Canagliflozin alleviates pulmonary hypertension by activating PPARγ and inhibiting its S225 phosphorylation.

Pulmonary hypertension (PH) is a progressive fatal disease with no cure. Canagliflozin (CANA), a novel medication for diabetes, has been found to have remarkable cardiovascular benefits. However, few studies have addressed the effect and pharmacological mechanism of CANA in the treatment of PH. Therefore, our study aimed to investigate the effect and pharmacological mechanism of CANA in treating PH. First, CANA suppressed increased pulmonary artery pressure, right ventricular hypertrophy, and vascular remodeling in both mouse and rat PH models. Network pharmacology, transcriptomics, and biological results suggested that CANA could ameliorate PH by suppressing excessive oxidative stress and pulmonary artery smooth muscle cell proliferation partially through the activation of PPARγ. Further studies demonstrated that CANA inhibited phosphorylation of PPARγ at Ser225 (a novel serine phosphorylation site in PPARγ), thereby promoting the nuclear translocation of PPARγ and increasing its ability to resist oxidative stress and proliferation. Taken together, our study not only highlighted the potential pharmacological effect of CANA on PH but also revealed that CANA-induced inhibition of PPARγ Ser225 phosphorylation increases its capacity to counteract oxidative stress and inhibits proliferation. These findings may stimulate further research and encourage future clinical trials exploring the therapeutic potential of CANA in PH treatment.

Fungicidal efficiency of DBD cold plasma against Aspergillus niger on dried jujube.

This study investigated the fungicidal efficiency and mechanism of action of dielectric barrier discharge cold atmosphere plasma (DBD-CAP) in inactivating Aspergillus niger (A. niger) spores. The disinfection efficacy and quality of dried jujube used as the processing application object were also studied. The results indicated that the Weibull + Tail model performed better for spore inactivation curves at different voltages among various treatment times, and the spore cells were reduced by 4.05 log (cfu/mL) in spores suspension at 70 kV after 15 min of treatment. This disinfection impact was further supported by scanning electron microscope (SEM) and transmission electron microscopy (TEM) images, which showed that the integrity of the cell membrane was damaged, and the intracellular content leaked out after DBD-CAP treatment. Elevated levels of reactive oxygen species (ROS) during the treatment increased the relative conductivity of cells, and leakage of nucleic acids and proteins further supported the disinfection impact. Additionally, the growth and toxicity of surviving A. niger spores after treatment were also greatly reduced. When DBD-CAP was applied to disinfecting dried jujube, the spore number exhibited a 2.67 log cfu/g reduction after treatment without significant damage observed onto the quality (P > 0.05).

Integrative analyses of whole-transcriptome sequencing reveals CeRNA regulatory network in pulmonary hypertension treated with FGF21.

Noncoding RNAs have been shown to play essential roles in hypoxic pulmonary hypertension (HPH). Our preliminary data showed that HPH is attenuated by fibroblast growth factor 21 (FGF21) administration. Therefore, we further investigated the whole transcriptome RNA expression patterns and interactions in a mice HPH model treated with FGF21. By whole-transcriptome sequencing, differentially expressed mRNAs, miRNAs, lncRNAs, and circRNAs were successfully identified in normoxia (Nx) vs. hypoxia (Hx) and Hx vs. hypoxia + FGF21 (Hx + F21). Differentially expressed mRNAs, miRNAs, lncRNAs, and circRNAs regulated by hypoxia and FGF21 were selected through intersection analysis. Based on prediction databases and sequencing data, differentially co-expressed mRNAs, miRNAs, lncRNAs, and circRNAs were further screened, followed by functional enrichment analysis. MAPK signaling pathway and epigenetic modification were enriched and may play fundamental roles in the therapeutic effects of FGF21. The ceRNA regulatory network of lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA was constructed with miR-7a-5p, miR-449c-5p, miR-676-3p and miR-674-3p as the core. In addition, quantitative real-time PCR experiments were employed to verify the whole-transcriptome sequencing data. The results of luciferase reporter assays highlighted the relationship between miR-449c-5p and XR_878320.1, miR-449c-5p and Stab2, miR-449c-5p and circ_mtcp1, which suggesting that miR-449c-5p may be a key regulator of FGF21 in the treatment of PH. Taken together, this study provides potential biomarkers, pathways, and ceRNA regulatory networks in HPH treated with FGF21 and will provide an experimental basis for the clinical application of FGF21 in PH.

Physical science research needed to evaluate the viability and risks of marine cloud brightening.

Marine cloud brightening (MCB) is the deliberate injection of aerosol particles into shallow marine clouds to increase their reflection of solar radiation and reduce the amount of energy absorbed by the climate system. From the physical science perspective, the consensus of a broad international group of scientists is that the viability of MCB will ultimately depend on whether observations and models can robustly assess the scale-up of local-to-global brightening in today's climate and identify strategies that will ensure an equitable geographical distribution of the benefits and risks associated with projected regional changes in temperature and precipitation. To address the physical science knowledge gaps required to assess the societal implications of MCB, we propose a substantial and targeted program of research-field and laboratory experiments, monitoring, and numerical modeling across a range of scales.

Polyp segmentation with interference filtering and dynamic uncertainty mining.

Objective.Accurate polyp segmentation from colo-noscopy images plays a crucial role in the early diagnosis and treatment of colorectal cancer. However, existing polyp segmentation methods are inevitably affected by various image noises, such as reflections, motion blur, and feces, which significantly affect the performance and generalization of the model. In addition, coupled with ambiguous boundaries between polyps and surrounding tissue, i.e. small inter-class differences, accurate polyp segmentation remains a challenging problem.Approach.To address these issues, we propose a novel two-stage polyp segmentation method that leverages a preprocessing sub-network (Pre-Net) and a dynamic uncertainty mining network (DUMNet) to improve the accuracy of polyp segmentation. Pre-Net identifies and filters out interference regions before feeding the colonoscopy images to the polyp segmentation network DUMNet. Considering the confusing polyp boundaries, DUMNet employs the uncertainty mining module (UMM) to dynamically focus on foreground, background, and uncertain regions based on different pixel confidences. UMM helps to mine and enhance more detailed context, leading to coarse-to-fine polyp segmentation and precise localization of polyp regions.Main results.We conduct experiments on five popular polyp segmentation benchmarks: ETIS, CVC-ClinicDB, CVC-ColonDB, EndoScene, and Kvasir. Our method achieves state-of-the-art performance. Furthermore, the proposed Pre-Net has strong portability and can improve the accuracy of existing polyp segmentation models.Significance.The proposed method improves polyp segmentation performance by eliminating interference and mining uncertain regions. This aids doctors in making precise and reduces the risk of colorectal cancer. Our code will be released athttps://github.com/zyh5119232/DUMNet.

Combined of plasma-activated water and dielectric barrier discharge atmospheric cold plasma treatment improves the characteristic flavor of Asian sea bass (Lates calcarifer) through facilitating lipid oxidation.

To explore the combination effects of plasma-activated water and dielectric barrier discharge (PAW-DBD) cold plasma treatment on the formation of volatile flavor and lipid oxidation in Asian sea bass (ASB), the volatile flavor compounds and lipid profiles were characterized by gas chromatography-ion mobility spectrometry and LC-MS-based lipidomics analyses. In total, 38 volatile flavor compound types were identified, and the PAW-DBD group showed the most kinds of volatile components with a significant (p < 0.05) higher content in aldehydes, ketones, and alcohols. A total of 1500 lipids was detected in lipidomics analysis, phosphatidylcholine was the most followed by triglyceride. The total saturated fatty acids content in PAW-DBD group increased by 105.02 µg/g, while the total content of unsaturated fatty acids decreased by 275.36 µg/g. It can be concluded that the PAW-DBD processing increased both the types and amounts of the volatile flavor in ASB and promoted lipid oxidation by altering lipid profiles.

Effect of plasma-activated lactic acid on microbiota composition and quality of puffer fish (Takifugu obscurus) fillets during chilled storage.

Fresh puffer fish (Takifugu obscurus) are susceptible to microbial contamination and have a very short shelf-life of chilled storage. Hence, this study aimed to evaluate the effects of plasma-activated lactic acid (PALA) on microbiota composition and quality attributes of puffer fish fillets during chilled storage. The results showed that PALA treatment effectively reduced the growth of bacteria and attenuated changes in physicochemical indicators (total volatile basic nitrogen, pH value, K value, and biogenic amines) of puffer fish fillets. Additionally, insignificant changes were observed in lipid oxidation during the first 8 days (p > 0.05). Illumina-MiSeq high-throughput sequencing revealed that PALA effectively inhibited the growth of Pseudomonas in puffer fish fillets and maintained the diverse characteristics of the microbial community. In combination with sensory analysis, PALA extended the shelf life of puffer fish fillets for 4 days, suggesting that PALA could be considered a potential fish fillet preservation method.

Effects of Gas Composition on the Lipid Oxidation and Fatty Acid Concentration of Tilapia Fillets Treated with In-Package Atmospheric Cold Plasma.

Cold plasma (CP) is a non-thermal preservation technology that has been successfully used to decontaminate and extend the shelf life of aquatic products. However, the preservation effect of CP treatment is determined by several factors, including voltage, time, and gas compositions. Therefore, this study aimed to investigate the effects of gas composition (GasA: 10% O2, 50% N2, 40% CO2; GasB: air; GasC: 30% O2, 30% N2, 40% CO2) on the lipid oxidation of tilapia fillets treated after CP treatment. Changes in the lipid oxidation values, the percentages of fatty acids, and sensory scores were studied during 8 d of refrigerator storage. The results showed that the CP treatment significantly increased all the primary and secondary lipid oxidation values measured in this study, as well as the percentages of saturated fatty acids, but decreased the percentages of unsaturated fatty acids, especially polyunsaturated fatty acids. The lipid oxidation values were significantly increased in the GasC-CP group. After 8 d, clearly increased percentages of saturated fatty acids, a low level of major polyunsaturated fatty acids (especially linoleic (C18:2n-6)), and a decrease in the percentages of eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) were found in GasC-CP; that is, the serious oxidation of lipids was found in the high O2 concentration group. In addition, the sensory score was also lower than that of the hypoxia CP group. Therefore, high O2 concentrations can enhance lipid oxidation and the changes in the fatty acid concentration. Controlling the O2 concentration is reasonable to limit the degree to which lipids are oxidized in tilapia after the in-package CP treatment.

LC-MS-based lipidomics analyses of alterations in lipid profiles of Asian sea bass (Lates calcarifer) induced by plasma-activated water treatment.

A lipidomics approach based on liquid chromatography-mass spectrometry was employed to investigate alterations in lipid profiles within the muscles of Asian sea bass (ASB) (Lates calcarifer) post-treatment with plasms-activated water (PAW). Lipidomics studies detected 1500 diverse lipid types in ASB muscles; the phosphatidylcholine (PC) lipid subclass constituted the highest number of lipids (21.07 %), followed by triglycerides (TGs, 20.53 %) and phosphatidylethanolamine (PE, 12.73 %). Comparative analysis between PAW-treated ASB and raw ASB revealed the presence of differentially abundant lipids, with 48 lipids accumulating at high levels and 92 at low levels. Pathway enrichment analysis identified a total of seven lipid-related metabolic pathways; glycerophospholipid metabolism emerged as the predominant pathway. Furthermore, the content of saturated fatty acids in PAW-treated ASB increased from 1059.81 µg/g (raw ASB) to 1099.77 µg/g. Conversely, the content of monounsaturated and polyunsaturated fatty acids decreased from 645.81 µg/g and 875.02 µg/g to 640.80 µg/g and 825.25 µg/g, respectively. Collectively, these results indicate significant alterations in ASB lipid profiles following PAW treatment, establishing a theoretical foundation for understanding the mechanism involved in promoting lipid oxidation.

Inactivation mechanism of cold plasma combined with 222 nm ultraviolet for spike protein and its application in disinfecting of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus that has precipitated a worldwide pandemic of coronavirus disease since 2019. Developing an effective disinfection strategy is crucial to prevent the risk of surface cross-contamination by SARS-CoV-2. This study employed pseudovirus and the receptor-binding domain (RBD) protein of SARS-CoV-2 as models to investigate the spike protein inactivation process and its underlying mechanisms using a novel nonthermal technology. Cold plasma combined with 222 nm ultraviolet (CP+UV) treatment was applied to accelerate the generation of reactive species and enhance sterilization efficiency. The results indicated that the binding activity of RBD protein was completely inhibited at specific concentrations (0.01-0.05 mg/cm2) with corresponding treatment times of 15-30 s. The mechanism potentially involves the reactive species generated by CP+UV, which react with the spike protein RBD of SARS-CoV-2, leading to the loss of SARS-CoV-2 infectivity by causing damage to the ß-sheet structure and chemical bonds in the RBD protein. Validated by a biosafety level 3 (BSL3) laboratory, the CP+UV treatment for 30 s could completely inactivate SARS-CoV-2 with a concentration of 19054 ± 1112 TCID50/cm2. Therefore, this study potentially provides a novel disinfection strategy for the inactivation of SARS-CoV-2 on surface cross-contamination.

Lc-ms-based lipidomics analyses revealed changes in lipid profiles in Asian sea bass (Lates calcarifer) with dielectric barrier discharge (DBD) atmospheric plasma treatment.

A comprehensive LC-MS-based lipidomics analysis of Asian sea bass (Lates calcarifer) muscle after dielectric barrier discharge (DBD) atmospheric plasma treatment was performed. Through the analysis, 1500 lipid species were detected, phosphatidylcholine (PC, 27.80%) was the most abundant lipid, followed by triglyceride (TG, 20.50%) and phosphatidylethanolamine (PE, 17.10%). Among them, 125 lipid species were detected and identified as differentially abundant lipids in Asian sea bass (ASB). PCA and OPLS-DA showed that ASB lipids changed significantly after DBD treatment. Moreover, glycerophospholipid metabolism was key metabolic pathways, as PC, PE, and lysophosphatidylcholine (LPC) were key lipid metabolites. The findings concerning fatty acids revealed that the saturated fatty acids (SFA) content of ASB after DBD treatment increased by 8.54%, while the content of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) decreased by 13.77% and 9.16%, respectively. Our study establishes a foundation for the lipid oxidation mechanism of ASB following DBD treatment.

Optimization of cold plasma combined treatment process and its effect on the quality of Asian sea bass (Lates calcarifer) during refrigerated storage.

BACKGROUND: Cold plasma exhibits broad applicability in the realm of fish sterilization and preservation. The combination process of plasma-activated water and dielectric barrier discharge (PAW-DBD) was optimized, and its disinfection effects on bass fillets were studied. RESULTS: The best conditions for disinfection of PAW-DBD were as follows. Bass fillets were soaked in PAW for 150 s, and then treated by DBD system at 160 kV for 180 s. The total viable count (TVC) reduced by 1.68 log CFU g-1 . On the 15th day of refrigerated storage, TVC of PAW-DBD group was 7.01 log CFU g-1 , while the PAW and DBD group exhibited a TVC of 7.02 and 7.01 log CFU g-1 on day 12; the TVC of the control group was 7.13 log CFU g-1 on day 6. The sensory score, water-holding capacity, and 2-thiobarbituric acid reactive substance values of the PAW-DBD group were significantly higher than those of PAW and DBD group (P < 0.05), whereas the TVC, Pseudomonas spp. count, and pH of the group were significantly lower (P < 0.05) during refrigerated storage. CONCLUSION: PAW-DBD treatment can enhance the disinfection effect, maintain good quality, and extend the storage period of bass fillets. © 2023 Society of Chemical Industry.

Dynamic Phosphorylation of G9a Regulates its Repressive Activity on Chromatin Accessibility and Mitotic Progression.

Phosphorylation of Ser10 of histone H3 (H3S10p), together with the adjacent methylation of Lys9 (H3K9me), has been proposed to function as a 'phospho-methyl switch' to regulate mitotic chromatin architecture. Despite of immense understanding of the roles of H3S10 phosphorylation, how H3K9me2 are dynamically regulated during mitosis is poorly understood. Here, it is identified that Plk1 kinase phosphorylates the H3K9me1/2 methyltransferase G9a/EHMT2 at Thr1045 (pT1045) during early mitosis, which attenuates its catalytic activity toward H3K9me2. Cells bearing Thr1045 phosphomimic mutant of G9a (T1045E) show decreased H3K9me2 levels, increased chromatin accessibility, and delayed mitotic progression. By contrast, dephosphorylation of pT1045 during late mitosis by the protein phosphatase PPP2CB reactivates G9a activity and upregulates H3K9me2 levels, correlated with decreased levels of H3S10p. Therefore, the results provide a mechanistic explanation of the essential of a 'phospho-methyl switch' and highlight the importance of Plk1 and PPP2CB-mediated dynamic regulation of G9a activity in chromatin organization and mitotic progression.

Clinical outcomes of intraluminal Iodine-125 seed strand brachytherapy and percutaneous nephrostomy in patients with ureteral carcinoma.

BACKGROUND: We aimed to evaluate the safety and efficacy of intraluminal iodine-125 seed strand brachytherapy and percutaneous nephrostomy in patients with ureteral carcinoma. METHODS: From January 2014 to January 2023, 48 patients with ureteral cancer not suitable for surgical resection were enrolled. Iodine-125 seed strand was inserted in 26 patients under c-arm CT and fluoroscopic guidance (Group A), and 22 patients underwent percutaneous nephrostomy without seed strand (Group B). The clinical outcomes (technical success rate, tumor sizes, hydronephrosis Girignon grade, complications, objective response rate (ORR), disease control rate (DCR), and survival time) were evaluated and compared. RESULTS: A total of 53 seed strands were successfully inserted and replaced in Group A, with a technical success rate of 100%. No procedure-related death or severe complications occurred in both group. Migration of seed strand or drainage tube was the most common complication. The Girignon grade of hydronephrosis was significantly improved 1, 3 and 6 months after procedure in both groups. DCR in Group A were 96.2%, 80.0%, and 70.0% at 1-, 3-, and 6-month follow up, respectively. At 1 and 6 months later, ORR in Group A were significantly higher than those in Group B (p < 0.05). The median overall survival were 30.0 months in Group A and 16.1 months in Group B, respectively (p = 0.04). The median progression-free survival were 11.1 months in Group A and 6.9 months in Group B, respectively (p = 0.09). CONCLUSION: Intraluminal Iodine-125 seed strand brachytherapy and percutaneous nephrostomy is safe and effective in patients with ureteral carcinoma, with higher ORR and median overall survival than patients underwent percutaneous nephrostomy without seed strand.

Delivery of chiral D-cysteine by pH-responsive mesoporous silica nanoparticles for effective bacterial inhibition.

Efficient and highly controllable antibacterial effects, as well as good biocompatibility, are required for antibacterial materials to overcome multi-drug resistance in bacteria. Herein, mesoporous silica nanomaterials (MSNs) carriers with a particle mean size of 60 nm and pore size of 7.9 nm were prepared, which was followed by loading with D-cysteine (D-Cys) and modified with Polyethyleneimine (PEI) molecules on the outer surface (named as D@MSNs-P). The prepared D@MSNs-P showed a good pH response in the range of 5-7, and the rate of antibacterial agent D-Cys released from nanocarriers was much faster at lower pH (pH 5) than that at higher pH (pH 6-7), which favors the rapid control of the pathogenic bacteria. In a working pH (pH 5), D@MSNs-P exhibited broad-spectrum antibacterial activities against Escherichia coli, Staphylococcus aureus, Salmonella enteritidis, and Listeria monocytogenes with the highest antibacterial efficiency of 99.9%, 99.8%, 98.1%, and 96.2%, respectively, which is much higher than that of pure D-Cys, pure MSNs, D@MSNs, and PEI group. The outstanding antibacterial activity of D@MSNs-P was attributed to the synergistic effect of the unique structure of MSNs and chiral D-Cys molecules. In addition, the prepared D@MSNs-P has no cytotoxicity to HepG2 cells (Human hepatoma cells) at the concentration of 0.4-12.8 mg/mL and even can promote cell proliferation at high concentrations. Our results open a new door for designing the most promising nanomaterials for pH response release and controllable antimicrobial.

Mechanism Exploration of Amyloid-ß-42 Disaggregation by Single-Chain Variable Fragments of Alzheimer's Disease Therapeutic Antibodies.

Alzheimer's disease (AD) is a specific neurodegenerative disease. This study adopts single-chain variable fragments (scFvs) as a potential immunotherapeutic precursor for AD. According to the remarkable effects of monoclonal antibodies, such as the depolymerization or promotion of Aß42 efflux by Crenezumab, Solanezumab, and 12B4, it is attractive to prepare corresponding scFvs targeting amyloid-ß-42 protein (Aß42) and investigate their biological activities. Crenezumab-like scFv (scFv-C), Solanezumab-like scFv (scFv-S), and 12B4-like scFv (scFv-12B4) were designed and constructed. The thermal stabilities and binding ability to Aß42 of scFv-C, scFv-S, and scFv-12B4 were evaluated using unfolding profile and enzyme-linked immunosorbent assay. As the results indicated that scFv-C could recognize Aß42 monomer/oligomer and promote the disaggregation of Aß42 fiber as determined by the Thioflavin-T assay, the potential mechanism of its interaction with Aß42 was investigated using molecular dynamics analysis. Interactions involving hydrogen bonds and salt bonds were predicted between scFv-C and Aß42 pentamer, suggesting the possibility of inhibiting further aggregation of Aß42. The successfully prepared scFvs, especially scFv-C, with favorable biological activity targeting Aß42, might be developed for a potentially efficacious clinical application for AD.

Safety and efficacy of iodine-125 seed strand for intraluminal brachytherapy on ureteral carcinoma.

Objective: Our aim is to evaluate the safety and efficacy of iodine-125 seed strand for intraluminal brachytherapy on ureteral carcinoma. Methods: From November 2014 to November 2021, 22 patients with ureteral cancer not suitable for surgical resection were enrolled. Iodine-125 seed strand was inserted under c-arm CT and fluoroscopic guidance. The technical success rate, complications, disease control rate, and survival time were evaluated. Hydronephrosis Girignon grade and ureteral cancer sizes before and after treatment were compared. Results: A total of 46 seed strands were successfully inserted and replaced, with a technical success rate of 100% and median procedure time of 62 min. No procedure-related death, ureteral perforation, infection, or severe bleeding occurred. Minor complications were observed in eight (36.4%) patients, and migration of seed strand was the most common complication. Six months after seed strand brachytherapy, one complete response, three partial responses, and five stable diseases were evaluated, and the disease control rate was 64.3%. The Girignon grade of hydronephrosis was significantly improved 1 to 3 months after seed strand insertion. Disease control rates were 94.4, 62.5, and 64.3% at 1-, 3-, and 6-month follow-up. Twenty patients were successfully followed up, with a mean follow-up of 18.0 ± 14.5 months. The median overall survival and progress-free survival were 24.7 and 13.0 months, respectively. Conclusion: Iodine-125 seed strand is safe and effective for intraluminal brachytherapy and can be used as an alternative to patients with ureteral carcinoma who are not suitable for surgical resection or systemic combined therapy.

Sonochemical Effects on the Preparation, Structure and Function of Gliadin-(-)-Epigallo-Catechin 3-Gallate Conjugates.

It is essential to understand the mechanism of action of ultrasound synergistic free radical oxidation to promote covalent reactions between proteins and polyphenols. (-)-epigallo-catechin 3-gallate (EGCG) with rich bioactivity could be used to increase the functional properties of cereal protein-gliadin (GL). This study systematically explored the role of ultrasound treatment (US) on the binding mechanisms of GL and EGCG. Electrophoresis and high-performance liquid chromatography (HPLC) confirmed the greater molecular mass of the covalent complexes in the ultrasound environment. Quantitative analysis by the phenol content revealed that the ultrasound environment increased the EGCG content in the covalent complex by 15.08 mg/g of protein. The changes in the spatial structure of the proteins were indicated by Fourier infrared and ultraviolet spectroscopy. Additionally, scanning electron microscopy (SEM) and atomic force microscopy (AFM) found that US disrupted the aggregation of GL and the clustered structure of the covalent complexes. The results demonstrated that the water solubility of ultrasonic conjugates was significantly increased by 8.8-64.19%, the digestion rate was more efficient, and the radical scavenging capacity was twice that of GL. This research contributes to the theoretical basis for broadening the application of polyphenols in modifying protein.

Unraveling the Antibacterial Mechanism of Plasma-Activated Lactic Acid against Pseudomonas ludensis by Untargeted Metabolomics.

Plasma-activated liquid is a novel non-thermal antibacterial agent against a wide spectrum of foodborne bacteria, yet fewer studies focused on its disinfection of meat spoilage bacteria. In this study, the antibacterial properties of plasma-activated lactic acid (PALA) on Pseudomonas lundensis, isolated and identified from spoilage beef, were investigated. A plasma jet was used to treat lactic acid (0.05-0.20%) for 60-120 s. The results presented that the 0.2% LA solution treated with plasma for 120 s caused a 5.64 log reduction. Additionally, the surface morphology, membrane integrity and permeability were altered slightly and verified by scanning electron microscopy, double staining of SYTO-9 and propidium iodide, and a K+ test kit. The intracellular organization of the cells, observed by transmission electron microscopy, was damaged significantly. Increased intracellular reactive oxygen species (ROS) levels exceeded the antioxidant ability of glutathione (GSH), leading to a reduction in the activity of malate dehydrogenase (MDH), succinic dehydrogenase (SDH) and intracellular ATP levels. Metabolomics analysis indicated that the energy and synthesis of essential components, such as DNA and amino acid-related metabolic pathways, were disturbed. In conclusion, this research established a theoretical basis for the use of PALA in refrigerated beef preservation by shedding light on the bacteriostatic effect of PALA against Pseudomonas lundensis.