Red light-induced localized release of carbon monoxide for alleviating postoperative cognitive dysfunction.

Inflammation within the central nervous system (CNS), which may be triggered by surgical trauma, has been implicated as a significant factor contributing to postoperative cognitive dysfunction (POCD). The relationship between mitigating inflammation at peripheral surgical sites and its potential to attenuate the CNS inflammatory response, thereby easing POCD symptoms, remains uncertain. Notably, carbon monoxide (CO), a gasotransmitter, exhibits pronounced anti-inflammatory effects. Herein, we have developed carbon monoxide-releasing micelles (CORMs), a nanoparticle that safely and locally liberates CO upon exposure to 650 nm light irradiation. In a POCD mouse model, treatment with CORMs activated by light (CORMs + hv) markedly reduced the concentrations of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in both the peripheral blood and the hippocampus, alongside a decrease in ionized calcium-binding adapter molecule 1 in the hippocampal CA1 region. Furthermore, CORMs + hv treatment diminished Evans blue extravasation, augmented the expression of tight junction proteins zonula occludens-1 and occludin, enhanced neurocognitive functions, and fostered fracture healing. Bioinformatics analysis and experimental validation has identified Htr1b and Trhr as potential key regulators in the neuroactive ligand-receptor interaction signaling pathway implicated in POCD. This work offers new perspectives on the mechanisms driving POCD and avenues for therapeutic intervention.

Carbon monoxide-related fatalities: A fifteen-year single institution experience.

Introduction: The winter climate in Delhi is severe, with temperatures dropping below 10°C. As a result, individuals often resort to utilizing diverse heat sources such as electrical heating appliances, coal and gas geysers. Unfortunately, these sources are commonly associated with the emission of carbon monoxide (CO) which can accumulate in inadequately ventilated spaces. Exposure to this noxious gas can lead to acute lethargy and debilitation, leaving individuals in a state of helpless distress. Materials and Methods: The present study utilized a retrospective descriptive analysis to examine cases of fatal carbon monoxide exposure retrieved from the Department of Forensic Medicine archives at the esteemed All India Institute of Medical Sciences, New Delhi. Autopsy records were thoroughly examined with respect to various parameters including age, gender, seasonality of the incident, circumstances surrounding the death, source of carbon monoxide generation, post mortem observations, as well as toxicological analysis reports. Results and Discussion: This study entailed an analysis of 56 individuals who fell victim to carbon monoxide poisoning, with a staggering 95% of fatalities occurring during the winter season. The majority of the individuals affected belonged to the age bracket of 21-30 years. The most common sources of carbon monoxide exposure were linked to the use of coal-burning earthen or iron vessels for room heating, as well as structural fires. With the exception of one case, all incidents were accidental in nature. Additionally, nearly all of the victims were discovered in enclosed spaces with heating equipment in close proximity, and evidence of a struggle was noted on the crime scene or with the deceased. Conclusion: The findings of this study indicate that the principal contributor to the inadvertent build-up of lethal concentrations of carbon monoxide gas is the utilization of heating appliances within inadequately ventilated, enclosed spaces. Due to the scentless and non-irritating properties of this gas, individuals who are asleep may be unable to detect its presence in their surroundings, thereby leading to a silent death. To mitigate such risks, the installation of carbon monoxide detectors is crucial. Additionally, it is of utmost importance to raise public awareness regarding the perils associated with using fire pots, coal burning and electrical heating appliances in areas with insufficient ventilation.

The association of exhaled carbon monoxide with atrial fibrillation and left atrial size in the Framingham Heart Study.

Background: Exhaled carbon monoxide (eCO) is associated with subclinical and overt cardiovascular disease and stroke. The association between eCO with left atrial size, prevalent, or incident atrial fibrillation (AF) are uncertain. Methods: eCO was measured using an Ecolyzer instrument among Framingham Heart Study Offspring and Omni participants who attended an examination from 1994 to 1998. We analyzed multivariable-adjusted (current smoking, and other covariates including age, race, sex, height, weight, systolic blood pressure, diastolic blood pressure, diabetes, hypertension treatment, prevalent myocardial infarction [MI], and prevalent heart failure [HF]). Cox and logistic regression models assessed the relations between eCO and incident AF (primary model), and prevalent AF and left atrial (LA) size (pre-specified secondary analyses). We also conducted secondary analyses adjusting for biomarkers, and interim MI and interim HF. Results: Our study sample included 3814 participants (mean age 58 ± 10 years; 54.4 % women, 88.4 % White). During an average of 18.8 ± 6.5 years follow-up, 683 participants were diagnosed with AF. eCO was associated with incident AF after adjusting for established AF risk factors (HR, 1.31 [95 % CI, 1.09-1.58]). In secondary analyses the association remained significant after additionally adjusting for C-reactive protein and B-type natriuretic peptide, and interim MI and CHF, and in analyses excluding individuals who currently smoked. eCO was not significantly associated with LA size and prevalent AF. Conclusion: In our community-based sample of individuals without AF, higher mean eCO concentrations were associated with incident AF. Further investigation is needed to explore the biological mechanisms linking eCO with AF.

Mechanisms and therapeutic targets of carbon monoxide poisoning: A focus on reactive oxygen species.

Carbon monoxide (CO) poisoning presents a substantial public health challenge that necessitates the identification of its pathological mechanisms and therapeutic targets. CO toxicity arises from tissue hypoxia-ischemia secondary to carboxyhemoglobin formation, and cellular damage mediated by CO at the cellular level. The mitochondria are the major targets of neuronal damage caused by CO. Under normal physiological conditions, mitochondria produce reactive oxygen species (ROS), which are byproducts of aerobic metabolism. While low ROS levels are crucial for essential cellular functions, including signal transduction, differentiation, responses to hypoxia and immunity, transcriptional regulation, and autophagy, excess ROS become pathological and exacerbate CO poisoning. This review presents the evidence of elevated ROS being associated with the progression of CO poisoning. Antioxidant treatments targeting ROS removal have been proven effective in mitigating CO poisoning, underscoring their therapeutic potential. In this review, we highlight the latest advances in the understanding of the role and the clinical implications of ROS in CO poisoning. We focus on cellular sources of ROS, the molecular mechanisms underlying mitochondrial oxidative stress, and potential therapeutic strategies for targeting ROS in CO poisoning.

Improving the measurement of nitrogen stable isotopes in organic materials containing high C:N ratios using a 5A molecular sieve column.

The nitrogen stable isotope composition (δ15N) of plant materials has numerous applications. Plant materials like bark can have a very high C:N ratio. Incomplete C combustion in such samples interferes with the δ15N measurement due to CO production. We modified the standard setup for δ15N measurement using an elemental analyzer (EA) coupled to an isotope ratio mass spectrometer (IRMS) by incorporating a 5A molecular sieve column, which better separates N2 from CO. We compared this new modified setup and the standard one for the measurement of bark samples. Precision and accuracy for δ15N in standards with low C:N ratio were equivalent for the two methods. However, for bark the results obtained with the new method had better precision and accuracy than the standard method. Replicates are nevertheless recommended with the new method to ensure confidence in the results.•During elemental analysis, incomplete combustion of material with high C:N ratio can lead to CO formation, which interferes with δ15N IRMS measurements.•Here we use a 5A molsieve column to remove the CO interference in δ15N measurements Precision and accuracy on δ15N measurements of samples with high C content are significantly improved.

Carbonylation Reactions at Carbon-Centered Radicals with an Adjacent Heteroatom.

Heteroatoms are essential to living organisms and present in almost all molecules with medicinal usage. The catalytic functionalization at the carbon-centered radical with an adjacent heteroatom provides an effective way to value added moiety while retaining the unique physicochemical and pharmacological properties of heteroatoms, which can promote the development of pharmaceutical and fine chemical production. Carbonylative transformation was discovered nearly a century ago which is an efficient method for the synthesis of carbonyl-containing molecules with potent applications in both industry and academia. Despite numerous advances in new reaction development, carbonylative transformation involving adjacent heteroatom carbon radical remain a subject that deserves to be discussed. In this minireview, we systematically summarized and discussed the recent advances in carbonylative transformations involving carbon-centered radicals with an adjacent heteroatom, including oxygen (O), nitrogen (N), phosphorus (P), silicon (Si), sulfur (S), boron (B), fluorine (F), and chlorine (Cl). The related reaction mechanism was also discussed.

Mass Carbon Monoxide Poisoning at a Daycare: A Public Health Lesson.

INTRODUCTION: Carbon monoxide (CO) poisoning is a leading cause of preventable toxicity-related deaths in the United States. We describe a case series of 16 individuals who were exposed to CO due to a malfunctioning furnace at a Pennsylvania daycare, a state which did not mandate CO detectors in daycares. METHODS: An institutional review board-approved retrospective analysis was performed, and de-identified patient records were examined. Collected data included age, sex, race, ethnicity, CO concentrations, arrival time, time to hyperbaric oxygen center contact, and time to transfer and discharge. RESULTS: Emergency medical services transported 16 patients to a tertiary care emergency department (ED) with both adult and pediatric departments. Fourteen patients were 10 years of age or younger. Fifteen patients arrived within one hour. Sixty-two percent (N=10) were male, and 94% (N=15) identified as Hispanic. Emergency physicians, medical toxicologists, clinicians, interpreters, and volunteers from across the hospital system were mobilized to the ED to assist with management. CONCLUSION: This large-scale daycare CO poisoning represents a potentially avoidable mass casualty incident among children and daycare staff and necessitated significant coordination of care. CO detectors in Pennsylvania daycares would provide early warning for staff, prevent or minimize toxicity, inform first responders, and better prepare EDs to handle similar situations.

Low electric current in a bioelectrochemical system facilitates ethanol production from CO using CO-enriched mixed culture.

Fossil resources must be replaced by renewable resources in production systems to mitigate green-house gas emissions and combat climate change. Electro-fermentation utilizes a bioelectrochemical system (BES) to valorize industrial and municipal waste. Current electro-fermentation research is mainly focused on microbial electrosynthesis using CO2 for producing commodity chemicals and replacing petroleum-based infrastructures. However, slow production rates and low titers of metabolites during CO2-based microbial electrosynthesis impede its implementation to the real application in the near future. On the other hand, CO is a highly reactive gas and an abundant feedstock discharged from fossil fuel-based industry. Here, we investigated CO and CO2 electro-fermentation, using a CO-enriched culture. Fresh cow fecal waste was enriched under an atmosphere of 50% CO and 20% CO2 in N2 using serial cultivation. The CO-enriched culture was dominated by Clostridium autoethanogenum (≥89%) and showed electro-activity in a BES reactor with CO2 sparging. When 50% CO was included in the 20% CO2 gas with 10 mA applied current, acetate and ethanol were produced up to 12.9 ± 2.7 mM and 2.7 ± 1.1 mM, respectively. The coulombic efficiency was estimated to 148% ± 8% without an electron mediator. At 25 mA, the culture showed faster initial growth and acetate production but no ethanol production, and only at 86% ± 4% coulombic efficiency. The maximum optical density (OD) of 10 mA and 25 mA reactors were 0.29 ± 0.07 and 0.41 ± 0.03, respectively, whereas it was 0.77 ± 0.19 without electric current. These results show that CO electro-fermentation at low current can be an alternative way of valorizing industrial waste gas using a bioelectrochemical system.

TROPOMI unravels transboundary transport pathways of atmospheric carbon monoxide in Tibetan Plateau.

Numerous studies have reported in situ monitoring and source analysis in the Tibetan Plateau (TP), a region crucial for climate systems. However, a gap remains in understanding the comprehensive distribution of atmospheric pollutants in the TP and their transboundary pollution transport. Here, we analyzed the high-resolution satellite TROPOMI observations from 2018 to 2023 in Tibet and its surrounding areas. Our result reveals that, contrary to the results from in situ surface CO monitoring, Tibet exhibits a distinct seasonality in atmospheric carbon monoxide total column average mixing ratio (XCO), with higher levels in summer and lower levels in winter. This distinctive seasonal pattern may be related to the TP's 'air pump' effect and the Asia summer monsoon. Before 2022, the annual growth rate of XCO in Tibet was 1.63 %·year-1; however, it declined by 6.88 % in 2022. Source analysis and satellite observations suggest that CO from South Asia may enter Tibet either by crossing the Himalayas or through the Yarlung Zangbo Grand Canyon. We discovered that spring outbreaks of open biomass burning (OBB) in South and Southeast Asia led to an 11.57-27.98 % increase in XCO over Tibet. Favorable wind pattern and unique topography of the canyon promote the high concentrations CO transport to Tibet. Our greater concern is whether the TP will experience more severe transboundary pollution in the future.

Tumor-Targeted CO Nanodelivery System Design and Therapy for Hepatocellular Carcinoma.

In recent years, carbon monoxide (CO) has garnered increased attention as a novel green therapy for hepatocellular carcinoma (HCC) treatment. However, the CO donor is still limited in clinical application due to its lack of targeted ability and unstable release rate. Here, self-assembled amphiphilic nanomicelles glucose-polyethylene glycol (PEG)-lipoic acid (LA)-Fe2(CO)6 (Glu-Fe2(CO)6) are first designed as a CO donor and synthesized via a chemical method, combining glucose with Fe2(CO)6 through PEG-LA. Some advantages of this tumor-targeted Glu-Fe2(CO)6 delivery system include (I) good water-solubility, (II) the glutathione responsive CO slow release, (III) the active tumor-targeted ability of glucose as targeted ligands, and (IV) outstanding efficacy of antitumor and safety of CO therapy of HCC both in vitro and in vivo. These findings suggest that Glu-Fe2(CO)6 nanomicelles hold promise for enhancing antitumor therapeutic capabilities, presenting a novel tumor-targeted delivery strategy in gas therapy for HCC treatment.

An investigation of CO generation path upon loading coal from perspective of macromolecular simulation.

CO is a hazardous and pollutant gas that can be produced in many scenarios of coal-related operations. The study mainly investigated CO production process and mechanism when coal is subject to external forces. The effects of coal type, particle size, temperature, and inlet atmosphere on CO production from coal body fragmentation were investigated through coal loading experiments. Materials Studio software was used to carry out coal macromolecular mechanics simulation and molecular dynamics simulation, and the gas production mechanism of coal under loading was explored at the molecular level. It was found that under air atmosphere, the low degree of deterioration, small particle size, and elevated temperature are all more likely to cause coal samples to fragment and decompose to produce CO. The carbonyl group in the molecular structure of coal is shed or broken free radical fragments react with oxygen which may lead to CO formation.

The Prognostic Effect of Air Pollution in Patients Presenting to the Emergency Department with Carbon Monoxide Poisoning.

OBJECTIVE: Weather conditions such as low air temperatures, low barometric pressure, and low wind speed have been linked to more cases of carbon monoxide (CO) poisoning. However, limited literature exists regarding the impact of air pollution. This study aims to investigate the relationship between outdoor air pollution and CO poisoning in 2 distinct cities in Turkey. METHODS: A prospective study was conducted at 2 tertiary hospitals, recording demographic data, presenting complaints, vital signs, blood gas and laboratory parameters, carboxyhemoglobin (COHb) levels, meteorological parameters, and pollutant parameters. Complications and outcomes were also documented. RESULTS: The study included 83 patients (Group 1 = 44, Group 2 = 39). The air quality index (AQI) in Group 2 (61.7 ± 27.7) (moderate AQI) was statistically significantly higher (dirtier AQI) than that in Group 1 (47.3 ± 26.4) (good AQI) (P = 0.018). The AQI was identified as an independent predictor for forecasting the need for hospitalization (OR = 1.192, 95% CI: 1.036 - 1.372, P = 0.014) and predicting the risk of developing cardiac complications (OR: 1.060, 95% CI: 1.017 - 1.104, P = 0.005). CONCLUSIONS: The AQI, derived from the calculation of 6 primary air pollutants, can effectively predict the likelihood of hospitalization and cardiac involvement in patients presenting to the emergency department with CO poisoning.

Unveiling urban air quality dynamics during COVID-19: a Sentinel-5P TROPOMI hotspot analysis.

In India, the spatial coverage of air pollution data is not homogeneous due to the regionally restricted number of monitoring stations. In a such situation, utilising satellite data might greatly influence choices aimed at enhancing the environment. It is essential to estimate significant air contaminants, comprehend their health impacts, and anticipate air quality to safeguard public health from dangerous pollutants. The current study intends to investigate the spatial and temporal heterogeneity of important air pollutants, such as sulphur dioxide, nitrogen dioxide, carbon monoxide, and ozone, utilising Sentinel-5P TROPOMI satellite images. A comprehensive spatiotemporal analysis of air quality was conducted for the entire country with a special focus on five metro cities from 2019 to 2022, encompassing the pre-COVID-19, during-COVID-19, and current scenarios. Seasonal research revealed that air pollutant concentrations are highest in the winter, followed by the summer and monsoon, with the exception of ozone. Ozone had the greatest concentrations throughout the summer season. The analysis has revealed that NO2 hotspots are predominantly located in megacities, while SO2 hotspots are associated with industrial clusters. Delhi exhibits high levels of NO2 pollution, while Kolkata is highly affected by SO2 pollution compared to other major cities. Notably, there was an 11% increase in SO2 concentrations in Kolkata and a 20% increase in NO2 concentrations in Delhi from 2019 to 2022. The COVID-19 lockdown saw significant drops in NO2 concentrations in 2020; specifically, - 20% in Mumbai, - 18% in Delhi, - 14% in Kolkata, - 12% in Chennai, and - 15% in Hyderabad. This study provides valuable insights into the seasonal, monthly, and yearly behaviour of pollutants and offers a novel approach for hotspot analysis, aiding in the identification of major air pollution sources. The results offer valuable insights for developing effective strategies to tackle air pollution, safeguard public health, and improve the overall environmental quality in India. The study underscores the importance of satellite data analysis and presents a comprehensive assessment of the impact of the shutdown on air quality, laying the groundwork for evidence-based decision-making and long-term pollution mitigation efforts.

Understanding the effect of adsorption sites of CO at cobalt surface on its reactivity with H2/H by DFT calculations.

Cobalt (Co) is widely used in Fischer-Tropsch synthesis (FTS), converting synthesis gas, carbon monoxide + hydrogen (CO + H2), to long-chain hydrocarbons. The adsorption of CO on the Co surface is the key step in FTS. In this work, the effect of CO adsorption sites on the reactions between CO and H2 was investigated by using density functional theory (DFT). The energetics and structures of the reactions between the adsorbed CO (CO*) and H2/adsorbed H2 (H2*)/adsorbed H atom (H*) were calculated. The results show that the reaction between CO* and H2 is initiated by the molecular adsorption of H2 on the Co surface. The reactions between CO* and H2*/H* are influenced by CO adsorption sites. For the reaction system of CO* + H2*, it has the lowest reaction barrier when CO is adsorbed at the hcp site, while for CO* + H*, it has the lowest reaction barrier when CO is adsorbed on the top site. Kinetic analysis indicates that to improve the reactivity of CO + H2 in FTS, the adsorption of CO should be controlled to favour the top and bridge sites. This article is part of the theme issue 'Celebrating the 15th anniversary of the Royal Society Newton International Fellowship'.

Inhibitors of NLRP3 Inflammasome Formation: A Cardioprotective Role for the Gasotransmitters Carbon Monoxide, Nitric Oxide, and Hydrogen Sulphide in Acute Myocardial Infarction.

Myocardial ischaemia reperfusion injury (IRI) occurring from acute coronary artery disease or cardiac surgical interventions such as bypass surgery can result in myocardial dysfunction, presenting as, myocardial "stunning", arrhythmias, infarction, and adverse cardiac remodelling, and may lead to both a systemic and a localised inflammatory response. This localised cardiac inflammatory response is regulated through the nucleotide-binding oligomerisation domain (NACHT), leucine-rich repeat (LRR)-containing protein family pyrin domain (PYD)-3 (NLRP3) inflammasome, a multimeric structure whose components are present within both cardiomyocytes and in cardiac fibroblasts. The NLRP3 inflammasome is activated via numerous danger signals produced by IRI and is central to the resultant innate immune response. Inhibition of this inherent inflammatory response has been shown to protect the myocardium and stop the occurrence of the systemic inflammatory response syndrome following the re-establishment of cardiac circulation. Therapies to prevent NLRP3 inflammasome formation in the clinic are currently lacking, and therefore, new pharmacotherapies are required. This review will highlight the role of the NLRP3 inflammasome within the myocardium during IRI and will examine the therapeutic value of inflammasome inhibition with particular attention to carbon monoxide, nitric oxide, and hydrogen sulphide as potential pharmacological inhibitors of NLRP3 inflammasome activation.

"Three birds, one stone" strategy of NIR-responsive CO/H2S dual-gas Nanogenerator for efficient treatment of osteoporosis.

Osteoporosis (OP), the most prevalent bone degenerative disease, has become a significant public health challenge globally. Current therapies primarily target inhibiting osteoclast activity or stimulating osteoblast activation, but their effectiveness remains suboptimal. This paper introduced a "three birds, one stone" therapeutic approach for osteoporosis, employing upconversion nanoparticles (UCNPs) to create a dual-gas storage nanoplatform (UZPA-CP) targeting bone tissues, capable of concurrently generating carbon monoxide (CO) and hydrogen sulfide (H2S). Through the precise modulation of 808 nm near-infrared (NIR) light, the platform could effectively control the release of CO and H2S in the OP microenvironment, and realize the effective combination of promoting osteogenesis, inhibiting osteoclast activity, and improving the immune microenvironment to achieve the therapeutic effect of OP. High-throughput sequencing results further confirmed the remarkable effectiveness of the nanoplatform in inhibiting apoptosis, modulating inflammatory response, inhibiting osteoclast differentiation and regulating multiple immune signaling pathways. The gas storage nanoplatform not only optimized the OP microenvironment with the assistance of NIR, but also restored the balance between osteoblasts and osteoclasts. This comprehensive therapeutic strategy focused on improving the bone microenvironment, promoting osteogenesis and inhibiting osteoclast activity provides an ideal new solution for the treatment of metabolic bone diseases.

The relationship between air pollution and the occurrence of hypertensive disorders of pregnancy: Evidence from a study in Wuhan, China.

Ambient air pollution has been reported to be a risk factor for hypertensive disorders of pregnancy (HDP). Past studies have reported supportive evidence, but evidence from China is scarce and does not integrate the different periods of the pregnancy course. In this study, 1945 pregnant women with HDP and healthy pregnancies between 2016 and 2022 from the Renmin Hospital of Wuhan University registry network database were analysed. The geographic information, biological information and demographic information of the case were fused in the analysis. Machine learning methods were used to obtain the weight of the variable. Then, we used the generalized linear mixed model to evaluate the relationship between increased exposure to each pollutant at different periods of HDP and examined it in different groups. The results showed that SO2 had the predominate impact (12.65 %) on HDP compared with other air pollutants. SO2 exposure was associated with an increased risk of HDP. Increased unit SO2 concentrations were accompanied by an increased risk of HDP (OR = 1.33, 95 % CI: 1.13, 1.566), and the susceptible window for this effect was mainly in the first trimester (OR = 1.242, 95 % CI: 1.092, 1.412). In addition, SO2 exposure was associated with an increased risk of HDP in urban maternity (OR = 1.356, 95 % CI: 1.112, 1.653), obese maternity (OR = 3.58, 95 % CI: 1.608, 7.971), no higher education maternity (OR = 1.348, 95 % CI: 1.065, 1.706), nonzero delivery maternity (OR = 1.981, 95 % CI: 1.439, 2.725), maternal with first time maternity (OR = 1.247, 95 % CI: 1.007, 1.544) and other groups. In summary, SO2 exposure in early pregnancy is one of the risk factors for HDP, and the increased risk of HDP due to increased SO2 exposure may be more pronounced in obese, urban, low-education, and nonzero delivery populations.

Carbon monoxide-loaded red blood cells ameliorate metabolic dysfunction-associated steatohepatitis progression via enhancing AMP-activated protein kinase activity and inhibiting Kupffer cell activation.

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of nonalcoholic fatty liver disease characterised by fat accumulation, inflammation, oxidative stress, fibrosis, and impaired liver regeneration. In this study, we found that heme oxygenase-1 (HO-1) is induced in both MASH patients and in a MASH mouse model. Further, hepatic carbon monoxide (CO) levels in MASH model mice were >2-fold higher than in healthy mice, suggesting that liver HO-1 is activated as MASH progresses. Based on these findings, we used CO-loaded red blood cells (CO-RBCs) as a CO donor in the liver, and evaluated their therapeutic effect in methionine-choline deficient diet (MCDD)-induced and high-fat-diet (HFD)-induced MASH model mice. Intravenously administered CO-RBCs effectively delivered CO to the MASH liver, where they prevented fat accumulation by promoting fatty acid oxidation via AMP-activated protein kinase (AMPK) activation and peroxisome proliferator-activated receptor induction. They also markedly suppressed Kupffer cell activation and their corresponding anti-inflammatory and antioxidative stress activities in MASH mice. CO-RBCs also helped to restore liver regeneration in mice with HFD-induced MASH by activating AMPK. We confirmed the underlying mechanisms by performing in vitro experiments in RAW264.7 cells and palmitate-stimulated HepG2 cells. Taken together, CO-RBCs show potential as a promising cellular treatment for MASH.