The death risk of pediatric patients with cancer-related sepsis requiring continuous renal replacement therapy: a retrospective cohort study.

OBJECTIVE: To assess the outcome of patients with cancer-related sepsis requiring continuous renal replacement therapy (CRRT) in a single-center pediatric intensive care unit (PICU). METHOD: Children with sepsis who necessitate CRRT from January 2017 to December 2021 were enrolled. The patients with leukemia/lymphoma or solid tumors were defined as underlying cancer. Multivariate logistic regression analysis was performed to identify the death risk factors in patients with cancer-related sepsis. RESULTS: A total of 146 patients were qualified for inclusion. Forty-six (31.5%) patients with cancer-related sepsis and 100 (68.5%) non-cancer-related sepsis. The overall PICU mortality was 28.1% (41/146), and mortality was significantly higher in cancer-related sepsis patients compared with non-cancer patients (41.3% vs. 22.0%, p = 0.016). Need mechanical ventilation, p-SOFA, acute liver failure, higher fluid overload at CRRT initiation, hypoalbuminemia, and high inotropic support were associated with PICU mortality in cancer-related sepsis patients. Moreover, levels of IL-6, total bilirubin, creatinine, blood urea nitrogen, and international normalized ratio were significantly higher in non-survivors than survivors. In multivariate logistic regression analysis, pediatric sequential organ failure assessment (p-SOFA) score (OR:1.805 [95%CI: 1.047-3.113]) and serum albumin level (OR: 0.758 [95%CI: 0.581 -0.988]) were death risk factors in cancer-related sepsis receiving CRRT, and the AUC of combined index of p-SOFA and albumin was 0.852 (95% CI: 0.730-0.974). CONCLUSION: The overall PICU mortality is high in cancer-related sepsis necessitating CRRT. Higher p-SOFA and lower albumin were independent risk factors for PICU mortality.

Low field controllable continuous spin switching in the thulium-ytterbium single crystal.

We report the spin reorientation transition (SRT) and the low field controllable continuous spin switching (SSW) of the Tm0.75Yb0.25FeO3 (TYFO) single crystal in this study. The SRT, characterized by the transition from Γ2(Fx, Cy, Gz)-Γ4(Gx, Ay, Fz), occurs within the temperature range of 20-27 K. Under an external magnetic field of 50 Oe, the SSW occurs along the c-axis at approximately 98 K due to the reversal of Tm3+ magnetic moment induced by the magnetic coupling change between Tm3+ and Fe3+, transitioning from a parallel to an antiparallel alignment. Notably, a continuous SSW is observed along the a-axis at low temperatures, which has not been previously reported in rare earth orthoferrites. This unique behavior can be easily manipulated by low magnetic fields within the temperature range of 2-20 K. Both the spin reorientation transition and spin switching phenomena in the TYFO single crystal arise from interactions between rare earth ions and iron ions and can be effectively regulated by applied low magnetic fields, making it a promising material for low-field spin devices.

Expression of Multicopy Tandem Recombinant Ginseng Hexapeptide in Bacillus subtilis and the Evaluation of Antiaging Activity.

Ginseng oligopeptides are naturally occurring small-molecule peptides extracted from ginseng that exhibit positive effects on health and longevity. However, the current industrial production of ginseng oligopeptides primarily relies on plant extraction and chemical synthesis. In this study, we proposed a novel genetic engineering approach to produce active ginseng peptides through multicopy tandem insertion (5 and 15 times). The recombinant ginseng peptides were successfully produced from engineered Bacillus subtilis with an increasing yield from 356.55 to 2900 mg/L as the repeats multiple. Additionally, an oxidative stress-induced aging model caused by H2O2 was established to evaluate whether the recombinant ginseng peptides, without enzymatic hydrolysis into individual peptides, also have positive effects on antiaging. The results demonstrated that all two kinds of recombinant ginseng peptides could also delay cellular aging through various mechanisms, such as inhibiting cell cycle arrest, suppressing the expression of pro-inflammatory factors, and enhancing cellular antioxidant capacity.

Janus hydrogels: merging boundaries in tissue engineering for enhanced biomaterials and regenerative therapies.

In recent years, the design and synthesis of Janus hydrogels have witnessed a thriving development, overcoming the limitations of single-performance materials and expanding their potential applications in tissue engineering and regenerative medicine. Janus hydrogels, with their exceptional mechanical properties and excellent biocompatibility, have emerged as promising candidates for various biomedical applications, including tissue engineering and regenerative therapies. In this review, we present the latest progress in the synthesis of Janus hydrogels using commonly employed preparation methods. We elucidate the surface and interface interactions of these hydrogels and discuss the enhanced properties bestowed by the unique "Janus" structure in biomaterials. Additionally, we explore the applications of Janus hydrogels in facilitating regenerative therapies, such as drug delivery, wound healing, tissue engineering, and biosensing. Furthermore, we analyze the challenges and future trends associated with the utilization of Janus hydrogels in biomedical applications.

Ginsenoside Rk3 Regulates Tryptophan Metabolism along the Brain-Gut Axis by Targeting Tryptophan Hydroxylase and Remodeling the Intestinal Microenvironment to Alleviate Depressive-Like Behavior in Mice.

Depression is a neuropsychiatric disease that significantly impacts the physical and mental health of >300 million people worldwide and places a major burden on society. Ginsenosides are the main active ingredient in ginseng and have been proven to have various pharmacological effects on the nervous system. Herein, we investigated the antidepressant effect of ginsenoside Rk3 and its underlying mechanism in a murine model of depression. Rk3 significantly improved depression-like behavior in mice, ameliorated the disturbance of the hypothalamus-pituitary-adrenal axis, and alleviated neuronal damage in the hippocampus and prefrontal cortex of mice. Additionally, Rk3 improved the abnormal metabolism of tryptophan in brain tissue by targeting tryptophan hydroxylase, thereby reducing neuronal apoptosis and synaptic structural damage in the mouse hippocampus and prefrontal cortex. Furthermore, Rk3 reshaped the composition of the gut microbiota of mice and regulated intestinal tryptophan metabolism, which alleviated intestinal barrier damage. Thus, this study provides valuable insights into the role of Rk3 in the tryptophan metabolic cycle along the brain-gut axis, suggesting that Rk3 may have the potential for treating depression.

Ginsenoside Rg5 inhibits lipid accumulation and hepatocyte apoptosis via the Notch1 signaling pathway in NASH mice.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a prevalent chronic liver disease that lacks an FDA-approved treatment medicine. Despite the known antitumor and hypoglycemic properties of Ginsenoside Rg5, its effects and underlying mechanisms in the context of NASH remain largely unexplored. PURPOSE: This study aims to investigate the effect of Rg5 on NASH mice induced by a high-fat diet and CCl4. STUDY DESIGN: In vivo experiments, a mouse NASH model was established by a HFHC diet plus intraperitoneal injection of low-dose CCl4. In vitro experiments, a cellular steatosis model was established using free fatty acids (FFA) induced HepG2 cells. In addition, a fibrogenesis model was established using HSC-LX2 cells. METHODS: The effects of Ginsenoside Rg5 on lipid accumulation and oxidative damage were analyzed by ELISA kit, H&E staining, Oil Red O staining, flow cytometry and Western blot. The effects of Ginsenoside Rg5 on liver fibrosis were analyzed by Masson staining, Sirus Red staining, immunohistochemistry and Western blot. The effect of Ginsenoside Rg5 on Notch1 signaling pathway in liver was studied by protein Oil Red staining, protein immunoblotting and immunofluorescence. RESULTS: In terms of lipid accumulation, Rg5 has the ability to regulate key proteins related to lipogenesis, thereby inhibiting hepatic lipid accumulation and oxidative stress. Additionally, Rg5 can reduce the occurrence of hepatocyte apoptosis by regulating the p53 protein. Moreover, after Rg5 intervention, the presence of fibrotic proteins (α-SMA, Collagen 1, TGF-ß) in the liver is significantly suppressed, thus inhibiting liver fibrosis. Lastly, Rg5 leads to a decrease in the expression levels of Notch1 and its ligand Jagged-1 in the liver. CONCLUSION: In summary, the regulatory effects of Rg5 on the Notch1 signaling pathway play a crucial role in modulating hepatic lipid metabolism and preventing hepatocyte apoptosis, thereby impeding the progression of NASH. These findings highlight the potential of Rg5 as a promising natural product for interventions targeting NASH.

TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase.

Nonalcoholic fatty liver disease (NAFLD) encompasses a disease continuum from simple steatosis to nonalcoholic steatohepatitis (NASH). However, there are currently no approved pharmacotherapies for NAFLD, although several drugs are in advanced stages of clinical development. Because of the complex pathophysiology and heterogeneity of NAFLD, the identification of potential therapeutic targets is clinically important. Here, we demonstrated that tripartite motif 56 (TRIM56) protein abundance was markedly downregulated in the livers of individuals with NAFLD and of mice fed a high-fat diet. Hepatocyte-specific ablation of TRIM56 exacerbated the progression of NAFLD, while hepatic TRIM56 overexpression suppressed it. Integrative analyses of interactome and transcriptome profiling revealed a pivotal role of TRIM56 in lipid metabolism and identified the lipogenesis factor fatty acid synthase (FASN) as a direct binding partner of TRIM56. TRIM56 directly interacted with FASN and triggered its K48-linked ubiquitination-dependent degradation. Finally, using artificial intelligence-based virtual screening, we discovered an orally bioavailable small-molecule inhibitor of FASN (named FASstatin) that potentiates TRIM56-mediated FASN ubiquitination. Therapeutic administration of FASstatin improved NAFLD and NASH pathologies in mice with an optimal safety, tolerability, and pharmacokinetics profile. Our findings provide proof of concept that targeting the TRIM56/FASN axis in hepatocytes may offer potential therapeutic avenues to treat NAFLD.

Human Motion Generation: A Survey.

Human motion generation aims to generate natural human pose sequences and shows immense potential for real-world applications. Substantial progress has been made recently in motion data collection technologies and generation methods, laying the foundation for increasing interest in human motion generation. Most research within this field focuses on generating human motions based on conditional signals, such as text, audio, and scene contexts. While significant advancements have been made in recent years, the task continues to pose challenges due to the intricate nature of human motion and its implicit relationship with conditional signals. In this survey, we present a comprehensive literature review of human motion generation, which, to the best of our knowledge, is the first of its kind in this field. We begin by introducing the background of human motion and generative models, followed by an examination of representative methods for three mainstream sub-tasks: text-conditioned, audio-conditioned, and scene-conditioned human motion generation. Additionally, we provide an overview of common datasets and evaluation metrics. Lastly, we discuss open problems and outline potential future research directions. We hope that this survey could provide the community with a comprehensive glimpse of this rapidly evolving field and inspire novel ideas that address the outstanding challenges.

TGFA expression is associated with poor prognosis and promotes the development of cervical cancer.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are the second most common cancers in women aged 20-39. While HPV screening can help with early detection of cervical cancer, many patients are already in the medium to late stages when they are identified. As a result, searching for novel biomarkers to predict CESC prognosis and propose molecular treatment targets is critical. TGFA is a polypeptide growth factor with a high affinity for the epidermal growth factor receptor. Several studies have shown that TGFA can improve cancer growth and progression, but data on its impact on the occurrence and advancement of CESC is limited. In this study, we used clinical data analysis and bioinformatics techniques to explore the relationship between TGFA and CESC. The results showed that TGFA was highly expressed in cervical cancer tissues and cells. TGFA knockdown can inhibit the proliferation, migration and invasion of cervical cancer cells. In addition, after TGFA knockout, the expression of IL family and MMP family proteins in CESC cell lines was significantly reduced. In conclusion, TGFA plays an important role in the occurrence and development of cervical cancer. Therefore, TGFA may become a new target for cervical cancer treatment.

Rutin attenuates inflammation by downregulating AGE-RAGE signaling pathway in psoriasis: Network pharmacology analysis and experimental evidence.

BACKGROUND: Jueyin granules (JYG) is effective against psoriasis, but its utility components are not clear. Rutin is the main monomer of JYG, its therapeutic effect and mechanism on psoriasis need to be further clarified. PURPOSE: To explore the potential mechanisms of rutin on psoriasis through network pharmacology and experiments. METHODS: In vitro, cell viability was determined using the CCK8 assay, and inflammatory factors were identified using RT-qPCR. The hub genes and kernel pathways of action were identified by modular pharmacology analysis. In vivo, a BALB/c mice model of psoriasis was induced by Imiquimod (IMQ). The therapeutic effect and action pathway were detected through Western Blotting, RT-qPCR, histopathologic and immunohistochemical analysis. RESULTS: Rutin inhibited cell proliferation and expression of TNF-α and IL-6 in HaCaT cells. The hub genes include APP, INS, and TNF, while the kernel pathways contain the AGE-RAGE signaling pathway. In IMQ-induced psoriasis-like mice, rutin ameliorated skin lesions and inhibited cell proliferation. Rutin could attenuate inflammation by downregulating the AGE-RAGE signaling pathway. CONCLUSION: This study suggests that rutin can reduce IMQ-induced psoriasis like skin inflammation in mice, and regulation of AGE-RAGE signaling pathway may be one of its potential anti-inflammatory mechanisms. Rutin has a promising therapeutic use for the treatment of psoriasis.

Ginsenoside F4 Alleviates Skeletal Muscle Insulin Resistance by Regulating PTP1B in Type II Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with increasing morbidity. Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of the insulin signaling cascade and has attracted intensive investigation in the T2DM study. Ginseng is widely used to treat metabolic diseases, while the effects of ginsenoside F4 (F4) on T2DM have remained unknown. Here, we identify F4 as an inhibitor of skeletal muscle insulin resistance. The results showed that F4 significantly improved the hyperglycemic state of db/db mice, alleviated dyslipidemia, and promoted skeletal muscle glucose uptake. This phenomenon was closely related to the inhibition of the PTP1B activity. On the one hand, the inhibition of PTP1B activity by F4 resulted in increased insulin receptor (INSR) and insulin receptor substrate 1 tyrosine phosphorylation and enhanced insulin sensitivity. On the other hand, F4 as a PTP1B inhibitor inhibited the inositol-requiring enzyme 1 (IRE-1)/recombinant TNF receptor associated factor 2 (TRAF2)/c-Jun N-terminal kinase signaling pathway and alleviated skeletal muscle endoplasmic reticulum (ER) stress, thereby reducing IRS-1 serine phosphorylation. Both finally activated the PI3K/AKT signaling pathway and promoted glucose transporter protein 4 translocation to the cell membrane for glucose uptake. Taken together, our experiments demonstrate that F4 activates the insulin signaling pathway by inhibiting the activity of PTP1B while inhibiting the IRE-1/TRAF2/JNK signaling pathway, enhancing insulin sensitivity, and alleviating ER stress in the skeletal muscle of db/db mice. Our results indicate that F4 can be used as a PTP1B inhibitor for the treatment of T2DM.

Cerium oxide nanoparticles in diabetic foot ulcer management: Advances, limitations, and future directions.

Diabetic foot ulcer (DFU) is one of the most serious complications of diabetes, potentially resulting in wound infection and amputation under severe circumstances. Oxidative stress and dysbiosis are the primary factors that delay wound healing, posing challenges to effective treatment. Unfortunately, conventional approaches in these aspects have proven satisfactory in achieving curative outcomes. Recent research has increasingly focused on using nanoparticles, leveraging their potential in wound dressing and medication delivery. Their unique physical properties further enhance their therapeutic effectiveness. Among these nanoparticles, cerium oxide nanoparticles (CONPs) have garnered attention due to their notable beneficial effects on oxidative stress and microbial abundance, thus representing a promising therapeutic avenue for DFU. This review comprehensively assesses recent studies on CONPs in treating DFU. Furthermore, we elaborate on the wound healing process, ceria synthesis, and incorporating CONPs with other materials. Crucially, a thorough evaluation of CONPs' toxicity as a novel metallic nanomaterial for therapeutic use must precede their formal clinical application. Additionally, we identify the current challenges CONPs encounter and propose future directions for their development.

The role of neutrophils in diabetic ulcers and targeting therapeutic strategies.

Diabetic ulcers (DUs) are a common complication of diabetes with high morbidity, poor prognosis, and a high socio-economic burden. The main pathological manifestations of DUs are chronic inflammation, impaired re-epithelialization, and impaired angiogenesis. During the inflammatory phase, neutrophils are one of the main DU cell types and act by releasing neutrophil extracellular traps (NETs), leading to poor healing in DUs. This review summarizes the role of neutrophils in the pathology and treatment of DUs, with a view to potential novel therapies and therapeutic targets.

Electrical programmable multilevel nonvolatile photonic random-access memory.

Photonic Random-Access Memories (P-RAM) are an essential component for the on-chip non-von Neumann photonic computing by eliminating optoelectronic conversion losses in data links. Emerging Phase-Change Materials (PCMs) have been showed multilevel memory capability, but demonstrations still yield relatively high optical loss and require cumbersome WRITE-ERASE approaches increasing power consumption and system package challenges. Here we demonstrate a multistate electrically programmed low-loss nonvolatile photonic memory based on a broadband transparent phase-change material (Ge2Sb2Se5, GSSe) with ultralow absorption in the amorphous state. A zero-static-power and electrically programmed multi-bit P-RAM is demonstrated on a silicon-on-insulator platform, featuring efficient amplitude modulation up to 0.2 dB/µm and an ultralow insertion loss of total 0.12 dB for a 4-bit memory showing a 100× improved signal to loss ratio compared to other phase-change-materials based photonic memories. We further optimize the positioning of dual microheaters validating performance tradeoffs. Experimentally we demonstrate a half-a-million cyclability test showcasing the robust approach of this material and device. Low-loss photonic retention-of-state adds a key feature for photonic functional and programmable circuits impacting many applications including neural networks, LiDAR, and sensors for example.

Activation of endoplasmic reticulum stress by harmine suppresses the growth of esophageal squamous cell carcinoma.

The worldwide overall 5-year survival rate of esophageal squamous cell carcinoma (ESCC) patients is less than 20%, and novel therapeutic strategies for these patients are urgently needed. Harmine is a natural ß-carboline alkaloid, which received great interest in cancer research because of its biological and anti-tumor activities. The aim of this study is to examine the effects of harmine on ESCC and its mechanism. We investigated the effects of harmine on proliferation, cell cycle, apoptosis, and tumor growth in vivo. RNA sequencing (RNA-seq), real-time PCR, and western blotting were used to detect the mechanism. Harmine inhibited ESCC cell growth in vitro and tumor growth in vivo. Differentially expressed genes in harmine-treated ESCC cells were mainly involved in protein processing in the endoplasmic reticulum (ER). Real-time PCR and western blotting confirmed harmine-induced cellular ER stress. CRISPR-Cas9 knockout of C/EBP homologous protein (CHOP) abolished harmine-induced expression of death receptor 5 and apoptosis. Harmine also induced the expression of CHOP-mediated sestrin-2, which in turn contributes to autophagosome formation via suppressing the AMP-activated protein kinase-protein kinase B-mammalian target of rapamycin signaling pathway. In conclusion, our results demonstrate that harmine inhibits the growth of ESCC through its regulation of ER stress, suggesting that it is a promising candidate for ESCC treatment.

Clinical-mediated discovery of pyroptosis in CD8+ T cell and NK cell reveals melanoma heterogeneity by single-cell and bulk sequence.

Histologically, melanoma tissues had fewer positive cells percentage of pyroptosis-related genes (PRGs), GZMA, GSDMB, NLRP1, IL18, and CHMP4A in epidermal than in normal skin. Pyroptosis, a new frontier in cancer, affects the tumor microenvironment and tumor immunotherapy. Nevertheless, the role of pyroptosis remains controversial, which reason is partly due to the heterogeneity of the cellular composition in melanoma. In this study, we present a comprehensive analysis of the single-cell transcriptome landscape of pyroptosis in melanoma specimens. Our findings reveal dysregulation in the expression of PRGs, particularly in immune cells, such as CD8+ cells (representing CD8+ T cells) and CD57+ cells (representing NK cells). Additionally, the immunohistochemical and multiplex immunofluorescence staining experiments results further confirmed GZMA+ cells and GSDMB+ cells were predominantly expressed in immune cells, especially in CD8 + T cells and NK cells. Melanoma specimens secreted a minimal presence of GZMA+ merged CD8+ T cells (0.11%) and GSDMB+ merged CD57+ cells (0.08%), compared to the control groups exhibiting proportions of 4.02% and 0.62%, respectively. The aforementioned findings indicate that a reduced presence of immune cells within tumors may play a role in diminishing the ability of pyroptosis, consequently posing a potential risk to the anti-melanoma properties. To quantify clinical relevance, we constructed a prognostic risk model and an individualized nomogram (C-index=0.58, P = 0.002), suggesting a potential role of PRGs in malignant melanoma prevention. In conclusion, our integrated single-cell and bulk RNA-seq analysis identified immune cell clusters and immune gene modules with experiment validation, contributing to our better understanding of pyroptosis in melanoma.

Ginsenoside Rh4 Improves Hepatic Lipid Metabolism and Inflammation in a Model of NAFLD by Targeting the Gut Liver Axis and Modulating the FXR Signaling Pathway.

Non-alcoholic fatty liver disease (NAFLD) is a series of disorders of liver metabolism caused by the accumulation of lipids in the liver, which is considered the main cause of hepatocellular carcinoma. Our previous study demonstrated the promising efficacy of ginsenoside Rh4 in improving the intestinal tract and its related metabolites. Meanwhile, many studies in the literature have investigated the gut microbiota and its metabolites, such as bile acids (BAs) and short-chain fatty acids (SCFAs), which play a key role in the pathogenesis of NAFLD. Therefore, this study focused on whether Rh4 could achieve therapeutic effects on NAFLD through the gut-liver axis. The results showed that Rh4 exhibited sound therapeutic effects on the NAFLD model induced by the Western diet and CCl4 in mice. In the liver, the degrees of hepatic steatosis, lobular inflammation levels, and bile acid in the liver tissue were improved after Rh4 treatment. At the same time, Rh4 treatment significantly increased the levels of intestinal SCFAs and BAs, and these changes were accompanied by the complementary diversity and composition of intestinal flora. In addition, correlation analysis showed that Rh4 affected the expression of proteins involved in the farnesoid X receptor (FXR) signaling pathway in the liver and intestine, which modulates hepatic lipid metabolism, inflammation, and proteins related to bile acid regulation. In conclusion, our study provides a valuable insight into how Rh4 targets the gut-liver axis for the development of NAFLD, which indicates that Rh4 may be a promising candidate for the clinical therapy of NAFLD.

Ginsenoside Rk3 is a novel PI3K/AKT-targeting therapeutics agent that regulates autophagy and apoptosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Ginsenoside Rk3, an important and rare saponin in heat-treated ginseng, is generated from Rg1 and has a smaller molecular weight. However, the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized. Here, we investigated the mechanism by which ginsenoside Rk3, a tetracyclic triterpenoid rare ginsenoside, inhibits the growth of HCC. We first explored the possible potential targets of Rk3 through network pharmacology. Both in vitro (HepG2 and HCC-LM3 cells) and in vivo (primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice) studies revealed that Rk3 significantly inhibits the proliferation of HCC. Meanwhile, Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC. Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway to inhibit HCC growth, which was validated by molecular docking and surface plasmon resonance. In conclusion, we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC. Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.

Ginsenoside Rk3 Regulates Nonalcoholic Steatohepatitis by Modulation of Intestinal Flora and the PI3K/AKT Signaling Pathway in C57BL/6 Mice.

Non-alcoholic steatohepatitis (NASH) has become the most important reason of liver disease around the world and is predisposed to further progression to cirrhosis and hepatocellular carcinoma. Ginsenoside Rk3 has been reported to have a plenty of biological activities, including anti-apoptotic, anti-anemia, and protective effects against acute kidney injury. However, whether ginsenoside Rk3 can improve NASH has not been reported yet. Therefore, the purpose of this study is to investigate the protective effect of ginsenoside Rk3 against NASH and its mechanism of action. C57BL/6 mice were treated with different dosages of ginsenoside Rk3 after being established as a NASH model. Our results showed that Rk3 administration significantly improved liver inflammation, lipid deposition, and fibrosis caused by a high-fat-high-cholesterol (HFHC) diet and CCl4 injection in mice. Notably, ginsenoside Rk3 was discovered significantly to inhibit the PI3K/AKT signaling pathway. Additionally, treatment with ginsenoside Rk3 remarkably amended the abundance of short-chain fatty acids. These changes were associated with beneficial variations to the variety and composition of the intestinal microbiota. In conclusion, ginsenoside Rk3 ameliorates hepatic non-alcoholic lipid inflammation and triggers changes in the beneficial intestinal flora, helping to reveal host-microbe interactions. The outcomes of this study indicate that ginsenoside Rk3 is a promising drug candidate for the treatment of NASH.