Nature Communications最新文献

Optical aberrations significantly impair microscopic image quality across various domains, including cell biology and histopathology diagnostics. Traditional adaptive optics techniques, such as wavefront shaping and guide star utilization, face challenges, especially in imaging biological tissues. Here, we introduce a computational adaptive optics approach tailored for optically thick samples. Utilizing the tilt-tilt correlation from the optical memory effect, our method detects phase differences in aberrations caused by small tilts in the incident waves. Experimental validation demonstrates our technique’s capacity to enhance imaging of thick human tissues under substantial aberration conditions using a transmission-mode holotomography setup. Remarkably, our approach works robustly against sample movement, which is essential for enhanced imaging accuracy in critical biomedical applications.

The creation of chiral plasmonic architectures combining templates with achiral plasmonic particles leads to strong chiroptical responses that can be finely tuned via the characteristics of the colloidal building blocks. Here we show how elastomeric molds, pre-patterned with a hexagonal array of triskelia motifs, can guide the assembly of ordinary noble metal colloids into chiral plasmonic architectures with strong dichroism values. Under normal incidence, the chiral arrays made with gold and silver colloids showed g-factors of 0.18 and 0.4, respectively. In all cases, increasing the size of the colloid allows tuning the optical properties of the structure in the VIS-NIR range. When a superstrate layer is deposited onto the structures, the extrinsic chirality response of the 2D superlattice is revealed and strongly amplified by the chiral motifs under oblique inspection, leading to g-factors of ± 1.2 at ± 14°. Finally, these chiral plasmonic resonances sustained by the triskelion array are used to produce circularly polarized photoluminescence from achiral organic dyes placed on top with up to 20% of dissymmetry.

The global pursuit of carbon neutrality is driving efforts toward environmentally friendly aqueous electrode manufacturing. However, the inherent chemical reactivity of water with cathode materials remains a challenge to achieving this goal. Here, we design a class of aqueous processing solutions based on the kosmotropic effect. Ion hydration shells in the kosmotropic solutions are restructured to form an ordered state of anion–water clusters and to stabilize local hydration structure adjacent to cathode materials. Consequently, interfacial side reactions and structural degradation of Ni-rich cathode materials are mitigated. The kosmotropic solution-processed LiNi_0.8Co_0.1Mn_0.1O₂ cathode achieve high specific and areal capacities (≥ 205 mAh g^–1 and ≥ 3.7 mAh cm^–2) together with stable cyclability, which are comparable to those of commercial N-methyl-2-pyrrolidone (NMP)-processed cathodes. Techno-economic analysis demonstrates that this kosmotropic solution approach reduces energy consumption in battery manufacturing by 46% compared to the NMP-based process, highlighting its practical and sustainable viability.

Patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolism (VTE), but the underlying mechanistic basis remains poorly defined. Here, we find that colitogenic CD4⁺ T cells express tissue factor (TF) and promote rapid TF-dependent plasma thrombin generation. TF⁺CD3⁺CD4⁺ T cells are present in both the colons of mice with experimental colitis and blood and colonic tissue from patients with IBD. Expression of genes involved in regulating coagulation, including Protein C (PC; encoded by PROC) and its receptor (PROCR), are dysregulated in IBD patient gut biopsy tissues. Moreover, activated PC signalling reduces the procoagulant activity mediated by TF⁺CD4⁺ T cells. Our data thus identify TF-induced, colitogenic T cell-mediated thrombogenicity, and also demonstrate a new function for activated PC signalling in regulating T cell thrombo-inflammatory activity.

The chromosome 5p15.33 region, which encodes telomerase reverse transcriptase (TERT), harbors multiple germline variants identified by genome-wide association studies (GWAS) as risk for some cancers but protective for others. Here, we characterize a variable number tandem repeat within TERT intron 6, VNTR6-1 (38-bp repeat unit), and detect a strong link between VNTR6-1 alleles (Short: 24-27 repeats, Long: 40.5-66.5 repeats) and GWAS signals rs2242652 and rs10069690 within TERT intron 4. Bioinformatics analyses reveal that rs10069690-T allele increases intron 4 retention while VNTR6-1-Long allele expands a polymorphic G-quadruplex (G4, 35-113 copies) within intron 6, with both variants contributing to variable TERT expression through alternative splicing and nonsense-mediated decay. In two cell lines, CRISPR/Cas9 deletion of VNTR6-1 increases the ratio of TERT-full-length (FL) to the alternative TERT-β isoform, promoting apoptosis and reducing cell proliferation. In contrast, treatment with G4-stabilizing ligands shifts splicing from TERT-FL to TERT-β isoform, implicating VNTR6-1 as a splicing switch. We associate the functional variants VNTR6-1, rs10069690, and their haplotypes with multi-cancer risk and age-related telomere shortening. By regulating TERT splicing, these variants may contribute to fine-tuning cellular longevity and replicative potential in the context of stress due to tissue-specific endogenous and exogenous exposures, thereby influencing the cancer risk conferred by this locus.

Progeria syndromes are very rare, incurable premature aging conditions recapitulating most aging features. Here, we report a whole genome, multiparametric CRISPR screen, identifying 43 genes that can rescue multiple cellular phenotypes associated with progeria. We implement the screen in fibroblasts from Néstor-Guillermo Progeria Syndrome male patients, carrying a homozygous A12T mutation in BAF. The hits are enriched for genes involved in protein synthesis, protein and RNA transport and osteoclast formation and are validated in a whole-organism Caenorhabditis elegans model. We further confirm that BAF A12T can disrupt protein synthesis rate and fidelity, which could contribute to premature aging in patients. This work highlights the power of multiparametric genome-wide suppressor screens to identify genes enhancing cellular resilience in premature aging and provide insights into the biology underlying progeria-associated cellular dysfunction.

Mechanotransduction channels are widely expressed in both vertebrates and invertebrates, mediating various physiological processes such as touch, hearing and blood-pressure sensing. While previously known mechanotransduction channels in metazoans are primarily cation-selective, we identified Anoctamin-1 (ANOH-1), the C. elegans homolog of mammalian calcium-activated chloride channel ANO1/TMEM16A, as an essential component of a mechanosensory channel complex that contributes to the nose touch mechanosensation in C. elegans. Ectopic expression of either C. elegans or human Anoctamin-1 confers mechanosensitivity to touch-insensitive neurons, suggesting a cell-autonomous role of ANOH-1/ANO1 in mechanotransduction. Additionally, we demonstrated that the mechanosensory function of ANOH-1/ANO1 relies on CIB (calcium- and integrin- binding) proteins. Thus, our results reveal an evolutionarily conserved chloride channel involved in mechanosensory transduction in metazoans, highlighting the importance of anion channels in mechanosensory processes.

Clustered protocadherins (cPcdhs) belong to the cadherin superfamily and play important roles in neural development. cPcdhs mediate homophilic adhesion and lead to self-avoidance and tiling by giving neurons specific identities in vertebrates. Structures and functions of cPcdhs have been studied extensively in past decades, but the mechanisms behind have not been fully understood. Here we investigate the in situ assembly of cPcdh-γB4, a member in the γ subfamily of cPcdhs, by electron tomography and find that the full length cPcdh-γB4 does not show regular organization at the adhesion interfaces. By contrast, cPcdh-γB4 lacking the intracellular domain can generate an ordered zigzag pattern between cells and the cis-interacting mode is different from the crystal packing of the ectodomain. We also identify the residues on the ectodomain that might be important for the zigzag pattern formation by mutagenesis. Furthermore, truncation mutants of the intracellular domain reveal different assembly patterns between cell membranes, suggesting that the intracellular domain plays a crucial role in the intermembrane organization of cPcdh-γB4. Taken together, these results suggest that both ectodomain and intracellular domain regulate the in situ assembly of cPcdh-γB4 for homophilic cell adhesion, thereby providing mechanistic insights into the functional roles of cPcdhs during neuronal wiring.

Single-cell ATAC-seq technology advances our understanding of single-cell heterogeneity in gene regulation by enabling exploration of epigenetic landscapes and regulatory elements. However, low sequencing depth per cell leads to data sparsity and high dimensionality, limiting the characterization of gene regulatory elements. Here, we develop scAGDE, a single-cell chromatin accessibility model-based deep graph representation learning method that simultaneously learns representation and clustering through explicit modeling of data generation. Our evaluations demonstrated that scAGDE outperforms existing methods in cell segregation, key marker identification, and visualization across diverse datasets while mitigating dropout events and unveiling hidden chromatin-accessible regions. We find that scAGDE preferentially identifies enhancer-like regions and elucidates complex regulatory landscapes, pinpointing putative enhancers regulating the constitutive expression of CTLA4 and the transcriptional dynamics of CD8A in immune cells. When applied to human brain tissue, scAGDE successfully annotated cis-regulatory element-specified cell types and revealed functional diversity and regulatory mechanisms of glutamatergic neurons.

Polarons can naturally form in materials from the interaction of extra charge carriers with the atomic lattice. Ubiquitous, they are central to various phenomena such as high-T_c superconductivity, electrochromism, photovoltaics, photocatalysis or ion batteries. However, polaron formation remains poorly understood and mostly relies on historical models such as Landau–Pekar, Fröhlich, Holstein or Jahn–Teller polarons. Here, from advanced first-principles calculations, we show that the formation of intriguing medium-sized polarons in WO₃ does not fit with traditional models but instead arises from the local undoing of distortive atomic motions inherent to the pristine phase, which lowers the bandgap through dynamical covalency effects and drives charge trapping. We introduce the concept of the anti-distortive polaron and rationalize it from a quantum-dot model. We demonstrate that anti-distortive polarons are generic to different families of compounds and clarify how this new concept opens concrete perspectives for a better control of the polaronic state and related properties.