Detection of PatIent-Level distances from single cell genomics and pathomics data with Optimal Transport (PILOT).

Although clinical applications represent the next challenge in single-cell genomics and digital pathology, we still lack computational methods to analyze single-cell or pathomics data to find sample-level trajectories or clusters associated with diseases. This remains challenging as single-cell/pathomics data are multi-scale, i.e.

Mapping cardiac remodeling in chronic kidney disease.

Patients with advanced chronic kidney disease (CKD) mostly die from sudden cardiac death and recurrent heart failure. The mechanisms of cardiac remodeling are largely unclear. To dissect molecular and cellular mechanisms of cardiac remodeling in CKD in an unbiased fashion, we performed left ventricular single-nuclear RNA sequencing in two mouse models of CKD.

Sublethal necroptosis signaling promotes inflammation and liver cancer.

It is currently not well known how necroptosis and necroptosis responses manifest in vivo. Here, we uncovered a molecular switch facilitating reprogramming between two alternative modes of necroptosis signaling in hepatocytes, fundamentally affecting immune responses and hepatocarcinogenesis. Concomitant necrosome and NF-κB activation in hepatocytes, which physiologically express low concentrations of receptor-interacting kinase 3 (RIPK3), did not lead to immediate cell death but forced them into a prolonged "sublethal" state with leaky membranes, functioning as secretory cells that released specific chemokines including CCL20 and MCP-1.

Next-Generation Morphometry for pathomics-data mining in histopathology.

Pathology diagnostics relies on the assessment of morphology by trained experts, which remains subjective and qualitative. Here we developed a framework for large-scale histomorphometry (FLASH) performing deep learning-based semantic segmentation and subsequent large-scale extraction of interpretable, quantitative, morphometric features in non-tumour kidney histology. We use two internal and three external, multi-centre cohorts to analyse over 1000 kidney biopsies and nephrectomies.

Spatial multi-omic map of human myocardial infarction.

Myocardial infarction is a leading cause of death worldwide. Although advances have been made in acute treatment, an incomplete understanding of remodelling processes has limited the effectiveness of therapies to reduce late-stage mortality. Here we generate an integrative high-resolution map of human cardiac remodelling after myocardial infarction using single-cell gene expression, chromatin accessibility and spatial transcriptomic profiling of multiple physiological zones at distinct time points in myocardium from patients with myocardial infarction and controls.

MOJITOO: a fast and universal method for integration of multimodal single-cell data.

Motivation: The advent of multi-modal single-cell sequencing techniques have shed new light on molecular mechanisms by simultaneously inspecting transcriptomes, epigenomes and proteomes of the same cell. However, to date, the existing computational approaches for integration of multimodal single-cell data are either computationally expensive, require the delineation of parameters or can only be applied to particular modalities.

Results: Here we present a single-cell multi-modal integration method, named Multi-mOdal Joint IntegraTion of cOmpOnents (MOJITOO).

Chromatin-accessibility estimation from single-cell ATAC-seq data with scOpen.

A major drawback of single-cell ATAC-seq (scATAC-seq) is its sparsity, i.e., open chromatin regions with no reads due to loss of DNA material during the scATAC-seq protocol.

Zwitterionic chitooligosaccharide-modified ink-blue titanium dioxide nanoparticles with inherent immune activation for enhanced photothermal therapy.

Photothermal therapy (PTT) can trigger massive apoptosis of cancer cells, and this sharply increasing local apoptotic rate may recruit plenty of tumor-associated macrophages (TAMs). Although TAMs are recognized to display an M2-like subtype, which encourages tumor ontogenesis, they can be re-educated to a tumoricidal M1-like subtype by immunomodulatory reagents. Chitooligosaccharides (COSs) are endowed with immunomodulatory ability, but the positive electrical property limits their application; besides, their re-educating ability on TAMs is uncertain.

Single NIR Laser-Activated Multifunctional Nanoparticles for Cascaded Photothermal and Oxygen-Independent Photodynamic Therapy.

Inconvenient dual-laser irradiation and tumor hypoxic environment as well as limited judgment of treating region have impeded the development of combined photothermal and photodynamic therapies (PTT and PDT). Herein, BiSe@AIPH nanoparticles (NPs) are facilely developed to overcome these problems. Through a one-step method, free radical generator (AIPH) and phase transition material (lauric acid, LA, 44-46 °C) are encapsulated in hollow bismuth selenide nanoparticles (BiSe NPs).

A glutathione responsive nitric oxide release system based on charge-reversal chitosan nanoparticles for enhancing synergistic effect against multidrug resistance tumor.

The combination therapy of nitric oxide (NO) and anticancer drug was developed for reversing multidrug resistance (MDR). In order to avoid NO release during the blood circulation, and realize pinpointed release in the tumor cells, we designed a tumor-specific NO-release system based on 10-hydroxycamptothecin (HCPT)-loaded charge-reversal chitosan nanoparticles and covalently linked phenylsulfonyl furoxan (glutathione (GSH)-responsive NO donor) on the surface. The results showed that only 6.

One-pot synthesis of acid-induced in situ aggregating theranostic gold nanoparticles with enhanced retention in tumor cells.

In this work, we took advantage of a one-pot reaction to prepare tumor-targeting nanoparticles (Au@T), which could respond to the intracellular acidic environment and form aggregates to enhance the retention effect of nanoparticles in tumor cells. Au@T is composed of gold nanoparticles (Au NPs) modified with 4-mercaptobenzoic acid (MCBA), p-hydroxythiophenol (HTP), LA (lipoic acid)-PEG2K-OCH3 and LA-PEG2K-biotin. During blood circulation, Au@T remains well dispersed, making it inconspicuous.

Multivalent nanoparticles for personalized theranostics based on tumor receptor distribution behavior.

It is acknowledged that the targeting ability of multivalent ligand-modified nanoparticles (MLNs) strongly depends on the ligand spatial presentation determined by ligand valency. However, the receptor overexpression level varies between different types or stages of tumors. Thus, it is essential to explore the influence of ligand valency on the targeting ability of MLNs to tumors with different levels of receptor overexpression.

Reversible Shielding between Dual Ligands for Enhanced Tumor Accumulation of ZnPc-Loaded Micelles.

Herein, we report a ligand-reversible-shielding strategy based on the mutual shielding of dual ligands tethered to the surface of nanoparticles. To exemplify this concept, phenylboronic acid-functionalized poly(ethylene glycol)- b-poly(ε-caprolactone) (PBA-PEG-PCL) and galactose-functionalized diblock polymer (Gal-PEG-PCL) were mixed to form dual-ligand micelles (PBA/Gal). PBA and Gal residues could form a complex at pH 7.

"Three-in-One" Multifunctional Gatekeeper Gated Mesoporous Silica Nanoparticles for Intracellular pH-Activated Targeted Cancer Therapy.

Mesoporous silica nanoparticle (MSN)-based stimuli-responsive capped drug delivery systems have attracted extensive attention. However, most studies about capping agents only focus on the capping function. Here, a multifunctional capping agent (MFCA) was developed to integrate pore-capping, drug-loading, and tumor-targeting abilities.