• MAFLD is associated with increased hepatocytes NRF2 expression.
• NRF2 alleviates MAFLD by suppressing pyroptosis.
• NRF2 directly inhibits GSDMD expression to regulate pyroptosis.
• Targeting the NRF2–pyroptosis (GSDMD) axis offers a potential therapeutic strategy for MAFLD.

• Canonical Hippo pathway activated in nphp1-deficient disease models and patients.

• Kibra was a key upstream molecule in regulating the activation of canonical Hippo pathway in nphp1-deficient disease models and patients and closely related to renal cyst formation and fibrosis in nphp1^KO mice.

Kinase inhibition–based therapies are recommended for a small subset of LC patients with driver mutations. Through enabling technologies and bioinformatics, we demonstrate the potential of KI-based therapies based on the patient specific needs. Thus, most LC patients become eligible for such treatment algorithms.

Genome-wide profiling reveals the redistribution of m6A modification on pseudogene-derived lncRNAs and m6A redistribution-relevant dysregulation of pseudogenes in HGSOC. RPS15AP12, as a representative processed pseudogene, is up-regulated by FTO-mediated demethylation and acts as a miRNA sponge to promote RPS15A expression via competitively binding to miR-96-3p. The RPS15AP12/ RPS15A axis exhibits an anti-tumour effect via inhibiting innate immune response in ovarian cancer.

Zinc finger protein 36 bounds to the 3′ untranslated region of Ythdc2 mRNA, facilitating its degradation. Ythdc2 can bind to SLC7A11 mRNA to accelerate its decay, thereby reducing glutathione levels and aggravating ferroptosis-induced cardiac hypertrophy.

Our study identified that the proportions of CD39+ Tregs and moDCs in the peripheral blood were correlated with the response to immunotherapy in patients with advanced breast cancer. These two subpopulations are potential predictive biomarkers for determining patient prognosis, offering valuable guidance for treatment strategies.

In unilateral ischaemia–reperfusion injury (UIRI), Trem2 expression is upregulated by hypoxia via HIF-1α in macrophages, and the activation of Trem2 enhances phagocytosis and reduces cytokine production through the PI3K-AKT pathway in macrophages. An adoptive cell therapy using Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)-overexpressing macrophages effectively mitigates the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) in UIRI animals.

MIABEPIR, a brain endothelial piRNA, as a key regulator of neurovascular dysfunction in maternal immune activation. MIABEPIR modulates BBB integrity and endothelial autophagy through the Dapk2 pathway, highlighting a potential therapeutic target for neurodevelopmental disorders.

Schematic model detailing the molecular mechanisms of LINC01088 in normal brain cells and GBM cells.

LINC01088 is transcriptionally upregulated by SP1.

LINC01088 acts as a scaffold platform to bind USP7 and HLTF.

USP7, as a deubiquitinating enzyme of HLTF, participates in inhibiting the ubiquitin-proteasome degradation of HLTF.

HLTF transcriptionally upregates the expression of downstream SLC7A11, and ferroptosis of GBM cells was inhibited.

1. ModRNAs-transfected hADSCs exhibit pulsed and transient expression, enabling efficient production of functional VEGFA and bFGF proteins.
2. Intracardiac injection of these engineered hADSCs leads to the enhancement of cardiac function and the improvement of electrical conduction.
3. The hADSCs^dual mainly exerts its effect on myocardial infarction by promoting stable vascular regeneration and suppressing cell apoptosis.

The role of m5C in cancers. The role of m5C regulators- writers, erasers, and readers- in various cancer types, including NSCLC, PCa, GC, AML, BCa, and HCC.

Irisin is identified as a crucial factor in muscle‒kidney crosstalk, inhibiting cGAS-STING signaling and preventing dsDNA leakage via integrin αV/β5 in tubular epithelial cells (TECs), thus mitigating tubular injury and inflammation.

Elevated expression levels of SH3GL1 in patients with diffuse large B-cell lymphoma (DLBCL) was associated with poor prognostic outcomes.

SH3GL1 plays an important role in promoting DLBCL cell survival through the regulation of ferritin heavy chain 1 (FTH1)-mediated ferroptosis and doxorubicin resistance.

SH3GL1 can be a valuable prognostic biomarker and a potential target for anti-DLBCL intervention in the future .

• Brain-centric lncRNAs regulate gene networks, and their disruption is linked to MDD.
• In MDD, altered lncRNAs disrupt gene regulation by changing chromatin looping or modifying chromatin accessibility.
• These changes lead to neuronal dysfunction, affecting neural circuitry and synaptic plasticity.
• The result is impaired brain function, contributing to the symptoms of MDD.

• Topical tyrosine kinase 2 (TYK2) inhibitor alleviates psoriasis-like dermatitis.
• Topical TYK2 inhibitor reduces psoriasis progression through restraining the inflammatory responses of keratinocytes.
• The inhibition of TYK2 regulates the inflammatory response of keratinocytes through AKT-SP1-NGFR-AP1 pathway.

• Ferroptosis-related mechanisms significantly affect the biology of CD4⁺ T-cell subsets and are further involved in inflammatory diseases.
• Crosstalk between CD8⁺ T cells and tumour cells induces ferroptosis in the tumour microenvironment.
• Glutathione peroxidase 4 loss promotes regulatory T-cell ferroptosis to enhance anti-tumour immunity.

We confirmed GI-Y2 as a novel inhibitor of GSDMD. GI-Y2 directly interacts with the Arg10 residue of GSDMD and reduces the membrane binding of GSDMD-N. We constructed macrophage membrane-coated GI-Y2 nanoparticles to enhance the targeting of GI-Y2 to macrophages in atheromatous plaques and demonstrated its vascular protective effect.

This review explores vascularised organoids in oncology, highlighting their advantages over 2D cultures and animal models in replicating the tumour microenvironment. It examines fabrication methods, vascularisation techniques and advancements in biomaterials, emphasising their applications in studying vasculature–cancer interactions, drug screening and advancing cancer research and clinical practice.

Schematic depiction of MAPK signalling pathway and its cellular effects within the context of BRAF^V600E inhibition and PROTAC-mediated degradation.

EJCs protected the methylation sites of the NFATc1 gene (located in the inner exon fragment of 50–200 nt) from hypermethylation and degradation, and the “shields” disappeared when the exon fragment was extended to 300 nt. Downstream, YTHDF2 induced the degradation of NFATc1 transcripts without site restriction. EJCs act as “shields” to regulate the m6A region selectivity of the NFATc1 gene, thereby determining the characteristics of the m6A distribution in this gene.

Schematic mechanism of inhibitor of differentiation 2 (Id2)-mediated interferon-γ (IFN-γ) expression upregulation in the pathogenesis of rheumatoid arthritis (RA).

• Intratumoral Fusobacterium nucleatum exhibits significant spatial heterogeneity within breast cancer tissues.
• F. nucleatum colonization alters the expression of key proteins involved in tumour progression and migration.
• The MAPK signalling pathway is a critical mediator of F. nucleatum-induced breast cancer cell proliferation and migration.
• VEGFD and PAK1 are potential therapeutic targets to mitigate F. nucleatum-induced tumour progression.

• Study involved 427 women with HIV.
• Identified 245 aberrant DNA methylation sites and 85 methylation regions in CD4+ T cells linked to the HIV-1 reservoir.
• Highlighted genes are involved in viral replication, immune defence, and host genome integration.
• Findings suggest potential molecular targets for eradication strategies.

In gastric cancer cells harbouring p53 mutations, ovarian tumour domain-containing 5 (OTUD5) transcription is upregulated due to the inactivation of p53, allowing OTUD5 to stabilise glutathione peroxidase 4 (GPX4) protein, inhibit ferroptosis and thereby promoting gastric cancer progression .

Citrullinization is a post-translational modification that has rarely been studied. Our research found that enzyme peptididylarginine deiminase 4 (PADI4) facilitates the citrullination of protein arginine methyltransferase 2 (PRMT2), a process essential for the stabilization of PRMT2 expression and the enhancement of its function in promoting the transcription of IDs family (ID1 and ID2) via histone arginine methylation. This mechanism subsequently increases cancer stem cells (CSCs) stemness and contributes to the cisplatin resistance observed in oesophageal squamous cell carcinoma (OSCC). Mutations at the R312 site or inhibition by GSK484 can attenuate stemness in OSCC, thereby reducing cisplatin resistance.

NOP2/Sun RNA methyltransferase 2 (NSUN2) promotes 5-methylcytosine (m5C) modification of Ring Finger Protein 115 (RNF115) mRNA, which is subsequently bound by YBX1. Then, YBX1 interacts with Eukaryotic Translation Initiation Factor 4A1 (EIF4A1) to promote RNF115 mRNA looping and translation. Subsequently, RNF115 interacts with dihydroorotate dehydrogenase (DHODH) to promote its K27 ubiquitination and inhibit the autophagic degradation of DHODH to resist ferroptosis and promote hepatocellular carcinoma (HCC) progression.

The BBB hinders mAb-based brain disorder therapies.

A brain-targeted B-cell-depleting mAb for MS that efficiently crosses the BBB via hTfR1 was developed using Brainshuttle technology (1A and 1B).

The Brainshuttle-CD20 mAb was well tolerated (2A and 2B) and displayed B-cell-killing properties (1C), paving the way for future development and clinical translation of TfR1-targeting therapies for increased brain penetration.

LINC02776 was significantly upregulated in platinum-resistant ovarian cancer (OC) patients compared to those sensitive to platinum therapy. LINC02776 directly binds catalytic domain of PARP1 to enhance PARP1-dependent polyADP-ribosylation, thereby promoting homologous recombination (HR) restoration.