• The combination regimen yielded promising efficacy in NSCLC patients after EGFR-TKI resistance, particularly those with PD-L1-positive tumours.
• Higher peritumour NK cell and lower peripheral helper T cell were associated with favourable ORR and longer PFS, respectively.
• After disease progression, the proportion of S100A9⁺ MDSC increased, but Treg cells decreased.

• The ESCC-TRCs replicates the characteristics of ESCC stem cells, which are inhibited by ZSH-2208.

• In vivo and in vitro experiments demonstrated that ZSH-2208, a novel RA analogue, effectively inhibits the growth of ESCC-TRCs through the RARγ–TNFAIP3 axis.

• Low levels of TNFIP3 protein may be associated with improved survival probability in ESCC patients.

During intestinal ischaemia, mitochondrial oxygen uptake is reduced when cellular oxygen partial pressure decreases to below the threshold required to maintain normal oxidative metabolism.

Upon reperfusion, intestinal hypoxia may persist because microcirculatory flow remains impaired and/or because available oxygen is consumed by enzymes, intestinal cells and neutrophils.

1. Developing the Programmed Cell Death Index (PCDI) utilizing multiple machine learning algorithms for patients with less-defined subtype diffuse large B-cell lymphoma.

2. The difference in clinical characteristics, circulating tumour DNA burden and immune profiling between patients with distinct PCDI groups.

3. A potentially effective regimen was speculated for patients with high PCDI scores who tend to exhibit worse progression-free survival.

1. ATF3 deficiency led to degradation of P21 through ubiquitination, which abolished the G1 phase arrest.

2. VSMCs had no time window to repair the damaged DNA, leading to generation of micronuclei in cytoplasm.

3. Cytoplasmic micronuclei facilitating the activation of cGAS–STING pathway, thus inducing the phenotypic switch and apoptosis of VSMCs

Hypoxia plays a pro-inflammatory role by increasing phosphoglycerate kinase 1 (PGK1) activity and reducing the binding of the deubiquitinating enzyme ubiquitin-specific peptidase 14 to NOD-like receptor family pyrin domain containing 3 (NLRP3), thereby reducing the ubiquitination level of NLRP3. CBR-470-1, a specific inhibitor of PGK1, can reduce PGK1 activity to reverse the role of hypoxia in the progression of osteoarthritis.

(1) TTN knockout results in decreased ANKRD1 expression, impairing DNA damage repair.

(2) Impaired DNA repair increases apoptosis and enhances radiosensitivity in rectal cancer cells.

(3) Radiotherapy in TTN-deficient cancer cells induces immune cell infiltration, including CD4⁺ and CD8⁺ T cells.

(4) Apoptosis and immune modulation contribute to improved radiotherapy outcomes in rectal cancer.

1. Long non-coding RNA (lncRNA) AC010789.1 was downregulated in hair follicle tissues from androgenic alopecia (AGA) and upregulated in hair follicle stem cells (HFSCs).
2. LncRNA AC010789.1 promoted the proliferation and migration of HFSCs.
3. FTO/hnRNPA2B1-mediated m⁶A modification of lncRNA AC010789.1 promoted HFSCs growth by activating S100A8/Wnt/β-catenin signalling.
4. Exosome-derived AC010789.1 accelerated HFSCs proliferation.

The newly discovered peptide PDBAG1 is the first small molecule substance found to directly target and degrade C1QBP, demonstrating significant tumour inhibitory effects and therapeutic potential.

• Cancer-associated fibroblasts (CAFs) can enhance PD-L1 glycosylation through the glycosyltransferase EDEM3, contributing to immune evasion during tumour progression.
• EDEM3 predominantly activates the recruit M2-like macrophages via a glucose metabolism-dependent mechanism.
• Blocking glucose utilization antagonizes recruiting and polarizing M2-like macrophages synergistically with PD-1 antibody to improve anticancer immunity.

• Four phyla, five classes, nine orders, 17 families and 36 genera have been found associated with NSCLC prognosis.
• We identified a protective microbial cluster associated with delayed recurrence and a harmful microbial cluster related to shorter survival and earlier recurrence.
• We identified Peptococcus as an independent, detrimental prognostic factor for NSCLC, potentially impacting prognosis via TNF signalling.

1. After a 3-year follow-up, this study further confirms that the combination therapy of atezolizumab and bevacizumab has long-term efficacy in mucosal melanoma.

2. Patients with upper site melanoma and NRAS mutation exhibited a more favourable response to this combination treatment.

3. Inflammatory cell infiltration, angiogenic status and activation of the SMAD2 and p38 MAPK pathways may be prognostic indicators.

1. Euchromatic histone lysine methyltransferase 2 (EHMT2) is overexpressed in advanced prostate cancer, restraining catastrophic chromosomal instability (CIN) and enhancing cell fitness.

2. EHMT2 functions via the centromeric R-loop-driven ATR–CHK1–Aurora B pathway to promote chromosomal stability.

3. EHMT2 confers enzalutamide resistance via activating Aurora B.

4. Cullin 3 (CUL3) promotes EHMT2 destabilisation via deubiquitination.

Disturbed flow degrades endothelial MAPK6 through the TRIM21-regulated ubiquitin‒proteasome pathway, consequently promoting inflammation via EGR1-mediated nuclear import of NF-κB p65 and downstream CXCL12 transcription, leading to acceleration of plaque formation.

Our investigation discloses a pivotal relationship between PINK1 and Prdx2 in the context of HFpEF.

Notably, PINK1, in addition to its role in mitochondrial autophagy, can increase Prdx2 expression, effectively remove ROS and attenuate cardiomyocyte apoptosis by modulating the JNK and p38 pathways, thereby alleviating myocardial lipotoxicity and improving HFpEF cardiac function.

Our studies offer valuable insights, opening avenues for the development of innovative therapeutic strategies in the prevention and treatment of HFpEF .

• Human NK cells can be efficiently transfected with mRNA to safely express an EphA2-CAR without genomic alterations.

• EphA2-targeted CAR-NK cells exhibit enhanced cytotoxicity against paediatric sarcomas, including rhabdomyosarcoma, Ewing sarcoma and osteosarcoma.

• This study demonstrate the potential of CAR-NK cell therapies to improve outcomes in hard-to-cure paediatric sarcomas and provides a foundation for their clinical evaluation.

A comprehensive multi-omics solution capable of obtaining fragmentomics landscape of cfDNA was developed and followed by an integrated model for non-invasive early diagnosis of DLBCL, achieving excellent efficacy of R-CHOP before DLBCL treatment.

Protein acetylation and deacetylation influence metabolic reprogramming in tumour cells by regulating the function and activity of various signalling pathways, transcription factors and metabolic enzymes.

CENPM is the key gene that drives ACC metastasis, and a robust biomarker for ACC prognosis.

Silencing CENPM impedes ACC metastasis in vitro and in vivo by physical interaction with immune checkpoint ligand FGL1.

FGL1 is overexpressed in ACC and promotes ACC metastasis.

• Single-cell multi-omics analysis revealed distinct immune cell populations and their functional states in anti-NMDARE.
• Systematical analysis identified key immunoregulation programs involved in disease progression.
• Interactions via cytokines among immune cells may intensify the inflammatory response and disease activity, providing therapeutic implications.

1. Nanopore adaptive sampling sequencing is reliable for the analysis of germline alterations by improving the characterization of LSR and detecting SNV even at low coverage.

2. The protocol we set up can be immediately used in routine molecular diagnosis labs for the characterization of large-scale rearrangements.

•NaY-based proteomics enables cost-effective and efficient plasma proteome screening.

•Prospective cohorts uncover plasma protein dynamics across benign and malignant nodules and different cancer stages.

•Machine learning models achieve high-accuracy lung cancer diagnosis from plasma profiles.

•A minimal biomarker panel identified via NaY-based proteomics enables low-cost, multitasking capabilities for diagnosis and staging.

Durable 5-year End-of-Study results from the ‘first-in-the-world’ gene therapy trial for Fabry disease.

1. Alterations of the lower respiratory tract microbiome indicate different clinical responses to ICB within advanced NSCLC.
2. Reduced microbial diversity of lower respiratory tracts impairs anti-tumoral performances.
3. Microbe-derived metabolites perform as a dominant regulator to remodify the microecological environment in lower respiratory tracts.
4. Multi-omics sequencings of the lower respiratory tract possess the potential to predict the long-term clinical responses to ICB among advanced NSCLC.

1. Cytidine/uridine monophosphate kinase 2 (CMPK2) expression is up-regulated in the nasal mucosa of patients and mice with allergic rhinitis (AR).

2. CMPK2 caused NLRP3 inflammasome activation via mitochondrial DNA (mtDNA)-STING pathway.

3. Blocking CMPK2 or STING signalling significantly reduced the activation of NLRP3 in house dust mite (HDM)-challenged mice and human nasal epithelial cells (HNEPCs).

We identified a subpopulation of tumor cells with lower expression levels of APOE in both mRNAs and proteins that were highly associated with more advanced stages and metastasis of PTC by integrating single-cell sequencing and spatial transcriptome assays.

• High RECQL4 expression limits survival and can act as an independent prognostic factor in melanoma patients.

• RECQL4 has the potential to act as a negative feedback mediator of immune checkpoint-targeted therapy by limiting signatures associated with therapeutic efficacy.

• RECQL4 favours an immune-evasive phenotype by downregulating major histocompatibility complex class II molecules.

This review discusses the regulatory mechanisms and pathological significance of pseudouridylation in human diseases, with a special emphasis on its involvement in tumourigenesis. Furthermore, the potential therapeutic advantages of targeting pseudouridylation are explored, offering novel strategies for disease treatment.

Working model illustrating the underlying mechanism of perturbation of microtubule nucleation and assembling the spindle by D417N missense variant.

• This study provides single-cell landscape of human liver samples across different ALD stages.
• The ALB⁺ KRT7⁺ epithelium were enriched in ALD patients, and the function of this epithelial population varied significantly across ALD stages.
• ALB⁺KRT7⁺ epithelium from advanced alcohol-related cirrhosis had malignant transformation potential and tumour promotion activity.
• The comprehensive changes of parenchymal and nonparenchymal cells in the ALD livers lay a hidden danger for the further malignant progression.

Our work demonstrates a pathogenic role of endothelial Annexin A8 in atherosclerosis. The upregulation of AnxA8 in both human and mice atherosclerotic plaques strongly suggest that AnxA8 promotes disease progression through regulation of adhesion molecules expression and influx of immune cells to the intima. Therapeutic interventions to reduce AnxA8 expression in endothelial cells may delay atherosclerosis progression.