Ameliorative effect of total ginsenosides from heat-treated fresh ginseng against cyclophosphamide-induced liver injury in mice.

This study evaluated the effect of heat treatment on the conversion of ginsenoside and the ameliorative effect of heat-treated total ginsenoside (HG) from fresh ginseng on cyclophosphamide (CTX)-induced liver injury. LC-MS analysis revealed that the content of rare ginsenosides increased markedly after heat treatment. HG significantly attenuated CTX-induced hepatic histopathological injury in mice. Western blotting analysis showed that untreated total ginsenoside (UG) and HG regulated the Nrf2/HO-1 and TLR4/MAPK pathways. Importantly, these results may be relevant to the modulation of the intestinal flora. UG and HG significantly increased the short-chain fatty acids (SCFAs)-producing bacteria Lactobacillus and reduced the LPS-producing bacteria Bacteroides and Parabacteroides. These changes in intestinal flora affected the levels of TNF-α, LPS and SCFAs. In short, UG and HG alleviated CTX-induced liver injury by regulating the intestinal flora and the LPS-TLR4-MAPK pathway, and HG was more effective. HG has the potential to be a functional food that can alleviate chemical liver injury.

Energy metabolism analysis of exogenous glutamate on promoting co-accumulation of astaxanthin yield and biomass in Phaffia rhodozyma D3.

Effective metabolic regulators play an essential role in regulating astaxanthin biosynthesis in Phaffia rhodozyma. In this study, it was found that 5 mM glutamate increased the astaxanthin yield and biomass of P. rhodozyma D3 to 22.34 mg/L and 6.12 g/L, which were 1.22 and 1.33 times higher than the control group, respectively. Meanwhile, glucose uptake was increased and the level of reactive oxygen species (ROS) was reduced with 5 mM glutamate. To further explore the interrelationship between glutamate and astaxanthin synthesis, the energy metabolism of P. rhodozyma D3 with and without glutamate was analysed. Glutamate promoted the Embden-Meyerhof-Parnas pathway (EMP) metabolic flux, modulated the tricarboxylic acid (TCA) cycle and the pentose phosphate pathway (PPP), activated the ornithine cycle and purine metabolism, and provided more ATP and NADPH for astaxanthin accumulation. This study clarified the possible mechanism by which glutamate promoted astaxanthin accumulation in P. rhodozyma.

Physicochemical properties and in vitro digestibility of ginseng starches under citric acid-autoclaving treatment.

In this study, the effects of citric acid-autoclaving (CA-A) treatment on physicochemical and digestive properties of the native ginseng starches were investigated. The results showed that ginseng starch exhibited a B-type crystal structure with a low onset pasting temperature of 44.23 ± 0.80 °C, but high peak viscosity and setback viscosity of 5897.34 ± 53.72 cP and 692.00 ± 32.36 cP, respectively. The granular morphology, crystal and short-range ordered structure of ginseng starches were destroyed after CA-A treatment. The more short-chain starches were produced, resulting in the ginseng starches solubility increased. In addition, autoclaving, citric acid (CA) and CA-A treatment promoted polymerization and recrystallization of starch molecules, increased the proportion of amylopectin B1, and B3 chains, and improved molecular weight and resistant starch (RS) content of ginseng starches. The most significant multi-scale structural change was induced by CA-A treatment, which reduced the relative crystallinity of ginseng starch from 28.26 ± 0.24 % to 2.75 ± 0.08 %, and increased the content of RS to 54.30 ± 0.14 %. These findings provided a better understanding of the structure and properties of Chinese ginseng starches and offered new ideas for the deep processing of ginseng foods.

Ginseng Glucosyl Oleanolate from Ginsenoside Ro, Exhibited Anti-Liver Cancer Activities via MAPKs and Gut Microbiota In Vitro/Vivo.

Ginseng is widely recognized for its diverse health benefits and serves as a functional food ingredient with global popularity. Ginsenosides with a broad range of pharmacological effects are the most crucial active ingredients in ginseng. This study aimed to derive ginseng glucosyl oleanolate (GGO) from ginsenoside Ro through enzymatic conversion and evaluate its impact on liver cancer in vitro and in vivo. GGO exhibited concentration-dependent HepG2 cell death and markedly inhibited cell proliferation via the MAPK signaling pathway. It also attenuated tumor growth in immunocompromised mice undergoing heterograft transplantation. Furthermore, GGO intervention caused a modulation of gut microbiota composition by specific bacterial populations, including Lactobacillus, Bacteroides, Clostridium, Enterococcus, etc., and ameliorated SCFA metabolism and colonic inflammation. These findings offer promising evidence for the potential use of GGO as a natural functional food ingredient in the prevention and treatment of cancer.

Prevention of High-Fat-Diet-Induced Dyslipidemia by Lactobacillus plantarum LP104 through Mediating Bile Acid Enterohepatic Axis Circulation and Intestinal Flora.

This work aimed to investigate the alleviative mechanism of Lactobacillus plantarum LP104 (LP104) isolated from kimchi on high-fat-diet-induced dyslipidemia by targeting the intestinal flora and bile acid (BA) metabolism. Oral administration of LP104 over 8 weeks reduced body weight gain and body fat, as well as ameliorating serum and hepatic dyslipidemia in HFD-fed C57BL/6N mice significantly. LP104 intervention also increased the ileal tauro-α/ß-muricholic acid sodium salt (T-α-MCA or T-ß-MCA) and tauroursodeoxycholic acid (TUDCA) concentrations to suppress the enterohepatic farnesoid X receptor/fibroblast growth factor 15-fibroblast growth factor receptor 4 (FXR/FGF15-FGFR4) signaling pathway, which stimulated the hepatic cholic acid (CA) and chenodeoxycholic acid (CDCA) de novo synthesis through using cholesterol. Then, LP104 treatment accelerated BA excretion with the feces and cholesterol efflux to improve HFD-caused hyperlipidemia effectively. The 16S rRNA gene high-throughput sequencing revealed that LP104 promoted intestinal flora rebalance by increasing the abundances of Bacteroides, Akkermansia, Lactobacillus, and Clostridium and decreasing the abundance of Oscillospira and Coprococcus. Meanwhile, Spearman correlation analysis demonstrated that the differential flora were closely related to BA signaling molecules including CA, CDCA, T-α-MCA, T-ß-MCA, and TUDCA after LP104 intervention. These findings provided new evidence that LP104 had the potential to be used as a naturally functional food for the prevention of dyslipidemia.

Multi-Parametric Exploration of a Selection of Piezoceramic Materials for Bone Graft Substitute Applications.

This work was devoted to the first multi-parametric unitary comparative analysis of a selection of sintered piezoceramic materials synthesised by solid-state reactions, aiming to delineate the most promising biocompatible piezoelectric material, to be further implemented into macro-porous ceramic scaffolds fabricated by 3D printing technologies. The piezoceramics under scrutiny were: KNbO3, LiNbO3, LiTaO3, BaTiO3, Zr-doped BaTiO3, and the (Ba0.85Ca0.15)(Ti0.9Zr0.1)O3 solid solution (BCTZ). The XRD analysis revealed the high crystallinity of all sintered ceramics, while the best densification was achieved for the BaTiO3-based materials via conventional sintering. Conjunctively, BCTZ yielded the best combination of functional properties-piezoelectric response (in terms of longitudinal piezoelectric constant and planar electromechanical coupling factor) and mechanical and in vitro osteoblast cell compatibility. The selected piezoceramic was further used as a base material for the robocasting fabrication of 3D macro-porous scaffolds (porosity of ~50%), which yielded a promising compressive strength of ~20 MPa (higher than that of trabecular bone), excellent cell colonization capability, and noteworthy cytocompatibility in osteoblast cell cultures, analogous to the biological control. Thereby, good prospects for the possible development of a new generation of synthetic bone graft substitutes endowed with the piezoelectric effect as a stimulus for the enhancement of osteogenic capacity were settled.

High-Performance Lithium Metal Batteries Enabled by a Fluorinated Cyclic Ether with a Low Reduction Potential.

Electrolyte engineering is crucial for developing high-performance lithium metal batteries (LMB). Here, we synthesized two cosolvents methyl bis(fluorosulfonyl)imide (MFSI) and 3,3,4,4-tetrafluorotetrahydrofuran (TFF) with significantly different reduction potentials and add them into LiFSI-DME electrolytes. The LiFSI/TFF-DME electrolyte gave an average Li Coulombic efficiency (CE) of 99.41 % over 200 cycles, while the average Li CEs for MFSI-based electrolyte is only 98.62 %. Additionally, the TFF-based electrolytes exhibited a more reversible performance than the state-of-the-art fluorinated 1,4-dimethoxylbutane electrolyte in both Li||Cu half-cell and anode-free Cu||LiNi0.8 Mn0.1 Co0.1 O2 full cell. More importantly, the decomposition product from bis(fluorosulfonyl)imide anion could react with ether solvent, which destroyed the SEI, thus decreasing cell performance. These key discoveries provide new insights into the rational design of electrolyte solvents and cosolvents for LMB.

A methodological framework for assessing pastoral socio-ecological system vulnerability: A case study of Altay Prefecture in Central Asia.

Vulnerability analysis is important for enhancing sustainability, especially for highly interlinked pastoral socio-ecological systems. This study presents a modified methodological framework for assessing the vulnerability of pastoral socio-ecological systems based on the interactions between social and ecological subsystems and their vulnerabilities. Altay Prefecture (Northwest China), a typical pastoral area located in Central Asia, was chosen for the case study. The ecological vulnerability index (EVI) and socio-ecological vulnerability index (SEVI) of Altay Prefecture from 2001 to 2018 were assessed and classified into five levels. The results showed that the distribution pattern of EVI was spatially heterogeneous, with EVI increasing from north to south and from west to east. The EVI was high in low-altitude deserts, decreased with altitude rising from 1300 m to 2200 m, and increased when the altitude exceeded 2200 m. The average EVI increased from 2001 to 2010 and decreased from 2010 to 2018, with the highest EVI in 2010 and the lowest in 2018. The SEVI of western counties was lower than that of eastern counties; the SEVI of all counties continuously decreased from 2001 to 2018, with a higher rate from 2010 to 2018. Social adaptive capacity, increased by the policies that aim at protecting grasslands and improving livelihoods, was the main influencing factor of the SEVI dynamic. These results will help to identify key areas with high EVI for grassland ecosystem management and strengthen the adaptive capacity for addressing vulnerability. Furthermore, the presented methodological framework can be adopted in vulnerability assessments of similar pastoral areas or natural resource-based socio-ecological systems.

Metabolite analysis of soybean oil on promoting astaxanthin production of Phaffia rhodozyma.

BACKGROUND: Astaxanthin is a carotenoid with strong antioxidant property. In addition, it has anti-cancer, anti-tumor, anti-inflammatory and many other functions. The micro-organisms that mainly produce astaxanthin are Haematococcus pluvialis and Phaffia rhodozyma. Compared with H. pluvialis, P. rhodozyma has shorter fermentation cycle and easier to control culture conditions, but the yield of astaxanthin in P. rhodozyma is low. This article studied how to improve the astaxanthin production of P. rhodozyma. RESULTS: The results showed that when 10 mL L-1 soybean oil was added to the culture medium, astaxanthin production increased significantly, reaching 7.35 mg L-1 , which was 1.4 times that of the control group, and lycopene and ß-carotene contents also increased significantly. Through targeted metabolite analysis, the fatty acids in P. rhodozyma significantly increased under the soybean oil stimulation, especially the fatty acids closely related to the formation of astaxanthin esters, included palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1n9), linoleic acid (C18:2n6), α-linolenic acid (C18:3n3) and γ-linolenic acid (C18:3n6), thereby increasing the astaxanthin esters content. CONCLUSION: It showed that the addition of soybean oil can promote the accumulation of astaxanthin by promoting the increase of astaxanthin ester content. © 2022 Society of Chemical Industry.

Optimization of culture medium and scale-up production of astaxanthin using corn steep liquor as substrate by response surface methodology.

Astaxanthin is a natural carotenoid with strong antioxidant activity. In this paper, the effects of carbon source, corn steep liquor, distiller grains, and initial pH on the growth and astaxanthin production of Phaffia rhodozyma D3 were evaluated. The optimal medium composition was 32 g/L glucose, 12 g/L corn steep liquor as nitrogen source, and the initial pH was 6.7. Phaffia rhodozyma D3 was cultured in a shake flask under these optimized conditions, the biomass was 6.47 g/L, the astaxanthin/OD475 was 15.16, and the astaxanthin content was 1.41 mg/g. The astaxanthin content was further increased to 4.70 mg/g by the combination of TiO2 stimulation and the expanding cultivation of P. rhodozyma D3 in a 5 L fermenter, which was 2.81 times that of the control group. Expanding fermentation implies the possibility of large-scale production in the astaxanthin industry. Corn steep liquor was used as an alternative nitrogen source to culture P. rhodozyma D3, which could both reduce the production cost of astaxanthin and increased the by-products utilization rate.

The ameliorative effect of probiotics on diet-induced lipid metabolism disorders: A review.

High-fat diet induces lipid metabolism disorders that has become one of the grievous public health problems and imposes a serious economic and social burden worldwide. Safety probiotics isolated from nature are regarded as a novel supplementary strategy for preventing and improving diet-induced lipid metabolism disorders and related chronic diseases. The present review summarized the latest researches of probiotics in high fat diet induced lipid metabolism disorders to provide a critical perspective on the regulatory function of probiotics for future research. Furthermore, the screening criteria and general sources of probiotics with lipid-lowering ability also outlined to enlarge microbial species resource bank instantly, which promoted the development of functional foods with lipid-lowering strains from nature. After critically reviewing the lipid-lowering potential of probiotics both in vitro and in vivo and even in clinical data of humans, we provided a perspective that probiotics activated AMPK signaling pathway to regulate fat synthesis and decomposition, as well as affected positively the gut microbiota structure, intestinal barrier function and systemic inflammatory response, then these beneficial effects are amplified along Gut-liver axis, which regulated intestinal flora metabolites such as SCFAs and BAs by HMGCR/FXR/SHP signaling pathway to improve high fat diet induced lipid metabolism disorders effectively.

Remarkable impact of commercial sterilizing on ginsenosides transformation in fresh ginseng pulp based on widely targeted metabolomics analysis.

Terpenoids such as ginsenosides are the most important phytochemicals and functional components in ginseng. Commercial sterilizing with high temperature and high pressure is also one of the common methods of ginseng food processing. However, the changes of terpenoids in fresh ginsengs commercially sterilized are unclear. In this study, fresh ginseng pulp (FGP) was commercially sterilized at 121℃ for 30 min, and terpenoid compounds were analyzed by widely targeted metabolomics based on UPLC-ESI-MS/MS system. The commercial sterilization induced the changes of 88 terpenoid compounds including 30 types of ginsenosides, and many minor ginsenoside Rh4, Rg6, Rk2, F4, Rs3, Rk3, Rk1, Rg5, Rg3, Rg4 were remarkably increased in fresh ginseng pulp. Importantly, the ginsenoside ST3 was detected and F4, Rg3, and Rg5 were also found in fresh ginseng pulp. Commercial sterilizing at 121℃ for 30 min will remarkably affect the species and number of ginsenosides in ginseng food.

Super-Reversible CuF2 Cathodes Enabled by Cu2+ -Coordinated Alginate.

Copper fluoride (CuF2 ) has the highest energy density among all metal fluoride cathodes owing to its high theoretical potential (3.55 V) and high capacity (528 mAh g-1 ). However, CuF2  can only survive for less than five cycles, mainly due to serious Cu-ion dissolution during charge/discharge cycles. Herein, copper dissolution is successfully suppressed by forming Cu2+ -coordinated sodium alginate (Cu-SA) on the surface of CuF2  particles during the electrode fabrication process, by using water as a slurry solvent and sodium alginate (SA) as a binder. The trace dissolved Cu2+ in water from CuF2  can in situ cross-link with SA binder forming a conformal Cu-SA layer on CuF2  surface. After water evaporation during the electrode dry process, the Cu-SA layer is Li-ion conductor but Cu2+ insulator, which can effectively suppress the dissolution of Cu-ions in the organic 4 m LiClO4 /ethylene carbonate/propylene carbonate electrolyte, enhancing the reversibility of CuF2 . CuF2  electrode with SA binder delivers a reversible capacity of 420.4 mAh g-1  after 50 cycles at 0.05 C, reaching an energy density of 1009.1 Wh kg-1 . Cu2+ cross-link polymer coating on CuF2  opens the door for stabilizing the high-energy and low-cost CuF2  cathode for next-generation Li-ion batteries.

Ameliorative effect of Lactobacillus plantarum Lp2 against cyclophosphamide-induced liver injury in mice.

Cyclophosphamide (CTX) is a widely used anticancer drug that can cause liver injury, but there is no effective treatment available at present. The antioxidant properties of Lactobacillus plantarum Lp2 in vitro and its effect on CTX-induced liver injury in mice were investigated thoroughly. The order of antioxidant capacity of the fermentate of Lp2 was as followed: fermented supernatant > cell-free extract > intact cell. BALB/c mice were intraperitoneally injected with 80 mg/kg BW/d CTX for 3 days to build a liver injury model, then treated with Lp2 fermented supernatant (Lp2-s) and Lp2 culture broth (Lp2). After 10 days, the indicators of oxidative stress and liver injury were measured. Both Lp2-s and Lp2 restored the levels of T-SOD, CAT, GSH-Px, MDA, GSH, ALT, and AST. The western blotting results showed that Lp2-s and Lp2 ameliorated CTX-induced oxidative damage and hepatocyte apoptosis via inhibiting MAPKs pathway and strengthening Nrf2/HO-1/NQO1 antioxidant defense system, thus inhibiting the mitochondrial-mediated apoptosis pathway. Therefore, both Lp2-s and Lp2 had similar protective effects on CTX-induced liver injury.

Sr and Mg Doped Bi-Phasic Calcium Phosphate Macroporous Bone Graft Substitutes Fabricated by Robocasting: A Structural and Cytocompatibility Assessment.

Bi-phasic calcium phosphates (BCPs) are considered prominent candidate materials for the fabrication of bone graft substitutes. Currently, supplemental cation-doping is suggested as a powerful path to boost biofunctionality, however, there is still a lack of knowledge on the structural role of such substituents in BCPs, which in turn, could influence the intensity and extent of the biological effects. In this work, pure and Mg- and Sr-doped BCP scaffolds were fabricated by robocasting from hydrothermally synthesized powders, and then preliminarily tested in vitro and thoroughly investigated physically and chemically. Collectively, the osteoblast cell culture assays indicated that all types of BCP scaffolds (pure, Sr- or Sr-Mg-doped) delivered in vitro performances similar to the biological control, with emphasis on the Sr-Mg-doped ones. An important result was that double Mg-Sr doping obtained the ceramic with the highest ß-tricalcium phosphate (ß-TCP)/hydroxyapatite mass concentration ratio of ~1.8. Remarkably, Mg and Sr were found to be predominantly incorporated in the ß-TCP lattice. These findings could be important for the future development of BCP-based bone graft substitutes since the higher dissolution rate of ß-TCP enables an easier release of the therapeutic ions. This may pave the road toward medical devices with more predictable in vivo performance.

Salt-in-Salt Reinforced Carbonate Electrolyte for Li Metal Batteries.

The instability of carbonate electrolyte with metallic Li greatly limits its application in high-voltage Li metal batteries. Here, a "salt-in-salt" strategy is applied to boost the LiNO3 solubility in the carbonate electrolyte with Mg(TFSI)2 carrier, which enables the inorganic-rich solid electrolyte interphase (SEI) for excellent Li metal anode performance and also maintains the cathode stability. In the designed electrolyte, both NO3 - and PF6 - anions participate in the Li+ -solvent complexes, thus promoting the formation of inorganic-rich SEI. Our designed electrolyte has achieved a superior Li CE of 99.7 %, enabling the high-loading NCM811||Li (4.5 mAh cm-2 ) full cell with N/P ratio of 1.92 to achieve 84.6 % capacity retention after 200 cycles. The enhancement of LiNO3 solubility by divalent salts is universal, which will also inspire the electrolyte design for other metal batteries.

The effect of Lactobacillus rhamnosus B10 on alcoholic liver injury and intestinal microbiota in alcohol-induced mice model.

Lactobacillus rhamnosus B10 (L. rhamnosus B10) isolated from the baby feces was given to an alcohol mice model, aiming to investigate the effects of L. rhamnosus B10 on alcoholic liver injury by regulating intestinal microbiota. C57BL/6N mice were fed with liquid diet Lieber-DeCarli with or without 5% (v/v) ethanol for 8 weeks, and treated with L. rhamnosus B10 at the last 2 weeks. The results showed that L. rhamnosus B10 decreased the serum total cholesterol (1.48 mmol/L), triglycerides (0.97 mmol/L), alanine aminotransferase (26.4 U/L), aspartate aminotransferase (14.2 U/L), lipopolysaccharide (0.23 EU/mL), and tumor necrosis factor-α (138 pg/mL). In addition, L. rhamnosus B10 also reduced the liver triglycerides (1.02 mmol/g prot), alanine aminotransferase (17.8 mmol/g prot) and aspartate aminotransferase (12.5 mmol/g prot) in alcohol mice, thereby ameliorating alcohol-induced liver injury. The changes of intestinal microbiota composition on class, family and genus level in cecum were analyzed. The intestinal symbiotic abundance of Firmicutes was elevated while gram-negative bacteria Proteobacteria and Deferribacteres was decreased in alcohol mice treated with L. rhamnosus B10 for 2 weeks. In summary, this study provided evidence for the therapeutic effects of probiotics on alcoholic liver injury by regulating intestinal flora.

Enhancing Li+ Transport in NMC811||Graphite Lithium-Ion Batteries at Low Temperatures by Using Low-Polarity-Solvent Electrolytes.

LiNix Coy Mnz O2 (x+y+z=1)||graphite lithium-ion battery (LIB) chemistry promises practical applications. However, its low-temperature (≤ -20 °C) performance is poor because the increased resistance encountered by Li+ transport in and across the bulk electrolytes and the electrolyte/electrode interphases induces capacity loss and battery failures. Though tremendous efforts have been made, there is still no effective way to reduce the charge transfer resistance (Rct ) which dominates low-temperature LIBs performance. Herein, we propose a strategy of using low-polarity-solvent electrolytes which have weak interactions between the solvents and the Li+ to reduce Rct , achieving facile Li+ transport at sub-zero temperatures. The exemplary electrolyte enables LiNi0.8 Mn0.1 Co0.1 O2 ||graphite cells to deliver a capacity of ≈113 mAh g-1 (98 % full-cell capacity) at 25 °C and to remain 82 % of their room-temperature capacity at -20 °C without lithium plating at 1/3C. They also retain 84 % of their capacity at -30 °C and 78 % of their capacity at -40 °C and show stable cycling at 50 °C.

Antioxidant Mechanism of Lactiplantibacillus plantarum KM1 Under H2O2 Stress by Proteomics Analysis.

Lactiplantibacillus plantarum KM1 was screened from natural fermented products, which had probiotic properties and antioxidant function. The survival rate of L. plantarum KM1 was 78.26% at 5 mM H2O2. In this study, the antioxidant mechanism of L. plantarum KM1 was deeply analyzed by using the proteomics method. The results demonstrated that a total of 112 differentially expressed proteins (DEPs) were screened, of which, 31 DEPs were upregulated and 81 were downregulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that DEPs participated in various metabolic pathways such as pyruvate metabolism, carbon metabolism, trichloroacetic acid cycle, amino acid metabolism, and microbial metabolism in diverse environments. These metabolic pathways were related to oxidative stress caused by H2O2 in L. plantarum KM1. Therefore, the antioxidant mechanism of L. plantarum KM1 under H2O2 stress provided a theoretical basis for its use as a potential natural antioxidant.

Elaidic acid induced NLRP3 inflammasome activation via ERS-MAPK signaling pathways in Kupffer cells.

Trans fatty acids (TFA) in food can cause liver inflammation. Activation of NOD-like receptor protein-3 (NLRP3) inflammasome is a key factor in the regulation of inflammation. Accumulating evidence suggests that ERS-induced NLRP3 inflammasome activation underlies the pathological basis of various inflammatory diseases, but the precise mechanism has not been fully elucidated. Therefore, this paper focused on TFA, represented by elaidic acid (EA), to investigate the mechanism of liver inflammation. Levels of mRNA and protein were detected by RT-qPCR and Western blotting, the release of proinflammatory cytokines was measured by ELISA, and intracellular Ca2+ levels were determined by flow cytometer using Fluo 4-AM fluorescent probes. Our research indicated that EA induced the endoplasmic reticulum stress (ERS) response in Kupffer cells (KCs), accompanied by the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which resulted in NLRP3 inflammasome formation, and eventually increased the release of inflammatory factors. NLRP3 inflammasome activation was inhibited when KCs were pretreated with ERS inhibitors (4-PBA) and MAPK selective inhibitors. Furthermore, when ERS was blocked, the MAPK pathway was inhibited.