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PubMed2026

The extracellular matrix in cancer-associated fibrosis: molecular mechanisms and clinical relevance.

The ECM is a dynamic component of the tumor microenvironment with a critical role in cancer progression, invasion, metastasis, immune exclusion, and response to therapy. Recent advances in proteomic analyses investigating the insoluble ECM fractions (termed "matrisome analysis"), along with single-cell RNA sequencing and spatial transcriptomics, have revealed cancer-specific patterns of ECM remodeling. These studies have identified a panel of recurrently upregulated ECM proteins, including annexin A1, fibrillin-1, fibronectin, periostin, and tenascin-C, actively contributing to tumor growth, invasion, angiogenesis, and immune exclusion. The expression of the cancer-associated ECM is largely driven by cancer-associated fibroblasts (CAFs), whose molecular diversity has been dissected through single-cell profiling and consolidated in emerging CAF atlases across cancers. By investigating the matrisome composition and CAF heterogeneity, these studies have unraveled the pivotal role of the stroma in shaping tumor biology. Based on these discoveries, ECM proteins and CAFs are now being explored as biomarkers and therapeutic targets. Future integration of multi-omics datasets with clinical outcomes will help to translate these insights into novel biomarkers for patient stratification and stroma-directed therapeutic interventions.

Humans↗
PubMed2026

Microplastics and nanoplastics-related genes signature predicts prognosis in pancreatic ductal adenocarcinoma and functional validation of interleukin 1 alpha.

BACKGROUND: Microplastics and nanoplastics (MNPs), as emerging environmental pollutants, have garnered significant attention from the global scientific community due to their potential threats to human health, particularly their association with the occurrence and development of cancer. The goal of our study is to create a predictive marker for pancreatic ductal adenocarcinoma (PAAD) based on MNPs-related genes, with the purposes of predicting survival outcomes and assessing the tumor immune microenvironment. METHODS: Using multi-cohort data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC), we assessed the association between MNPs and PAAD prognosis through the Xiantao Academic (https://www.xiantao.love/). The development of a prognostic signature was followed by an assessment of its significance through the Kaplan-Meier method, time-dependent receiver operating characteristic (ROC), and decision curve analysis (DCA). The validity of the risk model was confirmed through the ICGC and GSE71729 cohorts. The model was then assessed for levels of tumor immune infiltration. To explore MNPs-related genes expression characteristics within immune cells in PAAD, we performed single-cell RNA sequencing and spatial transcriptomics analysis through the Sparkle Platform (https://grswsci.top/). Finally, in vitro experiments were conducted to investigate the biological function of interleukin 1 alpha (IL1A). RESULTS: A four-gene signature comprising XDH, IL1A, KIF20A, and ASPM, based on MNPs, was developed to stratify PAAD patients into two distinct risk groups. The high-risk group showed a significantly poorer prognosis. A similar trend was verified in the external cohorts ICGC and GSE71729. The signature risk score affected immune cell infiltration in the PAAD microenvironment. The infiltration of B cells, CD8+ T cells, cytotoxic cells, immature dendritic cells (iDCs), mast cells, plasmacytoid dendritic cell (pDC), T cells, Tem cells, T follicular helper (TFH) cells, and T helper 17 (Th17) cells had a positive correlation with the low-risk group. In contrast, high-risk patients tended to have increased number of T helper (Th2) cells and higher expression of SIGLEC15, CD274, IGSF8. Knockdown of IL1A in PAAD cells inhibited their tumor proliferation ability in vitro. CONCLUSIONS: Using MNPs-related genes, we built a prognostic model for PAAD, revealing that patients with high-risk scores are likely to have a worse prognosis. This model is designed to develop personalized treatment strategies tailored to the specific needs of each patient, thereby improving clinical outcomes for PAAD patients. Furthermore, IL1A could be a promising therapeutic candidate for PAAD.

Microplastics↗
PubMed2026

Targeting USP22 reprograms the tumor microenvironment and sensitizes KRAS/p53-driven lung cancer to anti-PD-1 immunotherapy.

RATIONALE: Ubiquitin-specific peptidase 22 (USP22), a deubiquitinase and component of the "Death-from-Cancer" 11-gene signature, is overexpressed in multiple malignancies and linked to recurrence, therapy resistance, and poor prognosis. Its role in KRAS/p53-driven lung cancer and the response to immune checkpoint inhibitors (ICIs) remains poorly defined. Here, we investigated USP22 as a potential therapeutic target in KRAS/p53-driven lung cancer. METHODS: A conditional Usp22 knockout (Usp22-KO) was generated in the KRASG12D; p53-/- (KP) mouse model. Cancer progression was monitored by micro-computed tomography (micro-CT). Multiplex immunofluorescence (mIF), RNA sequencing, and spatial transcriptomics profiled cancer and tumor microenvironment (TME) changes. Responses to anti-PD-1/PD-L1 therapies were compared between KP and Usp22-KO KP (KPU-) lung cancers. RESULTS: USP22 was highly expressed in early-stage KRAS/p53-driven mouse lung cancers and strongly correlated with proliferation marker Ki67. Usp22 deletion suppressed cancer growth, prolonged survival, and promoted cancer differentiation. Spatial transcriptomics and mIF revealed reduced CD206+ M2 macrophages, myeloid-derived suppressor cells (MDSCs), TGF-β1, and angiogenesis, along with increased functional CD8+ T cells. Mechanistically, USP22 regulated gene expression and protein stability, reducing c-Myc, PD-L1, TGF-β1, and SPARC upon Usp22 loss. Compared with KP cancer, KPU- and SPARC-knockdown KP cancers showed reduced macrophage chemotaxis and impaired basal- and TGF-β1-induced M2 polarization of RAW264.7 cells, suggesting that TGF-β1 and SPARC downregulation partially contributes to decreased M2 macrophage infiltration in KPU- cancers. Notably, Usp22 loss enhanced the efficacy of anti-PD-L1 and anti-PD-1 therapies in orthotopic and subcutaneous KP lung cancer models, respectively. USP22 and SPARC expression were also strongly correlated in human lung cancers. CONCLUSIONS: USP22 promotes progression and immune evasion in KRAS/p53-driven lung cancer. Targeting USP22 reprograms the TME, suppresses oncogenic signaling, and sensitizes tumors to ICI, establishing USP22 as a promising therapeutic target.

Animals↗
PubMed1988

[Circahoral rhythms of the skin biopotentials outside of digestion and their relationship to the periodic motility of the gastrointestinal tract].

Circahoral rhythms of the skin surface potentials recorded simultaneously with periodic motor activity of stomach in 4 dogs and 7 healthy subjects revealed the rhythms to be an electrophysiological equivalent of the latter in dogs. A "migration" of the group potentials in a certain spatial-temporal sequence was observed among the leads. It corresponded to the cycles of periodic motor activity of the stomach in dogs. The circahoral rhythms are a major topic for research in humans, too.

Adult↗
PubMed1984

Models for positional signalling, the threefold subdivision of segments and the pigmentation pattern of molluscs.

Models of biological pattern formation are discussed. The regulatory features expected from the models are compared to those observed experimentally. It will be shown that: (i) Stable gradients appropriate to supply positional information can be produced by local autocatalysis and long-range inhibition. (ii) Spatially ordered sequences of differentiated cell states can emerge if these cell states mutually activate each other on long range but exclude each other locally. Segmentation results from the repetition of three such cell states, S, A and P (and not of only two, as is usually assumed). With a repetition of three states, each segment has a defined polarity. The confrontation of P cells and S cells lead to the formation of a segment border (...P/SAP/SAP/S...) while the A-P confrontation is a prerequisite for appendage formation. Mutations of Drosophila affecting larval segmentation are discussed in terms of this model. (iii) The two models for the generation of sequences of structures in space (positional information including interpretation versus mutual activation) lead to different predictions with respect to intercalary regeneration. This allows a distinction between the two models on the basis of experiments. (iv) The pigmentation patterns of certain molluscs emerge from a coupled oscillation of cells (that is, a lateral inhibition in time, instead of space). The oblique lines result from a chain of triggering events.

Animals↗
PubMedDate not supplied

[Participation of the hippocampus in delayed spatial choice and discrimination of time intervals in rhesus macaques].

Participation of the hippocampus in morpho-functional systems of delayed spatial choice and differentiation of trace reflexes to time was shown in 2 macaco rhesus by the method of phase-correlational analysis. Application of 0.05 per cent solution of amysyl into the hippocampus disturbed the behaviour of monkeys, probably, as a result of desintegration of entire morpho-functional system regulating spatial-temporal sequence of nervous processes of delayed behavioural act.

Animals↗
PubMed1988

A pattern formation mechanism to control spatial organization in the embryo of Drosophila melanogaster.

It is known that cells are already committed to a particular segment at the cellular blastoderm stage during embryogenesis of Drosophila melanogaster. Recently, several segmentation genes have been observed to be expressed in a sequence of banded spatial patterns in the syncytial blastoderm, prior to the formation of the cellular blastoderm. It is demonstrated in this paper that a two component reaction-diffusion (RD) system with net production functions which are antisymmetric with respect to the uniform steady-state values, is capable of producing a sequence of seven spatial patterns in the syncytial blastoderm. The sequence of patterns obtained exhibit a strong preference for banded or striped patterns. The first pattern is a simple anteroposterior gradient while the second is a gradient in the dorsoventral direction. The next five patterns are a sequence of banded patterns which exhibit frequency doubling, i.e. the number of bands in each pattern tend to be double the number in the previous pattern. The predicted pattern sequence is comparable to that observed in the expression of some segmentation genes. It is suggested that a pattern formation mechanism based on such an RD system may exist in the embryo where it produces a sequence of prepatterns to regulate the expression of various segmentation genes leading ultimately to a segmented embryo. There is sufficient spatial information in the sequence of banded prepatterns for the segments to be unique.

Animals↗
PubMed1992

Perceptual and academic patterns of learning-disabled/gifted students.

This research explored ways gifted children with learning disabilities perceive and recall auditory and visual input and apply this information to reading, mathematics, and spelling. 24 learning-disabled/gifted children and a matched control group of normally achieving gifted students were tested for oral reading, word recognition and analysis, listening comprehension, and spelling. In mathematics, they were tested for numeration, mental and written computation, word problems, and numerical reasoning. To explore perception and memory skills, students were administered formal tests of visual and auditory memory as well as auditory discrimination of sounds. Their responses to reading and to mathematical computations were further considered for evidence of problems in visual discrimination, visual sequencing, and visual spatial areas. Analyses indicated that these learning-disabled/gifted students were significantly weaker than controls in their decoding skills, in spelling, and in most areas of mathematics. They were also significantly weaker in auditory discrimination and memory, and in visual discrimination, sequencing, and spatial abilities. Conclusions are that these underlying perceptual and memory deficits may be related to students' academic problems.

Achievement↗
PubMed1995

SD filtering for enhancement of a nuclear medicine image sequence.

This paper explores the use of an image sequence processing algorithm, called the simultaneous diagonalization (SD) filter, which can be effectively applied to long noisy image sequences. This filter was developed to filter a spatially invariant image sequence to form one new image in which a desired feature is enhanced and one or more undesired features (and noise) are suppressed in the filtered image. This filtering technique, applied to a long noisy image sequence, can be used to achieve significant data compression for image storage and provide surprisingly good enhanced image reconstructions. For this investigation, SD filtering is applied to a temporal image sequence, a renogram, with compression of a very noisy 180-image sequence to a 4-image set. The renogram, a nuclear medicine technique, was chosen due to its low signal-to-noise ratio over a long image sequence. Before the application of the SD filter, classical image processing techniques, median and averaging filtering, are used as a preliminary method to reduce the image sequence noise content. Compared to any of the images in the original image sequence, the reconstructed images are remarkably good. The SD filter with prefiltering, thus, can collect information distributed over a 180-image temporal sequence with low signal-to-noise ratio.

Algorithms↗
PubMed1980

Localization of SV40 genes within supercoiled loop domains.

Recent studies indicate that eukaryotic DNA is organized into supercoiled loop domains. These loops appear to be anchored at their bases to an insoluble nuclear skeleton or matrix. Most of the DNA in the loops can be released from the matrix by nuclease digestion; the residual DNA remaining with the nuclear matrix represents sequences at the base of the loops, and possibly other sequences which are intimately associated with the nuclear matrix for other reasons. Using a quantitative application of the Southern blotting technique, we have found this residual DNA from SV40 infected 3T3 cells to be enriched in SV40 sequences, indicating that they reside near matrix-DNA attachment points. An enrichment of 3-7 fold relative to total cellular DNA, was found in each of three different lines of SV40 infected 3T3 cells. Control experiments with globin genes showed no such enrichment in this residual matrix DNA. This sequence specificity suggests that the spatial organization of DNA sequences within loops may be related to the functionality of these sequences within the cell.

Animals↗
PubMed2025

Stereo-cell: Spatial enhanced-resolution single-cell sequencing with high-density DNA nanoball-patterned arrays.

Single-cell sequencing technologies have advanced our understanding of cellular heterogeneity and biological complexity. However, existing methods face limitations in throughput, capture uniformity, cell size flexibility, and technical extensibility. We present Stereo-cell, a spatial enhanced-resolution single-cell sequencing platform based on high-density DNA nanoball (DNB)-patterned arrays, which enables scalable and unbiased cell capture at a wide input range and supports high-fidelity transcriptome profiling. Stereo-cell further allows integration with imaging-based modalities and multiomics strategies, including immunofluorescence and epitope profiling. This platform is also compatible with profiling extracellular vesicles, microstructures, and large cells, whereas its spatial resolution facilitates in situ analysis of cell-cell interactions, cellular microenvironments, and subcellular transcript localization. Together, Stereo-cell provides a flexible framework for expanding single-cell research applications.

Animals↗
PubMed1986

Transcription initiation of the Saccharomyces cerevisiae iso-1-cytochrome c gene. Multiple, independent T-A-T-A sequences.

The expression of the Saccharomyces cerevisiae CYC1 gene, which encodes iso-1-cytochrome c, produces a family of messenger RNAs whose 5' ends map in the region from position +7 to -93 relative to the first nucleotide at position +1 of the protein-coding DNA sequence. The mechanism of transcription initiation of the CYC1 gene has been examined by using linker-scanning deletions and gene fusions. The various CYC1 derivatives with mutations in the 5' non-coding region were constructed, reintroduced into yeast using a multicopy plasmid, and the mRNA starts mapped by primer extension. The results indicate that four, and possibly five T-A-T-A sequences are located within the 5' non-coding region of the CYC1 gene, and that each T-A-T-A is required for a specific subset of mRNA starts. This conclusion has been confirmed by oligonucleotide mutagenesis of a chromosomal CYC1 T-A-T-A sequence. A loose spatial relationship also exists between the T-A-T-A sequences and the mRNA start sites, and this distance relationship varies from 100 to 60 base-pairs (+/- 15 base-pairs).

Base Sequence↗
PubMed1990

Spatial harmonics and pattern specification in early Drosophila development. Part I. Bifurcation sequences and gene expression.

Molecular probes have now provided an unprecedented wealth of detail revealing the changing spatial patterns of gene products in early Drosophila development. This is examined for dynamic properties which might provide insights into the underlying behaviour of the patterning process. What emerges is that transcripts and protein products of members of the major categories of zygotically active genes involved in segmentation pass through transient spatial patterns that are suggestive of harmonic sequences arising from spatial frequency-doubling bifurcations. That is to say, these patterns are typically periodic in space and show a doubling in the number of domains of spatial expression as development proceeds. One of these patterns reflects the primary functional role of the gene in the establishment of the spatial pattern. The different categories of segmentation gene pass through these transients at different rates, those with the longest functional wavelength progressing most slowly. Each gene in a category has its own unique phase relationship to other members, as well as particular variations on the harmonic sequence theme. The result is that the developing embryo experiences a spatial hierarchy of phase-shifted patterning influences that span the range from the whole embryo to single segments, providing progressively more spatial resolution in the patterning process. The characteristic transients and the dynamic relationships between genes of the different categories suggest that gene products expressed in longer-wavelength patterns act as bifurcation parameters on the dynamic system generating the next shorter wavelength category. Such parametric influences are known to result in frequency-doubling bifurcations in Turing reaction-diffusion systems. A general model is proposed of a hierarchically-nested set of quasi-autonomous dynamic systems involving gene activities that can generate the progressively finer spatial order that emerges during embryogenesis. This model has implications for the general stability properties of evolving epigenetic systems.

Animals↗
PubMed1995

Adapted techniques for clinical MR imaging of tendons.

To determine whether the echo time of magnetic resonance gradient-echo and spin-echo imaging sequences may be important for the occurrence of high signal strength from tendon with pathological alterations, imaging sequences with sufficient spatial resolution and very short echo times were developed for whole-body imagers with standard gradient system. The sequences were applied on the Achilles tendons of five healthy volunteers and seven patients with achillodynia. Some affected regions inside tendon, probably corresponding with tissue with subtle edema in the collagen bundles were only revealed in images recorded with very short echo times TE < 5 ms, whereas stronger affections and protons in liquids between the fiber bundles were also shown in images with longer echo times TE > 10 ms. Gradient-echo methods allow shorter echo times than spin-echo techniques for a given gradient system of the imager and given spatial resolution. So minimum echo time gradient-echo sequences should be used for sensitive imaging of tendon alterations, because no considerable signal dephasing due to susceptibility effects were found in tendon.

Achilles Tendon↗
PubMed1984

The effects of visual and spatial interference on spatial working memory.

Baddeley and Lieberman (1980) have shown that processing within spatial working memory is disrupted by a spatial secondary task, but not significantly by a visual processing secondary task. In the present study their experiment was replicated under broadly similar circumstances. The spatial and verbal primary tasks involved remembering descriptions of spatially arranged or nonsense sequences of digits, respectively. The secondary visual and spatial tasks involved either judging the level of brightness or pressing an unseen matrix of buttons in a predetermined sequence. In contrast to the finding of Baddeley and Lieberman, both the visual and spatial secondary tasks significantly impaired spatial working memory. Neither of these secondary tasks significantly interfered with concurrent verbal processing. The present findings suggest that spatial working memory draws from resources from both visual and spatial quarters.

Adult↗
PubMed2025

scBSP: a fast and accurate tool for identifying spatially variable features from high-resolution spatial omics data.

MOTIVATION: Emerging spatial omics technologies empower comprehensive exploration of biological systems from multi-omics perspectives in their native tissue location in 2D and 3D space. However, the limited sequencing depth, increasing spatial resolution, and growing spatial spots in spatial omics technologies present significant computational challenges in identifying biologically meaningful molecules with variable spatial distributions across various omics modalities. RESULTS: We introduce scBSP, an open-source, versatile, and user-friendly package for identifying spatially variable features in large-scale spatial omics data. scBSP demonstrates significantly enhanced computational efficiency, processing high-resolution spatial omics data within seconds, and exhibits robust cross-platform performance by consistently identifying spatially variable features with high reproducibility across various sequencing platforms. AVAILABILITY AND IMPLEMENTATION: scBSP is available for download from R CRAN at https://cran.r-project.org/web/packages/scBSP/index.html and PyPI at https://pypi.org/project/scbsp/.

Software↗