Unveiling the hidden risks: Pesticide residues in aquaculture systems.

The present study systematically assessed the presence and ecological risks of 79 pesticides in various aquaculture systems, namely pond aquaculture (PA), greenhouse aquaculture (GA), and raceway aquaculture (RA) at different aquaculture stages, along with evaluating the pesticide removal of four tailwater treatment systems. Sixteen herbicides and two fungicides were identified, with the total concentrations ranging from 8.33 ng/L to 3248.45 ng/L. The PA system demonstrated significantly higher concentrations (p < 0.05) and a wider range of pesticide residues compared to the GA and RA systems. Prometryn, simetryn, atrazine, and thifluzamide were found to be the predominant pesticides across all three aquaculture modes, suggesting their significance as pollutants that warrant monitoring. Additionally, the findings indicated that the early aquaculture stage exhibits the highest levels of pesticide concentration, underscoring the importance of heightened monitoring and regulatory interventions during this phase. Furthermore, among the four tailwater treatment systems analyzed, the recirculating tailwater treatment system exhibited the highest efficacy in pesticide removal. A comprehensive risk assessment revealed minimal ecological risks in both the aquaculture and tailwater environments. However, the pesticide mixtures present high risks to algae and low to medium risks to aquatic invertebrates and fish, particularly during the early stages of aquaculture. Simetryn and prometryn were identified as high-risk pesticides. Based on the prioritization index, simetryn, prometryn, diuron, and ametryn are recommended for prioritization in risk assessment. This study offers valuable data for pesticide control and serves as a reference for the establishment of a standardized pesticide monitoring and management system at various stages of aquaculture.

Understanding vegetation phenology responses to easily ignored climate factors in china's mid-high latitudes.

Previous studies have primarily focused on the influence of temperature and precipitation on phenology. It is unclear if the easily ignored climate factors with drivers of vegetation growth can effect on vegetation phenology. In this research, we conducted an analysis of the start (SOS) and end (EOS) of the growing seasons in the northern region of China above 30°N from 1982 to 2014, focusing on two-season vegetation phenology. We examined the response of vegetation phenology of different vegetation types to preseason climatic factors, including relative humidity (RH), shortwave radiation (SR), maximum temperature (Tmax), and minimum temperature (Tmin). Our findings reveal that the optimal preseason influencing vegetation phenology length fell within the range of 0-60 days in most areas. Specifically, SOS exhibited a significant negative correlation with Tmax and Tmin in 44.15% and 42.25% of the areas, respectively, while EOS displayed a significant negative correlation with SR in 49.03% of the areas. Additionally, we identified that RH emerged as the dominant climatic factor influencing the phenology of savanna (SA), whereas temperature strongly controlled the SOS of deciduous needleleaf forest (DNF) and deciduous broadleaf forest (DBF). Meanwhile, the EOS of DNF was primarily influenced by Tmax. In conclusion, this study provides valuable insights into how various vegetation types adapt to climate change, offering a scientific basis for implementing effective vegetation adaptation measures.

Electron Accumulation Induced by Electron Injection-Incomplete Discharge on NiFe LDH for Enhanced Oxygen Evolution Reaction.

Optimizing the local electronic structure of electrocatalysts can effectively lower the energy barrier of electrochemical reactions, thus enhancing the electrocatalytic activity. However, the intrinsic contribution of the electronic effect is still experimentally unclear. In this work, the electron injection-incomplete discharge approach to achieve the electron accumulation (EA) degree on the nickel-iron layered double hydroxide (NiFe LDH) is proposed, to reveal the intrinsic contribution of EA toward oxygen evolution reaction (OER). Such NiFe LDH with EA effect results in only 262 mV overpotential to reach 50 mA cm-2, which is 51 mV-lower compared with pristine NiFe LDH (313 mV), and reduced Tafel slope of 54.8 mV dec-1 than NiFe LDH (107.5 mV dec-1). Spectroscopy characterizations combined with theoretical calculations confirm that the EA near concomitant Vo can induce a narrower energy gap and lower thermodynamic barrier to enhance OER performance. This study clarifies the mechanism of the EA effect on OER activity, providing a direct electronic structure modulation guideline for effective electrocatalyst design.

Strengthening the Synergy between Oxygen Vacancies in Electrocatalysts for Efficient Glycerol Electrooxidation.

Defect-engineered bimetallic oxides exhibit high potential for the electrolysis of small organic molecules. However, the ambiguity in the relationship between the defect density and electrocatalytic performance makes it challenging to control the final products of multi-step multi-electron reactions in such electrocatalytic systems. In this study, controllable kinetics reduction is used to maximize the oxygen vacancy density of a Cu─Co oxide nanosheet (CuCo2O4 NS), which is used to catalyze the glycerol electrooxidation reaction (GOR). The CuCo2O4-x NS with the highest oxygen-vacancy density (CuCo2O4-x-2) oxidizes C3 molecules to C1 molecules with selectivity of almost 100% and a Faradaic efficiency of ≈99%, showing the best oxidation performance among all the modified catalysts. Systems with multiple oxygen vacancies in close proximity to each other synergistically facilitate the cleavage of C─C bonds. Density functional theory calculations confirm the ability of closely spaced oxygen vacancies to facilitate charge transfer between the catalyst and several key glycolic-acid (GCA) intermediates of the GOR process, thereby facilitating the decomposition of C2 intermediates to C1 molecules. This study reveals qualitatively in tuning the density of oxygen vacancies for altering the reaction pathway of GOR by the synergistic effects of spatial proximity of high-density oxygen vacancies.

Identification of Panax notoginseng origin using terahertz precision spectroscopy and neural network algorithm.

Panax notoginseng (P. notoginseng), a Chinese herb containing various saponins, benefits immune system in medicines development, which from Wenshan (authentic cultivation) is often counterfeited by others for large demand and limited supply. Here, we proposed a method for identifying P. notoginseng origin combining terahertz (THz) precision spectroscopy and neural network. Based on the comparative analysis of four qualitative identification methods, we chose high-performance liquid chromatography (HPLC) and THz spectroscopy to detect 252 samples from five origins. After classifications using Convolutional Neural Networks (CNNs) model, we found that the performance of THz spectra was superior to that of HPLC. The underlying mechanism is that there are clear nonlinear relations among the THz spectra and the origins due to the wide spectra and multi-parameter characteristics, which makes the accuracy of five-classification origin identification up to 97.62%. This study realizes the rapid, non-destructive and accurate identification of P. notoginseng origin, providing a practical reference for herbal medicine.

Identification of CREB5 as a prognostic and immunotherapeutic biomarker in glioma through multi-omics pan-cancer analysis.

BACKGROUND: The functional relevance of cyclic adenosine monophosphate (cAMP)-response element-binding protein 5 (CREB5) in cancers remains elusive, despite its significance as a member of the CREB family. The current research aims to explore the role of CREB5 in multiple cancers. METHODS: Pan-cancer analysis was performed to explore the expression patterns, prognostic value, mutational landscape as well as single-cell omic, immunologic, and drug sensitivity profiles of CREB5. Furthermore, we incorporated five distinct machine learning algorithms and determined that the least absolute shrinkage and selection operator-COX (LASSO-COX) algorithm, which exhibited the highest C index, was the optimal selection. Subsequently, we constructed a prognostic model centered around CREB5-associated genes. To elucidate the biological function of CREB5 in glioma cells, several assays including cell counting kit-8 (CCK-8), wound healing, transwell, flow cytometric were performed. RESULTS: CREB5 was overexpressed in pan-cancer and was linked to unfavorable prognosis, particularly in glioma. Furthermore, genetic alterations were determined in various types of cancer, and modifications in the CREB5 gene were linked to the prognosis. The single-cell omics and enrichment analyses showed that CREB5 was predominantly expressed in malignant glioma cells and was critically involved in the regulation of various oncogenic processes. Elevated levels of CREB5 were strongly linked with the infiltration of cancer-associated fibroblasts and the Th1 subset of CD4+ T cells. The validated CREB5-associated prognostic model reliably predicted the prognosis and drug response of glioma patients. The in vitro experiments showed that CREB5 promoted glioma cell proliferation, invasion, migration, and gap phase 2/mitotic (G2/M) phase arrest and recruited M2 macrophages into glioma cells. CONCLUSION: CREB5 has the potential to act as an oncogene and a biological marker in multiple cancers, particularly glioma.

Structure-activity relationship study of anti-wear additives in rapeseed oil based on machine learning and logistic regression.

Anti-wear performance is a crucial quality of lubricants, and it is important to conduct research into the structure-activity relationship of anti-wear additives in bio-based lubricants. These lubricants are eco-friendly and energy-efficient. A literature review resulted in the construction of a dataset comprising 779 anti-wear properties of 79 anti-wear additives in rapeseed oil, at various loadings and additive levels. The anti-wear additives were classified into six groups, including phosphoric acid, formate esters, borate esters, thiazoles, triazine derivatives, and thiophene. Logistic regression analysis revealed that the quantity and kind of anti-wear agents had significant effects on the anti-wear properties of rapeseed oil, with phosphoric acid being the most effective and thiophene being the least effective. To identify the specific structural data that affect the anti-wear capabilities of additives in bio-based lubricants of rapeseed oil, a random forest classification model was developed. The results showed a 0.964 accuracy (ACC) and a 0.931 Matthews Correlation Coefficient (MCC) on the test set. The ranking of importance and characterization of MACCS descriptors in the model confirms that anti-wear additives with chemical structures containing P, O, N, S and heterocyclic groups, along with more than two methyl groups, improve the anti-wear performance of rapeseed oil. The application of data analysis and machine learning to investigate the classifications and structural characteristics of anti-wear additives in rapeseed oil provides data references and guiding principles for designing anti-wear additives in bio-based lubricants.

Association between increased BMI and cognitive function in first-episode drug-naïve male schizophrenia.

Objective: Although the adverse effects of obesity in schizophrenia are documented, there is limited research exists on the implications for untreated initial schizophrenia. Our investigation aimed to explore the connections between BMI and cognitive function in first-episode drug-naïve (FEDN)schizophrenia. Methods: We enrolled 143 FEDN schizophrenia patients, and collected data on their body mass index, fasting blood glucose and lipid levels. Cognitive function was measured with the MATRICS Consensus Cognitive Battery (MCCB). Using correlation and regression analysis to assess the relationship between BMI and cognitive performance. Results: The prevalence rate of overweight plus obesity in FEDN schizophrenia patients was 33.57%. Patients with FEDN schizophrenia exhibited extensive cognitive impairment, and those who were overweight/obesity demonstrated more severe impairments in working memory and visual learning when compared to normal/under weight counterparts. Correlation analysis indicated a negative association between working memory and BMI and TG, as well as a link between visual learning and BMI and LDL-C. Multiple linear regression analysis revealed that a higher BMI predicted a decrease in working memory in FEDN schizophrenia patients. Conclusion: Our results indicate that the rate of overweight plus obesity is high in FEDN schizophrenia patients, and there is an association between BMI and cognitive function in schizophrenia, particularly in relation to working memory.

Models for Meibomian gland dysfunction: In vivo and in vitro.

Meibomian gland dysfunction (MGD) is a chronic abnormality of the Meibomian glands (MGs) that is recognized as the leading cause of evaporative dry eye worldwide. Despite its prevalence, however, the pathophysiology of MGD remains elusive, and effective disease management continues to be a challenge. In the past 50 years, different models have been developed to illustrate the pathophysiological nature of MGD and the underlying disease mechanisms. An understanding of these models is crucial if researchers are to select an appropriate model to address specific questions related to MGD and to develop new treatments. Here, we summarize the various models of MGD, discuss their applications and limitations, and provide perspectives for future studies in the field.

Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses.

The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.

A pan-cancer multi-omics analysis of lactylation genes associated with tumor microenvironment and cancer development.

Background: Lactylation is a significant post-translational modification bridging the gap between cancer epigenetics and metabolic reprogramming. However, the association between lactylation and prognosis, tumor microenvironment (TME), and response to drug therapy in various cancers remains unclear. Methods: First, the expression, prognostic value, and genetic and epigenetic alterations of lactylation genes were systematically explored in a pan-cancer manner. Lactylation scores were derived for each tumor using the single-sample gene set enrichment analysis (ssGSEA) algorithm. The correlation of lactylation scores with clinical features, prognosis, and TME was assessed by integrating multiple computational methods. In addition, GSE135222 data was used to assess the efficacy of lactylation scores in predicting immunotherapy outcomes. The expression of lactylation genes in breast cancers and gliomas were verified by RNA-sequencing. Results: Lactylation genes were significantly upregulated in most cancer types. CREBBP and EP300 exhibited high mutation rates in pan-cancer analysis. The prognostic impact of the lactylation score varied by tumor type, and lactylation score was a protective factor for KIRC, ACC, READ, LGG, and UVM, and a risk factor for CHOL, DLBC, LAML, and OV. In addition, a high lactylation score was associated with cold TME. The infiltration levels of CD8+ T, γδT, natural killer T cell (NKT), and NK cells were lower in tumors with higher lactylation scores. Finally, immunotherapy efficacy was worse in patients with high lactylation scores than other types. Conclusion: Lactylation genes are involved in malignancy formation. Lactylation score serves as a promising biomarker for predicting patient prognosis and immunotherapy efficacy.

LncRNA-SNHG5 mediates activation of hepatic stellate cells by regulating NF2 and Hippo pathway.

Long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) is an oncogene found in various human cancers. However, it is unclear what role SNHG5 plays in activating hepatic stellate cells (HSCs) and liver fibrosis. In this study, SNHG5 was found to be upregulated in activated HSCs in vitro and in primary HSCs isolated from fibrotic liver in vivo, and inhibition of SNHG5 suppressed HSC activation. Notably, Neurofibromin 2 (NF2), the main activator for Hippo signalling, was involved in the effects of SNHG5 on HSC activation. The interaction between SNHG5 and NF2 protein was further confirmed, and preventing the combination of the two could effectively block the effects of SNHG5 inhibition on EMT process and Hippo signaling. Additionally, higher SNHG5 was found in chronic hepatitis B patients and associated with the fibrosis stage. Altogether, we demonstrate that SNHG5 could serve as an activated HSCs regulator via regulating NF2 and Hippo pathway.

Ent-atisane diterpenoids from Euphorbia wallichii and their anti-influenza A virus activity.

The study entailed the investigation of the roots of Euphorbia wallichii, which resulted in the isolation of 29 ent-atisane diterpenoids (1-29), 14 of which were previously unknown. These previously undescribed ones were named euphorwanoids A-N (3-5, 7, 9, and 10-18). Various techniques, including comprehensive spectroscopic methods and calculated electronic circular dichroism, were employed to determine their molecular structures. Additionally, the absolute configurations of ten ent-atisane diterpenoids (1, 2, 5, 6, 8, 9, 11, 12, 14 and 16) were established through X-ray crystallographic analyses. All isolated compounds' potential to inhibit the influenza A virus in vitro were evaluated. Compounds 18, 20, and 24 exhibited notable antiviral activity against the A/Puerto Rico/8/1934 strain. Their effective concentrations for reducing viral activity (EC50 values) were found to be 8.56, 1.22, and 4.97 µM, respectively. An intriguing aspect of this research is that it marks the first instance of ent-atisane diterpenes displaying anti-H1N1 activity. Empirical NMR rules were established with Δδ to distinguish the R/S configurations of C-13 and C-16 in ent-atisanes.

The protective effect of intranasal immunization with influenza virus recombinant adenovirus vaccine on mucosal and systemic immune response.

Influenza virus is a kind of virus that poses several hazards of animal and human health. Therefore, it is important to develop an effective vaccine to prevent influenza. To this end we successfully packaged recombinant adenovirus rAd-NP-M2e-GFP expressing multiple copies of influenza virus conserved antigens NP and M2e and packaged empty vector adenovirus rAd-GFP. The effect of rAd-NP-M2e-GFP on the activation of dendritic cell (DC) in vitro and in vivo was detected by intranasal immunization. The results showed that rAd-NP-M2e-GFP promoted the activation of DC in vitro and in vivo. After the primary immunization and booster immunization of mice through the nasal immune way, the results showed that rAd-NP-M2e-GFP induced enhanced local mucosal-specific T cell responses, increased the content of SIgA in broncho alveolar lavage fluids (BALF) and triggered the differentiation of B cells in the germinal center. It is proved that rAd-NP-M2e-GFP can significantly elicit mucosal immunity and systemic immune response. In addition, rAd-NP-M2e-GFP could effectively protect mice after H1N1 influenza virus challenge. To lay the foundation and provide reference for further development of influenza virus mucosal vaccine in the future.

Pan-cancer Multi-omics Analysis Reveals HMGN1 as a Potential Prognostic and Immune Infiltration-associated Biomarker.

BACKGROUND: The High Mobility Group Nucleosomal Binding Domain 1 Gene (HMGN1) is crucial for epigenetic regulation. However, the specific function of HMGN1 in cancer development is unclear. METHODS: Raw data on HMGN1 expression were procured from Genotype-Tissue Expression (GTEx), the University of Alabama- Birmingham CANcer data analysis Portal (UALCAN), and The Cancer Genome Atlas (TCGA). Thereafter, the pan-cancer analysis was implemented to understand the HMGN1 expression patterns, prognostic value, and immunological features. Furthermore, the Gene Set Enrichment Analysis (GSEA) was executed via R language. In addition, the relationship between HMGN1 and the sensitivity of antitumor drugs was also determined. Finally, real-time PCR (RT-PCR) experiments were carried out. RESULTS: Pan-cancer analysis revealed that HMGN1 was upregulated in several solid tumors and was associated with pathological staging and poor prognosis. In addition, HMGN1 was found to be involved in regulating the tumor microenvironment. The GSEA enrichment analysis indicated that HMGN1 assisted in the regulation of oncogenic processes, especially metabolic and immune pathways. Furthermore, HMGN1 expression was linked to microsatellite instability (MSI) and tumor mutational burden (TMB) across diverse tumor types. RT-PCR assays indicated that HMGN1 was overexpressed in the gastric and breast cancer cell lines and tissues. CONCLUSION: This study highlighted the potential of HMGN1 as a biomarker for pan- - cancer analysis.

Development of a live-attenuated chimeric vaccine against the emerging Usutu virus.

Usutu virus (USUV) is an emerging arthropod-borne flavivirus that has expanded into multiple European countries during the past several decades. USUV infection in human has been linked to severe neurological complications, and no vaccine is now available against USUV. In this work, we develop a live-attenuated chimeric USUV vaccine (termed ChinUSUV) based on the full-length infectious cDNA clone of the licensed Japanese encephalitis virus (JEV) vaccine strain SA14-14-2. In vitro studies demonstrate that ChinUSUV replicates efficiently and maintains its genetic stability. Remarkably, ChinUSUV exhibits a significant attenuation phenotype in multiple mouse models even compared with the licensed JEV vaccine. A single immunization with ChinUSUV elicits potent IgG and neutralizing antibody responses as well as T cell response. Passive transfer of sera from ChinUSUV-immunized mice confers significant protection against lethal homologous challenge in suckling mice. Taken together, our results suggest that ChinUSUV represents a potential USUV vaccine candidate that merits further development.

Expression of FAP in Oral Leukoplakia and Oral Squamous Cell Carcinoma.

OBJECTIVE: This study aimed to investigate the potential of fibroblast activation protein (FAP) as a biomarker in the progression of oral leukoplakia (OLK) carcinogenesis. This was achieved by evaluating FAP expression at different levels of the organisation, namely oral normal mucosa (NM), OLK, and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Altogether, 88 paraffin-embedded tissue samples were examined, including 55 cases of OLK, 13 cases of OSCC, and 20 cases of NM (control group). An exhaustive investigation was performed to examine FAP expression in NM, OLK, and OSCC tissues via immunohistochemistry (IHC). The relationship between FAP expression and clinical pathologic characteristics was analysed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB) also proved the expression of FAP in NM, OLK, and OSCC cells. Aberrant FAP expression in OLK and OSCC was explored using in vitro experiments. RESULTS: Immunohistochemical results showed that high FAP expression was significantly correlated with histopathologic grade (P = .038) but not correlated with age, sex, or region (P = .953, .622, and .108, respectively). The expression level of FAP in NM tissues (0.15 ± 0.01) was minimal, whereas it was observed in OLK (0.28 ± 0.04) and OSCC (0.39 ± 0.02) tissues with a noticeable increase in expression levels (P < .001). The expression level of FAP in OLK with severe abnormal hyperplasia (S-OLK) tissues (0.33 ± 0.04) was significantly higher than in OLK with mild abnormal hyperplasia (MI-OLK, 0.26 ± 0.02) and OLK with moderate abnormal hyperplasia (MO-OLK, 0.28 ± 0.03) tissues (P < .001 and P = .039, respectively). The results of RT-PCR illustrated that the relative expression of FAP mRNA in OLK cells (2.63 ± 0.62) was higher than in NM cells (0.87 ± 0.14), but lower than in OSCC cells (5.63 ± 1.06; P = .027 and .012, respectively). FAP expression was minimal in NM cells (0.78 ± 0.06), modest in OLK cells (1.04 ± 0.06), and significantly elevated in OSCC cells (1.61 ± 0.09) based on the results of WB (P < .001). CONCLUSIONS: Significant variations in FAP expression were observed in NM, OLK, and OSCC tissues and cells. These findings revealed that FAP may be a reliable biomarker for the early diagnosis and evaluation of OLK carcinogenesis.

Data-driven assessment of soil total nitrogen on the Qinghai-Tibet Plateau.

The investigation of soil total nitrogen (STN) holds significant importance in the preservation and sustainability of Earth's ecosystems. The Qinghai-Tibet Plateau (QTP), renowned as the world's most expansive plateau and characterized by its exceptionally delicate ecosystem, demands an in-depth exploration of its STN content. In this study, we use a machine learning approach to extrapolate point-scale measured STN stocks to the entire QTP and calculated STN storage from 0 to 2 m. Our results show that the XGB algorithm performs well in modeling STN despite variations in simulation accuracy for specific depth ranges. The spatial distribution of STN across the QTP exhibits pronounced heterogeneity, especially for the 0-50 cm soil layer, with relatively higher STN stocks in the southeast and lower stocks in the northwest of QTP. The vertical distribution reveals a gradual decrease in STN storage with increasing depth. The 0-50 cm soil layer holds the highest STN stocks, averaging around 0.78 kg/m2, which is almost the sum of STN stocks in the 50-100 cm and 100-200 cm soil layers. Meanwhile, the STN stocks are smaller in permafrost zone than that in non-permafrost zone. We also investigate the impact factors that control the spatiotemporal distribution of STN. It indicates that vegetation, precipitation, temperature, and elevation are the major factors for STN distribution, while physical properties of the soil have a relatively smaller impact. These findings are crucial for understanding the distribution and evolution of STN on the QTP.

Ginsenoside Rg3 promotes hepatic stellate cell ferroptosis by epigenetically regulating ACSL4 to suppress liver fibrosis progression.

BACKGROUND: Ginsenoside Rg3 (G-Rg3), extracted from Panax notoginseng, possesses hepatoprotective properties. Hepatic stellate cells (HSCs) activation is responsible for liver fibrosis. Recent studies have reported the suppressive effects of G-Rg3 on HSC activation and proliferation. Ferroptosis is a novel iron regulated cell death. ACSL4, a key indicator of ferroptosis, is commonly methylated in various diseases. PURPOSE: However, the role of ACSL4 methylation-mediated HSC ferroptosis in G-Rg3 inhibition of hepatic fibrosis needs to be explored. METHODS: Effects of G-Rg3 on inhibiting fibrosis were evaluated in vivo and in vitro. The impact of G-Rg3 on HSC ferroptosis was assessed in vitro. Furthermore, the expression of ACSL4, ACSL4 methylation and microRNA-6945-3p (miR-6945-3p) levels were determined. RESULTS: G-Rg3 significantly alleviated CCl4-induced liver fibrosis, accompanied by collagen downregulation. In vitro, G-Rg3 contributed to HSC inactivation, leading to decreased collagen production. G-Rg3 induced HSC ferroptosis, characterized by increased iron accumulation, depletion of glutathione, malondialdehyde levels, and generation of lipid reactive oxygen species. Moreover, G-Rg3 promoted ACSL4 demethylation and restored its expression. Notably, DNMT3B counteracted the effect of G-Rg3-mediated inhibition of ACSL4 methylation and was targeted by miR-6945-3p. Further investigations revealed that G-Rg3 suppressed ACSL4 methylation through miR-6945-3p-mediated DNMT3B inhibition. Consistent with this, miR-6945-3p inhibition reversed G-Rg3-induced ACSL4 expression and HSC ferroptosis. CONCLUSION: G-Rg3 inhibits ACSL4 methylation by miR-6945-3p-mediated DNMT3B inhibition, thereby promoting HSC ferroptosis and mitigating liver fibrosis.