A Multi-Layered Framework for Modeling Human Biology: From Basic AI Agents to a Full-Body AI Agent.

We envision the Full-Body AI Agent as a comprehensive AI system designed to simulate, analyze, and optimize the dynamic processes of the human body across multiple biological levels. By integrating computational models, machine learning tools, and experimental platforms, this system aims to replicate and predict both physiological and pathological processes, ranging from molecules and cells to tissues, organs, and entire body systems. Central to the Full-Body AI Agent is its emphasis on integration and coordination across these biological levels, enabling analysis of how molecular changes influence cellular behaviors, tissue responses, organ function, and systemic outcomes.

Development and Evaluation of a Vinyl Sulfone-Based Fluorine-18 Labeling Method for Constructing PSMA-targeted Prostate Cancer Imaging Agents.

Purpose: Since prostate-specific membrane antigen (PSMA) is widely expressed in nearly all stages of prostate cancer (PCa), PSMA tracers can be considered a viable diagnostic tool for PCa. Compared to Ga-labeled PSMA agents, F-labeled analogues have various advantages, including the ability to achieve large scale production; easy to commercialize due to its longer half-life; and the ability to image late time points. Because [F]vinyl sulfone (VS) is a good intermediate for labeling thiol groups in mild conditions with high labeling yield, we explored the use of various VS groups for PSMA modifications in this study.

Approach to Chelating Radioactivity using Carbon Dots for Positron Emission Tomography Imaging.

With the rapid development of the radiotheranostic field, developing new methods to produce radiolabeled agents has become a critical area of exploration. We hypothesized that the inert carbon shell of carbon dots (CDs) could serve as a robust chelation strategy to overcome the stability issue of radiometal complexes, including the recoil energy issue of alpha (α)-emitting radioisotopes. To investigate this, we utilized radioactive copper-64 (Cu) as a surrogate for therapeutic isotopes and optimized a synthetic route for encapsulating Cu within CDs (Cu@C).

Development of F-Labeled Positron Emission Tomography Agents Targeting Fibroblast Activation Protein.

Fibroblast activation protein (FAP) is expressed in activated fibroblasts but not in quiescent fibroblasts. Thus, it allows us to use this membrane-anchored enzyme as a target for radionuclide-based tumor diagnosis and treatment and the diagnosis of nonmalignant diseases. In this report, we synthesized and evaluated a series of F-labeled FAP inhibitors (FAPIs), aiming to obtain PET agents with good distribution and tumor specificity.

The landscape of malignant transition: Unraveling cancer cell-of-origin and heterogeneous tissue microenvironment.

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells.

Preliminary Study of Radionuclide-Labeled MerTK-Targeting PET Imaging Agents for the Diagnosis of Melanoma.

MerTK PET imaging holds potential as a promising approach for assessing tumor aggressiveness and monitoring treatment response. In this study, we synthesized a series of F- and Ga-labeled tracers derived from MerTK inhibitors for detection of MerTK expression. Among the synthesized agents, the dimeric compounds [Ga] and [Ga] demonstrated good and stability, high affinities to the MerTK receptor, and good MerTK-targeting specificity.

One-Step Synthesis of [F]Aromatic Electrophile Prosthetic Groups via Organic Photoredox Catalysis.

To avoid the harsh conditions that are oftentimes adopted in direct radiofluorination reactions, conjugation of bioactive ligands with F-labeled prosthetic groups has become an important strategy to construct novel PET agents under mild conditions when the ligands are structurally sensitive. Prosthetic groups with [F]fluoroarene motifs are especially appealing because of their stability in physiological environments. However, their preparation can be intricate, often requiring multistep radiosynthesis with functional group conversions to prevent the decomposition of unprotected reactive prosthetic groups during the harsh radiofluorination.

SexAnnoDB, a knowledgebase of sex-specific regulations from multi-omics data of human cancers.

Background: Sexual differences across molecular levels profoundly impact cancer biology and outcomes. Patient gender significantly influences drug responses, with divergent reactions between men and women to the same drugs. Despite databases on sex differences in human tissues, understanding regulations of sex disparities in cancer is limited.

Radiogenomics-Based Risk Prediction of Glioblastoma Multiforme with Clinical Relevance.

Glioblastoma multiforme (GBM)is the most common and aggressive primary brain tumor. Although temozolomide (TMZ)-based radiochemotherapy improves overall GBM patients' survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudo-progression (PsP) is a treatment-related reaction with an increased contrast-enhancing lesion size at the tumor site or resection margins miming tumor recurrence on MRI.

Synthesis of Cu-, Co-, and Ga-Labeled Radiopharmaceuticals Targeting Neurotensin Receptor-1 for Theranostics: Adjusting In Vivo Distribution Using Multiamine Macrocycles.

The development of theranostic radiotracers relies on their binding to specific molecular markers of a particular disease and the use of corresponding radiopharmaceutical pairs thereafter. This study reports the use of multiamine macrocyclic moieties (MAs), as linkers or chelators, in tracers targeting the neurotensin receptor-1 (NTSR-1). The goal is to achieve elevated tumor uptake, minimal background interference, and prolonged tumor retention in NTSR-1-positive tumors.

Chelator boosted tumor-retention and pharmacokinetic properties: development of Cu labeled radiopharmaceuticals targeting neurotensin receptor.

Purpose: Accumulating evidence suggests that neurotensin (NTS) and neurotensin receptors (NTSRs) play key roles in lung cancer progression by triggering multiple oncogenic signaling pathways. This study aims to develop Cu-labeled neurotensin receptor 1 (NTSR1)-targeting agents with the potential for both imaging and therapeutic applications.

Method: A series of neurotensin receptor antagonists (NRAs) with variable propylamine (PA) linker length and different chelators were synthesized, including [Cu]Cu-CB-TE2A-iPA-NRA ([Cu]Cu-4a-c, i = 1, 2, 3), [Cu]Cu-NOTA-2PA-NRA ([Cu]Cu-4d), [Cu]Cu-DOTA-2PA-NRA ([Cu]Cu-4e, also known as [Cu]Cu-3BP-227), and [Cu]Cu-DOTA-VS-2PA-NRA ([Cu]Cu-4f).

Biomedical Big Data Technologies, Applications, and Challenges for Precision Medicine: A Review.

The explosive growth of biomedical Big Data presents both significant opportunities and challenges in the realm of knowledge discovery and translational applications within precision medicine. Efficient management, analysis, and interpretation of big data can pave the way for groundbreaking advancements in precision medicine. However, the unprecedented strides in the automated collection of large-scale molecular and clinical data have also introduced formidable challenges in terms of data analysis and interpretation, necessitating the development of novel computational approaches.

Revealing chronic disease progression patterns using Gaussian process for stage inference.

Objective: The early stages of chronic disease typically progress slowly, so symptoms are usually only noticed until the disease is advanced. Slow progression and heterogeneous manifestations make it challenging to model the transition from normal to disease status. As patient conditions are only observed at discrete timestamps with varying intervals, an incomplete understanding of disease progression and heterogeneity affects clinical practice and drug development.

StemDriver: a knowledgebase of gene functions for hematopoietic stem cell fate determination.

StemDriver is a comprehensive knowledgebase dedicated to the functional annotation of genes participating in the determination of hematopoietic stem cell fate, available at http://biomedbdc.wchscu.cn/StemDriver/.

COV2Var, a function annotation database of SARS-CoV-2 genetic variation.

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has resulted in the loss of millions of lives and severe global economic consequences. Every time SARS-CoV-2 replicates, the viruses acquire new mutations in their genomes. Mutations in SARS-CoV-2 genomes led to increased transmissibility, severe disease outcomes, evasion of the immune response, changes in clinical manifestations and reducing the efficacy of vaccines or treatments.

Development of F-Labeled hydrophilic -cyclooctene as a bioorthogonal tool for PET probe construction.

We report the development of a hydrophilic F-labeled a-TCO derivative [F]3 (log  = 0.28) through a readily available precursor and a single-step radiofluorination reaction (RCY up to 52%). We demonstrated that [F]3 can be used to construct not only multiple small molecule/peptide-based PET agents, but protein/diabody-based imaging probes in parallel.

Exploring Acute Pancreatitis Clinical Pathways Using a Novel Process Mining Method.

Mining process models of medical behavior from electronic medical records is an effective way to optimize clinical pathways. However, clinical medical behavior is an extremely complex field with high nonlinearity and variability, and thus we need to adopt a more effective method. In this study, we developed a fuzzy process mining method for complex clinical pathways.

Cell-type-specific alternative polyadenylation promotes oncogenic gene expression in non-small cell lung cancer progression.

Disrupted alternative polyadenylation (APA) is frequently involved in tumorigenesis and cancer progression by regulating the gene expression of oncogenes and tumor suppressors. However, limited knowledge of tumor-type- and cell-type-specific APA events may lead to novel APA events and their functions being overlooked. Here, we compared APA events across different cell types in non-small cell lung cancer (NSCLC) and normal tissues and identified functionally related APA events in NSCLC.

LVPT: Lazy Velocity Pseudotime Inference Method.

The emergence of RNA velocity has enriched our understanding of the dynamic transcriptional landscape within individual cells. In light of this breakthrough, we embarked on integrating RNA velocity with cellular pseudotime inference, aiming to improve the prediction of cell orders along biological trajectories beyond existing methods. Here, we developed LVPT, a novel method for pseudotime and trajectory inference.

Preliminary Evaluation of F-Labeled Benzylguanidine Analogs as NET Tracers for Myocardial Infarction Diagnosis.

Purpose: Heart failure (HF) remains a major cause of late morbidity and mortality after myocardial infarction (MI). To date, no clinically established F-labeled sympathetic nerve PET tracers for monitoring myocardial infarction are available. Therefore, in this study, we synthesized a series of F-labeled benzyl guanidine analogs and evaluated their efficacy as cardiac neuronal norepinephrine transporter (NET) tracers for myocardial imaging.

COVIDanno, COVID-19 annotation in human.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 19 (COVID-19), has caused a global health crisis. Despite ongoing efforts to treat patients, there is no universal prevention or cure available. One of the feasible approaches will be identifying the key genes from SARS-CoV-2-infected cells.

Automated CT Pancreas Segmentation for Acute Pancreatitis Patients by combining a Novel Object Detection Approach and U-Net.

Acute pancreatitis is an inflammatory disorder of the pancreas. Medical imaging, such as computed tomography (CT), has been widely used to detect volume changes in the pancreas for acute pancreatitis diagnosis. Many pancreas segmentation methods have been proposed but no methods for pancreas segmentation from acute pancreatitis patients.

CVAM: CNA Profile Inference of the Spatial Transcriptome Based on the VGAE and HMM.

Tumors are often polyclonal due to copy number alteration (CNA) events. Through the CNA profile, we can understand the tumor heterogeneity and consistency. CNA information is usually obtained through DNA sequencing.

Inferring evolutionary trajectories from cross-sectional transcriptomic data to mirror lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) is a deadly tumor with dynamic evolutionary process. Although much endeavors have been made in identifying the temporal patterns of cancer progression, it remains challenging to infer and interpret the molecular alterations associated with cancer development and progression. To this end, we developed a computational approach to infer the progression trajectory based on cross-sectional transcriptomic data.

Increased tryptophan, but not increased glucose metabolism, predict resistance of pembrolizumab in stage III/IV melanoma.

Clinical trials of combined IDO/PD1 blockade in metastatic melanoma (MM) failed to show additional clinical benefit compared to PD1-alone inhibition. We reasoned that a tryptophan-metabolizing pathway other than the kynurenine one is essential. We immunohistochemically stained tissues along the nevus-to-MM progression pathway for tryptophan-metabolizing enzymes (TMEs; TPH1, TPH2, TDO2, IDO1) and the tryptophan transporter, LAT1.