRs in the liver. Proteomics studies unveiled the formation of distinct protein coronas that may greatly affect the biological behavior of NRs. This study not only provides a label-free technique for quantifying the pharmacokinetics and biodistribution of polymeric NRs but also highlights the significant impact of surface functional groups on the biological fate of polymeric NPs.

mRNA-based cancer therapeutics.

Due to the fact that mRNA technology allows the production of diverse vaccines and treatments in a shorter time frame and with reduced expense compared to conventional approaches, there has been a surge in the use of mRNA-based therapeutics in recent years. With the aim of encoding tumour antigens for cancer vaccines, cytokines for immunotherapy, tumour suppressors to inhibit tumour development, chimeric antigen receptors for engineered T cell therapy or genome-editing proteins for gene therapy, many of these therapeutics have shown promising efficacy in preclinical studies, and some have even entered clinical trials. Given the evidence supporting the effectiveness and safety of clinically approved mRNA vaccines, coupled with growing interest in mRNA-based therapeutics, mRNA technology is poised to become one of the major pillars in cancer drug development. In this Review, we present in vitro transcribed mRNA-based therapeutics for cancer treatment, including the characteristics of the various types of synthetic mRNA, the packaging systems for efficient mRNA delivery, preclinical and clinical studies, current challenges and future prospects in the field. We anticipate the translation of promising mRNA-based treatments into clinical applications, to ultimately benefit patients.

Controlled Self-Assembly of Discrete Amphiphilic Oligourethanes with a Cascade Self-Immolative Motif.

Discrete polymers offer an excellent platform for comprehending the interplay between precise chain structures, distinctive self-assembly behavior, and functional applications, whereas the development of discrete polymers with self-immolative properties remains scarce. Here, we modularly synthesize a library of discrete self-immolative oligourethanes containing N-naphthylcarbamate or N-(3-fluorophenyl)carbamate repeating units via iterative stepwise growth. These oligourethanes undergo not only cascade 1,6-elimination depolymerizations via photo-mediated removal of o-nitrobenzyl carbamate triggers but also selective cleavage of benzyl-O linkages under MS/MS conditions even without UV light irradiation. In aqueous media, these discrete oligourethanes self-assemble into different morphologies such as flat nanosheets, nanofibers, and nanoribbons, depending on the chain lengths and backbone compositions, and further morphological transitions are observed upon thermal annealing.

Glycyrrhizin protects against particulate matter-induced lung injury via regulation of endoplasmic reticulum stress and NLRP3 inflammasome-mediated pyroptosis through Nrf2/HO-1/NQO1 signaling pathway.

Particulate matter (PM) is a major environmental pollutant that contributes considerably to deaths worldwide. The pathogenesis of PM-induced lung injury (PILI) is far from elucidated and warrants effective intervention. An effective component of licorice, glycyrrhizin (GL), has been the subject of much research due to its anti-inflammatory and anti-oxidative capabilities. Although preventive properties of GL are well-known, the precise mechanism of GL in PILI has not yet been investigated. A mouse model of PILI was used to examine the protective effects of GL in vivo, and a human bronchial epithelial cells (HBECs) model was used in vitro. In order to determine whether GL mitigates PILI, its effects on endoplasmic reticulum (ER) stress, NLRP3 inflammasome-mediated pyroptosis and the oxidative response were examined. According to the findings, GL reduced PILI and activate anti-oxidative Nrf2/HO-1/NQO1 signaling in mice. Notably, the effect of GL on PM-induced ER stress and NLRP3 inflammasome-mediated pyroptosis was significantly attenuated by the Nrf2 inhibitor ML385. The data suggest that via the anti-oxidative Nrf2 signaling, GL may reduce oxidative stress-mediated ER stress and NLRP3 inflammasome-mediated pyroptosis. Therefore, GL may serve as a promising treatment for PILI.

Cationic Single-Unit Monomer Insertion (cSUMI): From Discrete Oligomers to the α-/ω-End and In-Chain Sequence-Regulated Polymers.

Single-unit monomer insertion (SUMI) has become an important strategy for the synthesis of sequence-controlled vinyl polymers due to its strong versatility and high efficiency. However, all reported SUMI processes are based on a free-radical mechanism, resulting in a limited number of monomer types being applicable to SUMI or a limited number of sequences of structural units that SUMI can synthesize. Herein, we developed a novel SUMI based on a cationic mechanism (cSUMI), which operates through a degenerative (similar to radical SUMI) but cationic chain transfer process. By optimizing the chain transfer agent (CTA) and monomer pairs, a high-efficiency cSUMI was achieved for vinyl ether and styrene monomers. Based on this reaction, a range of discrete oligomers containing vinyl ether and styrene moieties, and even α-/ω-end and in-chain sequence-regulated polymers were synthesized, most of which cannot be achieved by radical SUMI. In addition, we explored the application of these sequence-regulated polymers in the preparation of miktoarm star polymers, delivery of photosensitizers, and solubilization of fluorescence probes. The development of SUMI with a new mechanism will certainly broaden the scope of structures and sequences in precise vinyl-based polymers.

Transcriptome sequencing and metabolite analysis reveal the single and combined effects of microplastics and di-(2-ethylhexyl) phthalate on Peneaus vannamei.

Due to the rising usage of plastics, plastic debris are present throughout marine ecosystems and detrimentally affects marine biota. Additionally, plastics likely result in elusive toxicity effects due to addition of plasticizers. The aim of the present study was to reveal the potential effects and mechanism of microplastics (MPs), di-(2-ethylhexyl) phthalate (DEHP) and copollution of MPs and DEHP (MPs-DEHP) on Peneaus vannamei (P. vannamei) juveniles regarding oxidative stress, transcriptomics and metabolomics. MPs, DEHP and MPs-DEHP significantly induced the activities of superoxide dismutase (SOD) and catalase (CAT); MPs and DEHP have an antagonistic effect for malondialdehyde (MDA); suggesting that disorders of the antioxidant defence systems. 13, 133 and 58 differentially expressed genes and 21, 82 and 39 differentially expressed metabolites were responsible for the distinction of MPs, DEHP and MPs-DEHP groups, respectively. The combination of transcriptomic and metabolomic analyses showed that MPs, DEHP and MPs-DEHP exposure disturbed amino acid and lipid metabolism, and further induced inflammatory responses and dysfunction of purine metabolism. Furthermore, the presence of MPs might alleviate the biotoxicity of DEHP in P. vannamei. These findings provide new insights into the single and combined toxicological effects of MPs and additives for marine biota.

Omega-3 polyunsaturated fatty acids ameliorate PM2.5 exposure induced lung injury in mice through remodeling the gut microbiota and modulating the lung metabolism.

Short-term or long-term exposure to fine particulate matter (PM2.5) is related to increased incidences of respiratory diseases. This study aimed to investigate the influences of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) supplementation on oxidative stress, inflammation, lung metabolic profile, and gut microbiota in PM2.5-induced lung injury mice. Mice were divided into four groups (n = 15, per group): two unsupplemented groups, control group and PM2.5 group, and two supplemented groups with ω-3 PUFAs, ω-3 PUFAs group, and ω-3 PUFAs + PM2.5 group. Mice in the supplemented groups were placed on an ω-3 PUFAs-enriched diet (ω-3 PUFAs, 21 g/kg). During the 5th to 6th week of dietary supplementation, mice were exposed to PM2.5 by intra-tracheal instillation. ω-3 PUFAs ameliorate lung histopathological injury, reduce inflammatory responses and oxidative stress, affect lung metabolite profile, and modulate gut microbiota in PM2.5-induced lung injury mice. Thus, supplementary ω-3 PUFAs showed effectiveness in attenuation of PM2.5-induced lung injury, indicating that the interventions exhibited preventive and therapeutic potential.

Dendritic Quaternary-Encoded Oligourethanes for Data Encryption.

The use of sequence-defined digital polymers for data storage and encryption has received increasing attention due to their precision structures similar to natural biomacromolecules (e.g., DNA) but increased stability. However, the rapid development of sequencing techniques raises the concern of information leakage. Herein, dendritic quaternary-encoded oligourethanes bearing a photoresponsive trigger, self-immolative backbones, and a mass spectrometry tag of PEG dendron have been developed for data encryption. Although the sequence information in linear analogs can be readily deciphered by mass spectrometry, sequencing of dendritic oligourethanes cannot be achieved by either primary MS or tandem MS/MS owing to the unique spatial conformation. Intriguingly, the fragmentation pathways of a quaternary dendrimer under MS/MS conditions can be converted to 2772-bit 2D matrices with ≈1.98×1087 permutations, serving as high-strength encryption keys for highly reliable data encryption.

Digital micelles of encoded polymeric amphiphiles for direct sequence reading and ex vivo label-free quantification.

Identification and quantification of synthetic polymers in complex biological milieu are crucial for delivery, sensing and scaffolding functions, but conventional techniques based on imaging probe labellings only afford qualitative results. Here we report modular construction of precise sequence-defined amphiphilic polymers that self-assemble into digital micelles with contour lengths strictly regulated by oligourethane sequences. Direct sequence reading is accomplished with matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry, facilitated by high-affinity binding of alkali metal ions with poly(ethylene glycol) dendrons and selective cleavage of benzyl-carbamate linkages. A mixture of four types of digital micelles could be identified, sequence-decoded and quantified by MALDI and MALDI imaging at cellular, organ and tissue slice levels upon in vivo administration, enabling direct comparison of biological properties for each type of digital micelle in the same animal. The concept of digital micelles and encoded amphiphiles capable of direct sequencing and high-throughput label-free quantification could be exploited for next-generation precision nanomedicine designs (such as digital lipids) and protein corona studies.

Fibroblast growth factor 10 protects against particulate matter-induced lung injury by inhibiting oxidative stress-mediated pyroptosis via the PI3K/Akt/Nrf2 signaling pathway.

Particulate matter (PM) is a major environmental contaminant that causes and worsens respiratory diseases. Fibroblast growth factor 10 (FGF10), a paracrine fibroblast growth factor that specifically stimulates repair and regeneration after injury, has been shown to protect against PM-induced lung injury. However, the underlying mechanisms are still unclear. In this study, the protective effects of FGF10 were investigated using a PM-induced lung injury mouse model in vivo and BEAS-2B cells in vitro. According to the findings, FGF10 treatment alleviated PM-induced oxidative damage and pyroptosis in vivo and in vitro. Mechanistically, FGF10 activated antioxidative Nrf2 signaling. Inhibition of PI3K signaling with LY294002 or Nrf2 signaling with ML385 revealed that FGF10-mediated lung protection was mediated by the PI3K/Akt/Nrf2 pathway. These results collectively indicate that FGF10 inhibits oxidative stress-mediated pyroptosis via the PI3K/Akt/Nrf2 pathway, suggesting a possible therapy for PM-induced lung injury.

FGF10 mediates protective anti-oxidative effects in particulate matter-induced lung injury through Nrf2 and NF-κB signaling.

Background: Particulate matter (PM), a well-known environmental pollutant, is an independent risk factor associated with the morbidity of various respiratory diseases. Oxidative stress is an important pathophysiological mechanism related to PM exposure, which mediates redox-sensitive inflammatory signaling, leading to lung injury. Fibroblast growth factor 10 (FGF10), a paracrine fibroblast growth factor that mediates mesenchymal to epithelial signaling, participates in epithelial repair during lung injury. However, whether FGF10-mediated repair in PM-induced lung injury is related to the regulation of oxidative stress remains to be elucidated. Methods: In vivo, the C57BL/6 mice were randomly divided, with intratracheal instillation of 5 mg/kg FGF10 1 h before 4 mg/kg PM for 2 consecutive days. In vitro, the BEAS-2B cells were pretreated with 10 ng/mL FGF10 before exposed to 200 µg/mL PM. Besides, the specific Nrf2 inhibitor ML385 was adopted in vitro. The harvested lung tissues were pathologic grading scored. The state of oxidative stress was assessed with dihydroethidium (DHE) staining, malondialdehyde (MDA) activity, hydrogen peroxide (H2O2) assays and reactive oxygen species (ROS). The contents of IL-6 and IL-8 in bronchoalveolar lavage (BAL) as well as culture supernatant were quantified by ELISA. The protein levels of nuclear factor erythroid 2 related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) signaling from lung tissue as well as cell lysate were determined by Western blot. Results: In this study, recombinant FGF10 administration relieved the degree of lung injury, which is characterized by bronchitis, in a mouse model of PM exposure. In addition, reduced ROS levels, which are indicative of restrained oxidative stress, were also observed. Moreover, two redox-sensitive signaling pathways, Nrf2 and NF-κB, were found to be differentially regulated by FGF10. Using a cellular model of PM exposure, we found that the anti-inflammatory effect of FGF10 on NF-κB signaling was mediated through the regulation of oxidative stress. The anti-oxidative effect relied on the stimulation of Nrf2 signaling. Blockade of Nrf2 signaling with ML385 significantly compromised the anti-inflammatory effect of FGF10. Conclusions: These results underscore that the protective anti-oxidative effects of FGF10 in lung injury are mediated by the stimulation of Nrf2 signaling and inhibition of the NF-κB pathway.

Picrotoxane sesquiterpenoids: chemistry, chemo- and bio-syntheses and biological activities.

Covering: up to December 2021Picrotoxane sesquiterpenoids are a special category of natural products known to have a picrotoxane skeleton and are characterised by a highly oxidised cis-hydrindene core, lactone rings, and epoxide functionalities. Ever since the first picrotoxane was isolated from Menispermum cocculus in the early 19th century, these compounds have long attracted the attention of natural product chemists, synthetic chemists, and pharmacologists for their particular structures and powerful biological activities. This review extensively summarizes a total of 132 naturally occurring picrotoxane sesquiterpenoids, taking into account their distributions, structural classifications, chemical and bio-synthetic researches, and bioactivities. It provides a comprehensive and in-depth perspective for further investigation on picrotoxane sesquiterpenoids.

Hypoxic bone marrow mesenchymal stromal cells-derived exosomal miR-182-5p promotes liver regeneration via FOXO1-mediated macrophage polarization.

Mesenchymal stromal cells (MSCs) are attractive candidates for treating hepatic disorders given their potential to enhance liver regeneration and function. The paracrine paradigm may be involved in the mechanism of MSC-based therapy, and exosomes (Exo) play an important role in this paracrine activity. Hypoxia significantly improves the effectiveness of MSC transplantation. However, whether hypoxia preconditioned MSCs (Hp-MSCs) can enhance liver regeneration, and whether this enhancement is mediated by Exo, are unknown. In this study, mouse bone marrow-derived MSCs (BM-MSCs) and secreted Exo were injected through the tail vein. We report that Hp-MSCs promote liver regeneration after partial hepatectomy in mice through their secreted exosomes. Interestingly, MSC-Exo were concentrated in liver 6 h after administration and mainly taken up by macrophages, but not hepatocytes. Compared with normoxic MSC-Exo (N-Exo), hypoxic MSC-Exo (Hp-Exo) enhanced M2 macrophage polarization both in vivo and in vitro. Microarray analysis revealed significant enrichment of microRNA (miR)-182-5p in Hp-Exo compared with that in N-Exo. In addition, miR-182-5p knockdown partially abolished the beneficial effect of Hp-Exo. Finally, Hp-MSC-derived exosomal miR-182-5p inhibited theprotein expression of forkhead box transcription factor 1 (FOXO1) in macrophages, which inhibited toll-like receptor 4 (TLR4) expression and subsequently induced an anti-inflammatory response. These results highlight the therapeutic potential of Hp-Exo in liver regeneration and suggest that miR-182-5p from Hp-Exo facilitates macrophage polarization during liver regeneration by modulating the FOXO1/TLR4 signaling pathway.

Collagen­binding vascular endothelial growth factor (CBD­VEGF) promotes liver regeneration in murine partial hepatectomy.

Liver regeneration is a complex process that needs orchestration of multiple nonparenchymal cells including sinusoid endothelial cells. Vascular endothelial growth factor (VEGF) serves a crucial role in angiogenesis and liver regeneration. However, the lack of an high­efficiency delivery system target to the injured site reduces the local therapeutic efficacy of VEGF. In our previous study, collagen binding VEGF (CBD­VEGF) was established by fusing collagen binding domain (CBD) into the N­terminal of native VEGF and improved cardiac function after myocardial infraction. The present study investigated the therapeutic effect of CBD­VEGF on liver regeneration by a mouse model of partial hepatectomy. After injection through portal vein following 2/3 hepatectomy, CBD­VEGF was largely retained in the hepatic extracellular matrix for 48 h. Furthermore, CBD­VEGF application significantly promoted sinusoidal regeneration and remodeling in remanent liver tissue 48 h after hepatectomy. In addition, CBD­VEGF treatment significantly enhanced the proliferation of hepatocytes at 2 and 3 days post­surgery compared with native VEGF, concomitant with attenuated liver injury. In conclusion, these results demonstrated that CBD­VEGF could be a promising therapeutic strategy for liver regeneration.

Collagen-binding fibroblast growth factor ameliorates liver fibrosis in murine bile duct ligation injury.

Cholestatic liver injury, characterized by liver fibrosis, has increasingly become a global health problem, with no effective treatment available. Hepatic stellate cells (HSCs) differentiate into myofibroblasts, leading to excessive deposition of the extracellular matrix (ECM), which is a feature of liver fibrosis. Basic fibroblast growth factor (bFGF) has proven antifibrotic effects in chronic liver disease; however, the lack of an effective delivery system to the injury site reduces its therapeutic efficacy. The aim of this study was to assess the therapeutic effect of collagen-binding bFGF (CBD-bFGF) for the treatment of liver fibrosis in a murine bile duct ligation (BDL) model. We found that CBD-bFGF treatment significantly alleviated liver injury in the early phase of BDL injury, and was associated with decreased necroptotic cell death and inflammatory response. Moreover, CBD-bFGF had enhanced therapeutic effects for liver fibrosis on day 7 after surgery compared to those obtained with native bFGF treatment. In vitro, CBD-bFGF treatment notably inhibited TGF-ß1-induced LX-2 cell activation, migration, and contraction compared with native bFGF. In conclusion, CBD-bFGF may be a promising treatment for hepatic fibrosis.

Metabolic Dysfunction-associated Fatty Liver Disease is Associated with Greater Impairment of Lung Function than Nonalcoholic Fatty Liver Disease.

Background and Aims: We compared lung function parameters in nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD), and examined the association between lung function parameters and fibrosis severity in MAFLD. Methods: In this cross-sectional study, we randomly recruited 2,543 middle-aged individuals from 25 communities across four cities in China during 2016 and 2020. All participants received a health check-up including measurement of anthropometric parameters, biochemical variables, liver ultrasonography, and spirometry. The severity of liver disease was assessed by the fibrosis (FIB)-4 score. Results: The prevalence of MAFLD was 20.4% (n=519) and that of NAFLD was 18.4% (n=469). After adjusting for age, sex, adiposity measures, smoking status, and significant alcohol intake, subjects with MAFLD had a significantly lower predicted forced vital capacity (FVC, 88.27±17.60% vs. 90.82±16.85%, p<0.05) and lower 1 s forced expiratory volume (FEV1, 79.89±17.34 vs. 83.02±16.66%, p<0.05) than those with NAFLD. MAFLD with an increased FIB-4 score was significantly associated with decreased lung function. For each 1-point increase in FIB-4, FVC was diminished by 0.507 (95% CI: -0.840, -0.173, p=0.003), and FEV1 was diminished by 0.439 (95% CI: -0.739, -0.140, p=0.004). The results remained unchanged when the statistical analyses was performed separately for men and women. Conclusions: MAFLD was significantly associated with a greater impairment of lung function parameters than NAFLD.