Biology subjects

Hu, Q.

Publications and source records attributed to Hu, Q..

At least 91 records · Page 5Linked to original sources

bioRxiv2023

Advancing Glycan Analysis: A New Platform Integrating SERS, Boronic Acids, and Machine Learning Algorithms

Glycans are the most abundant and diverse fundamental biomolecules. Profiling glycans is essential to elucidate biomolecular mechanisms and to predict biological consequences; however, the analysis of glycans remains challenging due to their structural complexity. A novel glycan detection platform is established through the integration of surface-enhanced Raman spectroscopy (SERS), boronic acid receptors, and machine learning tools. SERS is able to distinguish isomeric structures and provide fingerprint information of molecules. Boronic acid receptors can selectively bind with glycans, and the reaction influences molecular vibrations, leading to unique Raman spectral patterns. For proof-of-concept, two boronic acids, 4-mercaptophenylboronic acid (4MBA) and 1-thianthrenylboronic acid (1TBA) were used for glycan detection. The spectra were analyzed by the machine learning algorithm. The sensing platform successfully recognized the stereoisomers (glucose, mannose, and galactose), the structural isomers with -1,4 and -1,6 glycosidic linkages, and the {beta}-1,4 glycosidic linkage within lactose molecules. The collective spectra that combine the spectra from both boronic acid receptors could improve the performance of the support vector machine model due to the enrichment of the structural information of glycans. In addition to qualitative analysis, this new sensor could quantify the mole fraction of sialic acid in lactose background using the machine learning regression technique. The quantification accuracy reached a coefficient of determination (R2) value of 0.998 and a normalized mean square error (NMSE) of 0.00195. This low-cost, rapid, and highly accessible sensor will provide the scientific community with another option for frequent glycan screening in standard biological laboratories.

bioengineering↗

bioRxiv2023

ErbB inhibition impairs cognition via disrupting myelination and aerobic glycolysis in oligodendrocytes

White matter abnormalities are an emerging feature of schizophrenia, yet the underlying pathophysiological mechanisms are largely unknown. Disruption of ErbB signaling that is essential for peripheral myelination has been genetically associated with schizophrenia and white matter lesions in schizophrenic patients. However, the roles of ErbB signaling in oligodendrocytes remain elusive. Here, we used a pan-ErbB inhibition strategy and demonstrated the synergistic functions of endogenous ErbB receptors in oligodendrocytes. Through analyses of the cellular, histological, biochemical, behavioral, and electrophysiological differences in mice with manipulation of ErbB activities in oligodendrocytes at different differentiation stages, we found that ErbB signaling regulates myelination and aerobic glycolysis in oligodendrocytes, and both functions are required for working memory. ErbB inhibition in oligodendrocytes at early differentiation stages induces hypomyelination by suppressing the differentiation of newly-formed oligodendrocytes. In contrast, ErbB inhibition in mature oligodendrocytes alters neither myelination nor oligodendrocyte numbers, but accelerates axonal conduction decline under energy stress. Mechanistically, mature oligodendrocytes with ErbB inhibition reduce the expression of lactate dehydrogenase A, failing to provide lactate to electrically active axons. Supplementation of L-lactate restores axonal conduction and working memory capacity that are suppressed by ErbB inhibition in mature oligodendrocytes. These findings reveal the indispensable roles of ErbB signaling in white matter integrity and function, and provide insights into the multifaceted contributions of white matter abnormalities to cognitive impairment.

neuroscience↗

bioRxiv2022

CAbiNet: Joint visualization of cells and genes based on a gene-cell graph

In routine single-cell RNA-sequencing (scRNA-seq) analysis workflows, cells are commonly visualized in 2D to show the patterns in the data. However, these visualization approaches do not give any information about the genes that define the cell groups or clusters. It is therefore desirable to display cells and genes simultaneously such that by their relative position to each other information about the genes expression in a cluster can be obtained. Here we propose "Correspondence Analysis based Biclustering on Networks" (CAbiNet) as a novel approach to jointly visualize cells and genes by a non-linear embedding approach, called biMAP. The biMAP allows for easy and interactive exploration of cells and their corresponding marker genes in a single plot. CabiNet additionally offers an intuitive way to perform biclustering jointly on cells and genes, providing a simplified workflow to annotate cell types on the biMAP. CAbiNet is accessible through GitHub as an R package.

bioinformatics↗

bioRxiv2022

Regulation of RAS palmitoyltransferases by accessory proteins and palmitoylation

SummaryPalmitoylation of cysteine residues at the C-terminal hypervariable regions in human HRAS and NRAS, which is necessary for the RAS signaling, is catalyzed by the acyltransferase DHHC9 in complex with its accessory protein GCP16. The molecular basis for the acyltransferase activity and the regulation of DHHC9 by GCP16 is not clear. Here we report the cryo-EM structures of the human DHHC9-GCP16 complex and its yeast counterpart -- the Erf2-Erf4 complex, demonstrating that GCP16 and Erf4 are not directly involved in the catalytic process but stabilize the architecture of DHHC9 and Erf2, respectively. We found that a phospholipid binding to an arginine-rich region of DHHC9 and palmitoylation on three residues (C24, C25, and C288) were essential for the catalytic activity of the DHHC9-GCP16 complex. Furthermore, we showed that GCP16 also formed complexes with DHHC14 and 18 to catalyze RAS palmitoylation. These findings provide insights into the regulation mechanism of RAS palmitoyltransferases.

molecular biology↗

bioRxiv2022

Spateo: multidimensional spatiotemporal modeling of single-cell spatial transcriptomics

Cells do not live in a vacuum, but in a milieu defined by cell-cell communication that can be measured via emerging high-resolution spatial transcriptomics approaches. However, analytical tools that fully leverage such data for kinetic modeling remain lacking. Here we present Spateo (aristoteleo/spateo-release), a general framework for quantitative spatiotemporal modeling of single-cell resolution spatial transcriptomics. Spateo delivers novel methods for digitizing spatial layers/columns to identify spatially-polar genes, and develops a comprehensive framework of cell-cell interaction to reveal spatial effects of niche factors and cell type-specific ligand-receptor interactions. Furthermore, Spateo reconstructs 3D models of whole embryos, and performs 3D morphometric analyses. Lastly, Spateo introduces the concept of "morphometric vector field" of cell migrations, and integrates spatial differential geometry to unveil regulatory programs underlying various organogenesis patterns of Drosophila. Thus, Spateo enables the study of the ecology of organs at a molecular level in 3D space, beyond isolated single cells.

systems biology↗

bioRxiv2022

RACK1 may participate in placental development via regulating proliferation and migration of trophoblast cell in pigs following intrauterine growth restriction

Intrauterine growth restriction (IUGR) is a severe complication in swine production. Placental insufficiency is responsible for inadequate fetal growth, but the specific etiology of placental dysfunction-induced IUGR in pigs remains poorly understood. In this work, placenta samples supplying the lightest-weight (LW) and mean-weight (MW) pig fetuses in the litter at day 65 (D65) of gestation were collected, and the relationship between fetal growth and placental morphologies and functions was investigated using histomorphological analysis, RNA sequencing, quantitative polymerase chain reaction, and in-vitro experiment in LW and MW placentas. Results showed that the folded structure of the epithelial bilayer of LW placentas followed a poor and incomplete development compared with that of MW placentas. A total of 632 differentially expressed genes (DEGs) were screened out between the LW and MW placentas, and RACK1 was found to be downregulated in LW placentas. The DEGs were mainly enriched in translation, ribosome, protein synthesis, and mTOR signaling pathway according to GO and KEGG enrichment analyses. In-vitro experiments indicated that the decreased RACK1 in LW placentas may be involved in abnormal development of placental folds (PFs) by inhibiting the proliferation and migration of porcine trophoblast cells. Taken together, these results revealed that RACK1 may be a vital regulator in the development of PFs via regulating trophoblast ribosome function, proliferation, and migration in pigs.

genetics↗

bioRxiv2022

Loss of ANT1 Increases Fibrosis and Epithelial Cell Senescence in Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease characterized by progressive lung scarring and remodeling. Although treatments exist that slow disease progression, IPF is irreversible and there is no cure. Cellular senescence, a major hallmark of aging, has been implicated in IPF pathogenesis, and mitochondrial dysfunction is increasingly recognized as a driver of senescence. Adenine nucleotide translocases (ANTs) are abundant mitochondrial ATP-ADP transporters critical for regulating cell fate and maintaining mitochondrial function. We sought to determine how alterations in ANTs influence cellular senescence in pulmonary fibrosis. We found SLC25A4 (ANT1) and SLC25A5 (ANT2) expression is reduced in the lungs of IPF patients and particularly within alveolar type II cells by single cell RNA sequencing. Loss of ANT1 by siRNA in lung epithelial cell lines resulted in increased senescence markers such as beta-galactosidase staining and p21 by Western Blot and RT-qPCR. Bleomycin treated ANT1 knockdown cells also had increased senescence markers when compared to bleomycin treated control cells. Global loss of ANT1 resulted in worse lung fibrosis and increased senescence in the bleomycin and asbestos-induced mouse models of pulmonary fibrosis. This data supports the concept that loss of ANT1 drives IPF pathogenesis through mitochondrial dysfunction associated cellular senescence (MiDaS). In summary, loss of ANT1 induces cellular senescence, leading to abnormal tissue remodeling and enhanced lung fibrosis in IPF. Modulation of ANTs presents a new therapeutic avenue that may alter cellular senescence pathways and limit pulmonary fibrosis.

cell biology↗

bioRxiv2022

Development of highly potent non-covalent inhibitors of SARS-CoV-2 3CLpro

The SARS-CoV-2 virus is the causal agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19). There is an urgent need for potent, specific antiviral compounds against SARS-CoV-2. The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses, and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, non-covalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC50 values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment. One-Sentence SummaryA oral non-covalent inhibitor of 3C-like protease effectively inhibits SARS-CoV-2 replication.

microbiology↗

bioRxiv2022

Mitotic clustering of pulverized chromosomes from micronuclei

Complex genome rearrangements can be generated by the catastrophic shattering of mis-segregated chromosomes trapped within micronuclei through a process known as chromothripsis. Since each chromosome harbors a single centromere, how acentric fragments derived from shattered chromosomes are inherited between daughter cells during mitosis remains unknown. Here we tracked micronucleated chromosomes by live-cell imaging and show that acentric fragments cluster in close spatial proximity throughout mitosis for biased partitioning to a single daughter cell. Mechanistically, the CIP2A-TOPB1 complex prematurely associates with DNA lesions within ruptured micronuclei during interphase, which poises chromosome fragments for clustering upon mitotic entry. Inactivation of CIP2A or TOPBP1 caused pulverized chromosomes to untether and disperse throughout the mitotic cell, consequently resulting in the mis-accumulation of DNA fragments in the cytoplasm. The inheritance of shattered chromosomes by a single daughter cell suggests that micronucleation can drive complex rearrangements that lack the DNA copy number oscillations characteristic of canonical chromothripsis. Comprehensive analysis of pan-cancer whole-genome sequencing data revealed clusters of DNA copy number-neutral rearrangements - termed balanced chromothripsis - across diverse cancer types resulting in the acquisition of known driver events. Thus, distinct patterns of chromothripsis can be explained by the spatial mitotic clustering of pulverized chromosomes from micronuclei.

cell biology↗

bioRxiv2022

Chimeric mRNA based COVID-19 vaccine elicits potent neutralizing antibodies and protection against Omicron and Delta

The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the efficacy and effectiveness of the two FDA-approved mRNA vaccines. Here, we explored various strategies to develop novel mRNAs vaccines to achieve safer and wider coverage of VOCs. Firstly, we constructed a cohort of mRNAs that feature a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2). Not present in the mRNA vaccines currently in use, the mutation abolished the cleavage between the S1 and S2 subunits, potentially enhancing the safety profile of the immunogen. Secondly, we systematically evaluated the induction of neutralizing antibodies (nAb) in vaccinated mice, and discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. Thirdly, the IgG produced in mice immunized with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs, which was further corroborated by challenging vaccinated mice with the live virus of VOCs. However, neither WA-Furin nor Beta-Furin mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original and the sublineages of Omicron variant. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we tested the concept of bivalent immunogen. Instead of just fusing two RBDs head-to-tail, we for the first time constructed an mRNA-based chimeric immunogen by introducing the RBD of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA was capable of inducing potent and broadly acting nAb against Omicron (both BA.1 and BA.2) and Delta, which paves the way to develop new vaccine candidate to target emerging variants in the future.

immunology↗

bioRxiv2022

Hand Gesture Prediction via Transient-phase sEMG using Transfer Learning of Dilated Efficient CapsNet: Towards Generalization for Neurorobotics

There has been an accelerated surge to utilize the deep neural network for decoding central and peripheral activations of the humans nervous system to boost up the spatiotemporal resolution of neural interfaces used in neurorobotics. Such algorithmic solutions are motivated for use in human-centered robotic systems, such as neurorehabilitation, prosthetics, and exoskeletons. These methods are proved to achieve higher accuracy on individual data when compared with the conventional machine learning methods but are also challenged by their assumption of having access to massive training samples. ObjectiveIn this letter, we propose Dilated Efficient CapsNet to improve the predictive performance when the available individual data is very minimum and not enough to train an individualized network for controlling a personalized robotic system. MethodWe proposed the concept of transfer learning using a new design of the dilated efficient capsular neural network to relax the need of having access to massive individual data and utilize the field knowledge which can be learned from a group of participants. In addition, instead of using complete sEMG signals, we only use the transient phase, reducing the volume of training samples to 20% of the original and maximizing the agility. ResultsIn experiments, we validate our model performance with various amounts of injected personalized training data (25%-100% of transient phase) that is segmented once by time and once by repetition. The results of this paper support the use of transfer learning using a dilated capsular neural network and show that with the use of such a model, the knowledge domain learned on a small number of subjects can be utilized to minimize the need for new data of new subjects while focusing only on the transient phase of contraction (which is a challenging neural interfacing problem).

bioengineering↗

bioRxiv2022

A novel intranasal administration adenoviral vector-based platform for rapid COVID-19 vaccine development

The coronavirus SARS-CoV-2 has a severe impact on global public health, and the emerging variants threaten the efficacy of the circulating vaccines. Here, we report that a single vaccination with a non-replicating chimpanzee adenovirus-based vaccine against the SARS-CoV-2 Delta variant (JS1-delta) elicits potent humoral, cellular and mucosal immunity in mice. Additionally, a single intranasal administration of JS1-delta provides effective protection against the Delta (B.1.617.2) variant challenge in mice. This study indicates that chimpanzee adenovirus type 3 (ChAd3) derived vector represents a promising platform for antiviral vaccine development against respiratory infections and JS1-delta is worth further investigation in human clinical trials. HighlightsO_LIA new chimpanzee adenoviral vaccine against the SARS-CoV-2 Delta variant was developed. C_LIO_LIThe vaccine elicited potent humoral, cellular and mucosal immunity in mice. C_LIO_LIThe vaccine protected mice from the Delta variant challenge. C_LI

immunology↗

bioRxiv2021

X-MyoNET: Biometric Identification using Deep Processing of Transient Surface Electromyography

The rapid development of the Internet and various applications such as the Internet of Medical Things (IoMT) has raised substantial concerns about personal information security. Conventional methods (e.g., passwords) and classic biological features (e.g., fingerprints) are security deficient because of potential information leakage and hacking. Biometrics that express behavioral features suggest a robust approach to achieving information security because of the corresponding uniqueness and complexity. In this paper, we consider identifying human subjects based on their transient neurophysiological signature captured using multichannel upper-limb surface electromyography (sEMG). An explainable artificial intelligence (XAI) approach is proposed to process the internal dynamics of temporal sEMG signals. We propose and prove the suitability of "transient sEMG" as a biomarker that can identify individuals. For this, we utilize the Gradient-weighted Class Activation Mapping (Grad-CAM) analysis to explain the networks attention. The outcome not only decodes and makes the unique neurophysiological pattern (i.e., motor unit recruitment during the transient phase of contraction) associated with each individual visualizable but also generates an optimizing two-dimensional (2D) spectrotemporal mask used to significantly reduce the size of the model and the trainable parameters. The resulting mask selectively and systematically samples the spectrotemporal characteristics of the users neurophysiological responses, discarding 40% of the input space while securing the accuracy of about 74% with much shallower neural network architecture. In the systematic comparative study, we find that our proposed model outperforms several state-of-the-art algorithms. For broader impacts, we anticipate our design of a compact, practical, interpretable, and robust identification system that requires only a minimal number of gestures and sensors (only 7% of the entire data set) to be a starting point for small and portable identification hardware.

bioengineering↗

bioRxiv2021

The Flowering Repressor SVP recruits the TOPLESS co-repressor to control flowering in chrysanthemum and Arabidopsis

Plant flowering time is a consequence of the perception of environmental and endogenous signals. The MCM1-AGAMOUSDEFICIENS-SRF-box (MADS-box) gene SHORT VEGETATIVE PHASE (SVP) is a pivotal repressor that negatively regulates the floral transition during the vegetative phase. The transcriptional corepressor TOPLESS (TPL) plays critical roles in many aspects of plant life. An interaction first identified between the second LXLXLX motif (LRLGLP) of CmSVP with CmTPL1-2, which can repress the expression of a key flowering factor CmFTL3 by binding its promotor CArG element in chrysanthemum. Genetic analysis suggested that the CmSVP-CmTPL1-2 transcriptional complex is a prerequisite for SVP to act as a floral repressor, which reduces CmFTL3 transcriptional activity. CmSVP rescued the phenotype of the svp-31 mutant in Arabidopsis, and overexpression of AtSVP or CmSVP in the Arabidopsis dominant negative mutation tpl-1 led to a loss-of-function in late flowering, which confirmed the highly conserved function of SVP in the two completely different species. Thus, we have validated a conserved machinery wherein SVP relies on TPL to inhibit flowering through the direct regulation of FT, which is more meaningful for the evolution of species and could be translated to high-quality cultivation and breeding of crops.

plant biology↗

bioRxiv2021

A novel mechanism of Euonymine inhibits in-stent restenosis through enhancing contractile phenotype of VSMCs by targeting AKT1 and p38MAPK

This study aimed to examine the inhibitory effects of Euonymine on in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) and oxidized low-density lipoprotein (ox-LDL)-induced proliferation, migration, and pro-apoptotic of vascular smooth muscle cells (VSMCs) in vitro, and its potential mechanisms. Euonymine is a monomer component extracted from Tripterygium hypoglaucum (Levl) Hutch. Using in vitro models of rabbit carotid balloon injury and porcine atherosclerotic coronary implantation, we confirmed that Euonymine inhibited ISR after PCI. Furthermore, Euonymine inhibited VSMC phenotypic transformation by targeting AKT1 to regulate the PTEN/AKT1/m TOR signaling pathway, with exertion of anti-proliferative, anti-migratory, and pro-apoptotic effects on ox-LDL-induced cell injury model. Additionally, the study demonstrated that Euonymine induced apoptosis of VSMCs via the p38MAPK-related mitochondria-dependent apoptotic pathway. Collectively, these findings indicated that Euonymine drug-eluting stents inhibited ISR after PCI by targeting AKT1 and p38MAPK to enhance the contractile phenotype of VSMCs to prevent intimal hyperplasia development. This provides insights into a potential therapeutic strategy involving the beneficial effect of Euonymine drug-eluting stent on ISR. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/466441v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1582ef9org.highwire.dtl.DTLVardef@73e133org.highwire.dtl.DTLVardef@1c5f318org.highwire.dtl.DTLVardef@daca49_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2021

Deep Heterogeneous Dilation of LSTM for Transient-phase Gesture Prediction through High-density Electromyography: Application in Neurorobotics

Deep networks have been recently proposed to estimate motor intention using conventional bipolar surface electromyography (sEMG) signals for myoelectric control of neurorobots. In this regard, Deepnets are generally challenged by long training times (affecting practicality and calibration), complex model architectures (affecting the predictability of the outcomes), and a large number of trainable parameters (increasing the need for big data). Capitalizing on our recent work on homogeneous temporal dilation in a Recurrent Neural Network (RNN) model, this paper proposes, for the first time, heterogeneous temporal dilation in an LSTM model and applies that to high-density surface electromyography (HD-sEMG), allowing for the decoding of dynamic temporal dependencies with tunable temporal foci. In this paper, a 128-channel HD-sEMG signal space is considered due to the potential for enhancing the spatiotemporal resolution of human-robot interfaces. Accordingly, this paper addresses a challenging motor intention decoding problem of neurorobots, namely, transient intention identification. Our approach uses only the dynamic and transient phase of gesture movements when the signals are not stabilized or plateaued, which can significantly enhance the temporal resolution of human-robot interfaces. This would eventually enhance seamless real-time implementations. Additionally, this paper introduces the concept of "dilation foci" to modulate the modeling of temporal variation in transient phases. In this work a high number (e.g., 65) of gestures is included, which adds to the complexity and significance of the understudied problem. Our results show state-of-the-art performance for gesture prediction in terms of accuracy, training time, and model convergence.

bioengineering↗

bioRxiv2021

High-resolution spatiotemporal transcriptomic maps of developing Drosophila embryos and larvae

Drosophila has long been a successful model organism in multiple fields such as genetics and developmental biology. Drosophila genome is relatively smaller and less redundant, yet largely conserved with mammals, making it a productive model in studies of embryogenesis, cell signaling, disease mechanisms, etc. Spatial gene expression pattern is critical for understanding of complex signaling pathways and cell-cell interactions, whereas temporal gene expression changes need to be tracked during highly dynamic activities such as tissue development and disease progression. Systematic studies in Drosophila as a whole are still impeded by lack of these spatiotemporal transcriptomic information. Drosophila embryos and tissues are of relatively small size, limiting the application of current technologies to comprehensively resolve their spatiotemporal gene expression patterns. Here, utilizing SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq), we dissected the spatiotemporal transcriptomic changes of developing Drosophila with high resolution and sensitivity. Our data recapitulated the spatial transcriptomes of embryonic and larval development in Drosophila. With these data, we identified known and previously undetected subregions in several tissues during development, and revealed known and potential gene regulatory networks of transcription factors within their topographic background. We further demonstrated that Stereo-seq data can be used for 3D reconstruction of Drosophila embryo spatial transcriptomes. Our data provides Drosophila research community with useful resources of spatiotemporally resolved transcriptomic information across developmental stages.

developmental biology↗

bioRxiv2021

Remarkable Adsorption Performance of Rutile TiO2 (110) Nanosheet for DNA Nucleobases: A First-Principles Study

The remarkable biocompatibility and supreme physical properties of nanostructured TiO2 have promised itself a strong future for biomedical applications. The present study reported a theoretical study on the adsorption of rutile TiO2 (110) nanosheet for DNA nucleobases using first-principles calculations. The calculations of the binding energy and work function demonstrate that the TiO2 nanosheet has remarkable adsorption strength to the DNA nucleobases, being more than 20 times larger than that of graphene and its derivatives. Further electronic band structure and density of state calculations elucidate the interaction mechanisms, which originate from dramatically reduced energy levels and strong hybridization of the 2p orbital of C, N and/or O with 3d orbital of Ti atoms near the Fermi level. The study directs a promising material at applications in DNA sensors and sequencers.

bioengineering↗