First report of plastic and non-plastic microparticles in stomach of slandertail lanternshark and shortspine spurdog from the edge of East China Sea.

This study investigates the presence of plastic and non-plastic microparticles in the gastrointestinal tracts of two deep-sea sharks, Etmopterus molleri (n = 118) and Squalus mitsukurii (n = 6), bycatch from the East China Sea continental shelf. We found a total of 117 microparticles, predominantly fibres (67.52 %), with blue (31.62 %) and black (23.94 %) being the most prevalent colours. E. molleri contained 70 microparticles (0.63 ± 0.93 items/shark), 61.42 % non-plastics like viscose and cotton, while plastics included polyethylene, polyethylene terephthalate, and acrylic. Despite S. mitsukurii's limited sample size, the results show that it takes in a lot of microparticles (47 microparticles, 7.83 ± 2.64 items/shark), 57.44 % non-plastics (viscose, cotton, and ethyl cellulose), and 42.56 % plastics. A positive correlation between microparticle presence and total length was observed for E. molleri. These results provide initial data on microparticle ingestion by these species, highlighting potential ecological risks and trophic transfer implications in deep-sea ecosystems.

Polarization-insensitive and high-efficiency edge coupler for thin-film lithium niobate.

In this Letter, we propose and demonstrate a fiber-to-chip edge coupler (EC) on an x-cut thin film lithium niobate (TFLN) for polarization-insensitive (PI) coupling. The EC consists of three width-tapered full-etched waveguides with silica cladding and matches well with a single-mode fiber (SMF). The measured results show that the minimum coupling losses for TE0/TM0 modes remain to be 0.9 dB/1.1 dB per facet, and the polarization dependent loss (PDL) is <0.5 dB over the wavelength range from 1260 to 1340 nm. Moreover, the EC features large misalignment tolerance of ±2 µm in the Z direction and ±1.5 µm in the X direction for both polarizations for a 1 dB penalty. To the best of our knowledge, this is the first realized O-band edge coupler on TFLN with SMF. The proposed device shows promising potential for integration into TFLN polarization diversity devices.

SNRPB promotes the progression of hepatocellular carcinoma via regulating cell cycle, oxidative stress, and ferroptosis.

Small Nuclear Ribonucleoprotein Polypeptides B and B1 (SNRPB) have been linked to multiple human cancers. However, the mechanism of SNRPB in hepatocellular carcinoma (HCC) and whether SNRPB has a synergistic effect with sorafenib in the treatment of HCC remain unclear. In this study, bioinformatic analysis found that SNRPB was an independent prognostic factor for HCC that exerted a critical effect on the progression of HCC. SNRPB was linked with immune checkpoints, cell cycle, oxidative stress and ferroptosis in HCC. Single cell sequencing analysis found that HCC cell subset with high expression of SNRPB, accounted for a higher proportion in HCC cells with higher stages, had higher expression levels of the genes which promote cell cycle, inhibit oxidative stress and ferroptosis, and had higher cell cycle score, lower oxidative stress score and ferroptosis score. Single-sample gene set enrichment analysis (ssGSEA) analysis found that 17 oxidative stress pathways and 68 oxidative stress-ferroptosis related genes were significantly correlated with SNRPB risk scores. SNRPB knockdown induced cell cycle G2/M arrest and restrained cell proliferation, while downregulated the expression of CDK1, CDK4, and CyclinB1. The combined treatment (SNRPB knockdown+sorafenib) significantly inhibited tumor growth. In addition, the expression of SLC7A11, which is closely-related to ferroptosis, decreased significantly in vitro and in vivo. Therefore, SNRPB may promote HCC progression by regulating immune checkpoints, cell cycle, oxidative stress and ferroptosis, while its downregulation inhibits cell proliferation, which enhances the therapeutic effect of sorafenib, providing a novel basis for the development of HCC therapies.

Identification and validation of methylation-CpG prognostic signature for prognosis of hepatocellular carcinoma.

Epigenetic biomarkers help predict the prognosis of cancer patients and evaluating the clinical outcome of immunization therapy. In this study, we present a personalized gene methylation-CpG signature to enhance the accuracy of survival prediction for individuals with hepatocellular carcinoma (HCC). Utilizing RNA sequencing and methylation datasets from GEO as well as TCGA, we conducted single sample GSEA (ssGSEA), WGCNA, as well as Cox regression. Through these analyses, we identified 175 oxidative stress and immune-related genes along with 4 CpG loci that are associated with the prognosis of HCC. Subsequently, we constructed a prognostic signature for HCC utilizing these 4 CpG sites, referred to as the HCC Prognostic Signature of Methylation-CpG sites (HPSM). Further investigation revealed an enrichment of immune-related signal pathways in the HPSM-low group, which demonstrated a positive correlation with better survival among HCC patients. Moreover, the methylation of the CpG sites in HPSM was found to be closely linked to drug sensitivity. In vitro experiments tentatively confirmed that promoter methylation regulated the expression of BMPER, one of the CpG sites within HPSM. The expression of BMPER was significantly correlated with cell death in the oxidative stress pathway, and overexpression of BMPER effectively inhibited HCC cell proliferation. Consequently, our findings suggest that HPSM is an independent predictive factor and holds promise for accurately predicting the prognosis of HCC patients.

Lipid-extracted muscle and liver tissues: Can they reveal mercury exposure of pelagic sharks?

Pelagic sharks are apex predators in oceanic ecosystems and tend to accumulate high amounts of mercury (Hg). The conventional method for assessing Hg exposure in sharks involves analyzing tissue samples without any chemical treatment. However, a substantial number of chemically treated tissue samples are still being preserved in laboratories or museums. It is critical to maximize the utilization of existing samples to reduce the need for additional sampling of pelagic sharks, especially endangered species. Lipid extraction is a widely employed pretreatment process for carbon isotope analysis in shark trophic ecology, while its impact on Hg quantification remains uncertain. Here, we evaluated the feasibility of using lipid-free muscle and liver tissues for investigation of Hg exposure in four endangered pelagic sharks inhabiting the eastern Pacific, including bigeye thresher (Alopias superciliosus), pelagic thresher (A. pelagicus), blue shark (Prionace glauca) and silky shark (Carcharhinus falciformis). Results showed that total Hg concentrations (THg) differed between untreated (THgbulk) and lipid-free (THglipid-free) samples for each tissue type of each species. In addition, dichloromethane-methanol extractions significantly altered the amount of Hg. This may result from the removal of lipoprotein compounds that vary between tissues and species. The THgbulk can be calculated by THglipid-free using the following formulas, THgbulk = 1.14 × THglipid-free + 0.30 and THgbulk = 0.33 × THglipid-free + 0.18, for muscle and liver tissues, respectively. These findings emphasize the applications of lipid-free tissues in THg analysis. This study may have important implications for improving evaluation of Hg exposure in endangered pelagic sharks.

LPS combined with CD47mAb enhances the anti­osteosarcoma ability of macrophages.

Macrophages are abundant in tumor tissues, and they affect the biological properties of tumor cells. The present findings indicated that osteosarcoma (OS) has a high proportion of tumor-promoting M2 macrophages. The CD47 protein can aid tumor cells in their immunological escape. It was identified that CD47 protein is abundant in both clinical OS tissues and OS cell lines. Lipopolysaccharide (LPS) is an activator of Toll-like receptor 4 present on the surface of macrophages, and it induces the polarization towards a pro-inflammatory phenotype; and macrophages of pro-inflammatory phenotype may present antitumor potential. CD47 monoclonal antibody (CD47mAb) can block the CD47-SIRPα signaling pathway, thus enhancing the antitumor ability of macrophages. Immunofluorescence staining confirmed that OS was rich in CD47 protein and M2 macrophages. In the present study, the antitumor potential of macrophages activated using LPS combined with the CD47mAb was assessed. LPS combined with CD47mAb greatly improved macrophages' capacity to phagocytize OS cells, according to the laser confocal experiments and flow cytometry. Furthermore, cell proliferation analysis, cell migration assay and apoptosis determination confirmed LPS-polarized macrophages might efficiently suppress OS cells growth and migration while promoting apoptosis. Taken together, the results of present study demonstrated that LPS combined with CD47mAb enhanced the anti-osteosarcoma ability of macrophages.

Assessment of the induced effect of selected iron hydroxysulfates biosynthesized using Acidithiobacillus ferrooxidans for biomineralization of acid mine drainage.

Soluble iron and sulfate in acid mine drainage (AMD) can be greatly removed through the formation of minerals facilitated by seed crystals. However, the difference in the effects of jarosite and schwertmannite as endogenous seed crystals to induce AMD mineralization remains unclear. This paper intends to study the effect of Fe2+ oxidation and Fe3+ mineralization in the biosynthesis of minerals using different addition amounts and methods of jarosite or schwertmannite. The results showed that the addition amount and method of different seed crystals had no effect on the Fe2+ bio-oxidation but would change the Fe3+ mineralization efficiency. With the same amount of seed crystals added, jarosite exhibited a higher capacity to promote Fe3+ mineralization than schwertmannite. Adding seed crystals before the initiation of Fe2+ oxidation (0 h) could significantly promote Fe3+ mineralization efficiency. With the increase of seed crystals, jarosite could not only shorten the time required for mineral synthesis but also improve the final mineral yield, whereas schwertmannite could only shorten the time required for mineral synthesis. When Fe2+ was completely oxidized to Fe3+ (48 h), the supplementary of jarosite could still effectively improve Fe3+ mineralization efficiency, but the addition of schwertmannite no longer affected the final mineralization degree.

Blocking Dectin-1 prevents colorectal tumorigenesis by suppressing prostaglandin E2 production in myeloid-derived suppressor cells and enhancing IL-22 binding protein expression.

Dectin-1 (gene Clec7a), a receptor for ß-glucans, plays important roles in the host defense against fungi and immune homeostasis of the intestine. Although this molecule is also suggested to be involved in the regulation of tumorigenesis, the role in intestinal tumor development remains to be elucidated. In this study, we find that azoxymethane-dextran-sodium-sulfate-induced and ApcMin-induced intestinal tumorigenesis are suppressed in Clec7a-/- mice independently from commensal microbiota. Dectin-1 is preferentially expressed on myeloid-derived suppressor cells (MDSCs). In the Clec7a-/- mouse colon, the proportion of MDSCs and MDSC-derived prostaglandin E2 (PGE2) levels are reduced, while the expression of IL-22 binding protein (IL-22BP; gene Il22ra2) is upregulated. Dectin-1 signaling induces PGE2-synthesizing enzymes and PGE2 suppresses Il22ra2 expression in vitro and in vivo. Administration of short chain ß-glucan laminarin, an antagonist of Dectin-1, suppresses the development of mouse colorectal tumors. Furthermore, in patients with colorectal cancer (CRC), the expression of CLEC7A is also observed in MDSCs and correlated with the death rate and tumor severity. Dectin-1 signaling upregulates PGE2-synthesizing enzyme expression and PGE2 suppresses IL22RA2 expression in human CRC-infiltrating cells. These observations indicate a role of the Dectin-1-PGE2-IL-22BP axis in regulating intestinal tumorigenesis, suggesting Dectin-1 as a potential target for CRC therapy.

A cuproptosis-related signature for predicting the prognosis of gastric cancer.

Background: Gastric cancer (GC) is one of the most common malignancies. Cuproptosis is a newly discovered type of cell death caused by protein toxicity stress, with copper having considerable importance in GC development. Methods: First, differentially expressed (DE) cuproptosis-related genes (CRGs) were screened in GC. The tumor mutation burden (TMB) of CRGs was analyzed. We then performed enrichment analyses of DE-CRGs. Next, we constructed a GC cuproptosis-related (CR) signature (CRs) using Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. The predictive efficacy was assessed using receiver operating characteristic (ROC) curves. Furthermore, we performed gene set enrichment analysis (GSEA). Different methods were used to assess tumor immunity of the CRs, and the Wilcoxon test was used to examine the expressions of m6A-, m7G-, and ferroptosis-related genes. The "pRRophetic" R package (The R Foundation for Statistical Computing) was used to predict the half maximal inhibitory concentration IC50 of common chemotherapeutic agents. Finally, the expression of CRGs in different clusters was analyzed using single-cell RNA sequencing (scRNA-seq). Results: We identified 8 DE-CRGs in GC. There were 9 CRGs with TMB values >1%. We constructed gene expression networks and CRs for GC. The DE-CRGs were involved in important mitochondrial metabolic pathways, and the CRs was a valuable independent prognosis factor. The GSEA revealed that angiogenesis and metabolic-related pathways were enriched in the high-risk group, whereas the low-risk group showed enrichment in DNA replication mismatch and repair pathways. The expressions of immunological checkpoints, ferroptosis-, m6A-, and m7G-related genes, type II interferon (INF) response, major histocompatibility complex (MHC class-I), and the IC50 of the copper-based carrier drug elesclomol were significantly different between the 2 groups of the CRs. Furthermore, the scRNA-seq analysis showed that most CRGs were mainly upregulated in endothelial cells. Conclusions: The novel CRs could predict the prognosis of GC.

AIM2 and NLRC4-driven inflammasome activation in adult-onset Still's disease and the preliminary therapeutic effect exploration of carboxyamidotriazole.

OBJECTIVES: This study aimed to explore the changes of four major inflammasomes in adult-onset Still's disease (AOSD) and preliminarily evaluate the therapeutic effect of carboxyamidotriazole (CAI), which has previously been reported to have the significant anti-inflammatory activity. METHOD: The mRNA expressions of proinflammatory cytokines and inflammasome components in peripheral blood mononuclear cells (PBMCs) from AOSD patients and healthy controls (HC) were determined by reverse transcription-quantitative PCR. Poly(dA:dT)-induced AIM2 inflammasome and flagellin-induced NLRC4 inflammasome activation models were established in bone marrow-derived macrophages (BMDMs). The levels of cytokines in serum and culture supernatants were measured by ELISA method. RESULTS: The serum levels of IL-1ß, IL-6, and TNF-α in AOSD patients were significantly higher than those in HC. However, the mRNA expressions of IL-1ß, IL-6, IL-18, and TNF-α in PBMCs did not differ markedly in AOSD patients in comparison with HC. Significantly increased mRNA levels of AIM2, NLRC4, ASC, and caspase-1 were observed in patients with AOSD when compared with HC, while NLRP1 and NLRP3 showed no change in AOSD samples. In addition, CAI treatment could significantly reduce the levels of IL-1ß, IL-6, and TNF-α secreted by AOSD PBMCs and inhibit AIM2 and NLRC4 inflammasomes activation in BMDMs. CONCLUSIONS: Increased levels of proinflammatory cytokines in AOSD might be associated with NLRC4 and AIM2 inflammasomes activation. CAI is likely to have the therapeutic potential for AOSD by inhibiting NLRC4 and AIM2 inflammasomes activation and reducing the proinflammatory cytokines and worthy of further investigation. These results provide new ideas for elucidating the pathogenesis of AOSD and providing specific targeted therapy. Key points • Significantly higher mRNA levels of AIM2 and NLRC4 inflammsome signaling were observed in AOSD patients compared with health controls, indicating that AIM2 and NLRC4 inflammsome activation might be related to the increased proinflammatory cytokines in AOSD. • CAI treatment markedly reduced the secretion levels of cytokines IL-1ß, IL-6, and TNF-α in AOSD PBMCs and inhibited AIM2 and NLRC4 inflammasome activation.

Reconstruction of Tumor-Induced Pelvic Defects With Customized, Three-Dimensional Printed Prostheses.

Background: Reconstruction of pelvis girdle stability after tumor-induced hemipelvectomy remains challenging. We surgically treated 13 patients with custom-made, three-dimensional printed hemipelvic prostheses. We aim to identify the preliminary outcomes for patients who have been managed with more mixed regions of prosthetic pelvic reconstruction and the feasibility of two reconstructive systems. Methods: Seven male patients and 6 female patients treated at our center between January 2019 and May 2021 were included. There were 11 primary sarcomas and 2 solitary bone metastases. After en bloc tumor resection, two types of personalized, three-dimensional printed prostheses were fixed to restore the stability and rebuild the load transfer. The position of the reconstructed hemipelvis was evaluated on an anteroposterior plain radiograph. The complications and outcomes were traced. One amputation specimen was discovered through histological analysis of the porous structure. Results: The operative duration was 467 ± 144 min, and the blood loss was 3,119 ± 662 ml. During a follow-up of 22.4 ± 8.5 months, two patients had delayed wound healing and one had a second-stage flap transfer. One patient with osteosarcoma died of pulmonary metastasis 27 months after surgery. Two patients with marginal resection suffered from local recurrence and had extra surgeries. One patient had traumatic hip dislocation 2 months after surgery and manipulative reduction was performed. The acetabular inclination of the affected side was 42.2 ± 4.3°, compared with 42.1 ± 3.9° on the contralateral side. The horizontal distance between the center of the femoral head and the middle vertical line was 10.4 ± 0.6 cm, while the reconstructed side was 9.8 ± 0.8 cm. No significant difference in acetabular position after surgery was found (p > 0.05). The amputation specimen harvested from one patient with local recurrence demonstrated bone and soft tissue ingrowth within the three-dimensional printed trabecular structure. Walking ability was preserved in all patients who are still alive and no prosthesis-related complications occurred. The MSTS score was 22.0 ± 3.7. Conclusions: Both types of custom-made, three-dimensional printed prostheses manifested excellent precision, mechanical stability, and promising functional rehabilitation. The porous structure exhibited favorable histocompatibility to facilitate the ingrowth of bone and soft tissue.

Case Report: 3D-Printed Prosthesis for Limb Salvage and Joint Preservation After Tibial Sarcoma Resection.

Introduction: Reconstruction of massive tibial defects in ankle joint-preserving surgery remains challenging though biological and prosthetic methods have been attempted. We surgically treated a patient with only 18-mm distal tibia remaining and reconstructed with a unique three-dimensional printed prosthesis. Case Presentation Intervention and Outcomes: A 36-year-old male presented to our clinic with complaints of gradually swelling left calf and palpable painless mass for five months. Imageological exam indicated a lesion spanning the entire length of the tibia and surrounding the vascular plexus. Diagnosis of chondrosarcoma was confirmed by biopsy. Amputation was initially recommended but rejected, thus a novel one-step limb-salvage procedure was performed. After en-bloc tumor resection and blood supply rebuilding, a customized, three-dimensional printed prosthesis with porous interface was fixed that connected the tumor knee prosthesis and distal ultra-small bone segment. During a 16-month follow-up, no soft tissue or prosthesis-related complications occurred. The patient was alive with no sign of recurrence or metastasis. Walking ability and full tibiotalar range of motion were preserved. Conclusions: Custom-made, three-dimensional printed prosthesis manifested excellent mechanical stability during the follow-up in this joint-preserving surgery. Further investigation of the durability and rate of long-term complications is needed to introduce to routine clinical practice.

A novel approach for treating acid mine drainage by forming schwertmannite driven by a combination of biooxidation and electroreduction before lime neutralization.

Acid mine drainage (AMD) contains abundant iron, sulfates, and various metal ions, and it causes environmental pollution. The traditional AMD lime neutralization forms a layer of iron hydroxide and gypsum on the surface of the lime particles, preventing continuous reaction and leading to excessive lime addition and neutralized sludge production. In this study, an approach for treating AMD using a cyclic process of biooxidation and electroreduction before lime neutralization was proposed, in which the Fe2+ in AMD was oxidized to Fe3+ and induced to form schwertmannite through Acidithiobacillus ferrooxidans. The remaining Fe3+ was reduced to Fe2+ using an electric field. After three biooxidation and two electroreduction cycles, 98.2% of Fe and 62.4% of SO42- in AMD precipitated as schwertmannite (Fe8O8(OH)5.16(SO4)1.37). The yield of schwertmannite reached 33.98 g/LAMD, with a high specific surface area of 112.59 m2/g. The lime dosage and sludge yield of the treated AMD in the subsequent neutralization stage (pH = 7.00) decreased by 85.0% and 74.5%, respectively, than those of raw AMD. The pilot test results showed that the integrated treatment of biooxidation-electroreduction cyclic mineralization and lime neutralization has practical applications.

Pharmacodynamics and pharmacokinetics of PLGA-based doxorubicin-loaded implants for tumor therapy.

The traditional systemic chemotherapy through intravenous infusion of doxorubicin (DOX) has many side effects. The aim of this study was to develop a PLGA-based DOX-loaded implant and to evaluate the efficacy and drug metabolism distribution of the implant in intratumoral chemotherapy for osteosarcoma (OS). In this study, implants containing DOX, poly(d,l-lactide-co-glycolide), and polyethylene glycol 4000 were prepared by melt-molding method. Then, the antitumor activity and systemic drug distribution of the implants were tested in a K7M2 OS bearing mouse model. The scanning electron microscope images showed that DOX was uniformly dispersed in the polymer matrix. Both the in vitro and in vivo release profiles of implants are characterized by three-phase release. Implantation of DOX-loaded implants into tumors can inhibit tumor growth in a dose-dependent manner. The pharmacokinetic behavior shows that intratumor chemotherapy through implants has a much higher drug concentration in tumors than in normal tissues, which may be the reason for improving antitumor activity and reducing systemic side effects. In summary, the drug release of the implants prepared in this study is sustained and stable, which promotes long-term local accumulation of drugs in tumors, improves the efficacy of chemotherapy and has low toxicity to normal tissues.

Reconstruction with 3D-printed prostheses after type I + II + III internal hemipelvectomy: Finite element analysis and preliminary outcomes.

Background: Prosthetic reconstruction after type I + II+ III internal hemipelvectomy remains challenging due to the lack of osseointegration and presence of giant shear force at the sacroiliac joint. The purpose of this study was to evaluate the biomechanical properties of the novel 3D-printed, custom-made prosthesis with pedicle screw-rod system and sacral tray using finite element analysis. Methods: Four models that included one intact pelvis were established for validation. Forces of 500 N and 2,000 N were applied, respectively, to simulate static bipedal standing and the most loaded condition during a gait cycle. Biomechanical analysis was performed, and the results were compared; the preliminary outcomes of four patients were recorded. Results: For the reconstructed hemipelvis, stress was mainly concentrated on the sacral screws, bone-prosthesis interface, and upper endplate of the L5 vertebra. The optimization of the design with the sacral tray structure could decrease the peak stress of the sacral screws by 18.6%, while the maximal stress of the prosthesis increased by 60.7%. The addition of the lumbosacral pedicle-rod system further alleviated stress of the sacral screws and prosthesis by 30.2% and 19.4%, respectively. The site of peak stress was contemporaneously transferred to the connecting rods within an elastic range. In the retrospective clinical study, four patients who had undergone prosthetic reconstruction were included. During a follow-up of 16.6 ± 7.5 months, the walking ability was found preserved in all patients who are still alive and no prosthesis-related complications had occurred except for one hip dislocation. The Musculoskeletal Tumor Society (MSTS) score was found to be 19.5 ± 2.9. Conclusion: The novel reconstructive system yielded favorable biomechanical characteristics and demonstrated promising preliminary outcomes. The method can be used as a reference for reconstruction after type I + II + III hemipelvectomy.

Carboxyamidotriazole exerts anti-inflammatory activity in lipopolysaccharide-induced RAW264.7 macrophages by inhibiting NF-κB and MAPKs pathways.

Carboxyamidotriazole (CAI), originally developed as a non-cytotoxic anti-cancer drug, was shown to have anti-inflammatory activity according to recent studies in a number of animal models of inflammation. However, its mechanism of action has not been characterized. Therefore, the present study was performed to identify the anti-inflammatory action of CAI in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and to identify the signal transduction pathways involved. The in vitro results revealed that CAI had no direct effect on the activity of cyclooxygenase (COX), suggesting a different anti-inflammatory mechanism compared with that of COX-inhibiting non-steroidal anti-inflammatory drugs. Further investigation in RAW264.7 macrophages revealed that CAI decreased the production of nitric oxide via decreasing the LPS-stimulated expression of inducible nitric oxide synthase, and downregulated both mRNA and protein expression levels of the cytokines tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6. CAI also significantly reduced the increased DNA-binding activity of nuclear factor (NF)-κB induced by LPS stimulation. With respect to the mechanisms involved on NF-κB activity, CAI exhibited suppression of the phosphorylation and degradation of the inhibitor of nuclear factor-κBα (IκB), and decreased the phosphorylation levels of the p65 subunit and its subsequent nuclear translocation. In addition, CAI significantly decreased the phosphorylated forms of p38, JNK and ERK, which were increased following LPS stimulation, while the total expression levels of p38, JNK and ERK remained unaltered. The results in the present study indicate that CAI alleviates the inflammatory responses of RAW 264.7 macrophages in response to LPS stimulation via attenuating the activation of NF-κB and MAPK signaling pathways and decreasing the levels of pro-inflammatory mediators. This offers a novel perspective for understanding the anti-inflammatory mechanism of CAI and suggests its potential use as a therapeutic treatment in inflammatory diseases with excessive macrophage activation.