LPS induces the transcription and expression of ZBP1 via STAT1, driving macrophage polarisation towards the pro-inflammatory M1-subtype macrophage, which results in inflammatory cell infiltration and cardiac dysfunction. In contrast, myeloid-specific ZBP1 deficiency shifts macrophages towards the anti-inflammatory M2 phenotype, reducing inflammatory cell infiltration and alleviating cardiac dysfunction. These findings highlight the role of macrophage-derived ZBP1 in septic cardiomyopathy, suggesting that ZBP1 could be a potential therapeutic target for septic cardiomyopathy.

Mφ, macrophage. KO fragment, knockout fragment of Zbp1 gene.

Seven robust meta-programs were identified in GC. The crosstalk between MP7 and myCAFs creates an immune lockdown microenvironment and promotes cancer metastasis, resulting in poor survival of GC patients.

• cGAS/STING signalling pathway was activated in macrophages infiltrating allografts.

• cGAS/STING signalling pathway in macrophages exacerbated allograft rejection, promoted antigen-presenting ability of macrophages and enhanced alloreactive T-cell responses in an IFN-α2-dependent manner.

• STING inhibition potentiated the therapeutic efficacy of CTLA4-Ig in OB.

A schematic illustration of engineered EVs (CD38-EVs-Dox) delivered via MNs or intravenous administration for plasmacytoma treatment. CD38-EVs encapsulated within MNs effectively enhanced tumour cell targeting compared to standard EVs in MNs and intravenously administered CD38-EVs, with reduced lung and spleen distribution.

Obesity affects various aspects of allergic airway diseases, including prevalence, endotypes, clinical features and therapeutic efficacy. Therefore, obesity-related allergic airway diseases represent a unique class of endotypes and phenotypes, which need much more in-depth research for tailored treatment.

USP22 promotes the proliferation of hepatocellular carcinoma cells via deubiquitinating and stabilising cyclin-dependent kinase CDK11B, and it inhibits Sorafenib-induced ferroptosis by decreasing H2BK120ub occupancy at TFRC TSS downstream region.

1. SNEP1 is downregulated in the cardiomyocyte of ICM mouse models and in patients.

2. SENP1 deSUMOylates the SUMO2-mediated modification of MEF2C at lysine 401 for protein stability.

3. The interaction with SENP1 controls the nuclear condensation of MEF2C to promote cardiomyocyte function.

4. Cardiac rescue of SENP1 alleviates ischemic heart injury in ICM mouse models by AAV9.

LSD1 deletion increased PD-L1 expression in tumor cells, rejuvenated effector CD8+ T cells, and enhanced antigen presentation. Combination therapy with an LSD1 inhibitor and anti-PD1 antibody remodeled the tumor microenvironment, reversing the acquired resistance and prolonging the duration of response to anti-PD1 therapy.

MDVs as a mechanism for mitochondrial quality control play a significant role in the development and progression of various diseases, such as tumours, neurodegenerative diseases (such as Parkinson's disease, Alzheimer's disease), cardiovascular diseases, skeletal muscle, etc.

In degenerated NPCs, AP-1 activation increased the accessibility of chromatin to transcriptionally upregulate CEMIP, while CEMIP disrupted ECM homeostasis through its regulation of HMW-HA degradation, and its contribution to fibrotic changes within NP tissues. The AP-1/CEMIP axis emerges as a novel target for the prevention and treatment of IDD.

• The gut microbiota regulates the gut–brain–immune axis, modulating neuroimmune interactions in inflammatory bowel disease (IBD).
• Microbiota-derived metabolites influence immune cells, driving cytokine release that activates dorsal root ganglion (DRG) neurons.
• DRG neurons secrete mediators, enabling bidirectional neuroimmune communication essential for intestinal homeostasis.
• Disruptions contribute to IBD, offering therapeutic targets. Graphic created with BioRender.com (https://biorender.com).

1. Colorectal cancer cells secrete lactate to upregulate VSIG4 in macrophages via the H3K18la-METTL14-m6A axis.

2. VSIG4 promotes fatty acid oxidation of macrophages and drives its M2-type polarization.

3. These VSIG4-expressing M2 macrophages promote tumour progression and an immunosuppressive microenvironment.

4. Inhibition of VSIG4 expression can synergistically enhance the therapeutic effect of anti-PD-1 antibody.

• Prolonged sedentary time leads to a depletion of Roseburia sp. CAG:471 and Firmicutes bacterium CAG:83, and suppresses arginine biosynthesis.
• Decreased L-citrulline and L-serine function as key microbial effectors mediating the adverse effect of sedentary time on insulin sensitivity.
• Targeting gut microbiota holds promise to combat insulin resistance induced by excessive sedentary time.

In this study, Thornton and colleagues utilised an induced pluripotent stem cell (iPSC)-based model of inherited erythromelalgia (IEM) to screen a library of 295 small molecules in search of potential pain-modulating compounds. Their screening identified four compounds that significantly reduced spontaneous firing in iPSC-derived nociceptor-like cells, with minimal associated toxicity .

1. This review discusses five major co-inhibitory receptors (PD-1, CTLA-4, LAG-3, TIM-3 and TIGIT) and their related mechanisms of T cell exhaustion in the tumour environment.

2. We also discuss the clinical application of checkpoint inhibitors (ICIs) in cancer immunotherapy.

3. The potential of bispecific antibodies (BsAbs) in cancer immunotherapy is highlighted.

1. In the established angiotensin II-induced AAA model, CD248 deficiency exacerbated aortic lesion, accompanied by lower collagen I content and p38 activation.

2. Silencing CD248 in VSMCs led to reduced MAP kinase activation and ECM production.

3. Furthermore, loss of CD248 in VSMCs destabilizes membrane receptors for angiotensin II and PDGF, a phenomenon possibly mediated by its C-terminal cytoplasmic tail.

• Kinase mutations in RTKs are primary or secondary drivers in multiple cancer types
• Some of these mutations confer resistance to type I but not to type II inhibitors in preclinical samples and in patients
• The biochemical characterization of mutations in oncogenic kinases based on their sensitivity to type I and type II inhibitors is crucial to inform clinical intervention

1. EVs were isolated from plasma of ME/CFS patients and healthy controls at baseline, and 15 min and 24 h postexercise.

2. Untargeted proteomics revealed dysregulation in energy metabolism, the complement system, and the endoplasmic reticulum stress response.

3. Changes in EV protein levels postexercise are associated with post-exertional malaise.

4. These findings suggest promising therapeutic targets for post-exertional malaise and ME/CFS pathophysiology.

Ovarian tumour domain-containing protein 3 (OTUD3) modified PLK1 through deubiquitinating K48-linked ubiquitination in the amino acid sequence 35–305 of PLK1. Decreased expression of OTUD3 after cerebral ischaemia-reperfusion resulted in increased PLK1 ubiquitination and decreased PLK1 protein expression. In turn, this inhibited the activation of the PI3K/AKT signalling pathway, reduced glutathione content, inhibited the activity of GPX4 and led to an increase in the generation of ROS, which ultimately contributed to the occurrence of ferroptosis in neuronal cells.