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Background Intrahepatic cholestasis of pregnancy (ICP) is a prevalent pregnancy-specific complication that presents with maternal itching and elevated serum bile acid levels. ICP is associated with unfavorable pregnancy outcomes, severely decreasing the pregnant woman’s quality of life. Timely identification of ICP is crucial for effective management and improved outcomes. Methods We collected urine samples from 8 patients with ICP and 8 healthy individuals. We used Liquid Chromatography-Mass Spectrometry (LC-MS) to detect metabolite expression levels, then conducted a series of bioinformatic analyses to explore the potential biological meanings of differentially expressed metabolites, and preliminarily discovered several candidate biomarkers. To validate these candidate biomarkers, we performed Gas Chromatography-Mass Spectrometry (GC-MS) detection and analyzed their diagnostic values using receiver operating characteristic (ROC) curve. Results Untargeted metabolomics data showed that 6129 positive peaks and 6218 negative peaks were extracted from each specimen. OPLS-DA analysis and the heat map for cluster analysis showed satisfactory capability in discriminating ICP specimens from controls. Subsequent analysis extracted 64 significantly differentially expressed metabolites, which could be potential biomarkers for diagnosis of ICP. Based on the KEGG enrichment analyses, six candidate biomarkers were preliminarily identified. Two most promising biomarkers (3-hydroxypropionic acid and uracil) were validated by targeted metabolomics analyses with the area under the curve (AUC) of 0.920 and 0.850 respectively. Conclusion Based on preliminary screening from untargeted metabolomics and subsequent validation through targeted metabolomics, 3-hydroxypropionic acid and uracil were identified as promising diagnostic biomarkers for ICP.

Increasing studies have reported that dysregulated lipid metabolism is an independent risk factor for breast cancer (BC); it would be, therefore, enlightening to investigate the relationship between metabolic reprogramming and the tumor microenvironment in the future. Ferroptosis, a novel form of programmed cell death, is characterized by glutathione (GSH) depletion and inactivation of glutathione peroxidase 4 (GPX4), the central regulator of the antioxidant system. While the close association between fatty acid metabolism and ferroptosis has been studied in various diseases, the interplay between the key fatty acid metabolic enzyme fatty acid synthase (FASN) and ferroptosis in BC remains unexplored. At the beginning of the current study, we demonstrated that FASN expression positively correlates with an immune-cold tumor microenvironment in BC. Subsequent findings revealed that FASN knockdown promotes GPX4 degradation-induced ferroptosis, thereby enhancing the efficacy of anti-programmed cell death protein 1 (PD-1) immunotherapy. Co-immunoprecipitation coupled with mass spectrometry (IP/MS) and co-IP experiments demonstrated that ubiquitin specific protease 5 (USP5) stabilizes GPX4 by binding to and deubiquitinating it. Furthermore, knockdown of FASN inhibited the palmitoylation of USP5, reducing its interaction with GPX4 and consequently increasing GPX4 ubiquitination and degradation. Our results demonstrate that FASN suppresses ferroptosis in BC by stabilizing GPX4 via USP5-mediated mechanisms, highlighting FASN inhibition as a potential therapeutic approach to enhance immunotherapy response.

Ferroptosis, a distinct form of non-apoptotic cell death characterized by iron dependency and lipid peroxidation, is increasingly linked to various pathological conditions in pregnancy and liver diseases. It plays a critical role throughout pregnancy, influencing processes such as embryogenesis, implantation, and the maintenance of gestation. A growing body of evidence indicates that disruptions in these processes can precipitate pregnancy-related disorders, including pre-eclampsia (PE), gestational diabetes mellitus (GDM), and intrahepatic cholestasis of pregnancy (ICP). Notably, while ICP is primarily associated with elevated maternal serum bile acid levels, its precise etiology remains elusive. Oxidative stress induced by bile acid accumulation is believed to be a significant factor in ICP pathogenesis. Similarly, the liver’s susceptibility to oxidative damage underscores the importance of lipid metabolism dysregulation and impaired iron homeostasis in the progression of liver diseases such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), cholestatic liver injury, autoimmune hepatitis (AIH), acute liver injury, viral hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). This review discusses the shared signaling mechanisms of ferroptosis in gestational and hepatic diseases, and explores recent advances in understanding the mechanisms of ferroptosis and its potential role in the pathogenesis of gestational and hepatic disorders, with the aim of identifying viable therapeutic targets.

BackgroundTriple-negative breast cancer (TNBC) is the most malignant breast cancer, highlighting the need for effective immunotherapeutic targets. The immune checkpoint molecule B7-H3 has recently gained attention as a promising therapeutic target due to its pivotal role in promoting tumorigenesis and cancer progression. However, the therapeutic impact of B7-H3 inhibitors (B7-H3i) remains unclear.MethodsTranscriptomic and metabolomic analyses were conducted to explore the underlying mechanisms of B7-H3 inhibition in TNBC. The therapeutic efficacy of the combined treatment strategy was substantiated through comprehensive phenotypic assays conducted in vitro and validated in vivo using animal models.ResultsB7-H3 blockade induces a “primed for death” stress state in cancer cells, leading to distinct alterations in metabolic pathways. Specifically, B7-H3 knockdown activated the AKT signaling pathway and upregulated sterol regulatory element-binding protein 1 (SREBP1), which in turn elevated FASN expression. The simultaneous inhibition of both B7-H3 and FASN more effectively attenuated the malignant progression of TNBC.ConclusionsOur findings propose an “immune attack-metabolic compensation” dynamic model and suggest the feasibility of a dual-targeting strategy that concurrently inhibits both B7-H3 and FASN to enhance therapeutic efficacy in TNBC patients.

Breast cancer remains the most common cancer among women globally and a leading cause of cancer-related death. Despite the promise of immunotherapy for triple-negative breast cancer (TNBC), its overall effectiveness is hindered by the cold tumor microenvironment (TME), characterized by sparse immune cell infiltration. This review explores the pivotal role of hypoxia in shaping the breast cancer TME and its influence on immunotherapy efficacy. As a defining feature of most solid tumors, including breast cancer, hypoxia drives aggressive tumor behavior, metastasis, and treatment resistance. The hypoxic TME promotes immune evasion and maintains the cold tumor phenotype. Targeting hypoxia offers a potential strategy for transforming cold breast tumors into hot tumors that respond more effectively to immunotherapy. This review consolidates existing insights into the interplay between hypoxia, tumor immunophenotypes, and immunotherapy in breast cancer. By analyzing the mechanisms through which hypoxia modulates the TME and immune response, it proposes innovative strategies to enhance immunotherapy outcomes. This comprehensive analysis lays the groundwork for developing more effective combination therapies to improve breast cancer prognosis.

The effects of polytetrafluoroethylene (PTFE), graphite, ultrahigh molecular weight polyethylene (UHMWPE), and their compounds on mechanical and tribological properties of glass-fiber-reinforced polyamide 6 (PA6/GF) were studied. The polymeric materials were blended using twin-screw extruder and subsequently injection molded for test samples. Mechanical properties were investigated in terms of hardness, tensile strength, and impact strength. Friction and wear experiments were run under ambient conditions at a rotating speed of 200 rpm and load of 100 N. The morphologies of the worn surfaces were also observed with scanning electron microscope. The results showed that graphite could increase the tensile strength of PA6/GF-15 composite, but the material became soft. Graphite/UHMWPE complex solid lubricants were effective in increasing the already high impact strength of PA6/GF-15 composite. 5% PTFE gave the maximum reduction in the coefficient of friction. However, PTFE/UHMWPE complex solid lubricants were the best choice for improving both friction and wear behaviors due to the lower friction coefficient and mass wear rate. Moreover, the worn surface of PA6 composites revealed that adhesive wear, abrasive wear, and fatigue wear occurred in this study.

MoS2 reinforced PDMS/MC nylon composites had been fabricated by in situ polymerization to further enhance the comprehensive properties of nylon material. Polydimethylsiloxane was pre-sythesized as the activator of the system and MoS2 was compounded as the wear-resisting agent. The thermal stability, mechanical properties, friction and wear properties of composites with different MoS2 contents were tested. The results showed that the crystallization and thermal stability of nylon matrix were increased with the addition of MoS2, while the tensile strength and impact strength were slightly reduced. The composites finally presented excellent friction properties with 3 wt% MoS2, whose friction coefficient was reduced to 0.75 (18.48% decrease) corresponding to the wear rate of 0.4145 נ10−8 g Nm−1.

Breast Cancer (BC) remains one of the most prevalent malignancies among women globally, with its pathogenesis and clinical progression being profoundly regulated by the tumor microenvironment (TME). Collagen, the most abundant extracellular matrix (ECM) component, plays multifaceted roles in shaping the TME of BC. Aberrant cllagen deposition, crosslinking, and remodeling alter tissue stiffness and architecture, driving tumor initiation, growth, invasion, and metastasis through integrin and discoidin domain receptor-mediated mechanosignaling, growth factor regulation, and metabolic reprogramming. Collagen rich stroma also acts as a physical and biochemical barrier that restricts T cell infiltration, promotes macrophage polarization, and impairs natural killer cell (NK) cytotoxicity, thereby facilitating immune evasion and therapeutic resistance. Specific collagen isoforms, including types I, III, V, VI, X, and XI, exhibit context-dependent tumor promoting or tumor restraining effects, underscoring the complexity of roles. Recent advances in targeting collagen biology, such as enzymatic degradation, inhibition of crosslinking enzymes, blockade of collagen receptors, and immune modulation strategies demonstrates promising preclinical results, with several approaches progressing to clinical trials. Future perspectives emphasize the integration of collagen targeting therapies with immunotherapy and chemotherapy, alongside the development of predictive biomarkers to stratify patients most likely to benefit. Collectively, collagen represents both a critical regulator of BC pathogenesis and a promising therapeutic target with significant translational potential.

MoS 2 reinforced PDMS/MC nylon composites had been fabricated by in situ polymerization to further enhance the comprehensive properties of nylon material. Polydimethylsiloxane was pre-sythesized as the activator of the system and MoS 2 was compounded as the wear-resisting agent. The thermal stability, mechanical properties, friction and wear properties of composites with different MoS 2 contents were tested. The results showed that the crystallization and thermal stability of nylon matrix were increased with the addition of MoS 2 , while the tensile strength and impact strength were slightly reduced. The composites finally presented excellent friction properties with 3 wt% MoS 2 , whose friction coefficient was reduced to 0.75 (18.48% decrease) corresponding to the wear rate of 0.4145 × 10 −8 g Nm −1 .