Biology subjects

Zhao, Z.

Publications and source records attributed to Zhao, Z..

At least 361 records · Page 20Linked to original sources

bioRxiv2022

Fatty acid binding protein 1 and fatty acid synthetase overexpression have differential effects on collagen III and cross-linking in Zongdihua pig tissues

The purpose of this study was to determine whether FABP1 and FAS regulate expression of collagen and its crosslinking via lysyl oxidase in Zongdihua pigs. We wished to identify processes affecting meat quality using molecular genetics to provide a basis for breeding improvement of these animals. We measured expression levels of FABP1 and related genes using qRT-PCR in longissimus dorsi muscle and subcutaneous adipose tissues. Primary adipocytes from fat tissues were isolated and FABP1 and FAS were overexpressed from recombinant plasmids. Our sequence analysis of the cloned genes indicated that FABP1 gene encodes a hydrophobic protein of 128 amino acids and contained 12 predicted phosphorylation sites and no transmembrane region. FAS encodes 333 amino acid hydrophobic protein containing with 26 phosphorylation sites and 0 transmembrane regions. The basal levels of FABP1 and FAS in pig tissues expression were 3 -3.5-fold higher in subcutaneous fat compared with muscle (P < 0.01). Recombinant expression plasmids were successfully transfected into the cloned preadipocytes and (a) overexpression of FAS resulted in significantly increased expression of COL3A1 gene (P < 0.05) and significantly inhibited lysyl oxidase LOX expression (P < 0.01); (b) overexpression of FABP1 significantly increased COL3A1 expression (P < 0.01) and significantly inhibited LOX expression (P < 0.05) and significantly reduced lysyl oxidase activity (P < 0.01). Therefore, enhancing FABP1 expression increases collagen accumulation and this preliminarily suggests that FAS and FABP1 can serve as fat-related candidate genes providing a theoretical basis for the study of fat deposition in Zongdihua pigs.

animal behavior and cognition↗

bioRxiv2022

Membrane wetting, molding and reticulation by protein condensates

Cells compartmentalize their components in liquid-like condensates, which can be reconstituted in vitro. Although these condensates interact with membrane-bound organelles, the potential of membrane remodeling and the underlying mechanisms are not well understood. Here, we demonstrate that interactions between protein condensates (including hollow ones) and membranes can lead to remarkable morphological transformations and describe these with theory. Modulation of solution salinity or membrane composition drives the condensate-membrane system through two wetting transitions, from dewetting, through a broad regime of partial wetting, to complete wetting. A new phenomenon, namely fingering or ruffling of the condensate-membrane interface is observed when sufficient membrane area is available, producing intricately curved structures. The observed morphologies are governed by the interplay of adhesion, membrane elasticity, and interfacial tension. Our results highlight the relevance of wetting in cell biology, and pave the way for the design of synthetic membrane-droplet based biomaterials and compartments with tunable properties.

biophysics↗

bioRxiv2022

Combined small molecule treatment accelerates timing of maturation in human pluripotent stem cell-derived neurons

The maturation of human pluripotent stem cell (hPSC)-derived neurons mimics the protracted timing of human brain development, extending over months and years to reach adult-like function. Prolonged in vitro maturation presents a major challenge to stem cell-based applications in modeling and treating neurological disease. We designed a high-content imaging assay based on morphological and functional readouts in hPSC-derived cortical neurons to reveal underlying pathways and to identify chemicals capable of accelerating neuronal maturation. Probing a library of 2688 bioactive drugs, we identified multiple compounds that drive neuronal maturation including inhibitors of LSD1 and DOT1L and activators of calcium-dependent transcription. A cocktail of 4 factors GSK-2879552, EPZ-5676, NMDA and Bay K 8644, which we collectively termed GENtoniK, triggered maturation across all assays tested including measures of synaptic density, electrophysiology and transcriptomics. Remarkably, GENtoniK was similarly effective in enhancing neuronal maturation in 3D cortical organoids and in spinal motoneurons, and improved aspects of cell maturation in non-neural lineages such as melanocytes and pancreatic beta cells. These results demonstrate that the maturation of multiple hPSC-derived cell types can be enhanced by simple pharmacological intervention and suggests that some of the mechanisms controlling the timing of human maturation are shared across lineages.

neuroscience↗

bioRxiv2022

Lipid-mediated organization of prestin in the outer hair cell membrane and its implications in sound amplification

Prestin is a high-density motor protein in the outer hair cells (OHCs), whose conformational response to acoustic signals alters the shape of the cell, thereby playing a major role in sound amplification by the cochlea. Despite recent structural determination in active and inhibited states, the details of prestins intimate interactions with the membrane, which are central to its function remained unresolved. Here, employing a large set (collectively, more than 0.5 ms) of coarse-grained molecule dynamics simulations, we characterize the nature of prestins lipid-protein interactions, demonstrating their impact on the organization of prestin at densities relevant to the OHCs and its effectiveness in reshaping OHCs. Beyond local enrichment/depletion of various lipid types, prestin causes drastic anisotropic membrane deformation, which in turn mediates a preferential membrane organization of prestin in which deformation patterns by neighboring prestin copies are aligned constructively. The reduced membrane rigidity accompanying this arrangement is hypothesized to maximize the mechanical impact of prestin on OHC reshaping during cochlear sound amplification. Prestins preferential arrangement is further verified by extended simulations demonstrating strong correlation between prestin neighbors in their orientations. These results demonstrate a strong case of protein-protein cooperative communication in membrane, purely mediated by their interactions with lipids.

biophysics↗

bioRxiv2022

Quantifying portable genetic effects and improving cross-ancestry genetic prediction with GWAS summary statistics

Polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of Europeans are known to have substantially reduced predictive accuracy in non-European populations, limiting its clinical utility and raising concerns about health disparities across ancestral populations. Here, we introduce a novel statistical framework named X-Wing to improve predictive performance in ancestrally diverse populations. X-Wing quantifies local genetic correlations for complex traits between populations, employs a novel annotation-dependent estimation procedure to amplify correlated genetic effects between populations, and combines multiple population-specific PRS into a unified score with GWAS summary statistics alone as input. Through extensive benchmarking, we demonstrate that X-Wing pinpoints portable genetic effects and substantially improves PRS performance in non-European populations, showing 18.7%-122.1% gain in predictive R2 compared to state-of-the-art methods based on GWAS summary statistics. Overall, X-Wing addresses critical limitations in existing approaches and may have broad applications in cross-population polygenic prediction.

genetics↗

bioRxiv2022

NetBCE: An Interpretable Deep Neural Network for Accurate Prediction of Linear B-Cell Epitopes

Identification of B-cell epitopes (BCEs) plays an essential role in the development of peptide vaccines, immuno-diagnostic reagents, and antibody design and production. In this work, we generated a large benchmark dataset comprising 126,779 experimentally-supported, linear epitope-containing regions in 3567 protein clusters from over 1.3 million B cell assays. Analysis of this curated dataset showed large pathogen diversity covering 176 different families. The accuracy in linear BCE prediction was found to strongly vary with different features, while the performance by sequence features was superior to that by structural features. To search more efficient and interpretive feature representations, a ten-layer deep learning framework for linear BCE prediction, namely NetBCE, was developed. NetBCE achieved high accuracy and robust performance with the average area under the curve (AUC) value of 0.846 in five-fold cross validation through automatically learning the informative classification features. NetBCE substantially outperformed the conventional machine learning algorithms and other tools, with an over 22.06% improvement of AUC value compared to other tools using an independent dataset. Through investigating the output of important network modules in NetBCE, epitopes and non-epitopes tended to present in distinct regions with efficient feature representation along the network layer hierarchy. The NetBCE tool will be useful for linear B-cell epitopes identification and more generally, immunological and computational biology research.

bioinformatics↗

bioRxiv2022

Comprehensive Analysis of the Expression and Prognosis for PSMBs in Clear Cell Renal Cell Carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most common malignances with an ever-increasing incidence and high mortality. Although comprehensive therapy has made great progress in recent years, the prognosis of most ccRCC patients is still poor. The proteasome {beta} subunits (PSMBs) are a group of genes composing the ubiquitin-proteasome pathway, which is the principal mechanism of protein catabolism in mammalian cytoplasm and nucleus and is essential for the regulation of almost all cellular processes. Growing evidence show s that the PSMBs play an important role in the occurrence and progression of various cancers. However, the expression and prognostic value of PSMBs in ccRCC have not been evaluated. MethodsTo solve this issue, ONCOMINE, UALCAN, Human Protein Atlas, cBioPortal, Metascape, GeneMANIA, STRING, DAVID 6.8, TIMER were used in this study. ResultsThe transcriptional expression levels of PSMB2/4/7/8/9/10 in ccRCC tissues were found to be significantly upregulated, and the mRNA expression levels of PSMB1/2/3/4/8/9/10 were associated with advanced tumor stage and tumor grade. Besides, higher mRNA expression of PSMB1/2/3/4/5/6/7/10 were associated with a shorter overall survival (OS). Furthermore, the protein expression level of PSMB4/7/8/9/10 in ccRCC was higher than normal renal tissues. Significant relationships were also found between the expression of PSMBs and the infiltration of immune-related cells. ConclusionsThe present study implied that PSMB4 and PSMB10 might act as potential therapy targets and prognostic biomarkers in ccRCC, which may contribute to available knowledge, improve the treatment designs, and enhance the accuracy of prognosis for patients with ccRCC.

bioinformatics↗

bioRxiv2022

Analysis and Identification of Necroptosis Landscape on Therapy and Prognosis in Bladder Cancer

Bladder cancer (BLCA) is one of the most common malignant tumors of the urinary system, but current therapeutic strategy based on chemotherapy and immune checkpoint inhibitors (ICIs) therapy cannot meet the treatment needs, which mainly owing to the endogenous or acquired apoptotic resistance of cancer cells. Targeting necroptosis provides a novel strategy for chemotherapy, targeted drugs, and improves the efficacy of ICIs because of strong immunogenicity of necroptosis. Therefore, we systemically analyzed necroptosis landscape on therapy and prognosis in BLCA. We firstly divided BLCA patients from The Cancer Genome Atlas (TCGA) database into two necroptosis-related clusters (C1 and C2). Necroptosis C2 showed a significantly better prognosis than C1, and the differential genes of C2 and C1 were mainly related to the immune response according to GO and KEGG analysis. Next, we constructed a novel necroptosis related genes (NRGs) signature consisting of SIRT6, FASN, GNLY, FNDC4, SRC, ANXA1, AIM2, and IKBKB to predict the survival of TCGA-BLCA cohort, the accuracy of NRGsocre was also verified by external datasets. In addition, a nomogram combining NRGscore and several clinicopathological features was established to predict the BLCA patients OS more accurately and conveniently. We also found that NRGscore was significantly related to the infiltration levels of CD8 T cells, NK cells, and iDC cells, the gene expression of CTLA4, PD1, TIGIT, and LAG3 of TME, the sensitivity to chemotherapy and targeted agents in BLCA patients. In conclusion, the NRGscore has an excellent performance in evaluating the prognosis, clinicopathologic features, tumor microenvironment (TME) and therapeutic sensitivity of BLCA patients, which could be utilized as a guide for chemotherapy, ICIs therapy, and combination therapy.

cancer biology↗

bioRxiv2022

Identification of two bZIP transcription factors that regulate development of pavement and trichome cells in Arabidopsis thaliana by single-cell RNA-sequencing

Epidermal cells are the main avenue for signal and material exchange between plants and the environment. Leaf epidermal cells primarily include pavement cells (PCs), guard cells, and trichomes cells (TCs), which differentiate from protodermal cells or meristemoids. The development and distribution of different epidermal cells are tightly regulated by a complex transcriptional regulatory network mediated by phytohormones, including jasmonic acid (JA), and transcription factors. Understanding how the fate of leaf epidermal cells is determined, however, is still largely unknown due to the diversity of cell types and the complexity of its regulation. Here, we characterized the transcriptional profiles of epidermal cells in 3-day-old true leaves of Arabidopsis thaliana using single-cell RNA-sequencing. We identified two genes encoding BASIC LEUCINE-ZIPPER (bZIP) transcription factors, namely the bZIP25 and bZIP53, which are highly expressed in PCs and early-stage meristemoid cells. Densities of PCs and TCs were found to increase and decrease, respectively, in bzip25 and bzip53 mutants, compared with wild-type plants. This trend was more pronounced in the presence of JA, suggesting that these transcription factors regulate the development of TCs and PCs in response to JA. IN A NUTSHELLO_ST_ABSBackgroundC_ST_ABSLeaf epidermal cells, comprised of trichome cells (TCs), guard cells (GCs), and pavement cells (PCs), are responsible for exchanging materials and information between plants and the surrounding aerial environment. Many genes have been identified in Arabidopsis thaliana and confirmed to be involved in the initiation and differentiation of TCs and PCs. The fate determination of TCs and PCs is tightly regulated by positive and negative regulators at the cellular level. The precise underlying molecular mechanisms responsible for the fate determination of TCs and PCs, however, are still unclear at this time. QuestionWhat are the transcriptomic profiles of different leaf epidermal cell types? Can we dissect the genes that are specifically expressed in certain epidermal cell types? What kinds of transcription factors are involved in regulating the fate determination of TCs and PCs? FindingsWe performed single cell RNA-seq to investigate the transcriptomic profiles of different leaf epidermal cell types and identified differentially expressed genes in each cell type. We found that genes that are involved in jasmonic acid signaling are highly expressed in early-stage meristemoid (EM) cells which can act as the precursor of PCs and perhaps of TCs. To investigate the regulatory mechanisms underlying EM development, we identified the transcription factors (TFs) in EM cells and found that two bZIP TF genes, bZIP25 and bZIP53, are highly expressed in EMs. Further analyses of these two genes using both loss-of-function and gain-of-function approaches indicated that bZIP25 and bZIP53 are functionally involved in promoting trichome formation but inhibit pavement cell development in response to jasmonic acid. Next stepsBesides of bZIP25 and bZIP53, we also identified other key genes, for example FES1B, in leaf epidermal cells. Our next step will be to explore the regulation of other key genes involved in the fate determination of different cell types in leaf epidermis.

plant biology↗

bioRxiv2022

Impact of hydrostatic pressure on organic carbon cycling of the deep-sea microbiome

Deep-sea microbial communities are exposed to high hydrostatic pressure. While some of these deep-sea prokaryotes are adapted to high-pressure conditions, the contribution of piezophilic (i.e., pressure-loving) and piezotolerant prokaryotes to the total deep-sea prokaryotic community remains unknown. Here we show that the metabolic activity of prokaryotic communities is increasingly inhibited with increasing hydrostatic pressure. At 4,000 m depth, the bulk heterotrophic prokaryotic activity under in situ hydrostatic pressure was only about one-third of that measured on the same community at atmospheric pressure conditions. Only [~]5% of the bathypelagic prokaryotic community are piezophilic while [~]85% of the deep-sea prokaryotes are piezotolerant. A small fraction ([~]10%) of the deep-sea prokaryotes is piezosensitive (mainly members of Bacteroidetes, Alteromonas) exhibiting specific survival strategies at meso- and bathypelagic depths. These piezosensitive bacteria elevated their activity by more than 100-fold upon depressurization. Hence, the consistently higher bulk metabolic activity of the deep-sea prokaryotic community measured upon depressurization is due to a rather small fraction of the prokaryotic community. Overall, the heterotrophic prokaryotic activity in the deep-sea is substantially lower than hitherto assumed with major impacts on the oceanic carbon cycling.

ecology↗

bioRxiv2022

HALO: A software tool for real-time head alignment in the MR scanner

Magnetic resonance imaging (MRI) studies in human subjects often require multiple scanning sessions/visits. Changes in a subjects head position across sessions result in different alignment between brain tissues and the magnetic field which leads to changes in magnetic susceptibility. These changes can have considerable impacts on acquired signals. Therefore, we developed the Head Alignment Optimization (HALO) tool. HALO provides real-time visual feedback of a subjects current head position relative to the position in a previous session. We verified that HALO enabled subjects to actively align their head positions to the desired position of their initial sessions. Our pilot sample of healthy subjects were able to improve their head alignment significantly using HALO and achieved good alignment with their first session meeting stringent criteria similar to that used for within-run head motion (less than 2mm translation or 2 degrees rotation in any direction from the desired position). Utilization of HALO in longitudinal studies will reduce the noise across sessions related to changes in magnetic susceptibility. HALO has been made publicly available.

neuroscience↗

bioRxiv2022

Single cell Transcriptome and T cell Repertoire Mapping of the Mechanistic Signatures and T cell Trajectories Contributing to Vascular and Dermal Manifestations of Behcet Disease

Behcets disease (BD) is a form of vasculitis characterized by complex multi-organ manifestations that may frequently recur and induce major tissue damage. Although genetic association studies have identified a number of risk factors, the etiology of BD and its tissue manifestations remains unknown, and the landscape of immune responses in BD is opaque, particularly in terms of inflammatory recurrence. In this study, we mapped the transcriptomes of the immune cell compartment in BD at single-cell resolution, sampling both circulation and affected skin in order to chart the immune interplay driving pathogenesis. Through comprehensive expression and communication analysis of the twenty major cell types identified, we observe striking mechanistic differences in immune response between BD skin lesions and peripheral circulation involving TNF signaling and T cell migration. Through integrated TCR sequencing, we further discover a pattern of clonal sharing between circulating and skin CD8+T cell populations along a trajectory defined by the acquisition of tissue-residential properties. In addition, we also identify a population of expanded CD4+ Tregs with the propensity to produce IL-32. Instead of suppressing effector T cell proliferation and function, IL-32 triggers increased expression of CD97, and may thus encourage prolonged local T cell activity in the skin. Collectively, our data serve to advance understandings of contributions of varying immune cell types to BD pathogenesis in the vasculature and skin, as well as the lifecycle patterns of T cells clones in this context. These data may also assist in further investigations of the mechanisms contributing to Treg dysfunction in systemic autoimmunity, while generating a conceptual model of T cell function contributing to BD recurrence.

immunology↗

bioRxiv2022

Cannabinoids regulate an insula circuit controlling water intake

The insular cortex, or insula, is a large brain region involved in the detection of thirst and the control of water intake. However our understanding of the topographical, circuit and molecular mechanisms the controlling water intake within the insula remains parcellated. We found that type-1 cannabinoid receptors (CB1) within the insular cortex participate to the regulation of water intake, and deconstructed circuit mechanisms of this control. Topographically, we revealed that the activity of excitatory neurons in both anterior (aIC) and posterior (pIC) insula increases in response to water intake, yet removal of CB1 receptors only in the pIC decreases water intake. Interestingly, we found that CB1 receptors are highly expressed in insula projections to the basolateral amygdala (BLA), while undetectable in the neighboring central part of the amygdala. Thus, we imaged the neurons of the anterior or posterior insula targeting the BLA (aIC-BLA and pIC-BLA), and found they oppositely respond to water intake, respectively decreasing and increasing their activity upon water drinking. Consistently, chemogenetic activation of pIC-BLA neurons decreased water intake. Finally, we uncovered CB1-dependent short term synaptic plasticity (depolarization-induced suppression of excitation, DSE) selectively in pIC-BLA, compared to aIC-BLA synapses. Altogether, our results support a model where CB1 signaling in the pIC-BLA pathway exerts a positive control on water intake.

neuroscience↗

bioRxiv2022

Pore-forming protein βγ-CAT promptly responses to fasting with capacity to deliver macromolecular nutrients

During animal fasting, the nutrient supply and metabolism switch from carbohydrates to a new reliance on the catabolism of energy-dense lipid stores. Assembled under tight regulation, {beta}{gamma}-CAT is a pore-forming protein and trefoil factor complex identified in toad Bombina maxima. Here, we determined that this protein complex is a constitutive component in toad blood, that actively responds to the animal fasting. The protein complex was able to promote cellular albumin and albumin-bound fatty acid uptake in a variety of epithelial and endothelial cells, and the effects were attenuated by a macropinocytosis inhibitor. Endothelial cell-derived exosomes containing largely enriched albumin and fatty acids, called nutrisomes, were released in the presence of {beta}{gamma}-CAT. These specific nutrient vesicles were readily taken by starved muscle cells to support their survival. The results uncovered that pore-forming protein {beta}{gamma}-CAT is a fasting responsive element able to drive cell vesicular import and export of macromolecular nutrients.

cell biology↗

bioRxiv2022

Fine oculomotor knowledge enhances high-acuity vision

It has long been debated how humans resolve fine details and perceive a stable visual world despite the fixational motion of their eyes, the incessant ocular jitter that occurs in the intervals between voluntary gaze shifts. Current theories assume these processes to rely solely on the visual input to the retina, without contributions from motor and/or proprioceptive sources. Here we show that contrary to this widespread assumption, the visual system has access to high-resolution extra-retinal knowledge of fixational eye motion and uses it to deduce spatial relations. Building on recent advances in gaze-contingent display control, we created a spatial discrimination task in which the stimulus configuration was entirely determined by oculomotor activity. Our results show that humans correctly infer geometrical relations even when no spatial information is delivered to the retina and accurately combine high-resolution extraretinal monitoring of gaze displacement with retinal signals. These findings reveal a multimodal strategy for encoding spatial details, in which fine oculomotor knowledge is used to interpret the fixational input to the retina.

neuroscience↗

bioRxiv2022

POU2AF2/C11orf53 functions as a co-activator of POU2F3 by maintaining chromatin accessibility and enhancer activity

Small cell lung cancer (SCLC), accounting for around 13% of all lung cancers, often results in rapid tumor growth, early metastasis, and acquired therapeutic resistance. The POU class 2 homeobox 3 (POU2F3) is a master regulator of tuft cell identity and defines a subtype of SCLC tumors (SCLC-P subtype) that lack the expression of neuroendocrine (NE) markers. Here, we have identified a previously uncharacterized protein, C11orf53, which is co-expressed with POU2F3 in both SCLC cell lines and patient samples, defining the same SCLC-P subtype. C11orf53 is an essential gene for the cell survivability of SCLC-P subtype, based on genome-wide CRISPR screening and genetic depletion of C11orf53 or POU2F3, inducing apoptosis in different SCLC-P subtype cell lines. Furthermore, our biochemical and genome-wide studies have demonstrated that C11orf53 is a novel chromatin-bound protein that occupies broad active enhancer domains and regulates gene expression at active enhancers. Mechanistically, C11orf53 directly interacts with POU2F3 at the POU domain, and is recruited to chromatin by POU2F3. Consequently, depletion of C11orf53 dramatically reduced enhancer H3K27ac levels and chromatin accessibility, resulting in a reduction of the expression of POU2F3-dependent tuft cell markers. Based on the expression pattern and molecular function of C11orf53, we have renamed it as "POU Class 2 Homeobox Associating Factor 2" (POU2AF2). In summary, our study has identified a new co-activator of POU2 family transcription factors, and sheds light on the therapeutic potential of targeting POU2AF2/POU2F3 heterodimer in human SCLC.

cancer biology↗

bioRxiv2022

Development of visual cortex in human neonates are selectively modified by postnatal experience

Experience-dependent cortical plasticity is a pivotal process of human brain development and essential for the formation of most cognitive functions. Although studies found that early visual experience could influence the endogenous development of visual cortex in animals, little is known about such impact on human infants. Using the multi-modal MRI data from developing human connectome project, we revealed the early structural and functional maps in the ventral visual cortex and their development across the first month of age. Particularly, we found the postnatal experience could modulate both the cortical morphology in ventral visual cortex and the functional circuit between bilateral primary visual cortices. But the cortical myelination and overall functional circuits of ventral cortex, particularly that of the high-order visual cortex, developed without significant influence of postnatal experience in such early period. These experience-dependent cortical properties were further validated in the preterm-born infants who have longer postnatal time but immature cortical development at birth. The results confirmed that the development of cortical thickness was dominated by the postnatal experience but the functional circuit might be determined by the overall maturity of visual cortex. These data suggest in human newborns that early postnatal experience shapes the structural and functional development of the visual cortex in selective and organized pattern.

neuroscience↗

bioRxiv2022

Real-time denoising of fluorescence time-lapse imaging enables high-sensitivity observations of biological dynamics beyond the shot-noise limit

A fundamental challenge in fluorescence microscopy is the inherent photon shot noise caused by the inevitable stochasticity of photon detection. Noise increases measurement uncertainty, degrades image quality, and limits imaging resolution, speed, and sensitivity. To achieve high-sensitivity imaging beyond the shot-noise limit, we provide DeepCAD-RT, a versatile self-supervised method for effective noise suppression of fluorescence time-lapse imaging. We made comprehensive optimizations to reduce its data dependency, processing time, and memory consumption, finally allowing real-time processing on a two-photon microscope. High imaging signal-to-noise ratio (SNR) can be acquired with 10-fold fewer fluorescence photons. Meanwhile, the self-supervised superiority makes it a practical tool in fluorescence microscopy where ground-truth images for training are hard to obtain. We demonstrated the utility of DeepCAD-RT in extensive experiments, including in vivo calcium imaging of various model organisms (mouse, zebrafish larva, fruit fly), 3D migration of neutrophils after acute brain injury, and 3D dynamics of cortical ATP (adenosine 5-triphosphate) release. DeepCAD-RT will facilitate the morphological and functional interrogation of biological dynamics with minimal photon budget.

biophysics↗