ProtoCode: Leveraging large language models (LLMs) for automated generation of machine-readable PCR protocols from scientific publications.

Protocol standardization and sharing are crucial for reproducibility in life sciences. In spite of numerous efforts for standardized protocol description, adherence to these standards in literature remains largely inconsistent. Curation of protocols are especially challenging due to the labor intensive process, requiring expert domain knowledge of each experimental procedure.

IQCELL: A platform for predicting the effect of gene perturbations on developmental trajectories using single-cell RNA-seq data.

The increasing availability of single-cell RNA-sequencing (scRNA-seq) data from various developmental systems provides the opportunity to infer gene regulatory networks (GRNs) directly from data. Herein we describe IQCELL, a platform to infer, simulate, and study executable logical GRNs directly from scRNA-seq data. Such executable GRNs allow simulation of fundamental hypotheses governing developmental programs and help accelerate the design of strategies to control stem cell fate.

Artificial intelligence-based computational framework for drug-target prioritization and inference of novel repositionable drugs for Alzheimer's disease.

Background: Identifying novel therapeutic targets is crucial for the successful development of drugs. However, the cost to experimentally identify therapeutic targets is huge and only approximately 400 genes are targets for FDA-approved drugs. As a result, it is inevitable to develop powerful computational tools that can identify potential novel therapeutic targets.

Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8+ T cells through reduction of tumor-associated macrophage and activation of the interferon pathway.

Lenvatinib is a multiple receptor tyrosine kinase inhibitor targeting mainly vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) receptors. We investigated the immunomodulatory activities of lenvatinib in the tumor microenvironment and its mechanisms of enhanced antitumor activity when combined with a programmed cell death-1 (PD-1) blockade. Antitumor activity was examined in immunodeficient and immunocompetent mouse tumor models.

CD24 tracks divergent pluripotent states in mouse and human cells.

Reprogramming is a dynamic process that can result in multiple pluripotent cell types emerging from divergent paths. Cell surface protein expression is a particularly desirable tool to categorize reprogramming and pluripotency as it enables robust quantification and enrichment of live cells. Here we use cell surface proteomics to interrogate mouse cell reprogramming dynamics and discover CD24 as a marker that tracks the emergence of reprogramming-responsive cells, while enabling the analysis and enrichment of transgene-dependent (F-class) and -independent (traditional) induced pluripotent stem cells (iPSCs) at later stages.

Dynamic simulation and metabolome analysis of long-term erythrocyte storage in adenine-guanosine solution.

Although intraerythrocytic ATP and 2,3-bisphophoglycerate (2,3-BPG) are known as direct indicators of the viability of preserved red blood cells and the efficiency of post-transfusion oxygen delivery, no current blood storage method in practical use has succeeded in maintaining both these metabolites at high levels for long periods. In this study, we constructed a mathematical kinetic model of comprehensive metabolism in red blood cells stored in a recently developed blood storage solution containing adenine and guanosine, which can maintain both ATP and 2,3-BPG. The predicted dynamics of metabolic intermediates in glycolysis, the pentose phosphate pathway, and purine salvage pathway were consistent with time-series metabolome data measured with capillary electrophoresis time-of-flight mass spectrometry over 5 weeks of storage.

A metabolic model of human erythrocytes: practical application of the E-Cell Simulation Environment.

The human red blood cell (RBC) has long been used for modeling of complex biological networks, for elucidation of a wide variety of dynamic phenomena, and for understanding the fundamental topology of metabolic pathways. Here, we introduce our recent work on an RBC metabolic model using the E-Cell Simulation Environment. The model is sufficiently detailed to predict the temporal hypoxic response of each metabolite and, at the same time, successfully integrates modulation of metabolism and of the oxygen transporting capacity of hemoglobin.

Paradoxical ATP elevation in ischemic penumbra revealed by quantitative imaging mass spectrometry.

Local responses of energy metabolism during brain ischemia are too heterogeneous to decipher redox distribution between anoxic core and adjacent salvageable regions such as penumbra. Imaging mass spectrometry combined by capillary electrophoresis/mass spectrometry providing quantitative metabolomics revealed spatio-temporal changes in adenylates and NADH in a mouse middle-cerebral artery occlusion model. Unlike the core where ATP decreased, the penumbra displayed paradoxical elevation of ATP despite the constrained blood supply.

Hypotaurine is an Energy-Saving Hepatoprotective Compound against Ischemia-Reperfusion Injury of the Rat Liver.

Metabolome analyses assisted by capillary electrophoresis-mass spectrometry (CE-MS) have allowed us to systematically grasp changes in small molecular metabolites under disease conditions. We applied CE-MS to mine out biomarkers in hepatic ischemia-reperfusion. Rat livers were exposed to ischemia by clamping of the portal inlet followed by reperfusion.

T-state stabilization of hemoglobin by nitric oxide to form alpha-nitrosyl heme causes constitutive release of ATP from human erythrocytes.

Upon hypoxia, erythrocytes utilize hemoglobin (Hb) to trigger activation of glycolysis through its interaction with band 3. This process contributes to maintenance of ATP, a portion of which is released extracellularly to trigger endothelium-dependent vasorelaxation. However, whether the ATP release results either from metabolic activation of the cells secondarily or from direct regulation of the gating through Hb allostery remains unknown.

In silico modeling and metabolome analysis of long-stored erythrocytes to improve blood storage methods.

There is currently no effective method for preventing ATP and 2,3-bisphosphoglycerate (2,3-BPG) depletion during long-term erythrocyte storage in the cold, although these metabolites are strongly associated with cell viability and oxygen delivery after transfusion. Metabolite reduction is caused by whole metabolic networks in the cell, which are regulated by various physical or chemical factors. Mathematical modeling is a powerful tool for integrating such complex and dynamic systems.