•This was the first gene therapy clinical trial to be completed for Fabry disease.

•There were no adverse events of any grade attributable to the cellular gene therapy intervention or host conditioning throughout the follow-up interval of 5 years.

•After reduced-intensity melphalan treatment, all patients engrafted their autologous modified α-gal A expressing cells.

•All patients synthesized and secreted α-gal A throughout the course of the study.

•Expression of α-gal A resulted in a decrease in plasma lyso-Gb3 in four of five patients and stabilization of kidney symptoms in all patients.

•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.

•Integration of AI with Single-Cell Informatics for Precision Medicine: The caiSC system combines artificial intelligence and single-cell data to improve diagnostics, treatment predictions, and personalized medical decision-making.

•Challenges in Data Coverage and Model Robustness: caiSC currently faces limitations due to incomplete data across cell types, diseases, and organs, as well as challenges in data quality and high computational demands, which affect model accuracy and clinical applicability.

•Future Potential and Regulatory Needs: The caiSC framework’s development could lead to innovations such as digital cell twins, enabling personalized simulations of cellular responses for better treatment planning, though regulatory certification is essential for safe clinical use.

•Hypoxia plays a pro-inflammatory role by increasing PGK1 activity and thereby decreasing the ubiquitination level of NLRP3.

•Hypoxia plays a pro-inflammatory role by increasing PGK1 activity, reducing the binding of the deubiquitinating enzyme USP14 to NLRP3, and reducing the ubiquitination level of NLRP3.

•CBR-470-1 reverses the role of hypoxia in the progression of osteoarthritis.

1. The association between TTN mutations and tumour mutation burden, as well as immune cell infiltration in READ, is examined.

2. TTN mutations enhance the radiation sensitivity of READ cells and weaken DNA damage repair in response to radiation.

3. TTN mutations increase the radiation sensitivity of READ cells by inhibiting ANKRD1.

4. The infiltration of CD8⁺ and CD4⁺ T cells induced by TTN mutations is essential for anti-tumour immunity.

5. TTN mutations serve as a biomarker for the pathological response to preoperative radiotherapy in READ.

•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.

•Adaptive sampling is suitable for the analysis of germline alterations.

•Improves the characterization of Large Scale Rearrangement and detects SNV at a minimum coverage of 10x.

•Allows flexibility of sequencing.

•Addressing unmet clinical needs in paediatric Sarcomas. Paediatric sarcomas, including rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma, exhibit poor survival rates in advanced disease stages. The lack of significant therapeutic progress over the past three decades necessitates innovative treatment approaches.

•Advancing immunotherapy with CAR-NK cells. Natural killer (NK) cells modified with chimeric antigen receptors (CARs) represent a promising strategy to overcome the limitations of CAR-T cells, particularly in solid tumours. CAR-NK cells are associated with enhanced tumour targeting, reduced off-target effects, and improved safety profiles.

•EphA2 as a therapeutic target. EphA2, a receptor overexpressed in multiple paediatric sarcomas, is identified as a viable target for CAR-based immunotherapy due to its critical role in tumour progression and angiogenesis.

•Innovations in mRNA-based engineering. This study demonstrates the feasibility of transient mRNA transfection to engineer NK cells for CAR expression, offering a non-integrative and safer alternative to viral transduction. Enhancements in mRNA stability through chemical modifications, can further optimise protein expression.

•Preclinical efficacy of EphA2-CAR NK cells. EphA2-specific CAR-NK cells exhibit superior cytotoxicity against sarcoma cell lines in vitro and demonstrate significant anti-tumour activity in in vivo mouse models of rhabdomyosarcoma and osteosarcoma.

•Clinical translation potential. The findings establish a strong preclinical rationale for the clinical evaluation of EphA2-targeted CAR-NK therapy as a novel immunotherapeutic option for paediatric sarcomas.

•Future research directions: Combining EphA2-CAR NK cells with immune checkpoint inhibitors or other immunomodulatory agents could further enhance therapeutic outcomes and durability. Advanced preclinical models mimicking human tumour microenvironments are needed to refine and optimise this therapeutic approach.

•Protein acetylation and deacetylation are key regulators of metabolic reprogramming in tumour cells.

•These modifications influence signalling pathways critical for tumour metabolism.

•They modulate the activity of transcription factors that drive gene expression changes.

•Metabolic enzymes are also affected, altering cellular metabolism to support tumour growth.

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

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

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

•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.

•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.

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

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

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

•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).

•LncRNA AC010789.1 promoted the proliferation and migration of HFSCs.

•FTO/hnRNPA2B1-mediated m⁶A modification of lncRNA AC010789.1 promoted HFSCs growth by activating S100A8/Wnt/β-catenin signalling.

•Exosome-derived AC010789.1 accelerated HFSCs proliferation.

•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.

•Our study developed an innovative nanomaterial, Zeolite NaY, which addressed the masking effect and improved the depth of the proteome.

•The performance of NaY-based plasma proteomics as a preclinical diagnostic tool was validated through both internal and external cohort.

•Furthermore, we explored the different patterns of plasma protein changes during the progression of lung cancer and used the explanations method to elucidate the roles of proteins in the multitask predictive model.

•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.

•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.

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

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

•EHMT2 confers enzalutamide resistance via activating Aurora B.

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

•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.

•Disturbed flow activates the ubiquitin‒proteasome degradation pathway of MAPK6 in endothelial cells, which is contingent on the binding of the ubiquitin ligase TRIM21 to MAPK6.

•Endothelial MAPK6 has an advantageous impact on decelerating plaque progression.

•MAPK6 regulates endothelial inflammation via the EGR1/CXCL12 axis.

•3-year follow-up study confirmed the therapeutic efficacy of atezolizumab combined with bevacizumab

•Tumors in the upper site and NRAS mutations are more sensitive to treatment

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

•Alterations of the lower respiratory tract microbiome indicate different clinical responses to ICB within advanced NSCLC.

•Reduced microbial diversity of lower respiratory tracts impairs anti-tumoral performances.

•Microbe-derived metabolites perform as a dominant regulator to remodify the microecological environment in lower respiratory tracts.

•Multi-omics sequencings of the lower respiratory tract possess the potential to predict the long-term clinical responses to ICB among advanced NSCLC.

•A subpopulation of tumor cells with lower expression levels of APOE was strongly associated with more advanced stages and metastasis of PTC.

•APOE-negative (APOE^–) cellsoverall exhibited weaker interactions with immune cells.

•A machine-learning bioinformatics model based on scRNA-seq data of in-situ thyroid cancer tissue was established to predict lymph node metastasis.

•Significant B cell clonal expansion, particularly in plasma cells, driven by antigen recognition.

•IFN-I pathway activation in plasma cells boosts their antibody production and potentially exacerbates immune dysregulation.

•TLR2 pathway activation in myeloid cells contributes to TNF-α secretion and could influence adaptive immune responses.

•A comprehensive multi-omics solution to specifically obtain an extensive fragmentomics landscape, presented by breakpoint characteristics of nucleosomes, CpG islands, DNase clusters and enhancers, besides typical methylation, copy number alteration of cfDNA.

•Integrated model of cfDNA multi-omics could be used for non-invasive early diagnosis of DLBCL.

•Integrated model of cfDNA multi-omics could effectively evaluate the efficacy of R-CHOP before DLBCL treatment.

•This study shows that AnxA8 is upregulated in aorta of atheroprone mice and in human atherosclerotic plaques.

•Germline AnxA8 deficiency reduces platelet and leukocyte recruitment to activated endothelium as well as atherosclerotic burden, plaque size, and macrophage accumulation in mice.

•AnxA8 regulates oxLDL-induced adhesion molecules expression in aortic endothelial cells. Our data strongly suggest that AnxA8 promotes disease progression through regulation of adhesion and influx of immune cells to the intima.

•Endothelial specific silencing of AnxA8 reduced atherosclerosis progression.

•Therapeutic interventions to reduce AnxA8 expression may delay atherosclerosis progression.

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

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

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

•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.

•Methods to detect pseudouridine were introduced from classic mass spectrometry-based methods to newer approaches such as nanopore-based technologies and BID sequencing, each with its advantages and limitations.

•RNA pseudouridylation is crucial for various biological processes, including tRNA homeostasis, tRNA transport, translation initiation regulation, pre-mRNA splicing, enhancement of mRNA translation, and translational fidelity.

•Increased pseudouridylation is frequently associated with tumour initiation, progression, and poor prognosis, whereas its reduction is predominantly implicated in non-tumour diseases.

•A comprehensive understanding of the inducing factors for RNA pseudouridylation will be essential for elucidating its role in diseases. Such insights can provide robust evidence for how pseudouridylation influences disease progression and offer new avenues for therapeutic strategies targeting pseudouridylation dysregulation.

•The therapeutic potential of RNA pseudouridylation in diseases is enormous, including inhibitors targeting pseudouridine synthases, the application of RNA pseudouridylation in RNA therapeutics, and its role as a biological marker.