Lipid metabolism reprogramming drives malignant proliferation and invasiveness in hepatocellular carcinoma (HCC). Beyond supplying energy and membrane components, lipids function as signaling molecules that modulate tumor cell epigenetics and the microenvironment. Accumulating research has clarified the implications of these metabolic alterations in HCC, providing a rationale for targeted therapies. This review summarizes key alterations in lipid metabolism within HCC and explores their mechanistic contributions to tumor progression. It further examines how lipid metabolic shifts in immune and stromal cells of the tumor microenvironment promote HCC advancement. Finally, we discuss the therapeutic potential of targeting lipid metabolism in liver cancer treatment.

Mitochondrial DNA (mtDNA) variability, especially heteroplasmy, is believed to affect cellular immunobiogenesis, particularly in monocytes in metabolic syndrome (MetS). This study aimed to identify associations of monocytic mtDNA variability with its phenotypic indices, including cytokine secretion and gene expression, and cardiometabolic parameters in patients with MetS.

The cross-sectional study recruited 87 adult participants, including 34 healthy blood donors (Control group), 21 obese patients (Obesity group), and 32 MetS patients (MetS group). Blood biochemistry tests were performed on venous blood samples, and monocytes (CD14+ cells) were isolated. Monocyte mtDNA was analyzed by next-generation sequencing to identify low (5–10%) and intermediate (10–95%) heteroplasmy, and homoplasmy (≥95%). Expression of genes related to mitochondrial biogenesis, mitochondrial uncoupling, oxidative stress system, and NF-κB signaling was assessed by quantitative real-time polymerase chain reaction. Monocytes cultured with and without lipopolysaccharide for 24 h were analyzed by enzyme-linked immunosorbent assay to assess the cytokine secretion stimulation index.

Monocyte mtDNA showed low variability, but alternative homoplasmies were significantly more common. Intermediate and low heteroplasmy from the protein-coding locus correlated with stenosis (r = 0.396; 95% confidence interval (CI) 0.067–0.647) and low-density lipoprotein levels (r = −0.258; 95% CI −0.45 – −0.043). Intermediate heteroplasmy from the rRNA locus correlated with blood insulin levels (r = −0.228; 95% CI −0.424 – −0.019). D-loop low heteroplasmy correlated with fasting blood glucose (r = 0.275; 95% CI 0.062–0.464). Homoplasmies were associated with creatinine, blood urea nitrogen, and alkaline phosphatase. Intermediate heteroplasmy in mtDNA was associated with the monocyte cytokine secretion stimulation index (R2 = 0.156, P = 0.003). However, there was no significant association between mtDNA variability and the expression of the various genes.

Monocyte mtDNA shows relatively low variability. Low and Intermediate heteroplasmy are associated with cardiometabolic parameters, and intermediate heteroplasmy is associated with the monocyte cytokine secretion stimulation index.

Acute leukemias with chimeric fusion genes involving FET (FUS, EWSR1, and TAF15) family proteins and ETS (E26 transformation-specific)-like transcription factors often present with unique clinical and pathological characteristics. This mini-review aims to summarize the clinical and pathological features of acute leukemia cases harboring rearrangements involving the fused in sarcoma (FUS) or Ewing sarcoma breakpoint region 1 (EWSR1) genes.

An extensive literature review was performed on reported acute leukemia cases with fusions involving FUS or EWSR1. The details of the reported cases, as well as summarized information, are presented.

Rare cases of acute leukemia have been found to harbor either FUS or EWSR1 gene rearrangements with ETS or non-ETS proteins as partners and demonstrate heterogeneous clinical and pathological features. Acute leukemias carrying FUS gene rearrangements present with diverse immunophenotypes and are predominantly, but not exclusively, acute myeloid leukemia (AML), with ERG as the most frequent fusion partner. In contrast, acute leukemias with EWSR1 gene rearrangements more commonly present as B-cell acute lymphoblastic leukemia (ALL) and mixed phenotypic acute leukemia (MPAL), with ZNF384 as the predominant partner. At present, FUS::ERG-positive AML is the only specific entity with a FET::ETS fusion that is formally recognized in the World Health Organization 5th edition hematolymphoid tumor classification (WHO-HEM5) and the International Consensus Classification (ICC) systems. Cytogenetic karyotyping and fluorescence in situ hybridization remain crucial tools for detecting chromosomal translocations in over half of acute leukemias harboring FUS or EWSR1 gene rearrangements. However, a subset of patients may exhibit a normal karyotype and require advanced molecular diagnostic methods. EWSR1-rearranged leukemias can be difficult to distinguish from Ewing sarcoma and therefore require particular attention.

As more cases and additional data become available, it may be justified to expand this category of acute leukemias to include other specific acute leukemia entities with fusions involving FET::ETS, such as FUS::FLI1 and FUS::FEV, in addition to FUS::ERG-positive AML. However, additional data are required to support such subclassification. In contrast, AML cases with EWSR1 rearrangements are exceedingly rare and display considerable variability. Cases of B-ALL or B/myeloid MPAL with the EWSR1::ZNF384 fusion may be more appropriately classified together with other ZNF384-rearranged leukemia subtypes. Advanced molecular diagnostic methods, especially RNA-based next-generation sequencing, are suggested to improve the accurate diagnosis of acute leukemias with FUS or EWSR1 fusions. Additional pathologic workup, particularly immunohistochemical staining with hematopoietic markers, is highly recommended to differentiate EWSR1-rearranged leukemia from Ewing sarcoma.

The immunosuppressive tumor microenvironment (TME) limits immunotherapy efficacy in intrahepatic cholangiocarcinoma (ICC). Understanding the molecular drivers of this TME is essential for developing new therapies. This study aimed to identify novel oncogenes that modulate the immune landscape of ICC using a multi-omics approach.

We integrated transcriptomic and proteomic data from our ICC cohorts with public datasets (TCGA-CHOL, GSE107943, OEP002768) to identify genes co-upregulated with PD-L1 (CD274). Single-cell RNA sequencing (scRNA-seq) was used to analyze cell-type-specific expression and intercellular communication. Clinical significance was validated through tissue microarrays and multiplex immunofluorescence in an independent ICC cohort.

Multi-omics screening identified TACC3 as a key candidate in ICC. Elevated TACC3 expression in ICC tissues correlated with poor prognosis and promoted tumor cell proliferation and migration. TACC3 activated the STAT3 pathway, increasing PD-L1 transcription. scRNA-seq showed TACC3/PD-L1 interaction in malignant epithelial cells, with PD-L1 co-expressed with FOXP3 in regulatory T cells (Tregs). Cell–cell communication analysis predicted strong interactions between malignant cells and Tregs. TACC3 knockdown reduced PD-L1 expression and inhibited STAT3 and AKT phosphorylation. Clinical validation confirmed co-expression of TACC3, PD-L1, and FOXP3, with high TACC3 levels linked to worse clinicopathological features and shorter progression-free survival.

Our study defines a TACC3-STAT3-PD-L1 axis driving immunosuppression in ICC. TACC3 fosters an immunosuppressive TME by upregulating PD-L1 and is associated with a Treg-rich contexture, suggesting that TACC3 may serve as a potential therapeutic target to overcome ICC immunosuppression.

Atherosclerosis is a chronic inflammatory vascular disease in which macrophages play central roles in lipid uptake, foam cell formation, plaque progression, plaque instability and, under certain conditions, plaque regression. This narrative review summarizes current knowledge on macrophage biology in atherosclerosis, with emphasis on macrophage phenotypic diversity, monocyte-endothelial interactions, foam cell formation, extracellular matrix remodeling, immune-cell interactions, cytokine signaling, mitochondrial dysfunction and cellular senescence. The review also discusses emerging macrophage-targeted strategies, including modulation of inflammatory activity, macrophage polarization, cholesterol efflux and lipid homeostasis. Although these approaches provide promising mechanistic and therapeutic insights, many remain at the preclinical stage. Further studies are needed to validate macrophage subtype-specific biomarkers, clarify the interaction between mitochondrial dysfunction and senescence, and evaluate safe and effective combination strategies for clinical translation.

While norepinephrine (NE) is the cornerstone of septic shock resuscitation, “macrocirculation–microcirculation decoupling” at high doses remains a critical clinical challenge. This study aimed to explore the quantitative tipping point where the NE dose shifts from a life-saving vasopressor to a microcirculatory toxin in septic intensive care unit patients.

In this prospective observational study (January–September 2025), we used handheld vital microscopy to monitor sublingual microcirculation (microvascular flow index [MFI], total vessel density, perfused vessel density, proportion of perfused vessels [PPV], and heterogeneity index [HI]) in adult septic patients within 24 hours of admission and on Day 3. Beyond standard linear analysis, generalized additive models were employed to identify the dose–response thresholds associated with microcirculatory deterioration, adjusted for Acute Physiology and Chronic Health Evaluation II, interleukin-6, and systemic hemodynamics.

Of 144 screened patients, 66 were analyzed. The NE dose showed strong linear correlations with lactate (r = 0.583, P < 0.001) and HI (r = 0.444, P < 0.001), and negative correlations with MFI (r = −0.492, P < 0.001). Crucially, generalized additive models analysis revealed a significant nonlinear “cliff effect”: when the NE dose exceeds the 0.71–0.80 µg/kg/min threshold (PPV: 0.71 µg/kg/min, HI: 0.72 µg/kg/min, MFI: 0.80 µg/kg/min), microcirculatory perfusion parameters deteriorate abruptly (all P < 0.05). Multivariable Cox regression identified an NE dose of 0.80 µg/kg/min as an independent predictor of increased mortality (hazard ratio = 1.32, 95% confidence interval: 1.28–3.10, P = 0.039).

In patients with septic shock, higher NE doses were associated with impaired microcirculatory perfusion and worse outcomes. These findings support individualized vasopressor titration and suggest that microcirculatory monitoring may help identify patients at risk of vasopressor-associated microvascular dysfunction.

Early detection of gastric cancer and timely identification and management of precancerous lesions are critical for reducing gastric cancer mortality and may contribute to incidence reduction and improved survival outcomes. Although gastroscopy remains the gold standard for gastric cancer screening and diagnosis, its invasiveness, discomfort during the procedure, and limited acceptability restrict population participation and screening coverage. Recently, rapid advances in liquid biopsy technologies have led to the discovery of numerous multi-omics biomarkers spanning genomics, transcriptomics, proteomics, and metabolomics, with promising diagnostic performance. However, their translational value for population-based gastric cancer screening and control remains insufficiently characterized. This review aims to provide a comprehensive overview of multi-omics biomarkers for gastric cancer screening and to evaluate their potential role in advancing population-level gastric cancer control. First, we synthesize multi-omics biomarkers with diagnostic and screening relevance across the continuum of gastric carcinogenesis, from chronic inflammation and atrophy to intestinal metaplasia, dysplasia, and early gastric cancer. Furthermore, we highlight the integrative value of multi-omics biomarkers, current limitations, translational challenges, and future opportunities for moving biomarkers from discovery to implementation in organized screening programs. In conclusion, multi-omics biomarkers have the potential to complement existing screening strategies by providing scalable, non-invasive, and risk-adapted approaches for early gastric cancer detection. Bridging the gap between biomarker discovery and real-world implementation will be essential for realizing their value in future gastric cancer screening programs.