A comprehensive review on biological funnel mechanism in lignin valorization: Pathways and enzyme dynamics.

Lignin, a significant byproduct of the paper and pulp industry, is attracting interest due to its potential utilization in biomaterial-based sectors and biofuel production. Investigating biological methods for converting lignin into valuable products is crucial for effective utilization and has recently gained growing attention. Several microorganisms effectively decomposed low molecular weight lignins, transforming them into intermediate compounds via upper and lower metabolic pathways. This review focuses on assessing bacterial metabolic pathways involved in the breakdown of lignin into aromatic compounds and their subsequent utilization by different bacteria through various metabolic pathways. Understanding these pathways is essential for developing efficient synthetic metabolic systems to valorize lignin and obtain valuable industrial aromatic chemicals. The concept of "biological funneling," which involves examining key enzymes, their interactions, and the complex metabolic pathways associated with lignin conversion, is crucial in lignin valorization. By manipulating lignin metabolic pathways and utilizing biological routes, many aromatic compounds can be synthesized within cellular factories. Although there is insufficient evidence regarding the complete metabolism of polyaromatic hydrocarbons by particular microorganisms, understanding lignin-degrading enzymes, regulatory mechanisms, and interactions among various enzyme systems is essential for optimizing lignin valorization. This review highlights recent advancements in lignin valorization, bio-funneling, multi-omics, and analytical characterization approaches for aromatic utilization. It provides up-to-date information and insights into the latest research findings and technological innovations. The review offers valuable insights into the future potential of biological routes for lignin valorization.

Cation-Triggered Growth of Nanowires for Enhanced Oxygen Evolution Reaction.

The oxygen evolution reaction (OER), which occurs in a variety of energy-related devices, necessitates optimization of the reaction pathways for efficient and scalable deployment. Nevertheless, fully harnessing the advanced structure of synthetic electrocatalysts remains a significant challenge due to the inevitable surface reconstruction process during OER. Here we present an efficient and flexible method to control the surface reconstruction process by engineering an electrolyte containing trace Co2+ cation. This controllable reconstruction process enhances fast charge transfer, facilitates electroactive species transport, and exposes the inner active site, significantly improving the OER kinetics. An impressive 60% increase in current density at an applied potential of 2.2 V (vs RHE) confirms its remarkable contribution to the performance. The identification of cation-triggered reconstruction for the formation of a well-defined surface provides a novel insight into understanding electrolyte engineering and offers a viable pathway to address activity and stable concerns in electrocatalysts.

Copper-Induced Supramolecular Peptide Assemblies for Multi-Pathway Cell Death and Tumor Inhibition.

Although self-assembly has emerged as an effective tool for fabricating biomaterials, achieving precise control over the morphologies and functionalities of the resultant assemblies remains an ongoing challenge. Inspired by the copper peptide naturally present in human plasma, in this study, we designed a synthetic precursor, FcGH. FcGH can self-assemble via two distinct pathways: spontaneous and Cu2+-induced. These two assembly pathways enabled the formation of assemblies with tunable morphologies by adjusting the amount of added Cu2+. We found that the nanoparticles formed by Cu2+-induced self-assembly exhibited a significantly higher cellular uptake efficiency than the wormlike fibers formed spontaneously. Moreover, this Cu2+-induced assembly process occurred spontaneously at a 1 : 1 molar ratio of Cu2+ to FcGH, avoiding the excessive use of Cu2+ and a tedious preparation procedure. By co-assembling with 10-hydroxycamptothecin (HCPT)-conjugated FcGH, Cu2+-induced supramolecular nanodrugs elicited multiple cell death modalities in cancer cells with elevated immunogenicity, enhancing the therapeutic effect compared to free HCPT. This study highlights Cu2+-induced self-assembly as an efficient tool for directing the assembly of nanodrugs and for synergistic tumor therapy.

Enzyme-Instructed Photoactivatable Supramolecular Antigens on Cancer Cell Membranes for Precision-Controlled T-Cell-Based Cancer Immunotherapy.

Cancer immunotherapies based on cytotoxic CD8+ T lymphocytes (CTLs) are highly promising for cancer treatment. The specific interaction between T-cell receptors and peptide-MHC-I complexes (pMHC-I) on cancer cell membranes critically determines their therapeutic outcomes. However, the lack of appropriate endogenous antigens for MHC-I presentation disables tumor recognition by CTLs. By devising three antigen-loaded self-assembling peptides of pY-K(Ag)-ERGD, pY-K(Ag)-E, and Y-K(Ag)-ERGD to noncovalently generate light-activatable supramolecular antigens at tumor sites in different manners, we report pY-K(Ag)-ERGD as a promising candidate to endow tumor cells with pMHC-I targets on demand. Specifically, pY-K(Ag)-ERGD first generates low-antigenic supramolecular antigens on cancer cell membranes, and a successive light pulse allows antigen payloads to efficiently release from the supramolecular scaffold, directly producing antigenic pMHC-I. Intravenous administration of pY-K(Ag)-ERGD enables light-controlled tumor inhibition when combined with adoptively transferred antigen-specific CTLs. Our strategy is feasible for broadening tumor antigen repertoires for T-cell immunotherapies and advancing precision-controlled T-cell immunotherapies.

Experimental study of a thin thermally grown oxide layer in thermal barrier coatings based on the SWT-BP algorithm and terahertz technology.

As a promising nondestructive testing (NDT) technique with a very adaptive physical modeling of wave transmission process, terahertz technology is used for the detection and characterization of nonpolar materials and the evaluation of layered and/or defective structures. THz-TDS can also be used to perform spectroscopic analysis and detect structural defects in thermal barrier coatings (TBCs) of aero-engines. Although it is generally difficult to measure the structure of the thin oxide layer of the thermal barrier coatings whose thickness is generally lower than 30 µm (the current axial resolution of the THz-TDS cannot exceed 30 µm). We were able to complete the detection of the oxide layer within 1-29 µm through simulation by using the SWT-BP algorithm. In this study, the analysis was performed on real-world samples, the fitting degree of the SWT-BP algorithm reached 0.77, and the minimum prediction error was less than 0.1 µm. The paper also put forward some improvement measures about the experimental results.

Commonly used software tools produce conflicting and overly-optimistic AUPRC values.

The precision-recall curve (PRC) and the area under the precision-recall curve (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluate 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in more than 3000 published studies. We find the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.

Micelles Cascade Assembly to Tandem Porous Catalyst for Waste Plastics Upcycling.

Catalytic upcycling of polyolefins into high-value chemicals represents the direction in end-of-life plastics valorization, but poses great challenges. Here, we report the synthesis of a tandem porous catalyst via a micelle cascade assembly strategy for selectively catalytic cracking of polyethylene into olefins at a low temperature. A hierarchically porous silica layer from mesopore to macropore is constructed on the surface of microporous ZSM-5 nanosheets through cascade assembly of dynamic micelles. The outer macropore arrays can adsorb bulky polyolefins quickly by the capillary and hydrophobic effects, enhancing the diffusion and access to active sites. The middle mesopores present a nanoconfinement space, pre-cracking polyolefins into intermediates by weak acid sites, which then transport into zeolites micropores for further cracking by strong Brønsted acid sites. The hierarchically porous and acidic structures, mimicking biomimetic protease catalytic clefts, ideally match the tandem cracking steps of polyolefins, thus suppressing coke formation and facilitating product escape. As a result, light hydrocarbons (C1-C7) are produced with a yield of 443 mmol gZSM-5 -1, where 74.3 % of them are C3-C6 olefins, much superior to ZSM-5 and porous silica catalysts. This tandem porous catalyst exemplifies a superstructure design of catalytic cracking catalysts for industrial and economical upcycling of plastic wastes.

Insecticidal Effects of Transgenic Maize Bt-Cry1Ab, Bt-Vip3Aa, and Bt-Cry1Ab+Vip3Aa against the Oriental Armyworm, Mythimna separata (Walker) in Southwest China.

The oriental armyworm, Mythimna separata (Walker), an important migratory pest of maize and wheat, is posing a severe threat to maize production in Asian countries. As source areas of spring-summer emigratory populations, the control of M. separata in southwestern China is of great significance for East Asian maize production. To assess the toxicity of Bt maize against the pest, bioassays of Bt-(Cry1Ab+Vip3Aa) maize (event DBN3601T), Bt-Cry1Ab maize (event DBN9936), and Bt-Vip3Aa maize (event DBN9501) were conducted in Yunnan province of southwest China. There were significant differences in insecticidal activity between the three Bt maize events, and DBN3601T presented the highest insecticidal role. The results also indicated that the insecticidal effect of various Bt maize tissues took an order in leaf > kernel > silk, which is highly consistent with the expression amounts of Bt insecticidal protein in leaf (69.69 ± 1.18 µg/g), kernel (11.69 ± 0.75 µg/g), and silk (7.32 ± 0.31 µg/g). In field trials, all larval population densities, plant damage rates, and leaf damage levels of DBN3601T maize were significantly lower than the conventional maize. This research indicated that the DBN3601T event had a high control efficiency against M. separata and could be deployed in southwest China for the management of M. separata.

mRNA-Seq of testis and liver tissues reveals a testis-specific gene and alternative splicing associated with hybrid male sterility in dzo.

Alternative splicing (AS) plays an important role in the co-transcription and post-transcriptional regulation of gene expression during mammalian spermatogenesis. The dzo is the male F1 offspring of an interspecific hybrid between a domestic bull (Bos taurus ♂) and a yak (Bos grunniens ♀) which exhibits male sterility. This study aimed to identify the testis-specific genes and AS associated with hybrid male sterility in dzo. The iDEP90 program and rMATS software were used to identify the differentially expressed genes (DEG) and differential alternative splicing genes (DSG) based on RNA-seq data from the liver (n = 9) and testis (n = 6) tissues of domestic cattle, yak, and dzo. Splicing factors (SF) were obtained from the AmiGO2 and the NCBI databases, and Pearson correlation analysis was performed on the differentially expressed SFs and DSGs. We focused on the testis-specific DEGs and DSGs between dzo and cattle and yak. Among the top 3,000 genes with the most significant variations between these 15 samples, a large number of genes showed testis-specific expression involved with spermatogenesis. Cluster analysis showed that the expression levels of these testis-specific genes were dysregulated during mitosis with a burst downregulation during the pachynema spermatocyte stage. The occurrence of AS events in the testis was about 2.5 fold greater than in the liver, with exon skipping being the major AS event (81.89% to 82.73%). A total of 74 DSGs were specifically expressed in the testis and were significantly enriched during meiosis I, synapsis, and in the piRNA biosynthesis pathways. Notably, STAG3 and DDX4 were of the exon skipping type, and DMC1 was a mutually exclusive exon. A total of 36 SFs were significantly different in dzo testis, compared with cattle and yak. DDX4, SUGP1, and EFTUD2 were potential SFs leading to abnormal AS of testis-specific genes in dzo. These results show that AS of testis-specific genes can affect synapsis and the piRNA biosynthetic processes in dzo, which may be important factors associated with hybrid male sterility in dzo.

The interspecific hybrid offspring of a domestic bull (Bos taurus) and a yak (Bos grunniens) display heterosis in meat and milk production. The hybrid offspring are particularly adaptable to the harsh environments of the Qinghai-Tibet Plateau. However, the male F1 to F3 offspring of this interspecies hybrid are infertile, and spermatogenesis is arrested at meiosis preventing the prolonged utilization of the benefits of heterosis. This study aimed to identify the testis-specific genes and alternative splicing (AS) associated with hybrid male sterility using RNA-Seq data from the liver and testis tissues of domestic cattle, yaks, and their F1 offspring (dzo). The expression of the testis-specific genes became disordered during mitosis and meiosis in dzo. Their testis-specific genes with AS events were enriched during synapsis and in the piRNA biosynthetic processes. In addition, we identified the potential splicing factors associated with abnormal testis-specific AS gene expression in dzo. These results reveal the important role of AS in the meiotic arrest of dzo.

Commonly used software tools produce conflicting and overly-optimistic AUPRC values.

The precision-recall curve (PRC) and the area under it (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluated 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in >3,000 published studies. We found the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.

Switchable Pickering Emulsions Stabilized via Synergistic Nanoparticles-Superamphiphiles Effects and Rapid Response to CO2/N2.

A CO2/N2-responsive emulsion provides milder reaction conditions, nontoxicity, and economic feasibility compared to other switchable surfactants. In this study, CO2/N2-responsive pickering emulsions were fabricated by using a compounded dispersion containing SiO2 nanoparticles (NPs) and superamphiphiles as the emulsifying agents. The synergistic effects of the SiO2 NPs and superamphiphiles significantly stabilized the emulsion at all of the tested concentrations and prevented complete phase separation of oil and water. The electrostatic interaction between the SiO2 NPs and superamphiphiles was disrupted after bubbling with CO2 for 30 s, resulting in the breaking of the emulsion. However, the dispersion recovered its interfacial activity after the introduction of N2 and again emulsified the emulsion. This reversible switching behavior was validated through three consecutive cycles of bubbling CO2/N2. The protonation and deprotonation of the SiO2 NPs and superamphiphiles in response to CO2/N2 facilitated reversible assembly and disassembly, which enabled the switching of the emulsions between inactive and active forms. The novel highly stable Pickering emulsions demonstrated rapid demulsification and emulsification in response to CO2/N2 and are promising for a wide range of applications.

HSFAS mediates fibroblast proliferation, migration, trans-differentiation and apoptosis in hypertrophic scars via interacting with ADAMTS8.

Hypertrophic scar (HS) is one of the most common sequelae of patients, especially after burns and trauma. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating HS remain underexplored. Human hypertrophic scar-derived fibroblasts (HSFBs) have been shown to exert more potent promoting effects on extracellular matrix (ECM) accumulation than normal skin-derived fibroblasts (NSFBs) and are associated with enhanced HS formation. The purpose of this study is to search for lncRNAs enriched in HSFBs and investigate their roles and mechanisms. LncRNA MSTRG.59347.16 is one of the most highly expressed lncRNAs in HS detected by lncRNA-seq and qRT-PCR and named as hypertrophic scar fibroblast-associated lncRNA (HSFAS). HSFAS overexpression significantly induces fibroblast proliferation, migration, and myofibroblast trans-differentiation and inhibits apoptosis in HSFBs, while knockdown of HSFAS results in augmented apoptosis and attenuated proliferation, migration, and myofibroblast trans-differentiation of HSFBs. Mechanistically, HSFAS suppresses the expression of A disintegrin and metalloproteinase with thrombospondin motifs 8 (ADAMTS8). ADAMTS8 knockdown rescues downregulated HSFAS-mediated fibroblast proliferation, migration, myofibroblast trans-differentiation and apoptosis. Thus, our findings uncover a previously unknown lncRNA-dependent regulatory pathway for fibroblast function. Targeted intervention in the HSFAS-ADAMTS8 pathway is a potential therapy for HS.

Swimming exercise ameliorates insulin resistance and nonalcoholic fatty liver by negatively regulating PPARγ transcriptional network in mice fed high fat diet.

BACKGROUND: Recent findings elucidated hepatic PPARγ functions as a steatogenic-inducer gene that activates de novo lipogenesis, and is involved in regulation of glucose homeostasis, lipid accumulation, and inflammation response. This study delved into a comprehensive analysis of how PPARγ signaling affects the exercise-induced improvement of insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD), along with its underlying mechanism. METHODS: Chronic and acute swimming exercise intervention were conducted in each group mice. IR status was assessed by GTT and ITT assays. Serum inflammatory cytokines were detected by Elisa assays. PPARγ and its target genes expression were detected by qPCR assay. Relative protein levels were quantified via Western blotting. ChIP-qPCR assays were used to detect the enrichment of PPARγ on its target genes promoter. RESULTS: Through an exploration of a high-fat diet (HFD)-induced IR and NAFLD model, both chronic and acute swimming exercise training led to significant reductions in body weight and visceral fat mass, as well as hepatic lipid accumulation. The exercise interventions also demonstrated a significant amelioration in IR and the inflammatory response. Meanwhile, swimming exercise significantly inhibited PPARγ and its target genes expression induced by HFD, containing CD36, SCD1 and PLIN2. Furthermore, swimming exercise presented significant modulation on regulatory factors of PPARγ expression and transcriptional activity. CONCLUSION: The findings suggest that swimming exercise can improve lipid metabolism in IR and NAFLD, possibly through PPARγ signaling in the liver of mice.

In situ photo-crosslinked hydrogel promotes oral mucosal wound healing through sustained delivery of ginsenoside Rg1.

Oral mucosal wounds exhibit an increased susceptibility to inflammation as a consequence of their direct exposure to a diverse range of microorganisms. This causes pain, slow healing, and other complications that interfere with patients' daily activities like eating and speaking. Consequently, patients experience a significant decline in their overall quality of life. Therefore, the pursuit of novel treatment approaches is of great importance. In this study, ginsenoside Rg1, a natural active substance extracted from ginseng root, was chosen as a therapeutic agent. It was encapsulated in a screened photo-crosslinked hydrogel scaffold for the treatment of mucosal defects in the rat palate. The results demonstrated that Rg1-hydrogel possessed excellent physical and chemical properties, and that oral mucosa wounds treated with Rg1-hydrogel exhibited the greatest healing performance, as evidenced by more pronounced wound re-epithelialization, increased collagen deposition, and decreased inflammatory infiltration. Subsequent investigations in molecular biology confirmed that Rg1-hydrogel stimulated the secretion of repair-related factors and inhibited the secretion of inflammatory factors. This study demonstrated that the hydrogel containing ginsenoside Rg1 significantly promotes oral mucosal tissue healing in vivo. Based on the findings, it can be inferred that the Rg1-hydrogel has promising prospects for the therapeutic management of oral mucosal wounds.

Optimal frequency determination for terahertz technology-based detection of colitis-related cancer in mice.

Colorectal cancer is a prevalent malignancy globally, often linked to chronic colitis. Terahertz technology, with its noninvasive and fingerprint spectroscopic properties, holds promise in disease diagnosis. This study aimed to explore terahertz technology's application in colitis-associated cancer using a mouse model. Mouse colorectal tissues were transformed into paraffin-embedded blocks for histopathological analysis using HE staining. Terahertz transmission spectroscopy was performed on the tissue blocks. By comparing terahertz absorption differences, specific frequency bands were identified as optimal for distinguishing cancerous and normal tissues. The study revealed that terahertz spectroscopy effectively differentiates colitis-related cancers from normal tissues. Remarkably, 1.8 THz emerged as a potential optimal frequency for diagnosing colorectal cancer in mice. This suggests the potential for rapid histopathological diagnosis of colorectal cancer using terahertz technology.

In Situ Construction of Ferrocene-Containing Membrane-Bound Nanofibers for the Redox Control of Cancer Cell Death and Cancer Therapy.

Precise manipulation of cancer cell death by harnessing reactive oxygen species (ROS) is a promising strategy to defeat malignant tumors. However, it is quite difficult to produce active ROS with spatial precision and regulate their biological outcomes. We succeed here in selectively generating short-lived and lipid-reactive hydroxyl radicals (•OH) adjacent to cancer cell membranes, successively eliciting lipid peroxidation and ferroptosis. DiFc-K-pY, a phosphorylated self-assembling precursor that consists of two branched Fc moieties and interacts specifically with epidermal growth factor receptor, can in situ produce membrane-bound nanofibers and enrich ferrocene moieties on cancer cell membranes in response to alkaline phosphatase. Within the acidic tumor microenvironment, DiFc-K-pY nanofibers efficiently convert tumoral H2O2 to active •OH around the target cell membranes via Fenton-like reactions, leading to lipid peroxidation and ferroptosis with good cellular selectivity. Our strategy successfully prevents tumor progression with acceptable biocompatibility through intratumoral administration.

Peroxisome biogenesis initiated by protein phase separation.

Peroxisomes are organelles that carry out ß-oxidation of fatty acids and amino acids. Both rare and prevalent diseases are caused by their dysfunction1. Among disease-causing variant genes are those required for protein transport into peroxisomes. The peroxisomal protein import machinery, which also shares similarities with chloroplasts2, is unique in transporting folded and large, up to 10 nm in diameter, protein complexes into peroxisomes3. Current models postulate a large pore formed by transmembrane proteins4; however, so far, no pore structure has been observed. In the budding yeast Saccharomyces cerevisiae, the minimum transport machinery includes the membrane proteins Pex13 and Pex14 and the cargo-protein-binding transport receptor, Pex5. Here we show that Pex13 undergoes liquid-liquid phase separation (LLPS) with Pex5-cargo. Intrinsically disordered regions in Pex13 and Pex5 resemble those found in nuclear pore complex proteins. Peroxisomal protein import depends on both the number and pattern of aromatic residues in these intrinsically disordered regions, consistent with their roles as 'stickers' in associative polymer models of LLPS5,6. Finally, imaging fluorescence cross-correlation spectroscopy shows that cargo import correlates with transient focusing of GFP-Pex13 and GFP-Pex14 on the peroxisome membrane. Pex13 and Pex14 form foci in distinct time frames, suggesting that they may form channels at different saturating concentrations of Pex5-cargo. Our findings lead us to suggest a model in which LLPS of Pex5-cargo with Pex13 and Pex14 results in transient protein transport channels7.

ICI efficacy information portal: a knowledgebase for responder prediction to immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have led to durable responses in cancer patients, yet their efficacy varies significantly across cancer types and patients. To stratify patients based on their potential clinical benefits, there have been substantial research efforts in identifying biomarkers and computational models that can predict the efficacy of ICIs, and it has become difficult to keep track of all of them. It is also difficult to compare findings of different studies since they involve different cancer types, ICIs, and various other details. To make it easy to access the latest information about ICI efficacy, we have developed a knowledgebase and a corresponding web-based portal (https://iciefficacy.org/). Our knowledgebase systematically records information about latest publications related to ICI efficacy, predictors proposed, and datasets used to test them. All information recorded is checked carefully by a manual curation process. The web-based portal provides functions to browse, search, filter, and sort the information. Digests of method details are provided based on the original descriptions in the publications. Evaluation results of the effectiveness of the predictors reported in the publications are summarized for quick overviews. Overall, our resource provides centralized access to the burst of information produced by the vibrant research on ICI efficacy.

A Cascade-Targeted Enzyme-Instructed Peptide Self-Assembly Strategy for Cancer Immunotherapy through Boosting Immunogenic Cell Death.

Immunogenic cell death (ICD) approaches by encumbering mitochondrial functions provide great promise for the treatment of malignant tumors, but these kinds of ICD strategies are still in their infancy. Here, one multifunctional drug-loaded, cascade-targeted, and enzyme-instructed self-assembling peptide nanomedicine (Comp. 4) for ICD-based cancer therapy is constructed. Comp. 4 consists of 1) lonidamine (LND) that specifically interferes with mitochondrial functions; 2) a programmed death ligand 1 (PD-L1) binding peptide sequence (NTYYEDQG) and a mitochondria-specific motif (triphenylphosphonium, TPP) that can sequentially control the cell membrane and mitochondria targeting capacities, respectively; and 3) a -GD FD FpD Y- assembly core to in situ organize peptide assemblies responsive to alkaline phosphatase (ALP). Comp. 4 demonstrates noticeable structural and morphological transformations in the presence of ALP and produces peptide assemblies in mouse colon cancer cells (CT26) with high expressions of both ALP and PD-L1. Moreover, the presence of PD-L1- and mitochondria-specific motifs can assist Comp. 4 for effective endocytosis and endosomal escape, forming peptide assemblies and delivering LND into mitochondria. Consequently, Comp. 4 shows superior capacities to in vivo induce abundant mitochondrial oxidative stress, provoke robust ICD responses, and produce an immunogenic tumor microenvironment, successfully inhibiting CT26 tumor growth by eliciting a systemic ICD-based antitumor immunity.

Ginsenoside Rg1 alleviates lipopolysaccharide-induced pyroptosis in human periodontal ligament cells via inhibiting Drp1-mediated mitochondrial fission.

OBJECTIVE: The present study aimed to investigate whether Ginsenoside Rg1 alleviated lipopolysaccharide (LPS) - induced pyroptosis of human periodontal ligament cells (HPDLCs) and further explore the underlying mechanism. DESIGN: Cell viability was detected using the CCK-8 assay. Proinflammatory cytokine secretion and lactate dehydrogenase release were examined by ELISA. Flow cytometry analysis was conducted to determine the pyroptosis ratio, and ATP production was estimated using the ATP assay kit. Fluorescence staining was utilized to visualize mitochondrial morphology and analyze mitochondrial reactive oxygen species (mtROS), and the mitochondrial membrane potential level. Western blot and qRT-PCR were used to determine the expression of signaling pathway-related proteins and mRNA, respectively. RESULTS: The results discovered that Ginsenoside Rg1 treatment enhanced cell viability in comparison to LPS stimulation, attenuated pyroptosis in HPDLCs, and reduced the release of lactate dehydrogenase, IL-1ß, and IL-18 significantly. Additionally, we found that Ginsenoside Rg1 upregulated ATP content and mitochondrial membrane potential level while reducing aberrant mitochondrial fission and mtROS production. Mechanistically, we found that Ginsenoside Rg1 upregulated dynamin-related protein 1 (Drp1) phosphorylation at Ser 637 in an AMP-activated protein kinase (AMPK)-dependent manner, and reduced pyroptosis-related proteins expression, including NLRP3, ASC, Caspase-1, and GSDMD-NT. CONCLUSIONS: These findings demonstrate that Ginsenoside Rg1 treatment attenuates LPS-induced pyroptosis and inflammation damage in HPDLCs, which may connect to the activation of the AMPK/Drp1/NLRP3 signaling pathway. Moreover, the results offer a potential theoretical foundation for applying Ginsenoside Rg1 in inflammatory diseases such as periodontitis.