This paper gives a short personal retrospective of some of the AFM methods developed in the Grutter group. It gives an overview of methods developed with the aim of measuring properties with high spatial and temporal resolution. Frequency mode AFM has over the past 40 years developed into a spatially resolving technique allowing spectroscopy of quantum dots and traps in semiconductors with single charge sensitivity. Properties can also be measured on ultrafast time scales by using pump-probe techniques, resolving a 100 fs short optical pulse. Two major challenges are addressed in a brief outlook: reproducible tip fabrication and open-source automatisation to increase throughput and statistics.

The S100 proteins are a group of calcium-binding proteins that are widely expressed in vertebrates and participate in various biological and pathological processes, including cell proliferation, differentiation, inflammation, infection, and autoimmunity. S100A8 and S100A9, members of the S100 family that predominantly exist as heterodimers (S100A8/A9), are primarily localized in myeloid cells such as neutrophils, monocytes, and dendritic cells (DCs). Accumulating studies have identified S100A8/A9 as critical damage-associated molecular patterns (DAMPs) or alarmins. Upon engagement with their receptors, S100A8/A9 can drive the production of cytokines, chemokines, and adhesion factors, thereby initiating and amplifying immune responses. Current literature reports that S100A8/A9 is upregulated in various autoimmune diseases, and targeted inhibition of S100A8/A9 holds significant therapeutic potential for these diseases. Recently, emerging studies have demonstrated a close association between S100A8/A9 and the pathogenesis of autoimmune eye diseases. Elucidating the signaling pathways mediated by S100A8/A9 is critical for the prevention and treatment of these ocular disorders. Therefore, we here summarize the biological characteristics of S100A8/A9 and their roles in the onset and progression of three autoimmune eye diseases, including autoimmune uveitis, Sjögren's dry eye disease (SjDED), and thyroid-associated ophthalmopathy (TAO), with particular emphasis on their utility as diagnostic biomarkers. Furthermore, we discuss current therapeutic strategies targeting S100A8/A9 and propose promising future research directions for S100A8/A9 interventions in autoimmune eye diseases.

Apricot (Prunus armeniaca L.) is an economically significant fruit crop worldwide with remarkable germplasm diversity, and its fruit quality is primarily determined by key metabolites (e.g., sugars, organic acids, and flavonoids). However, current apricot genome assemblies remain incomplete, with substantial unanchored regions that hamper analyses of genomic evolution and the regulatory mechanisms underlying fruit quality. Here, we generated the first gap-free telomere-to-telomere (T2T) de novo assembly of the P. armeniaca genome (248.3 Mb) and annotated 22 786 protein-coding genes across eight chromosomes. Combined analyses of metabolomic and transcriptomic data, we characterized the transcriptomic and metabolic landscape of apricot across five developmental stages and assigned 3198 metabolites and their co-expressed genes to five functional metabolic-gene modules. DNA methylome profiling further revealed dynamic epigenetic reprogramming during fruit development, characterized by decreases in CG and CHG methylation and an increase in CHH methylation. Notably, higher CHH DNA methylation in promoter regions was associated with the upregulation of leucoanthocyanidin reductase (PaLAR) and dihydroflavonol 4-reductase (PaDFR), contributing to anthocyanin biosynthesis during ripening. Moreover, we identified PaTT2 as a potential regulator of proanthocyanidin biosynthesis and directly activates PaLAR, as evidenced by Y1H and dual-luciferase assays. Our study sheds light on the epigenetic and metabolic regulatory networks of apricot, serving as a valuable foundation for molecular breeding and genetic enhancement.

Achieving efficient hydrogen evolution reaction (HER) in alkaline media remains a fundamental challenge due to the sluggish kinetics of water dissociation. In this study, we introduce an in situ-grown phenolic -OH-rich 2D covalent organic framework (IPREM-COF) with an imine-enamine linkage on a nickel foam (Nif) surface (IPREM-COF@Nif). Here, Nif and IPREM-COF serve as inorganic and organic materials, respectively, where the inorganic-organic interphase electronic mobility results in a significant enhancement of the alkaline HER. A well-defined lattice matching of Ni(111) with the 2D IPREM-COF lattice permits hetero structural (inorganic-organic) correlative electronic modulation for better catalytic performance. Imine (-CN), aminal (-CC-NH-) linkage, and hydroxyl (-OH) functional groups, combined with the Nif substrate, significantly enhance the HER performance under basic conditions, which is crucial for industrial applications. Moreover, under alkaline conditions, during the Volmer step, proton donation can be facilitated by IPREM-COF, which contains phenolic -OH groups capable of serving as internal proton donors. The synergistic interactions between the catalytic active sites of COF and the electron-rich Nif substrate significantly lowers the overpotential, enhancing the HER kinetics in alkaline media, achieving a remarkable overpotential of 56 mV at 10 mA cm-2, and surpassing the performance of the state-of-the-art Pt/C catalyst. Operando Raman spectroscopy further reveals the potential-induced evolution of the active catalytic species, providing direct mechanistic insights into the enhanced HER activity of IPREM-COF@Nif. Theoretical calculations reveal that a charge of 0.276e is transferred from the IPREM-COF@Nif surface to the adsorbed hydrogen atom, which facilitates the alkaline water splitting process. These findings position IPREM-COF@Nif as a highly promising non-precious electrocatalyst, presenting a viable alternative to noble metals for scalable and sustainable hydrogen production.

The CRISPR-Cas12 family encompasses diverse RNA-guided nucleases with both DNA- and RNA-targeting subtypes. They can trigger antiviral activities through either direct elimination of invading nucleic acids or activating broad collateral cleavage to induce abortive infection. Here, we report a novel type V CRISPR effector BaCas12a3 that causes growth inhibition through a unique tRNA-cleavage mechanism. Plasmid interference and western blot assays showed that BaCas12a3 induces host growth arrest without DNA damage response, suggestive of the absence of double-strand DNA breaks. Indeed, biochemical characterization of the BaCas12a3-crRNA ribonucleoprotein unraveled that the effector is an RNA-activating nuclease that cleaves the 3' terminal CCA of tRNAs. Cryo-EM structures of BaCas12a3 reveal a conserved bilobed architecture featuring a unique tRNA-loading domain (tRLD) adjacent to the RuvC catalytic center. Structural and mutagenesis analyses show that the tRLD domain, together with a zinc ribbon domain, form a gated substrate groove. Target RNA binding induces conformational changes that open the groove and expose the RuvC active site, enabling specific tRNA 3' end cleavage while preventing other non-specific degradation. Our findings identify the tRLD domain aside the RuvC active site responsible for the tRNA recognition in BaCas12a3, expanding the functional diversity of CRISPR immunity.

We covalently conjugated the Th epitope DT331-345 with the MG3 peptide and co-encapsulated the conjugate with an iNKT cell agonist into liposomes to prepare a vaccine. The DT-MG3/GCS-11 formulation elicited strong antibody responses and promoted T-cell responses. Notably, its combination with PD-L1 inhibitor BMS-202 suppressed tumor growth and prolonged the survival in tumor-bearing mice.

Hostile interpretation bias is a key cognitive factor associated with aggression; however, empirical research findings among adult populations remain inconsistent and lack systematic integration. This study aimed to quantitatively synthesise the association between hostile interpretation bias and aggression in adults and to examine potential moderators. A systematic search across 7 Chinese and English databases, initially covering records through December 13, 2025 and updated through March 16, 2026, identified 40 eligible studies, comprising 43 independent samples, 89 effect sizes, and a total sample size of 27,399. A three-level meta-analysis was conducted to account for the dependence among multiple effect sizes from the same study. Meta-analytic findings showed a moderate positive correlation between hostile interpretation bias and aggression (r = .304). Moderation analyses further showed that the individualism-collectivism cultural dimension, aggression type (reactive vs. proactive), and aggression form (physical vs. verbal) significantly moderated this association. Specifically, the association strength was higher in cultures with stronger collectivist tendencies, reactive aggression, and physical aggression. Overall, these findings suggest that biased interpretations of ambiguous social cues are reliably associated with adult aggression, which is consistent with social information processing and related cognitive models. The results further suggest that prevention-oriented interventions may need to consider cultural context and aggression subtype, although causal and clinical implications require further evidence.

Well-established evidence supports cross-modal interactions of sensory brain plasticity. Here, we extend cross-modality beyond the boundaries of sensory regions and provide first-time evidence in adult healthy humans that motor plasticity influences homeostatic visual plasticity. To this end, we employed repetitive transcranial magnetic stimulation (rTMS), known to modulate the excitation/inhibition balance in the primary motor cortex (M1), while examining the impact of this intervention on ocular dominance plasticity induced by short-term monocular deprivation (MD). Specifically, participants completed, in counterbalanced order, two neuromodulation sessions delivering either Active or Sham rTMS (10 Hz, 1600 pulses), during a 90-min MD period. We show that Active but not Sham rTMS significantly increased amplitudes of peak-to-peak motor evoked potentials, confirming facilitatory cortico-spinal after-effects driven by M1 stimulation. While robust ocular dominance shifts were observed for both rTMS conditions, greater increases of cortico-spinal excitability scaled with smaller ocular dominance shifts, suggesting interference of primary visual cortex plasticity ensuing a modulation of M1 excitability and competitive interactions between motor and visual plasticity. These results hint at global homeostatic mechanisms governing adult cortical plasticity across distant networks and highlight the need to consider cross-modal interactions between motor and visual systems when designing learning and rehabilitation strategies for adults.

Accurate, patient-specific vascular geometry is pivotal for diagnosis, planning, and device design, yet existing statistical shape modeling (SSM) pipelines rely on linear priors and topology-specific preprocessing that limit realism, scalability, and interoperability. We present HUG-VAS, a Hierarchical NURBS Generative framework for Vascular models, that unifies NURBS-based 3D shape encoding with diffusion-based generative modeling to synthesize fine-grained, CFD-ready aortic anatomies. HUG-VAS factorizes shape into (i) vessel centerlines generated by a denoising diffusion model and (ii) cross-sectional radius profiles synthesized by a classifier-free guided diffusion model conditioned on the centerline, thereby decoupling and preserving stochastic variability across these two anatomical layers. Beyond unconditional synthesis, we enable training-free, zero-shot conditional generation via diffusion posterior sampling from image-derived prompts (e.g., sparse 3D points, slice contours, or partial surface patches), supporting interactive semi-automatic segmentation, editing and robust reconstruction under degraded imaging. Trained on 21 patient-specific MRA cases, HUG-VAS generates multi-branch aortas with supra-aortic vessels whose biomarker distributions closely match the source cohort, and whose watertight NURBS outputs directly integrate with downstream CFD solvers. To our knowledge, HUG-VAS is the first SSM frameworks to unify NURBS parameterization, hierarchical diffusion, and DPS-based zero-shot conditional generation, enabling reconstruction and completion of vascular geometry from sparse, partial geometric priors without retraining.