Biology subjects

Qiao, S.

Publications and source records attributed to Qiao, S..

At least 19 recordsLinked to original sources

bioRxiv2026

FFPERescuer: deep unsupervised domain adaptation for the reconstruction of gene expression profiles derived from formalin-fixed paraffin-embedded samples

Formalin-fixed paraffin-embedded (FFPE) tumor tissues often suffer from RNA degradation, posing a long-standing challenge for reliable transcriptomic profiling. Here, we propose FFPERescuer, a deep learning framework employing unsupervised domain adaptation, to rectify distorted gene expression data. FFPERescuer comprises a partial encoder that maps a small subset of genes to high-level representations and a decoder to reconstruct full gene expression profiles. On simulated data with varying noise levels, FFPERescuer faithfully recovered gene expression profiles, achieving high Pearson correlation coefficients (PCCs > 0.85) with the ground truth. In FF-FFPE-matched cohorts, FFPERescuer significantly enhanced expression profile concordance, with average PCCs increased by 23% (P < 0.05). Applying to cancer subtyping, FFPERescuer improved classification accuracy from 67% to 92%, recapitulated subtype-specific biological properties lost in the FFPE-derived data, and enhanced survival associations. Our studies provide a powerful framework for reliable transcriptomic profiling from FFPE-archived tumor samples that are widely available in the clinic.

bioinformatics↗

bioRxiv2026

A correlational study of ABCA3 and SCN4B as exercise-related biomarkers of patients with Stanford type A aortic dissection

BackgroundAccumulating evidence indicates that moderate exercise may reduce the incidence of Stanford type A aortic dissection (TAAD), but the specific mechanisms remain unclear. This study aims to identify exercise-related biomarkers in TAAD patients and to investigate their underlying mechanisms. MethodsTranscriptome data related to TAAD and exercise-related genes were obtained from publicly available databases. Candidate biomarkers for TAAD were identified through an integrative approach incorporating differential expression analysis, machine learning, and expression level assessment, leading to the construction of a diagnostic model. Subsequently, functional enrichment, immune infiltration, regulatory network analysis, and computational drug prediction were conducted to systematically investigate the pathological mechanisms and translational potential of the indentified biomarkers. ResultsABCA3 and SCN4B were identified as exercise-related biomarkers in TAAD progression. A nomogram incorporating these two biomarkers exhibited strong diagnostic performance for identifying the disease. Functional enrichment analysis revealed potential involvement of these biomarkers in disease progression through pathways including circadian rhythm regulation and ribosome biosynthesis. Additionally, immune cells like M1 macrophages and naive B cells, as well as regulatory factors including hsa-miR-1343-3p and XIST, were found to be involved in this process. Finally, zonisamide and MRS1097 were identified through computation prediction as potential therapeutic drugs. ConclusionABCA3 and SCN4B were identified as exercise-related biomarkers associatied with TAAD and represent potential valuable targets for both diagnosis and treatment strategies.

bioinformatics↗

bioRxiv2025

Heightened empathic responses led by imbalanced cortico-amygdala circuit in Shank3 autism mouse model

Affective empathy is defined as individual percept and respond to another emotion appropriately, an essential building block for human society. Historically, aberrant empathy was considered as major characteristics of autistic individuals but recently it has been challenged. It required mechanistic understanding of the empathy process, especially how autistic individual percept other emotion. By evaluating the social fear transfer response, we reported a critical role of Shank3 gene, one of the most replicated causative autism genes, in cortico-amygdala circuit in balancing and integrating affective empathy process using preclinical mouse models. We found that Shank3 complete deletion mouse model exhibited unexpected exaggerated affective responses, which was encoded by defective neural dynamics of Shank3-deficient cingulate projecting amygdala circuit. This work for the first time showcased an interplay between gene and affective empathy responses in mouse and laid the groundwork for modeling empathy in autism and other neuropsychiatric disease.

neuroscience↗

bioRxiv2025

SONIC: A Benchmarking Paradigm for Brain-Computer Interfaces

Brain-computer interfaces (BCIs) can restore function for individuals with neuro-logical disorders and have the potential to transform the way people interact with digital systems. However, the development of advanced BCI applications, such as fluent speech synthesis, is dependent on the underlying information transfer capacity of the physical neural interface employed. A significant barrier to progress has been the lack of standardized, application-agnostic methods for benchmarking BCI system performance prior to clinical trials. Here, we introduce SONIC, a novel preclinical benchmarking paradigm designed to evaluate the information transfer rate (ITR) of a BCI system. This paradigm treats the brain and BCI as a noisy communication channel, where information is sent into the brain via precisely controlled sensory stimuli and read out by the neural interface. We implemented this paradigm in an ovine model by presenting rapid sequences of pure tones while recording neural activity from the primary auditory cortex with the Paradromics Connexus(C) BCI, a fully implanted system utilizing high-density intracortical micro-electrode arrays with wireless power and data transmission. A convolutional neural network was used to decode tones based on neural features. Our results demonstrate an achieved ITR of over 200 bits per second (bps), which is the highest reported BCI ITR to date. For reference, this rate exceeds the linguistic information content of human speech. This ITR is achieved with a total neural interface, filtering, and data aggregation delay of 56 milliseconds. Further analysis demonstrated that ITR remains high (> 100 bps) for the lowest total delay tested (11 ms), supporting the needs of latency-sensitive applications (e.g., direct speech synthesis). This work establishes a new benchmark for BCI performance and demonstrates that the Connexus BCI possesses the bandwidth necessary to support highly advanced applications. This benchmark provides a robust framework for preclinical BCI evaluation, enabling principled system design optimization to accelerate the translation of next-generation neurotechnology.

bioengineering↗

bioRxiv2024

Risk factors, prognostic factors, and nomograms for distant metastasis in patients with triple-negative breast cancer: a population-based study

BackgroundTriple-negative breast cancer (TNBC) is associated with a poor prognosis, higher invasiveness compared to other breast cancer variants, and limited treatment options. Due to the lack of conventional treatment methods, TNBC patients are prone to distant metastasis. The purpose of this study is to evaluate the clinical and pathological characteristics of TNBC patients, predict the impact of risk factors on their prognosis, and establish a predictive model to assist doctors in treating TNBC patients and improving their outcomes. MethodsWe conducted a retrospective study on patients with TNBC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. We gathered tumor characteristics and treatment data from these patients. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors for distant metastasis in TNBC patients, while univariate and multivariate Cox proportional hazards regression analyses were utilized to determine independent prognostic factors for TNBC patients with distant metastasis. Based on these factors, a new nomogram was constructed, and patients were categorized into high and low-risk groups using the nomogram scores. The prognosis of the patients was analyzed using Kaplan-Meier (K-M) survival analysis. ResultsThis study enrolled a total of 16,959 patients with TNBC, among whom 730 (4.3%) had distant metastasis at the time of diagnosis. Independent risk factors for distant metastasis in TNBC patients encompass being married, having an invasive lobular carcinoma (ILC) pathology, advanced T stage, advanced N stage, no radiotherapy, no surgery, and tumor size exceeding 50mm. The area under the curve (AUCs) for the training set and validation set were 0.892 and 0.907, respectively. The independent prognostic factors for patients with distant metastasis were being unmarried (P < 0.001), not undergoing surgery (P < 0.001), and not receiving chemotherapy (P < 0.001). The AUCs for the training set at 12, 36, and 60 months were 0.751, 0.709, and 0.691, respectively, while the AUCs for the validation set at 12, 36, and 60 months were 0.690, 0.690, and 0.732, respectively. The AUCs for the extended test set at 12, 36, and 60 months were 0.741, 0.727, and 0.718 respectively. The results of the calibration curve, decision curve analysis (DCA), and K-M survival curve confirm that both nomograms can accurately predict the occurrence of distant metastasis and prognosis in TNBC patients. ConclusionWe constructed two nomograms to predict distant metastasis risk in TNBC patients and prognosis in patients with distant metastasis. Our findings suggest that they could serve as effective predictive tools and may assist in clinical decision-making.

cancer biology↗

bioRxiv2024

Gut bacteria-derived succinate induces enteric nervous system regeneration

Enteric neurons control gut physiology by regulating peristalsis, nutrient absorption, and secretion1. Disruptions in microbial communities caused by antibiotics or enteric infections result in the loss of enteric neurons and long-term motility disorders2-5. However, the signals and underlying mechanisms of this microbiota-neuron communication are unknown. We studied the effects of microbiota on the recovery of the enteric nervous system after microbial dysbiosis caused by antibiotics. We found that both enteric neurons and glia are lost after antibiotic exposure, but recover when the pre-treatment microbiota is restored. Using murine gnotobiotic models and fecal metabolomics, we identified neurogenic bacterial species and their derived metabolite succinate as sufficient to rescue enteric neurons and glia. Unbiased single-nuclei RNA-seq analysis uncovered a novel neural precursor-like population marked by the expression of the neuronal gene Nav2. Genetic fate-mapping showed that Plp1+ enteric glia differentiate into neurons following antibiotic exposure. In contrast, Nav2+ neurons expand upon succinate treatment and indicate an alternative mode of neuronal regeneration under recovery conditions. Our findings highlight specific microbial species, metabolites, and the underlying cellular mechanisms involved in neuronal regeneration, with potential therapeutic implications for peripheral neuropathies.

neuroscience↗

bioRxiv2023

A Fuzzy sequencer for rapid DNA fragment counting and genotyping

High-throughput sequencing technologies generate a vast number of DNA sequence reads simultaneously, which are subsequently analyzed using the information contained within these fragmented reads. The assessment of sequencing technology relies on information efficiency, which measures the amount of information entropy produced per sequencing reaction cycle. In this study, we propose a fuzzy sequencing strategy that exhibits information efficiency more than twice of currently prevailing cyclic reversible terminator sequencing methods. To validate our approach, we developed a fully functional and high-throughput fuzzy sequencer. This sequencer implements a highly efficient fluorogenic sequencing-by-synthesis chemistry and underwent testing across various application scenarios, including copy-number variation detection, noninvasive prenatal testing, transcriptome profiling, mutation genotyping, and metagenomic profling. Our findings unequivocally demonstrate that the fuzzy sequencing strategy outperforms existing methods in terms of information efficiency and delivers accurate resequencing results with faster turnaround times. One Sentence SummaryA fuzzy sequencer can exceed current limit of information efficiency of DNA sequencers for resequencing applications.

genomics↗

bioRxiv2023

Energy metabolism modulates the regulatory impact of activators on gene expression

Gene expression is a regulated process fueled by ATP consumption. Therefore, regulation must be coupled to constraints imposed by the level of energy metabolism. Here, we explore this relationship both theoretically and experimentally. A stylized mathematical model predicts that activators of gene expression have variable impact depending on metabolic rate. Activators become less essential when metabolic rate is reduced and more essential when metabolic rate is enhanced. We find that in the Drosophila eye, expression dynamics of the yan gene are less affected by loss of EGFR-mediated activation when metabolism is reduced, and the opposite effect is seen when metabolism is enhanced. The effects are also seen at the level of pattern regularity in the adult eye, where loss of EGFR-mediated activation is mitigated by lower metabolism. We propose that gene activation is tuned by energy metabolism to allow for faithful expression dynamics in the face of variable metabolic conditions.

developmental biology↗

bioRxiv2023

Causal evidence of coherent theta rhythms in the modulation of multiregional communication

Neuromodulatory interventions seek to treat neuropsychiatric disorders by manipulating multiregional communication across the mesolimbic mood network. Modulations of multiregional communication are rarely measured directly and are often inferred from correlated neural activity such as neural coherence. Whether and how neural coherence reflects dynamic multiregional communication remains unclear. To address this limitation, we performed a causal-correlation analysis of theta-frequency (4-10 Hz) rhythms and mesolimbic multiregional communication. Selectively stimulating sender sites while recording from receiver sites revealed a mechanism of dynamic multiregional communication involving theta-coherent neural dynamics across a network of sender-receiver-modulator sites. Modulator site activity was highly theta-coherent with the receiver site activity, less theta-coherent with sender site activity, site specific and not shared by neighboring sites in the same region. These results reveal fundamental mechanisms of dynamic multiregional communication and support the use of theta-coherence as a target for neuromodulatory interventions in the mesolimbic mood network.

neuroscience↗

bioRxiv2023

Structure and evolution of Alanine/Serine Decarboxylases and the engineering of theanine production

Ethylamine (EA), the precursor of theanine biosynthesis, is synthesized from alanine decarboxylation by alanine decarboxylase (AlaDC) in tea plants. AlaDC evolves from serine decarboxylase (SerDC) through neofunctionalization and has lower catalytic activity. However, lacking structure information hinders the understanding of the evolution of substrate specificity and catalytic activity. In this study, we solved the X-ray crystal structures of AlaDC from Camellia sinensis (CsAlaDC) and SerDC from Arabidopsis thaliana (AtSerDC). Tyr341 of AtSerDC or the corresponding Tyr336 of CsAlaDC is essential for their enzymatic activity. Tyr111 of AtSerDC and the corresponding Phe106 of CsAlaDC determine their substrate specificity. Both CsAlaDC and AtSerDC have a distinctive zinc finger and have not been identified in any other Group II PLP-dependent amino acid decarboxylases. Based on the structural comparisons, we conducted mutation screen of CsAlaDC. The results indicated that the mutation of L110F or P114A in the CsAlaDC dimerization interface significantly improved the catalytic activity by 110% and 59%, respectively. Combining a double mutant of CsAlaDCL110F/P114A with theanine synthetase increased theanine production 672% in an in vitro system. This study provides the structural basis for the substrate selectivity and catalytic activity of CsAlaDC and AtSerDC and provides a route to more efficient biosynthesis of theanine.

biochemistry↗

bioRxiv2023

Epidemiological evaluation and identification of the insect vector of soybean stay-green associated virus

In recent years, the emergence of soybean stay-green syndrome (SGS), also referred to as "zhengqing", in the Huang-Huai-Hai region of China has resulted in significant yield losses, with some areas experiencing a complete reduction in seed yield. SGS is a phenomenon characterized by the delayed senescence of soybean, resulting in stay-green leaves, flat pods, and stunted seed development at harvest. Our group was the first to identify a distinct geminivirus, named soybean stay-green associated geminivirus (SoSGV), as the causative agent of SGS by fulfilling Kochs postulate. To further understand the epidemiology of SoSGV, in this study, we collected 368 stay-green samples from 17 regions in 8 provinces including the Huang-Huai-Hai region and surrounding areas of China. The results showed that 228 samples tested positive for SoSGV (61.96%), and 96.93% of these positive samples showed severe pod deflation. Our epidemiological assessment reveals SGS caused by the SoSGV is prevalent in the fields, and it is undergoing geographical expansion and genetic differentiation. Additionally, we determined the other natural hosts grown in the Huang-Huai-Hai region of China. By capturing insects in the field and conducting laboratory vector transmission tests, we confirmed that the common brown leafhopper (Orosius orientalis) is the transmitting vector of SoSGV. With a better understanding of the epidemiology of SoSGV and its transmission, we can develop more effective strategies for managing and mitigating its impact on soybean yields.

microbiology↗

bioRxiv2022

Lipoprotein sorting to the cell surface via a crosstalk between the Lpt and Lol pathways during outer membrane biogenesis

Lipopolysaccharide (LPS) and lipoprotein, two essential components of the outer membrane (OM) in Gram-negative bacteria, play critical roles in bacterial physiology and pathogenicity. LPS translocation to the OM is mediated by LptDE, yet how lipoproteins sort to the cell surface remains elusive. Here we report the identification of an inventory of lipoproteins that are transported to the cell surface via LptDE. Notably, we determined crystal structures of LptDE from Pseudomonas aeruginosa and its complex with an endogenous Escherichia coli lipoprotein YifL. The paLptDE-YifL structure demonstrates that YifL translocates to the OM via LptDE, in a manner similar to LPS transport. The {beta}-barrel domain serves as a passage for the proteinaceous moiety while its acyl chains are transported outside. Our finding has been corroborated by results from native mass spectrometry, immunofluorescence, and photocrosslinking assays, revealing a unique mechanism through which lipoproteins are translocated across the OM in an ATP- and LPS-dependent manner. Moreover, our study expands the scope of current knowledge of lipoprotein sorting by disclosing a crosstalk between the Lpt and Lol pathways.

microbiology↗

bioRxiv2022

Single-Cell RNA-seq of Heart Reveals Intercellular Communication Drivers of Myocardial Fibrosis in Diabetic Mice

Diabetes-induced cardiomyopathy is characterized by myocardial fibrosis as a main pathology. In-depth study of cardiac heterogeneity and cell-to-cell interactions will help to reveal the pathogenesis of diabetic myocardial fibrosis and provide potential targets for the treatment of this disease. Here, we insighted into the intercellular communication drivers underlying myocardial fibrosis in mouse heart with high-fat-diet (HFD)/streptozotocin (STZ)-induced diabetes at single-cell resolution. Intercellular and protein-protein interaction networks of fibroblasts and macrophages, endothelial cells, as well as fibroblasts and epicardial cells reveal critical changes in ligand-receptor interactions such as Pdgf(s)-Pdgfra and Efemp1-Egfr, which promote the development of a profibrotic microenvironment during diabetes progression and confirm that specific inhibition of Pdgfra axis can significantly improve diabetic myocardial fibrosis. We further identified the phenotypically distinct Hrchi and Postnhi fibroblast subpopulations that are associated with pathological extracellular matrix remodeling, of which Hrchi fibroblasts are the most profibrogenic under diabetic conditions. Finally, we validated the role of Itgb1 hub gene mediated intercellular communication drivers of diabetic myocardial fibrosis in Hrchi fibroblasts, and confirmed the result by AAV9-mediated Itgb1 knockdown in the heart of diabetic mice. In summary, cardiac cell mapping provides novel insights into intercellular communication drivers underlying pathological extracellular matrix remodeling during diabetic myocardial fibrosis.

cell biology↗

bioRxiv2021

Reduced sera neutralization to Omicron SARS-CoV-2 by bothinactivated and protein subunit vaccines and the convalescents

Omicron variant continues to spread all over the world. There are lots of scientific questions remaining to be answered for such a devastating variant. There are a dozen of vaccines already in clinical use. The very urgent scientific question would be whether or not these vaccines can protect Omicron variant. Here, we tested the sera from both convalescents and vaccine recipients receiving either inactivated or protein subunits vaccines (CoronaVac from Sinovac, or BBIBP-CoV from Sinopharm, or ZF2001 from Zhifei longcom) for the binding antibody titers (ELISA) and neutralization antibodies titers (pseudovirus neutralization assay). We showed that Omicron do have severe immune escape in convalescents, with 15 of 16 were negative in neutralization. By contrast, in vaccinees who received three jabs of inactivated or protein subunit vaccine, the neutralizing activity was much better preserved. Especially in the ZF2001 group with an extended period of the second and third jab (4-6 months) remains 100% positive in Omicron neutralization, with only 3.1-folds reduction in neutralizing antibody (NAb) titer. In this case, we proposed that, the multi-boost strategy with an extended interval between the second and third jab for immune maturation would be beneficial for NAb against devastating variants such as Omicron.

immunology↗

bioRxiv2021

A histidine cluster determines YY1-compartmentalized coactivators and chromatin elements in phase-separated super-enhancers

As an oncogenic transcription factor, Yin Yang 1 (YY1) regulates enhancer and promoter connection. However, gaps still exist in understanding how YY1 coordinates coactivators and chromatin elements to assemble super-enhancers. Here, we demonstrate that YY1 activates FOXM1 gene expression through forming liquid-liquid phase separation to compartmentalize both coactivators and enhancer elements. In the transactivation domain of YY1, a histidine cluster is essential for its activities of forming phase separation, which can be extended to additional proteins. Coactivators EP300, BRD4, MED1 and active RNA polymerase II are components of YY1-rich nuclear puncta. Consistently, histone markers for gene activation, but not repression, colocalize with YY1. Importantly, multiple enhancer elements and the FOXM1 promoter are bridged by YY1 to form super-enhancers. These studies propose that YY1 is a general transcriptional activator, and promotes phase separation with incorporation of major coactivators and stabilization by distal enhancers to activate target gene expression.

cell biology↗

bioRxiv2021

From Text-based Genome, Population Variations, and Transcriptome Datafiles to SQLite Database and Web Application: A Bioinformatical Study on Alfalfa

In this study, a web database application with the Flask framework was developed to implement three types of queries and visualize the results over a bioinformatical dataset from Alfalfa (Medicago sativa). A backend SQLite database was constructed from genome FASTA, population variations, transcriptome, and annotation files with extensions ".fasta", ".gff", "vcf", ".annotate", etc. Further, a supplementary command-line-based Java application was also developed for faster access to the database without direct SQL programming. Overall, Python, Java, and HTML were the main programming languages used in this application. Those scripts and the development procedures are valuable for bioinformaticians to build online databases from similar raw datasets of other species.

bioinformatics↗

bioRxiv2021

GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme

To achieve precise cellular regulation, E3 ubiquitin ligases must be configured to match substrate quaternary structures. Here, by studying the yeast GID complex, mutation of which is Glucose-Induced Degradation deficient, we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryo EM structures show that to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two otherwise functional GID E3s assemble into a 20-protein Chelator-GIDSR4, which resembles an organometallic supramolecular chelate. The Chelator-GIDSR4 assembly avidly binds multiple Fbp1 degrons and positions Fbp1 so that its protomers are simultaneously ubiquitylated at lysines near its allosteric and substrate binding sites. Significantly, key structural and biochemical features -including capacity for supramolecular assembly - are preserved in the human ortholog, the CTLH E3. Based on our integrative structural, biochemical and cell biological data, we propose that higher-order E3 ligase assembly generally underlies multipronged targeting, capable of simultaneously incapacitating multiple protomers and functionalities of oligomeric substrates.

biochemistry↗

bioRxiv2021

Leaf economics explained by optimality principles

The worldwide leaf economics spectrum relates leaf lifespan (LL) to leaf dry mass per unit area (LMA)1. By combining three well-supported principles2-4, we show that an isometric relationship between these two quantities maximizes the leafs net carbon gain. This theory predicts a spectrum of equally competent LMA-LL combinations in any given environment, and how their optimal ratio varies across environments. By analysing two large, independent leaf-trait datasets for woody species1,5, we provide quantitative empirical support for the predicted dependencies of LL on LMA and environment in evergreen plants, and for the distinct predicted dependencies of LMA on light, temperature, growing-season length and aridity in evergreen and deciduous plants. We thereby resolve the long-standing question of why deciduous LMA tends to increase (with increasing LL) towards the equator, while evergreen LMA and LL decrease6. We also show how the statistical distribution of LMA within communities can be modelled as an outcome of environmental selection on the global pool of species with diverse values of LMA and LL.

ecology↗