Biology subjects

Zeng, F.

Publications and source records attributed to Zeng, F..

At least 19 recordsLinked to original sources

bioRxiv2026

PIEZO1 marks a low neuroendocrine state and supports cisplatin tolerance in small cell lung cancer

Small cell lung cancer (SCLC) is initially sensitive to platinum chemotherapy, yet resistant disease frequently develops with altered neuroendocrine (NE) identity. The mechanisms linking these cell states to treatment tolerance remain incompletely understood. Here, we integrate chemoresistant cell models with patient bulk multiomics, single-cell and spatial transcriptomic data to investigate the mechanosensitive channel PIEZO1. In H69AR cells, PIEZO1 upregulation accompanied loss of NE markers and enrichment of mesenchymal programmes; increased PIEZO1 expression and reduced cisplatin sensitivity were also observed in H446DDP cells. Across patient-derived data sources, PIEZO1 was associated with low NE activity within malignant populations, despite its substantially higher abundance in vascular and stromal cells. State-blind CNV analyses and cross-sectional state ordering supported a cell-state association that was only weakly explained by detectable subclones and varied with hypoxia across models. Spatial analyses localized PIEZO1-rich signals to stromal and vascular interface regions, while composition-adjusted tumour-core analyses showed little residual covariance with tumour programmes. PIEZO1 depletion reduced intracellular calcium-associated signals and cisplatin IC50 and increased drug-induced apoptosis. Conversely, Yoda1 increased calcium signals and cisplatin tolerance in parental cells. Patient light-chain phosphorylation, YAP localization and partial pharmacological reversal by verteporfin supported an actomyosin-YAP-linked mechanism. PIEZO1 depletion also reduced SMAD2/3 and mesenchymal-associated readouts. Finally, transcript enrichment profiles and PIEZO1-IGF2BP2 covariation nominated a potential m6A regulatory layer. Together, these findings identify PIEZO1 as a low-NE state-associated marker and contributor to cisplatin tolerance, and motivate a calcium-cytoskeleton-YAP model for further mechanistic testing.

cancer biology↗

bioRxiv2026

Immune determinants of leuprolide-associated cardiovascular risk in prostate cancer

Leuprolide, a widely used androgen-deprivation therapy (ADT) for prostate cancer (PC), has been associated with increased cardiovascular events (CVE), although the underlying mechanisms remain unclear. Through integrated spatial transcriptomic analyses of murine heart and immune-stromal profiling in patient blood, we identified immune programs linked to leuprolide-associated CVE risk. Spatial analyses revealed the distinct organization of lymphoid (T+B cells) aggregates and inflammatory macrophages in the plaque following leuprolide exposure that accompanied by ventricular hypertrophy, relative to normal vasculature. Parallel profiling of circulatory soluble and cellular components in patients demonstrated CD8+T cell enriched pattern in ~44% of patients, including memory and type 1 cytotoxic subsets that linked to treatment-induced CVE, such as ventricular dysfunctions, but no contribution of adipocytokines. These translational findings highlight the stratification of leuprolide-associated CVE risk in PC patients based on circulating T cell profiling and could guide the risk mitigation with alternative ADT agents.

immunology↗

bioRxiv2026

OmniTCR: a foundation model unifying T cell receptor recognition prediction and conditional sequence generation

T cell receptor (TCR) recognition prediction and receptor generation are traditionally modelled separately, leaving vast TCR sequence collections disconnected from smaller TCR-peptide-MHC datasets. Here we present OmniTCR, a 113-million-parameter autoregressive foundation model pretrained on 328 million formatted human immune-sequence records. Sequence-type tokens and complementary component orders enable joint learning from individual TCR chains and partial or complete TCR-pMHC associations. On unseen epitopes, OmniTCR achieved AUPRCs of 0.7009 for peptide-TCR{beta}; recognition and 0.8235 for TCR-pMHC interaction prediction, exceeding the strongest evaluated comparators by 0.3396 and 0.3451, respectively. It distinguishes cancer from healthy repertoires across 11 independent pan-cancer cohorts (mean AUROC, 0.9436). The model achieved the highest sequence recovery on internal and external generation benchmarks. Structural modelling supported the plausibility of selected pMHC-conditioned CDR3{beta}; candidates. OmniTCR bridges heterogeneous immune sequence data, providing a foundation for computational immunology and receptor design.

bioinformatics↗

bioRxiv2026

Siglec-15 is a glyco-immune checkpoint in prostate cancer regulating immune evasion and metastasis

Prostate cancer is a leading cause of cancer-related mortality in men, and effective treatment options are limited for advanced and metastatic disease. The sialoglycan immune checkpoint Siglec-15 has emerged as a key mediator of tumour-associated immune suppression in several malignancies; however, its expression and functional role in prostate cancer remain poorly defined. Here, using dual immunofluorescence and immunohistochemistry, we demonstrate that Siglec-15 is expressed by prostate tumour epithelial cells, immunosuppressive macrophage phenotypes, and bone-resorbing osteoclasts within the tumour microenvironment. Mechanistically, we show that direct Siglec-15 receptor crosslinking, either by antibodies or tumour cell-derived conditioned medium, promotes monocyte-to-macrophage differentiation, generating macrophages with immunosuppressive and pathogenic phenotypes. Using therapeutic antibodies, we show that Siglec-15 blockade suppresses supernatant-induced monocyte to macrophage differentiation, allowing for the recovery of CD8 T-cell activation. Furthermore, we reveal that macrophage colony-stimulating factor (M-CSF) driven monocyte-derived macrophage differentiation is partially dependent on Siglec-15 signalling, with Siglec-15 blockade enhancing CD8 T-cell responses. In addition, anti-Siglec-15 treatment suppressed osteoclast differentiation, highlighting a dual role for Siglec-15 in prostate cancer immune suppression and bone remodelling. Consistent with these in vitro findings, therapeutic Siglec-15 blockade significantly reduced subcutaneous tumour growth in a CD8 T-cell-dependent manner and prolonged survival in a mouse model of prostate cancer metastasis. Together, these findings identify Siglec-15 as a central regulator of the prostate cancer glyco-immune axis, linking tumour-associated macrophage immune suppression with osteoclast-mediated bone remodelling, providing a compelling rationale for the clinical development of Siglec-15-targeted therapies for patients with advanced disease.

cancer biology↗

bioRxiv2026

Phagocytic activity of perivascular cell promotes CNS injury pathology

Injury, stroke, and neurological diseases cause persistent accumulation of cellular debris that deteriorates lesion microenvironment and impedes central nervous system (CNS) repair. Debris clearance in the injured CNS has long been attributed primarily to microglia and infiltrating macrophages. Here, we identify perivascular cells as previously unrecognized phagocytes that expand after injury and exhibit robust phagocytic activity. Perivascular cell phagocytosis is conserved across multiple mouse models of CNS injury and human stroke lesions. These cells exhibit key hallmarks of phagocytosis, including LC3-associated phagocytosis for efficient lysosomal degradation. Mechanistically, phosphatidylserine serves as the eat-me signal and Axl mediates myelin debris uptake. Myelin phagocytosis drives perivascular cell proliferation, fibrosis and lesion progression. Genetic deletion of Axl in perivascular cells or pharmacological inhibition with the FDA-approved Axl inhibitor Gilteritinib reduces pathology and improves functional recovery after spinal cord injury. Together, these findings establish Axl-dependent perivascular cell phagocytosis as a therapeutic target for CNS repair.

neuroscience↗

bioRxiv2026

A Comprehensive DNA Methylome BodyMap across 12 Organs/Tissues from Spaceflight Mice

Spaceflight imposes unique physiological stresses on mammals, including microgravity and cosmic radiation, which drive complex molecular adaptations. However, the systemic and temporal dynamics of space-induced epigenetic regulation remain poorly understood. We constructed a comprehensive DNA methylome BodyMap across 12 organs or tissues from mice exposed to long-duration spaceflight across three time points using Reduced Representation Bisulfite Sequencing (RRBS). We also performed RNA-seq for five organs and integrated with DNA methylome. We mapped the methylome and transcriptome landscapes and found that spaceflight induces limited but highly tissue-specific differentially methylated CpGs (DMCs). Most spaceflight-induced methylation changes were reverted toward baseline within one to six months of post-flight. Functional enrichment analysis of DMCs highlighted metabolic and mitochondrial dysregulation commonly across organs, while developmental responses in immune, reproductive, and structural tissues were tissue-specific. Transcriptome data revealed that spaceflight suppressed immune and increased inflammatory responses at the multi-organ level, triggering a phenomenon resembling aging. Our study provides a comprehensive DNA methylome BodyMap across 12 organs/tissues in spaceflight mice, elucidating the tissue specificity of epigenetic changes. These insights are essential for developing biomarkers and countermeasures to safeguard astronaut health during extended missions.

genomics↗

bioRxiv2025

Siglec-engaging immunosuppressive sialoglycans are upregulated in prostate cancer and are targetable to suppress bone metastasis

Prostate cancer is a leading cause of male cancer-related deaths over the age of 50. New treatment options for prostate cancer are urgently needed, especially for tumours that have spread to bone. Aberrant sialylation holds substantial potential for the discovery of new therapeutic targets but has remained relatively unexplored in the context of prostate cancer, primarily due to the lack of reliable reagents for detecting tumour sialoglycans in clinical tissue. Here, we address this knowledge gap using high-affinity Siglec-based sialoglycan-binding reagents (HYDRAs) to quantify tumour sialoglycans in tissues representing the full clinical heterogeneity of prostate tumours. Using HYDRA immunohistochemistry, we show that sialoglycans that can engage Siglec-3, -7, and -9 are upregulated in primary prostate cancer tissue and sialoglycan ligands for Siglec-7 correlate with prostate cancer bone metastasis and poorer patient prognosis. Analysis of prostate-derived tumours growing in bone reveals Siglec receptors are expressed by immune cells in the bone metastatic tumour microenvironment, suggesting that this axis may play a role in immune cell functions in bone metastatic prostate cancer. Indicating this is clinically actionable, an engineered bisialidase (E-612) can effectively strip Siglec ligands from prostate cancer cells and prolong survival times of mice with bone metastasis. Our findings identify a novel mechanism involving Siglec-engaging sialoglycans in driving the growth of prostate cancer bone metastasis and demonstrate how this axis can be targeted to impede lethal prostate cancer progression.

cancer biology↗

bioRxiv2025

Structure-based analysis unveils co-origin of LPOR and nitrogenase-like proteins

Structures of nitrogenases, dark-operative protochlorophyllide oxidoreductases, and light-dependent protochlorophyllide oxidoreductases (LPOR) have been resolved. However, their evolutionary relatedness remains elusive. Here, we show, through structural alignment, that all subunits of nitrogenase-like proteins originated from a co-ancestral archaic one-subdomain precursor. LPOR evolved from the BchX/BchY subunits of nitrogenase-like chlorophyllide a oxidoreductase (COR), and the intermediary retinol dehydrogenase through possible genetic recombination. We thus establish previously unknown structural links among key enzymes involved in biological nitrogen-fixation (BNF) and photosynthesis, unraveling structure-guided functional evolution from a single-subunit iron protein to multi-subunit nitrogenase-like COR, and to the single-subunit LPOR for phototrophic metabolism via bacteriochlorophyll, retinal, and chlorophyll. This work also demonstrates structural similarities are imperative for inferring distant origins of functionally divergent proteins, particularly those lacking primary amino-acid sequence identity. Moreover, our findings coupled with AI may be exploited to design innovative light-driven CORs and/or light-utilizing nitrogenases with enhanced efficacy of photosynthesis and BNF. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/634645v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@9f9a2aorg.highwire.dtl.DTLVardef@4243ecorg.highwire.dtl.DTLVardef@796b4corg.highwire.dtl.DTLVardef@17373da_HPS_FORMAT_FIGEXP M_FIG C_FIG Video abstracthttps://www.youtube.com/watch?v=b0qBE1JMaH0 HighlightsO_LILPOR evolves from BchX and BchY subunits of the nitrogenase-like protein (NGLP) COR C_LIO_LIAll subunits of NGLPs can be traced back to the ancestral one-subdomain precursor C_LIO_LIRetinol dehydrogenase acts as a crucial intermediate in the COR to LPOR evolution C_LIO_LIStructure-based design of LUN is showcased to revolutionize protein engineering C_LI

evolutionary biology↗

bioRxiv2025

Molecular and structural basis of a subfamily of PrfH rescuing both the damaged and intact ribosomes stalled in translation

In bacteria, spontaneous mRNAs degradation and ribotoxin-induced RNA damage are two main biological events that lead to the stall of protein translation. The ubiquitous trans-translation system as well as several alternative rescue factors (Arfs) are responsible for rescuing the stalled ribosomes caused by truncated mRNAs that lack the stop codons. To date, protein release factor homolog (PrfH) is the only factor known to rescue the stalled ribosome damaged by ribotoxins. Here we show that a subfamily of PrfH, exemplified by PrfH from Capnocytophaga gingivalis (CgPrfH), rescues both types of stalled ribosomes described above. Our in vitro biochemical assays demonstrate that CgPrfH hydrolyzes the peptides attached to P-site tRNAs when in complex with both the damaged and intact ribosomes. Two cryo-EM structures of CgPrfH in complex with the damaged and intact 70S ribosomes revealed that CgPrfH employs two different regions of the protein to recognize two different stalled ribosomes to orient the GGQ motif for peptide hydrolysis. Thus, using a combination of bioinformatic, biochemical, and structural characterization described here, we have uncovered a family of ribosome rescue factors that possesses dual activities to resolve two distinct stalled protein translation in bacteria.

biochemistry↗

bioRxiv2024

Distribution-preserved compression of single-cell atlases for privacy-protected data dissemination and novel cell type discovery

We introduce SUREv2, a tool for constructing lightweight, transmittable, and privacy-preserving references from single cell atlases. SUREv2 introduces a compressed data structure that maintain the distribution of cells within these atlases and develops an out-of-reference scoring method for identifying novel cell populations. This user-friendly tool shall enhance the analysis of single cell datasets by providing a consistent, privacy-focused reference framework.

bioinformatics↗

bioRxiv2024

Building a single cell transcriptome-based coordinate system for cell ID with SURE

The growing scale of single cell data demands standardized cell identification. We develop SURE, a data-driven method that establishes a cell coordinate system through optimally-sized metacells exhibiting enhanced transcriptional homogeneity. This approach enables precise cellular state characterization while providing three key atlas functionalities: zero-shot query-to-reference mapping, out-of-atlas detection, and cell type annotation. SUREs hierarchical assembly pipeline successfully integrates large-scale atlas datasets, as demonstrated by constructing the Human Blood Metacell Atlas (HBMCA) from 5 million cells. Our method addresses the fundamental challenge of consistent cell positioning across diverse experimental contexts, facilitating robust comparative analyses between healthy and disease states.

bioinformatics↗

bioRxiv2024

Genomic and evolutionary evidence for drought adaptation of grass allopolyploid Brachypodium hybridum

Climate change increases the frequency and severity of drought worldwide, threatening the environmental resilience of cultivated grasses. However, the genetic diversity in many wild grasses could contribute to the development of climate-adapted varieties. Here, we elucidated the impact of polyploidy on drought response using allotetraploid Brachypodium hybridum (Bh) and its progenitor diploid species B. stacei (Bs). Our findings suggest that progenitor species genomic legacies resulting from hybridization and whole-genome duplications conferred greater ecological adaptive advantages to Bh over Bs. Genes related to stomatal regulation and immune response from S-subgenomes were under positive selection during speciation, underscoring their evolutionary importance in adapting to environmental stresses. Biased expression in polyploid subgenomes [B. stacei-type (Bhs) and B. distachyon-type (Bhd)] significantly influenced differential gene expression, with the dominant subgenome exhibiting more differential expression. B. hybridum adapted a drought escape strategy characterized by higher photosynthetic capacity and lower WUEi than Bs, driven by a highly correlated co-expression network involving genes in the circadian rhythm pathway. In summary, our study showed the influence of polyploidy on ecological and environmental adaptation and resilience in model Brachypodium grasses. These insights hold promise for informing the breeding of climate-resilient cereal crops and pasture grasses.

evolutionary biology↗

bioRxiv2024

Genetic variation in the activity of a TREM2-p53 signaling axis determines oxygen-inducedlung injury

Bronchopulmonary dysplasia (BPD), a chronic lung disease, is the most common major complication of preterm birth. Supplemental oxygen administration, while lifesaving in the neonatal period, remains a key determinant of BPD pathophysiology. Exposure of the immature lung to increased levels of oxygen elicits an inflammatory response resulting in abnormal lung development. However, not every premature infant is equally sensitive to develop BPD. Using genetically diverse mouse strains, we show that the innate immune response activated in the lungs of mice sensitive to hyperoxia that develop BPD-like lung injury differs from mice resilient to disease. Specifically, we identified a selective upregulation of triggering receptor expressed on myeloid cells 2 (TREM2) on lung macrophages and monocytes in the hyperoxia-sensitive C57BL/6J mouse strain. We show that loss of function of TREM2 signaling in myeloid cells resulted in a dramatically improved phenotype after neonatal hyperoxia exposure characterized by a dampened immune response, preserved alveolar structure, and preserved cell proliferative potential supporting normal lung development. At the molecular level, inhibition of TREM2 signaling dampened the magnitude of p53 activation and resulted in cell cycle arrest instead of apoptosis. These findings show that TREM2 is a critical regulator of the pathogenic innate immune response to hyperoxia and highlight its importance as a potential therapeutic target for mitigating injury in the hyperoxia-exposed developing lung.

immunology↗

bioRxiv2024

A benchmarking study of copy number variation inference methods using single-cell RNA-sequencing data

Single-cell RNA-sequencing (scRNA-seq) has emerged as a powerful tool for cancer research, enabling in-depth characterization of tumor heterogeneity at the single-cell level. Recently, scRNA-seq copy number variation (scCNV) inference methods have been developed, expanding the application of scRNA-seq to study genetic heterogeneity in cancer using transcriptomic data. However, the fidelity of these methods has not been investigated systematically. In this study, we benchmarked five commonly used scCNV inference methods, HoneyBADGER, CopyKAT, CaSpER, inferCNV, and sciCNV. We evaluated their performance across four different scRNA-seq platforms derived data from a multicenter study. We further evaluated the scCNV performance using scRNA-seq datasets derived from mixed samples consisting of five human lung adenocarcinoma cell lines and generated a clinical scRNA-seq dataset from a human small cell lung cancer patient to validate our findings. Our evaluation criteria included sensitivity and specificity of CNV detection, and subclone identification from mixed cancer samples. We found that the sensitivity and specificity of the five scCNV inference methods varied, depending on the selection of reference data, sequencing depths, and read lengths. Overall, CopyKAT and CaSpER exhibited superior performance to other methods, while inferCNV, sciCNV, and CopyKAT outperformed other methods in subclone identification accuracy. Remarkably, inferCNV achieved high accuracy in subclone identification when using data from a "single scRNA-seq protocol", however, when applying these methods to a dataset derived from multiple scRNA-seq platforms from the mixed samples, we found that batch effects significantly affected the performance of subclone identification for most methods, except for HoneyBADGER. Our benchmarking study revealed the strengths and weaknesses of each of the five scCNV inference methods and provided guidance for selecting the optimal CNV inference method using scRNA-seq data.

bioinformatics↗

bioRxiv2024

Human transmembrane protein 68 links triacylglycerol synthesis to membrane lipid homeostasis

Transmembrane protein 68 (TMEM68) is a recently identified mammalian triacylglycerol (TAG) synthase with high expression in the brain. How TMEM68 regulates cellular lipid metabolism in concert with other enzymatic pathways remains poorly understood. In this study, we assessed TMEM68 function in neuro- and gliablastoma cells by combining genetic gain- and loss-of-function approaches with lipidomics. We found that TMEM68 promotes TAG synthesis and lipid droplet formation independently of canonical acyl-CoA:diacylglycerol acyltransferase (DGAT) 1 and 2 enzymes and contributes a discrete fraction of basal cellular TAG storage. Notably, TMEM68 overexpression increased storage lipids at the expense of membrane lipids leading to a profound reduction of ether-linked glycerophospholipids (GPLs). Moreover, altered TMEM68 expression levels were associated with diminished prevalence of polyunsaturated GPLs. We conclude that TMEM68, besides its TAG synthesis function, acts as a multifaceted regulator of membrane lipid composition and polyunsaturated fatty acid homeostasis.

biochemistry↗

bioRxiv2024

Efficient Gene Editing and Overexpression of Gametophyte Transformation in a Model Fern

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-related nuclease (Cas) system allows precise and easy editing of genes in many plant species. However, this system has not yet been applied to any fern species due to the complex characteristics of fern genomes, genetics and physiology. Here, we established, for the first time, a protocol for gametophyte-based screening single-guide RNAs (sgRNAs) with high efficiency for CRISPR/Cas-mediated gene editing in a model fern species, Ceratopteris richardii. We utilized the C. richardii Actin promoter to drive sgRNA expression and enhanced CaMV 35S promoter to drive the expression of Streptococcus pyogenes Cas9 in this CRISPR-mediated editing system, which was employed to successfully edit a few genes (e.g., nucleotidase/phosphatase 1, CrSAL1; Cryptochrome 4, CRY4) and CrPDS, encoding a phytoene desaturase protein that resulted in an albino phenotype in C. richardii. Knockout of CrSAL1 resulted in significantly reduced stomatal conductance (gs), leaf transpiration rate (E), stomatal/pore length, and abscisic acid (ABA)-induced reactive oxygen species (ROS) accumulation in guard cells. Moreover, CrSAL1 overexpressing plants showed significantly increased net photosynthetic rate (A), gs, E and intrinsic water use efficiency (iWUE) as well as most of the stomatal traits and ROS production in guard cells compared to those in the wild-type (WT) plants. Taken together, the optimized CRISPR/Cas9 system provides a useful tool for functional genomics in a model fern species, allowing the exploration of fern gene functions for evolutionary biology, herbal medicine discovery and agricultural applications.

plant biology↗

bioRxiv2024

VPAC2 receptor signaling promotes pancreatic cancer cell growth and decreases the immunogenicity of the tumor microenvironment.

Identifying mechanisms underlying tumor growth and immune resistance is needed to treat pancreatic ductal adenocarcinoma (PDAC) effectively. The complexity of the tumor microenvironment (TME) suggests that the crosstalk between cells in the TME could drive drug resistance and relapse in PDAC. We have previously determined that vasoactive intestinal peptide (VIP) is overexpressed in PDAC and that VIP receptors expressed on T cells are a targetable pathway that sensitizes PDAC to anti-PD1 therapy. In this study, we show that pancreatic cancer cells engage in autocrine signaling of VIP through VIP-receptor 2 (VPAC2), and that high co-expression of VIP with VPAC2 leads to reduced relapse-free survival in PDAC patients. Mechanistically, we identified piwi-like RNA-mediated gene silencing2 (Piwil2) as a tumor-cell intrinsic protein downstream of VPAC2 that regulates cancer cell growth. In addition, we discovered TGF{beta}-1 as a potential tumor-extrinsic inhibitor of T cell function induced by VPAC2 signaling. In vivo, knock out and knockdown of VPAC2 on PDAC cells led to reduced tumor growth rate and increased sensitivity to anti-PD-1 therapy in various mouse models of PDAC that were T-cell dependent. Overall, these findings emphasize the implications of VIP/VPAC2 signaling in the PDAC tumor microenvironment and further support the rationale for developing VPAC2-specific antagonists. SignificanceThe autocrine VIP signaling via VPAC2 promotes cancer cell growth and dampens T cell function in pancreatic ductal adenocarcinoma and thus represents a potential therapeutic target in PDAC.

cancer biology↗

bioRxiv2023

OmniClustifyXMBD: Uncover putative cell stateswithin multiple single-cell omics datasets

Clustering plays a pivotal role in characterizing cell states in single-cell omics data. Nonetheless, there is a noticeable gap in clustering algorithms tailored for unveiling putative cell states across datasets containing samples with diverse phenotypes. To bridge this gap, we implement an innovative method termed OmniClustifyXMBD, which integrates adaptive signal isolation with cell clustering. The adaptive signal isolation effectively disentangles gene expression variations linked to distinct factors within individual cells. This separation restores cells to their inherent states, free from external influences. Concurrently, a clustering algorithm built upon a deep variational Gaussian mixture model is devised to identify these putative cell states. Experiments showcase the effectiveness of OmniClustifyXMBD in identifying putative cell states while minimizing the influence of various undesired variations, including batch effects and random inter-sample differences. Moreover, OmniClustifyXMBD demonstrates robustness in its results across different clustering parameters.

bioinformatics↗