Biology subjects

Shang, L.

Publications and source records attributed to Shang, L..

At least 19 recordsLinked to original sources

bioRxiv2026

Onsite fixation preserves phosphoprotein profile in human whole blood

Phospho-flow cytometry is increasingly used as a pharmacodynamic readout of kinase-pathway activity, including in JAK inhibitor trials. Phosphoprotein states are intrinsically labile ex vivo and are further altered by conventional workflows, which typically involve PBMC isolation, cryopreservation, and transit times of hours to days before measurement. Here, we fix whole blood at collection and quantify six phosphoproteins by mass cytometry, benchmarked against matched cryopreserved PBMCs. Unlike PBMCs, whole blood retained neutrophils, ~75-80% of which were pSTAT3-positive at baseline. Basal pSTAT3 was also markedly higher in whole blood monocytes (~41% positive vs. ~9% in PBMCs), whereas T, B, and NK cells differed by less than 1 percentage point. Stimulation produced subset-specific phosphorylation patterns that were retained after 6 weeks of storage. Because fixation does not require centrifugation and retains neutrophils, samples can be fixed at collection sites without on-site processing laboratories and analyzed centrally in batches.

immunology↗

bioRxiv2026

Paralemmin 2 is a shared, alternatively-spliced regulator of axon initial segments and paranodal junctions in oligodendrocytes

Nervous system function depends on highly specialized axonal membrane domains. For example, axon initial segments (AIS), nodes of Ranvier, and paranodal junctions are essential for action potential initia-tion and saltatory conduction. These domains use shared molecular machinery converging on the master scaffolding protein AnkyrinG (AnkG). Using endogenous AnkG-TurboID proximity proteomics, we identify Paralemmin 2 (Palm2), a previously uncharacterized CNS protein, as a shared component of the AIS and nodes of Ranvier in neurons, and paranodes in oligodendrocytes. Palm2 localizes transiently to the AIS and nodes during development, but is found at paranodes throughout life, reflecting cell type-specific splicing of a lipid-modified domain both necessary and sufficient for AnkG interaction. Mice lacking oli-godendroglial Palm2 assemble normal paranodes during development, but aged mice lose paranode in-tegrity due to loss of paranodal AnkG and Neurofascin-155. Our findings identify Palm2 as a lipid raft-associated regulator of axonal and oligodendroglial membrane domains and reveal cell type-specific pro-tein variants as a recurring principle for specializing axonal and glial membrane architectures.

neuroscience↗

bioRxiv2026

Telomere variant sequences encode the genetic blueprint for allele-specific telomere length

The ends of human chromosomes are capped by specialized nucleoprotein structures known as telomeres, which are essential for genome stability. Recent advances in long-read sequencing have enabled allele-specific telomere length measurements at nucleotide resolution, uncovering extreme heterogeneity in telomere length between alleles that is determined at birth and gradually shortens with age. However, the mechanisms underlying allele-specific telomere maintenance and its stability remain poorly understood. Here, we developed a high-resolution workflow combining PacBio and Nanopore long-read sequencing platforms to map allele-specific telomere length in clinical patient samples as well as telomerase-positive cancer cell lines. By tracing allele-specific telomeric sequence in family members across multiple generations, we show that telomeric variant sequences (TVSs) interspersed throughout the canonical repeat region are heritable (with mean similarity score > 0.95), allele-specific, and account for the extreme heterogeneity of telomere length between alleles. Targeted deletion of allele-specific TVSs using CRISPR-Cas9 resets telomere length, further confirming their causal role in the control of allele-specific telomere maintenance. Continuous cell proliferation likely drives the slow but stochastic evolution of allele-specific TVSs distribution, resulting in asymmetry in telomere inheritance from father and mother (p-value < 0.045). These results illustrate how the telomere inheritance may predict allele-specific vulnerability in telomere protection, providing a new paradigm for personalized telomere profiling in aging-related diseases.

genetics↗

bioRxiv2026

OneGenomeRice (OGR): A Genomic Foundation Model for Rice

The transition of genomics to a predictive intelligence discipline is driven by the advent of genomic foundation models. While substantial progress has been observed in all-life and human-centric models, plant species, particularly for the staple crops, remains hindered by a lack of models. Here we introduce OneGenome-Rice (OGR), a rice (Oryza sativa) genomic foundation model pre-trained on a genomic dataset comprising 422 high-quality genomes of cultivated and wild rice. OGR is engineered upon a Mixture of Experts (MoE) transformer architecture with 1.25-billion parameters and supports an ultra-long context window of up to 1 million base (Mb) pairs at single-nucleotide resolution. A comprehensive benchmark demonstrated that OGR significantly outperforms existing state-of-the-art multi-plant or all-life genome models in 11 categories (e.g. motif identification, sweep detection, etc). We further demonstrated the utility of OGR in several downstream applications, such as indica-japonica subspecies introgression analysis, identification of agronomy trait-associated functional loci and prediction of gene expression from DNA sequences. These results establish OGR as a promising foundational computational infrastructure for rice functional genomics and precision breeding. The OGR and its fine-tuned models, including pretrained weights, training code and the rice genomic benchmark suit, have been fully opened.

genomics↗

bioRxiv2025

Optimal transport modeling uncovers spatial domain dynamics in spatiotemporal transcriptomics studies

Spatiotemporal transcriptomics is an emerging and powerful approach that adds a temporal dimension to spatial transcriptomics, enabling the characterization of dynamic changes in tissue architecture during development or disease progression. Here, we present SpaDOT (Spatial Domain Transition detection), a computational method designed to identify spatial domains and infer their temporal dynamics across time points for spatiotemporal transcriptomics studies. SpaDOT employs a variational autoencoder (VAE) framework to capture a low-dimensional representation of the data, incorporating hidden clustering variables to define distinct spatial domains. In the process, SpaDOT integrates a Gaussian Process prior and graph neighbor information to explicitly model both global spatial continuity and local structural heterogeneity among spatial locations within each time point, while using optimal transport (OT) to derive time-varying embeddings and infer the relationships between spatial domains across time points. Through simulation and real data applications, we demonstrate the superiority of SpaDOT in spatial domain detection, latent space preservation, and domain transition tracking over time. In real data applications, SpaDOT accurately captures dynamic domain transitions, including the disappearance and re-emergence of domains due to technical variation. Notably, SpaDOT uncovers key aspects of valvulogenesis in the developing heart, revealing the splitting of a single valve structure into two distinct functional valves -- the atrioventricular valve and the semilunar valve.

bioinformatics↗

bioRxiv2025

Telomere 3'-overhang attrition and persistent telomeric DNA damage response in failing human hearts

BackgroundTelomere homeostasis is critical for normal cellular and organ function, and its dysregulation is implicated in aging and chronic diseases. Although telomere length (TL) is critical for normal telomere function, its functional status can also be altered by many other factors. The organization and protective status of telomere in failing human heart (FHH) remains incompletely understood. MethodsUsing left ventricular tissues from patients with idiopathic dilated cardiomyopathy (IDC), ischemic heart disease (IHD), and non-failing heart (NFH), we performed a comprehensive analysis that included measurements of overall TL and 3 overhang length in left ventricles and cardiomyocytes (CM), assessment of telomere-binding protein associations, and transcriptomic profiling through RNA sequencing. ResultsAlthough TL varied among individuals, reduced median TL was observed only in IDC, while both IDC and IHD showed an increased frequency of very short telomeres, falling below the 5th percentile, in CMs. Strikingly, significant telomere 3-overhang attrition was detected in both disease groups and strongly correlated with elevated H2AX phosphorylated on serine 139 ({gamma}H2AX) in heart tissues, indicating DNA damage. This was accompanied by persistent activation of ataxia telangiectasia mutated (ATM) protein-mediated DNA damage responses and the formation of telomere dysfunction-induced foci (TIFs) in CMs from FHH. Concomitantly, the association of telomeres with the single-stranded telomere-binding protein, Protection of Telomeres 1 (POT1), and the double-stranded telomere-interacting protein, telomere repeat-binding factor 2 (TERF2), was markedly reduced, accompanied by an increase in association of {gamma}H2AX and ssDNA binding protein, RPA with telomeres in IDC and IHD relative to NFH, signifying telomere de-protection. ConclusionsCM telomere dysfunction, characterized by 3 overhang attrition and de-protection, is a common feature in FHH, leading to persistent DNA damage response in telomeres. Better understanding of telomere biology throughout the progression of different heart diseases to heart failure will provide more effective prevention and treatment strategies. GRAPHICAL ABSTRACTHuman telomeres safeguard chromosome ends through a higher-order telomere-loop (t-loop) structure and the shelterin complex, preventing their recognition as DNA double-strand breaks (DSBs). In the failing human heart (FHH) with idiopathic dilated cardiomyopathy (IDC) and ischemic heart disease (IHD), cardiomyocyte telomeres lose protection due to disruption of the shelterin complex, driven by oxidative DNA damage from reactive oxygen species (ROS) targeting G-rich telomeric sequences. This leads to t-loop unfolding, DDR cascade activation, 3 overhang excision, and persistent DNA damage responses with Telomere Dysfunction-Induced Foci (TIFs) formation at the telomeric regions of cardiomyocytes in FHH. The ATM-mediated DDR, along with engagement of both classical non-homologous end joining (cNHEJ) and homologous recombination (HDR) repair pathways, is integral to FHH progression. This study underscores the significance of telomere 3 overhang attrition in the pathogenesis of FHH with IDC and IHD. Unlike changes in overall telomere length, 3 overhang shortening directly correlates with increased DNA damage in human myocardial tissue. Preventing telomere 3 overhang attrition and oxidative damage offers a promising avenue for attenuating heart disease progression toward heart failure. In particular, selective ATM inhibition, as opposed to ATR inhibition, presents a potential therapeutic strategy for patients with IDC and IHD. Future efforts to pinpoint deficiencies in cNHEJ and HDR pathways in failing human hearts may reveal novel targets for heart failure prevention and treatment, providing new strategies in the management of this patient population. CMs, cardiomyocytes; DDR, DNA double-strand break repair; FHH, failing human heart; ROS, reactive oxygen species; t-loop, telomere-loop. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/669993v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@1d21937org.highwire.dtl.DTLVardef@757f54org.highwire.dtl.DTLVardef@1fa7472org.highwire.dtl.DTLVardef@1f2e961_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Sealable capped nanovials for high-throughput screening of cell growth and function

Millions of modular nanoliter-scale compartments that isolate functionally rich single-cell and cell-to-cell communication data can scale biological discovery for the age of AI. Here, we introduce capped nanovials--suspendable, sealable microscale compartments formed by the docking of hydrogel capping particles into bowl-shaped nanovials--as a versatile system for culturing, analyzing, and sorting single cells and small colonies. This two-particle architecture enables localized confinement of cells and secreted products while maintaining compatibility with standard laboratory workflows such as wash and reagent exchange steps, fluorescence microscopy, and flow cytometry. Crucially, these compartments are formed via simple pipetting and centrifugation steps, making the platform highly democratized. We demonstrate the ability of capped nanovials to compartmentalize single mammalian, bacterial, and yeast cells and support growth into colonies, enabling selection based on proliferation and bioproduction. We further show that capped nanovials enhance single-cell secretion assays by reducing molecular crosstalk and increasing signal-to-noise ratios. Importantly, we demonstrate functional co-culture assays by permitting stable confinement of cell pairs, enabling detection and enrichment of antibody-secreting cells based on the ability of their secreted antibodies to activate co-encapsulated reporter T cells, achieving a signal-to-noise ratio of >30 and up to 100% selection purity. By combining the simplicity of standard lab handling with the resolution and throughput of traditional microfluidic compartmentalization approaches, capped nanovials provide a new class of scalable, accessible test tubes for modern single-cell biology.

bioengineering↗

bioRxiv2025

Unpacking similarity effects in visual memory search: categorical, semantic, and visual contributions

Visual memory search involves comparing a probe item against multiple memorized items. Previous work has shown that distractor probes from a different object category than the objects in the memory set are rejected more quickly than distractor probes from the same category. Because objects belonging to the same superordinate category usually share both visual and semantic features compared with objects of different categories, it is unclear whether the category effects reported in previous studies reflected visual and/or semantic target-distractor similarity. Here, we employed old/new recognition tasks to examine the role of categorical, semantic, and visual similarity in short- and long-term memory search. Participants (N=64) performed visual long-term memory (LTM) or short-term memory (STM) search tasks involving animate and inanimate objects. Trial-wise RT variability to distractor probes in LTM and STM search was modelled using regression analyses that included predictors capturing categorical target-distractor similarity (same or different category), semantic target-distractor similarity (from a distributional semantic model), and visual target-distractor similarity (from a deep neural network). We found that categorical, semantic, and visual similarity all explained unique variance in trial-wise memory search performance. However, their respective contributions varied with memory set size and task, with STM performance being relatively more strongly influenced by visual and categorical similarity and LTM performance being relatively more strongly influenced by semantic similarity. These results clarify the nature of the representations used in memory search and reveal both similarities and differences between search in STM and LTM.

neuroscience↗

bioRxiv2024

In Situ Integration of Porous Polyethylene Nanomembrane with Wound Exudates for Scarless Healing

Achieving scarless wound repair through innovative material designs, such as hydrogels infused with growth factors and cells, has been extensively explored. In this study, we introduce a scarless healing material called pgPE, which is based on a porous and biologically inert ultra-high molecular weight polyethylene (UHMWPE) nanomembrane. This highly flexible nanomembrane conforms closely to the wound site and effectively absorbs wound-associated species into its nanopores, forming pgPE in situ. The resulting pgPE creates an ideal environment that fosters physiological metabolism while acting as a barrier against pathogens. Our findings demonstrate that pgPE facilitates complete skin reconstruction, including the regeneration of hair follicles. Additionally, we characterized the immune microenvironment and hypoxic conditions, revealing that pgPE alleviates hypoxia and modulates immune responses, thereby promoting healing towards a scar-free outcome. The integration of wound-associated species within pgPE has been evidenced through three-dimensional Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) analysis of postmortem samples. This study highlights the potential of personalized solutions that align with physiological systems for enhanced wound healing.

bioengineering↗

bioRxiv2024

Activated Interferon Signaling Suppresses Age-Dependent Liver Cancer

Age is a major risk factor for liver cancer, as is the case for most adult human cancers. However, the underlying mechanisms are not well defined. A better understanding of the role of aging in liver and other cancers can facilitate approaches for risk assessment, early detection and prevention. We hypothesize that age-driven changes render aged liver more sensitive to oncogenic stress and hence tumorigenesis. To investigate how the liver changes with age, we documented the immune profile, transcriptome and epigenome of healthy livers from both young and aged mice, revealing pronounced alterations with aging. Notably, in aged hepatocytes, we identified heightened interferon (IFN) signaling, as well as simultaneous tumor suppressor and oncogene signaling at both bulk and single cell level, suggestive of an aged liver that is poised for neoplasia. To challenge this seemingly poised state, we employed adeno-associated virus (AAV)-mediated expression of a c-Myc oncogene in young and aged mouse liver hepatocytes in vivo. Analysis of aged hepatocytes expressing c-Myc revealed further elevated expression of IFN Stimulated Genes (ISGs). This ISG upregulation was evident in multiple models of oncogenic stress and transformation in older mice and also observed in aged humans with Metabolic dysfunction-Associated Steatohepatitis (MASH). We determined that Stat1 is both necessary and sufficient for the age specific elevated ISG expression in old wild type mice. Remarkably, inhibiting Jak/Stat signaling alongside ectopic c-Myc expression led to high-grade hepatocyte dysplasia and tumor formation, selectively in aged mice. Together, these results suggest that an aged liver is in a state of "precarious balance", due to concurrent activation of oncogenic and tumor suppressor pathways, but protected against neoplastic progression by IFN-signaling. Age-dependent activation of IFN signaling has been observed in many tissues and recent studies have demonstrated its detrimental consequences on aging, raising the question as to why IFN-signaling is activated during aging. We propose that aged tissues are intrinsically at higher risk of cancer and age-dependent activation of IFN-signaling is an adaptive process to protect from tumorigenesis, but one that also has maladaptive consequences.

cancer biology↗

bioRxiv2024

N6-methyladenosine in DNA promotes genome stability

DNA base lesions, such as incorporation of uracil into DNA or base mismatches, can be mutagenic and toxic to replicating cells. To discover factors in repair of genomic uracil, we performed a CRISPR knockout screen in the presence of floxuridine, a chemotherapeutic agent that incorporates uracil and fluoro-uracil into DNA. We identified known factors, such as uracil DNA N-glycosylase (UNG), and unknown factors, such as the N6-adenosine methyltransferase, METTL3, as required to overcome floxuridine-driven cytotoxicity. Visualized with immunofluorescence, the product of METTL3 activity, N6-methyladenosine, formed nuclear foci in cells treated with floxuridine. The observed N6-methyladenosine was embedded in DNA, called 6mA, and these results were confirmed using an orthogonal approach, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). METTL3 and 6mA were required for repair of lesions driven by additional base damaging agents, including raltitrexed, gemcitabine, and hydroxyurea. Our results establish a role for METTL3 and 6mA in promoting genome stability in mammalian cells, especially in response to base damage.

molecular biology↗

bioRxiv2024

Fourfold increase in photocurrent generation of Synechocystis sp. PCC 6803 by exopolysaccharide deprivation

Photosynthetic microorganisms, including algae and cyanobacteria, export electrons in a light-stimulated phenomenon called exoelectrogenesis. However, the route(s) by which electrons reach an external electrode from the cell remain(s) unclear. For the model cyanobacterium Synechocystis sp. PCC 6803, it has been established that electron transfer does not depend on direct extracellular electron transfer by type IV pili. However, the role of the exopolysaccharide matrix in which cells are embedded has not been investigated. We show that a Synechocystis mutant with substantially reduced exopolysaccharide production has a four-fold greater photocurrent than wild-type cells. This increase is due in part to increased adhesion of exopolysaccharide-deficient cells to electrodes. Stirred system experiments reveal that a substantial portion of the photocurrent depends on an endogenous diffusible electron mediator, supporting indirect extracellular electron transfer as the bioelectrochemical mechanism of exoelectrogenesis. These findings will be important in harnessing exoelectrogenesis for sustainable electricity generation in biophotovoltaic devices.

microbiology↗

bioRxiv2023

Category-based attention facilitates memory search

We often need to decide whether the object we look at is also the object we look for. When we look for one specific object, this process can be facilitated by preparatory feature-based attention. However, when we look for multiple objects at the same time (e.g., the products on our shopping list) such a strategy may no longer be possible, as research has shown that we can actively prepare to detect only one object at a time. Therefore, looking for multiple objects may additionally involve search in long-term memory, slowing down decision making. Interestingly, however, previous research has shown that memory search can be very efficient when distractor objects are from a different category than the items in the memory set. Here, using EEG, we show that this efficiency is supported by top-down attention at the category level. In Experiment 1, human participants (both sexes) performed a memory search task on individually presented objects of the same or different category as the objects in the memory set. We observed category-level attentional modulation of distractor processing from [~]150 ms after stimulus onset, expressed both as an evoked response modulation and as an increase in decoding accuracy of same-category distractors. In Experiment 2, memory search was performed on two concurrently presented objects. When both objects were distractors, spatial attention (indexed by the N2pc component) was directed to the object that was of the same category as the objects in the memory set. Together, these results demonstrate how attention can facilitate memory search. Significance statementWhen we are in the supermarket, we repeatedly decide whether a product we look at (e.g., a banana) is on our memorized shopping list (e.g., apples, oranges, kiwis). This requires searching our memory, which takes time. However, when the product is of an entirely different category (e.g., dairy instead of fruit), the decision can be made quickly. Here, we used EEG to show that this between-category advantage in memory search tasks is supported by top-down attentional modulation of visual processing: The visual response evoked by distractor objects was modulated by category membership, and spatial attention was quickly directed to the location of within-category (vs. between-category) distractors. These results demonstrate a close link between attention and memory.

neuroscience↗

bioRxiv2023

Status and Genetic Diversity of Hipposideros pratti in the Northernmost Part of Its Distribution

Hipposideros pratti is species of bat distributed in caves from Southeast Asia to the Qinling-Funiu Mountain area in China. To understand the dynamic changes in its distribution and evaluate the current health status of the species, we reviewed 48 caves in the northernmost area of the H. pratti distribution and conducted the first analysis of genetic diversity for the species in the region. H. pratti was only detected in three caves, the four previously distributed caves and the remaining 41 previously undistributed caves were not observed. An analysis based on microsatellite markers revealed a few key points. 1) The average number of observed alleles (Na) of H. pratti in the region was 3.94, and the average observed heterozygosity (Ho) was 0.5293. All three populations were in Hardy-Weinberg equilibrium. 2) Intra-population was the predominant genetic variation of the H. pratti population. 3) H. pratti in the region experienced a bottleneck effect. We found that the three caves where H. pratti are currently distributed face varying degrees of human interference and the populations are threatened. Management strategies, including appropriate countermeasures to reduce human interference in caves, are urgently needed.

zoology↗

bioRxiv2022

Improved humoral immunity and protection against influenza virus infection with a 3D porous biomaterial vaccine

New vaccine platforms that properly activate humoral immunity and generate neutralizing antibodies are required to combat emerging and re-emerging pathogens, including influenza virus. Biomaterial scaffolds with macroscale porosity have demonstrated tremendous promise in regenerative medicine where they have been shown to allow immune cell infiltration and subsequent activation, but whether these types of materials can serve as an immunization platform is unknown. We developed an injectable immunization platform that uses a slurry of antigen-loaded hydrogel microparticles that anneal to form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades to maximize humoral immunity. Antigen-loaded-microgels elicited a robust cellular humoral immune response, with increased CD4+ T follicular helper (Tfh) cells and prolonged germinal center (GC) B cells comparable to the commonly used adjuvant, aluminum hydroxide (Alum). By simply increasing the weight fraction of polymer material, we enhanced material stiffness and further increased antigen-specific antibody titers superior to Alum. Vaccinating mice with inactivated influenza virus loaded into this more highly crosslinked formulation elicited a strong antibody response and provided better protection against a high dose viral challenge than Alum. Thus, we demonstrate that by tuning physical and chemical properties alone, we can enhance adjuvanticity and promote humoral immunity and protection against a pathogen, leveraging two different types of antigenic material: individual protein antigen and inactivated virus. The flexibility of the platform may enable design of new vaccines to enhance innate and adaptive immune cell programming to generate and tune high affinity antibodies, a promising approach to generate long-lasting immunity against specific pathogens.

bioengineering↗

bioRxiv2022

Exosome-derived lncRNA HOXA-AS3 promotes castration resistance and progression of prostate cancer via the miR-29b-3p/Mcl-1/STAT3 axis

Prostate cancer is one of the leading causes of cancer-related deaths in men. While endocrine therapy is effective in the early stage of metastasis, significantly inhibits the progression of metastatic prostate cancer, most patients eventually develop CRPC. Tumor microenvironment are involved in the progression of prostate cancer as an "accomplice", cancer cell-secreted exosomes were identified as crucial messengers can carry lncRNAs to participate in intercellular communication. we revealed PC-3-derived exosomes promote androgen resistance in LNCaP cells. HOXA-AS3 as a ceRNA of miRNA-29b-3p affects the proliferation and invasion ability of prostate cancer cells. A series of molecular experiments, cell experiments and clinical tissue verification experiments confirmed that HOXA-AS3 participates in the castration resistance and progression of prostate cancer through regulating the miR-29b-3p/Mcl-1/STAT3/Cytochrome C/caspases-9 pathway. Dysregulation of HOXA-AS3 is observed in many cancer types, and this study shows the importance of this lncRNA in controlling prostate cancer cell progression, thus highlighting it as a potential biomarker for inhibiting prostate cancer progression and a target for immunotherapy.

genomics↗

bioRxiv2022

Supercharged Protein Nanosheets for Cell Expansion on Bioemulsions

Cell culture at liquid-liquid interfaces, for example at the surface of oil microdroplets, is an attractive strategy to scale up adherent cell manufacturing whilst replacing the use of microplastics. Such process requires the adhesion of cells at interfaces stabilized and reinforced by protein nanosheets displaying high elasticity, but also presenting cell adhesive ligands able to bind integrin receptors. In this report, supercharged albumins are found to form strong elastic protein nanosheets and mediate extracellular matrix (ECM) protein adsorption and cell adhesion. The interfacial mechanical properties and elasticity of supercharged nanosheets is characterized by interfacial rheology and behaviors are compared to those of native bovine serum albumin, human serum albumin and -lactalbumin. ECM protein adsorption to resulting supercharged nanosheets is then quantified via surface plasmon resonance and fluorescence microscopy, demonstrating the dual role supercharged albumins are proposed to play, as scaffold proteins structuring liquid-liquid interfaces and substrates for the capture of ECM molecules. Finally, the adhesion and proliferation of primary human epidermal stem cells is investigated, at pinned droplets, as well as on bioemulsions stabilized by corresponding supercharged nanosheets. This study demonstrates the potential of supercharged proteins for the engineering of biointerfaces for stem cell manufacturing, and draws structure-property relationships that will guide further engineering of associated systems.

bioengineering↗

bioRxiv2022

Machine-Learning-Based Olfactometry: Odor Descriptor Clustering Analysis for Olfactory Perception Prediction of Odorant Molecules

Although gas chromatography/olfactometry (GC/O) has been employed as a powerful analytical tool in odor measurement, its application is limited by the variability, subjectivity, and high cost of the trained panelists who are used as detectors in the system. The advancements in data-driven science have made it possible to predict structure-odor-relationship (SOR) and thus to develop machine-learning-based olfactometry (ML-GCO) in which the human panelists may be replaced by machine learning models to obtain the sensory information of GC-separated chemical compounds. However, one challenge remained in ML-GCO is that there are too many odor descriptors (ODs) being used to describe the sensory characteristics of odorants. It is impractical to build a corresponding model for each OD. To solve this issue, we propose a SOR prediction approach based on odor descriptor clustering. 256 representative ODs are firstly classified into 20 categories using a co-occurrence Bayesian embedding model. The categorization effect is explained according to the semantic relationships using a pre-trained Word2Vec model. Various molecular structure features including molecularly parameters, molecular fingerprints, and molecular 2D graphic features extracted by convolutional neural networks, are employed to predict the aforementioned odor categories. High prediction accuracies (Area under ROC curve was 0.800{+/-}0.004) demonstrate the rationality of the proposed clustering scenario and molecular feature extraction. This study makes the ML-GCO models much closer to the practical application since they can be expected as either an auxiliary system or complete replacement of human panelists to perform the olfactory evaluation.

molecular biology↗