Biology subjects

Qiao, H.

Publications and source records attributed to Qiao, H..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

Self-supervised denoising for structured illumination microscopy enables long-term super-resolution live-cell imaging

Detection noise significantly degrades the quality of structured illumination microscopy (SIM) images, especially under low-light conditions. Although supervised learning based denoising methods have shown prominent advances in eliminating the noise-induced artifacts, the requirement of a large amount of high-quality training data severely limits their applications. Here we developed a pixel-realignment-based self-supervised denoising framework for SIM (PRS-SIM) that trains an SIM image denoiser with only noisy data and substantially removes the reconstruction artifacts. We demonstrated that PRS-SIM generates artifact-free images with 10-fold less fluorescence than ordinary imaging conditions while achieving comparable super-resolution capability to the ground truth (GT). Moreover, the proposed method is compatible with multiple SIM modalities such as total internal reflective fluorescence SIM (TIRF-SIM), three-dimensional SIM (3D-SIM), lattice light-sheet SIM (LLS-SIM), and non-linear SIM (NL-SIM). With PRS-SIM, we achieved long-term super-resolution live-cell imaging of various bioprocesses, revealing the clustered distribution of clathrin coated pits and detailed interaction dynamics of multiple organelles and the cytoskeleton.

cell biology↗

bioRxiv2023

Zero-shot learning enables instant denoising and super-resolution in optical fluorescence microscopy

Computational super-resolution (SR) methods, including conventional analytical algorithms and deep learning models, have substantially improved optical microscopy. Among them, supervised deep neural networks have demonstrated outstanding SR performance, however, demanding abundant high-quality training data, which are laborious and even impractical to acquire due to the high dynamics of living cells. Here, we develop zero-shot deconvolution networks (ZS-DeconvNet) that instantly enhance the resolution of microscope images by more than 1.5-fold over the diffraction limit with 10-fold lower fluorescence than ordinary SR imaging conditions in an unsupervised manner without the need for either ground truths or additional data acquisition. We demonstrate the versatile applicability of ZS-DeconvNet on multiple imaging modalities, including total internal reflection fluorescence microscopy, three-dimensional (3D) wide-field microscopy, confocal microscopy, lattice light-sheet microscopy, and multimodal structured illumination microscopy (SIM), which enables multi-color, long-term, super-resolution 2D/3D imaging of subcellular bioprocesses from mitotic single cells to multicellular embryos of mouse and C. elegans.

bioengineering↗

bioRxiv2022

Soft and stretchable organic bioelectronics for continuous intra-operative neurophysiological monitoring during microsurgery

Continuous intra-operative neurophysiological monitoring (CINM) that provides precise mapping of neural anatomy through the entire microsurgery process is essential to preserve the structural and functional integrity of the nerve. However, bulky and rigid electrodes used currently in clinics are usually unable to reliably maintain continuous and stable contacts with the vulnerable and complex nerve networks, thus often resulting in detrimental post-operative complications, such as hemiplegia and sensory disturbances. Here, we describe a biomechanically compatible, suture-free, and individually reconfigurable CINM based on soft and stretchable organic electronic materials. Due to both low impedance and modulus of our conducting polymer electrodes, we achieved for the first time continuous recording of near-field action potential with high signal-to-noise ratio and minimal invasiveness during microsurgeries. Utilizing this unprecedented CINM modality, in conjunction with localized neurostimulation, we further demonstrated our approach in enabling optimal post-operative prognosis in preclinical animal models by preserving normal neural functions after a variety of tumor resection surgeries.

bioengineering↗

bioRxiv2022

Climate change has affected the spillover risk of bat-borne pathogens

Bat-borne viruses are a threat to global health and have in recent history had major impacts to human morbidity and mortality. Examples include diseases such as rabies, Ebola, SARS-Cov-1, and SARS-Cov-2 (COVID-19). Climate change could exacerbate the emergence of bat-borne pathogens by affecting the distribution and abundance of bats in tropical ecosystems. Here we report an assessment of historical climate and vampire bat occurrence data for the last century, which revealed a relationship between climatic variation and risk of disease spillover triggered by changes in bat distributions. This report represents one of the first examples of empirical evidence of global change effects on continental patterns of bat-borne pathogen transmission risk. We therefore recommend that more research is necessary on the impacts of climate change on bat-borne pathogen spillover risk, and that climate change impacts on bat-borne disease should be considered in global security initiatives. HighlightsO_LIBat-borne viruses are a threat to global health and include diseases such as rabies, Ebola, SARS-Cov-1, and SARS-Cov-2 (COVID-19). C_LIO_LIClimate change could exacerbate the emergence of bat-borne pathogens by affecting the distribution and abundance of bats. C_LIO_LIHere we report an assessment of historical climate and vampire-bat occurrence data for the last century, which reveals a relationship between climatic variation and risk of disease spillover triggered by changes in bat distributions. C_LI

systems biology↗

bioRxiv2022

Adverse PFAS effects on mouse oocyte in vitro maturation are associated with carbon-chain length and inclusion of a sulfonate group

Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals that are used in products such as non-stick cookware, stain-resistant coating, and food packaging. PFAS are characterized by their fluorinated carbon chains that make them hard to degrade and bioaccumulate in human and animals. Toxicological studies have shown PFAS toxic effects: cytotoxicity, immunotoxicity, neurotoxicity, and reproductive toxicity. Two major categories of PFAS are perfluoroalkyl carboxylic acid (PFCA) and perfluoroalkyl sulfonic acid (PFSA). In this study, we used a mouse-oocyte-in-vitro-maturation (IVM) system to study how the structures of PFAS, such as carbon-chain length and functional groups, determine their reproductive toxicity. We found the toxicity of PFAS is elevated with increasing carbon-chain length and the inclusion of the sulfonate group. Specifically, at 600 {micro}M, perfluorohexanesulfonic acid (PFHxS) and perfluorooctanesulfonic acid (PFOS) reduced the rates of both germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) as well as induced the formation of relatively large polar bodies. However, the shorter PFSA, perfluorobutanesulfonic acid (PFBS), and all PFCA did not show similar adverse cytotoxicity. We further examined mitochondria and cytoskeleton, two essential factors for cell division, in PFOS- and PFHxS-treated oocytes. We found that 600 {micro}M PFHxS and PFOS exposure induced excess reactive oxygen species (ROS) and decreased mitochondrial membrane potential (MMP). Cytoskeleton analysis revealed that PFHxS and PFOS exposure induced chromosome misalignment, abnormal F-actin organization, elongated the spindle formation, and symmetric division in the treated oocytes. Together, our study provides new information on the structure-toxicity relationship of PFAS. SynopsisReproductive toxicity of PFAS, a group of persistent organic pollutants, is determined by their chemical structures.

pharmacology and toxicology↗

bioRxiv2022

Longitudinal white matter alterations in SIVmac239 infected rhesus monkeys with and without regular cART treatment

ObjectiveWe use the SIV-mac239 infected Chinese rhesus monkeys to longitudinally investigate white matters alterations with and without regular combined antiretroviral therapy (cART) treatment, and its relationship with clinical tests. Material and methodsDiffusion tensor imaging (DTI), CD4 T cell counts, and CD4/CD8 were obtained at baseline, 10 days, 4th week,12th week, 24th week, and 36th week post virus inoculation. postinfection (wpi). Microstructural properties were examined within 76 white matter defined by DTI-WM atlas for rhesus macaques. Corrections for multiple comparisons were performed using a false discovery rate (p < 0.05, FDR). Correlation analyses between imaging markers and clinical measures (CD4 T-cell counts, CD4/CD8 ratio) were determined using Pearsons correlations. ResultsIn our model, White matter alterations in SIV-infected macaques can be detected as soon as 4 weeks post inoculation in several brain regions. And with time proceeding, the cART can reverse, relieve, or even progressive effects. CD4 T-cell count is mainly associated with DTI metrics before the cART, whereas CD4/CD8 ratio was associated with white matter alteration with and without cART. ConclusionSIV-mac239 infection can be an idol modal to explore HIV induced HIV associated brain alterations, and the first group of white matter alterations was as soon as 4 weeks post inoculation in structure next to the periventricular area. As the time progressed, cART can bring different effect to each region, including reversed, relieved, and even progressive effects. In addition, these changes are closely linked to CD4/CD8 ratio even after cART. Importance

animal behavior and cognition↗

bioRxiv2022

Phosphorylation Status of B beta Subunit Acts as a Switch to Regulate the Function of Phosphatase PP2A in Ethylene-mediated Root Growth Inhibition

The various combinations and regulations of different subunits of phosphatase PP2A holoenzymes underlie their functional complexity and importance. We found that phosphorylation status of B{beta} of PP2A acts as a switch to regulate the activity of PP2A. In the absence of ethylene, phosphorylated B{beta} leads to an inactivation of PP2A; the substrate EIR1 remains to be phosphorylated, preventing the EIR1 mediated auxin transport in epidermis, leading to normal root growth. Upon the ethylene treatment, the dephosphorylated B{beta} mediates the formation of A2-C4-B{beta} protein complex to activate PP2A, resulting in the dephosphorylation of EIR1 to promote auxin transport in epidermis of elongation zone, leading to root growth inhibition. Altogether, our research revealed a novel molecular mechanism by which the dephosphorylation of B{beta} subunit switches on the PP2A activity to dephosphorylate EIR1 to establish EIR1 mediated auxin transport in epidermis in elongation zone for root growth inhibition in response to ethylene. Significance StatementRoot growth is critical to the establishment of planted seedlings. Ethylene plays an important role in the root growth. Yet, the molecular mechanisms that how ethylene regulates the root growth are largely unexplored. This research sheds light on the molecular mechanisms of the determination of the functional specificity and activity of PP2A in response to stimulus in cell type specific manner and reveals the novel molecular mechanism through which ethylene signaling regulates EIR1 dephosphorylation through B{beta} dephosphorylation to active EIR1 mediated auxin transport in epidermis in elongation zone, leading to root growth inhibition.

plant biology↗

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↗

bioRxiv2022

Cerebral organoids for modeling of HSV-1-induced-multiscale neuropathology associated with Alzheimers disease and phenotypic rescue

Herpes simplex virus type I (HSV-1) infection is a potential risk factor involved in the pathogenesis of Alzheimers disease (AD) and contributes to the AD viral hypothesis. However, further understanding of the neuropathological effects of the HSV-1 infection is hampered by the limitations of existing infection models due to the distinct differences between human brains and other mammalians brains. Here we generated cerebral organoid models derived from pluripotent stem cells to investigate the HSV-induced pathogenesis associated with AD and the role of antiviral drugs in the phenotypic rescue. Our results identified that the HSV-1-infected cerebral organoids recapitulated multiscale neuropathology pertaining to the onset and progression of AD across the genetic, cellular, and tissue levels, including the multicellular A{beta} deposition, dysregulated endogenous AD mediators, reactive gliosis, neuroinflammation, and neural loss. Furthermore, we identified that two antiviral drugs, namely Ribavirin (RBV) and Valacyclovir (VCV), inhibited HSV-1 replication and rescued the neuropathological phenotypes associated with AD in the HSV-1-infected cerebral organoids, implying their therapeutic potential to slow down the progression of AD. Our study provides a high-fidelity human-relevant in-vitro HSV-1 infection model to reconstitute the multiscale neuropathological features associated with AD and discover therapeutic drug candidates relevant to the AD viral hypothesis. IMPORTANCEAD is a progressive neurodegenerative disorder characterized by neuronal death, brain atrophy, and cognitive impairment. HSV-1 is a neurotropic double-stranded DNA virus resulting in long-term neurological sequelae in adults. There is accumulating evidence indicating that AD may be associated with HSV-1 infections. In this study, we generated human-physiologically related cerebral organoids derived from human embryonic stem cells (hESCs) to investigate the influence of HSV-1 infection on the neuropathology associated with AD. We found that the HSV-1-infected cerebral organoids could model typical neuropathological features associated with AD. Additionally, we discovered that both RBV and VCV significantly rescued the HSV-1-induced pathological phenotypes associated with AD. These findings may open new avenues of consideration related to HSV-1 infection and AD. Furthermore, the contribution of these antiviral drugs to AD linked to HSV-1 infection will provide new clues to potential new therapies.

neuroscience↗

bioRxiv2022

Histone H3K4 methyltransferase DcATX1 promotes ethylene induced petal senescence in carnation

Petal senescence is controlled by a complex regulatory network. Epigenetic regulation like histone modification influences chromatin state and gene expression. However, involvement of histone methylation in regulating petal senescence is still largely unknown. Here, we found that the trimethylation of histone H3 at Lysine 4 (H3K4me3) is increased during the ethylene induced petal senescence in carnation (Dianthus caryophyllus L.). The H3K4me3 levels are positively associated with the expression of transcription factor DcWRKY75, ethylene biosynthetic genes DcACS1 and DcACO1, and senescence associated genes (SAGs) DcSAG12 and DcSAG29. Further, we identified that carnation DcATX1 (ARABIDOPSIS HOMOLOG OF TRITHORAX1) encodes a histone lysine methyltransferase which can methylate H3K4. Knockdown of DcATX1 delays ethylene induced petal senescence in carnation, which is associated with the downregulated expression of DcWRKY75, DcACO1 and DcSAG12. While overexpression of DcATX1 exhibits the opposite effects. DcATX1 promotes the transcription of DcWRKY75, DcACO1 and DcSAG12 by targeting to their promoters to elevate the H3K4me3 levels. Overall, our results demonstrate that DcATX1 is a H3K4 methyltransferase that promotes the expression of DcWRKY75, DcACO1 and DcSAG12 by regulating H3K4me3 levels, thereby accelerating ethylene induced petal senescence in carnation. This study further indicates that epigenetic regulation is important for plant senescence process. One sentence summaryA histone methyltransferase promotes ethylene induced petal senescence in cut flower

plant biology↗

bioRxiv2021

Perfluorononanoic acid impedes mouse oocyte maturation by inducing mitochondrial dysfunction and oxidative stress

Perfluorononanoic acid (PFNA), a member of PFAS, is frequently detected in human blood and tissues, even in follicular fluid of women. The exposure of PFNA, but not PFOA and PFOS, is positively correlated with miscarriage and increased time to pregnancy. Toxicological studies indicated that PFNA exposure is associated with immunotoxicity, hepatotoxicity, developmental toxicity, and reproductive toxicity in animals. However, there is little information regarding the toxic effects of PFNA on oocyte maturation. In this study, we investigated the toxic effects of PFNA exposure on mouse oocyte maturation in vitro. Our results showed that 600 M PFNA significantly inhibited germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) in mouse oocytes. Our further study revealed that PFNA induced abnormal metaphase I (MI) spindle assembly, evidenced by malformed spindles and mislocalization of p-ERK1/2 in PFNA-treated oocytes. We also found that PFNA induced abnormal mitochondrial distribution and increased mitochondrial membrane potential. Consequently, PFNA increased reactive oxygen species (ROS) levels, leading to oxidative stress, DNA damage, and eventually early-stage apoptosis in oocytes. In addition, after 14 h culture, PFNA disrupted the formation of metaphase II (MII) spindle in most PFNA-treated oocytes with polar bodies. Collectively, our results indicate that PFNA interferes with oocyte maturation in vitro via disrupting spindle assembly, damaging mitochondrial functions, and inducing oxidative stress, DNA damage, and early-stage apoptosis.

cell biology↗

bioRxiv2021

Accounting for dispersal improves the understanding of species abundance patterns

A long-standing question in ecology is how are species population distributed across space. The highest abundance has been hypothesized to be in the spatial or niche center, though mixed patterns from empirical studies has triggered a recent debate. Here we propose a conceptual framework based on environmental suitability and dispersal to interpret the mixed evidence. We demonstrate that the highest abundance could occur in the spatial center, in the niche center, or somewhere in-between the two centers, depending on the environmental setup and dispersal ability. We found that spatial and niche centers rarely overlap, suggesting the counteracting effect between the two factors, rather than reinforcement, is the norm in determining abundance patterns. The varied locations of highest abundance mirror the mixed evidence in literature, suggesting the "abundant-centre" and "abundant-niche centre" hypotheses are not mutually exclusive. This highlights the importance in understanding the biogeographic patterns through the lens of underlying mechanisms.

ecology↗

bioRxiv2020

Reinforcing neuron extraction and spike inference in calcium imaging using deep self-supervised learning

Calcium imaging is inherently susceptible to detection noise especially when imaging with high frame rate or under low excitation dosage. We developed DeepCAD, a self-supervised learning method for spatiotemporal enhancement of calcium imaging without requiring any high signal-to-noise ratio (SNR) observations. Using this method, detection noise can be effectively suppressed and the imaging SNR can be improved more than tenfold, which massively improves the accuracy of neuron extraction and spike inference and facilitate the functional analysis of neural circuits.

neuroscience↗

bioRxiv2020

The genomic and transcriptomic foundations of viviparous seed development in mangroves

Vivipary in plants refers to a specific seed development and reproductive strategy where seeds minimize the dormancy stage and germinate while still attached to their maternal plants. It is one of the most unique adaptive genetic features used by many mangrove species where elongated hypocotyls aid in quick root emergence to anchor the seedling in coastal intertidal wetlands. The genetic mechanisms behind mangrove vivipary, however, remain elusive. Using comparative genomic and transcriptomic technologies to investigate viviparous mangroves and their close inland relatives, we found that a full array of gene expression profiles were altered, including key plant hormone metabolic pathways, high expression of embryonic signature genes, and reduced production of proanthocyanidins and storage proteins. Along with these changes, a major gene regulating seed dormancy, Delay of Germination-1 (DOG1), is entirely missing or defunct within the entire linage of the four genera with true viviparous characteristics. These results suggest a systemic level change is required to warrant the genetic program of mangrove vivipary. Understanding of the molecular processes of vivipary could benefit the design of pregerminated propagules for forestation in harsh environments or prevent precocious germination of grain crops pre- and post-harvest.

genomics↗

bioRxiv2020

Iodoacetic acid disrupts mouse oocyte maturation by inducing oxidative stress and spindle abnormalities

Disinfection by-products (DBPs) are compounds produced during the water disinfection process. Iodoacetic acid (IAA) is one of the unregulated DBPs in drinking water, with potent cytotoxicity and genotoxicity in animals. However, whether IAA has toxic effects on oocyte maturation remains unclear. Here, we show that IAA exposure resulted in metaphase I (MI) arrest and polar-body-extrusion failure in mouse oocytes, indicating that IAA had adverse effects on mouse oocyte maturation in vitro. Particularly, IAA treatment caused abnormal spindle assembly and chromosome misalignment. Previous studies reported that IAA is a known inducer of oxidative stress in non-germline cells. Correspondingly, we found that IAA exposure increased the reactive oxygen species (ROS) levels in oocytes in a dose-dependent manner, indicating IAA exposure could induce oxidative stress in oocytes. Simultaneously, DNA damage was also elevated in the nuclei of these IAA-exposed mouse oocytes, evidenced by increased {gamma}-H2AX focus number. In addition, the un-arrested oocytes entered metaphase II (MII) with severe defects in spindle morphologies and chromosome alignment after 14-hour IAA treatment. An antioxidant, N-acetyl-L-cysteine (NAC), reduced the elevated ROS level and restored the meiotic maturation in the IAA. exposed oocytes, which indicates that IAA-induced maturation failure in oocytes was mainly mediated by oxidative stress. Collectively, our results indicate that IAA exposure interfered with mouse oocyte maturation by elevating ROS levels, disrupting spindle assembly, inducing DNA damage, and causing MI arrest.

cell biology↗

bioRxiv2020

Micromanipulation of prophase I chromosomes from mouse spermatocytes reveals high stiffness and gel-like chromatin organization

Meiosis produces four haploid cells after two successive divisions in sexually reproducing organisms. A critical event during meiosis is construction of the synaptonemal complex (SC), a large, protein-based bridge that physically links homologous chromosomes. The SC facilitates meiotic recombination, chromosome compaction, and the eventual separation of homologous chromosomes at metaphase I. We present experiments directly measuring physical properties of captured mammalian meiotic prophase I chromosomes. Mouse meiotic chromosomes are about ten-fold stiffer than somatic mitotic chromosomes, even for genetic mutants lacking SYCP1, the central element of the SC. Meiotic chromosomes dissolve when treated with nucleases, but only weaken when treated with proteases, suggesting that the SC is not rigidly connected, and that meiotic prophase I chromosomes are a gel meshwork of chromatin, similar to mitotic chromosomes. These results are consistent with a liquid- or liquid-crystal SC, but with SC-chromatin stiff enough to mechanically drive crossover interference.

cell biology↗

bioRxiv2020

Mixed Culture of Bacterial Cell for Large Scale DNA Storage

DNA emerged as novel material for mass data storage, the serious problem human society is facing. Taking advantage of current synthesis capacity, massive oligo pool demonstrated its high-potential in data storage in test tube. Herein, mixed culture of bacterial cells carrying mass oligo pool that was assembled in a high copy plasmid was presented as a stable material for large scale data storage. Living cells data storage was fabricated by a multiple-steps process, assembly, transformation and mixed culture. The underlying principle was explored by deep bioinformatic analysis. Although homology assembly showed sequence context dependent bias but the massive digital information oligos in mixed culture were constant over multiple successive passaging. In pushing the limitation, over ten thousand distinct oligos, totally 2304 Kbps encoding 445 KB digital data including texts and images, were stored in bacterial cell, the largest archival data storage in living cell reported so far. The mixed culture of living cell data storage opens up a new approach to simply bridge the in vitro and in vivo storage system with combined advantage of both storage capability and economical information propagation.

molecular biology↗

bioRxiv2020

Low bias DNA for sustainable and efficient data storage

In DNA data storage, the massive sequence complexity creates challenges in repeatable and efficient information readout. Here, our study clearly demonstrated that canonical polymerase chain reaction (PCR) created significant DNA amplification biases, which greatly hinder fast and stable data retrieving from hundred-thousand synthetic DNA sequences encoding over 2.85 megabyte (MB) digital data. To mitigate the amplification bias, we adapted an isothermal DNA amplification for low-bias amplification of DNA pool with massive sequence complexity, and named the new method isothermal DNA reading (iDR). By using iDR, we were able to robustly and repeatedly retrieve the data stored in DNA strands attached on magnetic beads (MB) with significantly decreased sequencing reads, compared with the PCR method. Therefore, we believe that the low-bias iDR method provides an ideal platform for robust DNA data storage, and fast and reliable data readout.

synthetic biology↗