The Cell Regulation Mechanism of Neurovascular Unit

Ischemic cerebrovascular disease is one of the three deadly diseases. It is characterised by high mortality and high morbidity. Because of no effective treatments of recombinant tissue plasminogen activator (rt-PA) and neuroprotectant, there are more and more research focus on neurovascular unit (NVU), which is composed of brain microvascular endothelial cells (BMECs), neuron, astrocyte(AS) and so on. Cell-cell signaling and coupling between these different compartments form the basis for normal function and repair of brain injury. In this mini-review, we will describe the relationship of CMECs, neuron and AS

Tracking Aqueous Proton Transfer by Two-Dimensional Infrared Spectroscopy and ab Initio Molecular Dynamics Simulations.

Proton transfer in water is ubiquitous and a critical elementary event that, via proton hopping between water molecules, enables protons to diffuse much faster than other ions. The problem of the anomalous nature of proton transport in water was first identified by Grotthuss over 200 years ago. In spite of a vast amount of modern research effort, there are still many unanswered questions about proton transport in water. An experimental determination of the proton hopping time has remained elusive due to its ultrafast nature and the lack of direct experimental observables. Here, we use two-dimensional infrared spectroscopy to extract the chemical exchange rates between hydronium and water in acid solutions using a vibrational probe, methyl thiocyanate. Ab initio molecular dynamics (AIMD) simulations demonstrate that the chemical exchange is dominated by proton hopping. The observed experimental and simulated acid concentration dependence then allow us to extrapolate the measured single step proton hopping time to the dilute limit, which, within error, gives the same value as inferred from measurements of the proton mobility and NMR line width analysis. In addition to obtaining the proton hopping time in the dilute limit from direct measurements and AIMD simulations, the results indicate that proton hopping in dilute acid solutions is induced by the concerted multi-water molecule hydrogen bond rearrangement that occurs in pure water. This proposition on the dynamics that drive proton hopping is confirmed by a combination of experimental results from the literature

Tracing blastomere fate choices of early embryos in single cell culture

Blastomeres of early vertebrate embryos undergo numerous fate choices for division, motility, pluripotency maintenance and restriction culminating in various cell lineages. Tracing blastomere fate choices at the single cell level in vitro has not been possible because of the inability to isolate and cultivate early blastomeres as single cells. Here we report the establishment of single cell culture system in the fish medaka, enabling the isolation and cultivation of individual blastomeres from 16- to 64-cell embryos for fate tracing at the single cell level in vitro. Interestingly, these blastomeres immediately upon isolation exhibit motility, lose synchronous divisions and even stop dividing in ≥50% cases, suggesting that the widely accepted nucleocytoplasmic ratio controlling synchronous divisions in entire embryos does not operate on individual blastomeres. We even observed abortive division, endomitosis and cell fusion. Strikingly, ~5% of blastomeres in single cell culture generated extraembryonic yolk syncytial cells, embryonic stem cells and neural crest-derived pigment cells with timings mimicking their appearance in embryos. We revealed the maternal inheritance of key lineage regulators and their differential expression in cleavage embryos. Therefore, medaka blastomeres possess the accessibility for single cell culture, previously unidentified heterogeneity in motility, division, gene expression and intrinsic ability to generate major extraembryonic and embryonic lineages without positioning cues. Our data demonstrate the fidelity and potential of the single cell culture system for tracking blastomere fate decisions under defined conditions in vitro

Towards General Loop Invariant Generation via Coordinating Symbolic Execution and Large Language Models

Loop invariants, essential for program verification, are challenging to auto-generate especially for programs incorporating complex memory manipulations. Existing approaches for generating loop invariants rely on fixed sets or templates, hampering adaptability to real-world programs. Recent efforts have explored machine learning for loop invariant generation, but the lack of labeled data and the need for efficient generation are still troublesome. We consider the advent of the large language model (LLM) presents a promising solution, which can analyze the separation logic assertions after symbolic execution to infer loop invariants. To overcome the data scarcity issue, we propose a self-supervised learning paradigm to fine-tune LLM, using the split-and-reassembly of predicates to create an auxiliary task and generate rich synthetic data for offline training. Meanwhile, the proposed interactive system between LLM and traditional verification tools provides an efficient online querying process for unseen programs. Our framework can readily extend to new data structures or multi-loop programs since our framework only needs the definitions of different separation logic predicates, aiming to bridge the gap between existing capabilities and requirements of loop invariant generation in practical scenarios. Experiments across diverse memory-manipulated programs have demonstrated the performance of our proposed method compared to the baselines with respect to efficiency and effectiveness.Comment: Preprint, under revie