Abstract Advances in single-cell technologies allow scrutinizing of heterogeneous cell states, however, detecting cell-state transitions from snap-shot transcriptome data remains challenging. To investigate cells with transient properties or mixed identities, we present MuTrans, a method based on multiscale reduction technique to identify the underlying stochastic dynamics that prescribes cell-fate transitions. By iteratively unifying transition across multiple scales, MuTrans constructs...

Given a large and complex network, we would like to find the best partition of this network into small number clusters. This question has been addressed in many different ways. Here propose strategy along lines optimal prediction for Markov chains associated with dynamics on these networks. We develop necessary ingredients such an strategy, compare our previous ones. show that when chain is lumpable, recover respect which lumpable. also discuss case well-clustered Finally, illustrate several...

Tooth development undergoes a series of complex reciprocal interactions between dental epithelium and the underlying mesenchymal cells.Compared with study in tooth crown formation, little is known about molecular mechanism roots.In present study, we conditionally knock out β-catenin gene (Ctnnb1) within developing odontoblasts cementoblasts during roots, observed rootless molars as well incomplete incisors.Histological analyses revealed intact structure molar labial side incisor, however,...

Motivated by the famous Waddington's epigenetic landscape metaphor in developmental biology, biophysicists and applied mathematicians made different proposals to construct for multi-stable complex systems. We aim summarize elucidate relationships among these theories from a mathematical point of view. systematically investigate compare three but closely related realizations recent literature: Wang's potential theory steady state distribution stochastic differential equations (SDEs),...

Oxidative stress is considered the major cause of tissue injury after cerebral ischemia. The nuclear factor erythroid 2-related 2 (Nrf2) pathway one most important defensive mechanisms against oxidative stresses and has been confirmed as a target for stroke treatment. Thus, we desired to find new Nrf2 activators test their neuronal protective activity both in vivo vitro.The herb-derived compound, Britanin, potent inducer system. Britanin can induce expression enzymes reverse oxygen-glucose...

Genetic switching driven by noise is a fundamental cellular process in genetic regulatory networks. Quantitatively characterizing this and its fluctuation properties key problem computational biology. With an autoregulatory dimer model as specific example, we design general methodology to quantitatively understand the metastability of gene system perturbed intrinsic noise. Based on large deviation theory, develop new analytical techniques describe calculate optimal transition paths between...

We present a data-driven point of view for rare events, which represent conformational transitions in biochemical reactions modeled by over-damped Langevin dynamics on manifolds high dimensions. first reinterpret the transition state theory and path from optimal control viewpoint. Given clouds sampled reaction dynamics, we construct discrete Markov process based an approximated Voronoi tesselation. use constructed to compute committor function whose level set automatically orders clouds....

This paper builds a convergence analysis of explicit tau-leaping schemes for simulating chemical reactions from the viewpoint stochastic differential equations. Mathematically, reaction process is pure jump on lattice with state-dependent intensity. The equation form master can be given via Poisson random measures. Based this form, different types proposed. In order to make problem well-posed, modified scheme considered. It shown that mean square strong $1/2$ and weak 1 scheme. novelty...

Swinhoeisterols A (1) and B (2), two novel sterols with an unprecedented 6/6/5/7 ring system, were isolated from the sponge Theonella swinhoei. The structures absolute configurations elucidated by spectroscopic analysis, X-ray single-crystal diffraction, modified Mosher's method, TDDFT/ECD calculations. cytotoxicity of these compounds toward A549 MG-63 cells encourages studies on their potential target using inverse virtual screening approach. predicted inhibitor h(p300) was corroborated in...

Two new biscembranoid-like compounds, bissubvilides A (1) and B (2), were isolated together with sarsolilide (3), the proposed biogenetic precursor to 1, from soft coral Sarcophyton subviride. The structures absolute configurations solved by spectroscopic analysis TDDFT/ECD DFT/NMR calculations. represent a novel skeleton presumed derive cembrane-type diene capnosane-type dienophile via Diels–Alder reaction. These two molecules exerted no cytotoxicity against MG-63 or A549 tumor cells HuH7...

Motivation: Estimating differentiation potency of single cells is a task great biological and clinical significance, as it may allow identification normal cancer stem cell phenotypes. However, very few single-cell models have been proposed, their robustness reliability across independent studies not yet fully assessed. Results: Using nine RNA-Seq experiments, we here compare four different to each other, in ability discriminate that ought differ terms potency. Two the approximate via network...

Given a complex local operator, such as the generator of Markov chain on large network, differential or sparse matrix that comes from discretization we would like to find its best finite dimensional approximation with given dimension. The answer this question is often simply by projection original operator eigensubspace dimension corresponds smallest largest eigenvalues, depending setting. representation subspaces, however, far being unique and our interest most localized bases for these...

Quantitatively understanding the robustness, adaptivity and efficiency of cell cycle dynamics under influence noise is a fundamental but difficult question to answer for most eukaryotic organisms. Using simplified budding yeast model perturbed by intrinsic noise, we systematically explore these issues from an energy landscape point view constructing considered system based on large deviation theory. Analysis shows that trajectory sharply confined ambient barrier, along this exhibits...

We present EPR-Net, a novel and effective deep learning approach that tackles crucial challenge in biophysics: constructing potential landscapes for high-dimensional non-equilibrium steady-state systems. EPR-Net leverages nice mathematical fact the desired negative gradient is simply orthogonal projection of driving force underlying dynamics weighted inner-product space. Remarkably, our loss function has an intimate connection with steady entropy production rate (EPR), enabling simultaneous...

Abstract Spatial transcriptomics and messenger RNA splicing encode extensive spatiotemporal information for cell states transitions. The current lineage-inference methods either lack spatial dynamics state transition or cannot capture different associated with multiple paths. Here we present tensor (STT), a method that uses transcriptomes through multiscale dynamical model to characterize multistability in space. By learning four-dimensional spatial-constrained random walk, STT reconstructs...

Background:Astragali radix is a traditional Chinese medicine with potential therapeutic effects on periodontitis; however, its underlying mechanisms require further investigation. Methods: We employed network pharmacology, molecular docking, dynamics simulations, and in vitro experiments to explore the actions of Astragali treating periodontitis. Results: A total 17 compounds (including most prevalent one, Kaempferol) from 464 corresponding targets were identified, which five major active...

This study aimed to investigate the effects of a sustained-release composite containing gelatin methacryloyl (Gel) and kaempferol (Ka, K) on experimental periodontitis symptoms in rats. Forty 6-week-old male rats were randomly assigned four treatment groups specific pathogen-free (SPF) environment: Control group (C), model (M), Gel alone (G), Gel_Ka composite-treated (G_K). Treatment periodontal status bilateral maxillary second molars each rat assessed by micro-CT imaging histology....

Understanding the dynamic nature of biological systems is fundamental to deciphering cellular behavior, developmental processes, and disease progression. Single-cell RNA sequencing (scRNA-seq) has provided static snapshots gene expression, offering valuable insights into states at a single time point. Recent advancements in temporally resolved scRNA-seq, spatial transcriptomics (ST), time-series (temporal-ST) have further revolutionized our ability study spatiotemporal dynamics individual...