Attention-based deep learning for accurate cell image analysis.

High-content analysis (HCA) holds enormous potential for drug discovery and research, but widely used methods can be cumbersome and yield inaccurate results. Noisy and redundant signals in cell images impede accurate deep learning-based image analysis. To address these issues, we introduce X-Profiler, a novel HCA method that combines cellular experiments, image processing, and deep learning modeling.

Pre-training with a rational approach for antibody sequence representation.

Introduction: Antibodies represent a specific class of proteins produced by the adaptive immune system in response to pathogens. Mining the information embedded in antibody amino acid sequences can benefit both antibody property prediction and novel therapeutic development. However, antibodies possess unique features that should be incorporated using specifically designed training methods, leaving room for improvement in pre-training models for antibody sequences.

Substrate binding and inhibition mechanism of norepinephrine transporter.

Norepinephrine transporter (NET; encoded by SLC6A2) reuptakes the majority of the released noradrenaline back to the presynaptic terminals, thereby affecting the synaptic noradrenaline level. Genetic mutations and dysregulation of NET are associated with a spectrum of neurological conditions in humans, making NET an important therapeutic target. However, the structure and mechanism of NET remain unclear.

A Combination of Machine Learning and PBPK Modeling Approach for Pharmacokinetics Prediction of Small Molecules in Humans.

Purpose: Recently, there has been rapid development in model-informed drug development, which has the potential to reduce animal experiments and accelerate drug discovery. Physiologically based pharmacokinetic (PBPK) and machine learning (ML) models are commonly used in early drug discovery to predict drug properties. However, basic PBPK models require a large number of molecule-specific inputs from in vitro experiments, which hinders the efficiency and accuracy of these models.

WUREN: Whole-modal union representation for epitope prediction.

B-cell epitope identification plays a vital role in the development of vaccines, therapies, and diagnostic tools. Currently, molecular docking tools in B-cell epitope prediction are heavily influenced by empirical parameters and require significant computational resources, rendering a great challenge to meet large-scale prediction demands. When predicting epitopes from antigen-antibody complex, current artificial intelligence algorithms cannot accurately implement the prediction due to insufficient protein feature representations, indicating novel algorithm is desperately needed for efficient protein information extraction.

Application scenario-oriented molecule generation platform developed for drug discovery.

Design of molecules for candidate compound selection is one of the central challenges in drug discovery due to the complexity of chemical space and requirement of multi-parameter optimization. Here we present an application scenario-oriented platform (ID4Idea) for molecule generation in different scenarios of drug discovery. This platform utilizes both library or rule based and generative based algorithms (VAE, RNN, GAN, etc.

Water Consolidation Performance of Acrylic-Polymer-Modified Materials and Their Concrete Impermeability Repair Characteristics.

Acrylic materials exhibit favorable grouting repair performance. However, their curing products are easily inclined to drying shrinkage, and their concrete impermeability repair characteristics have seldom been investigated. To improve material properties, reveal the impermeability repair mechanism, and address drying shrinkage, this study proposed the addition of styrene-acrylate copolymer emulsion (styrene-acrylic emulsion) to the grouting material to prepare two-component acrylate grouting materials.

Structural identification of vasodilator binding sites on the SUR2 subunit.

ATP-sensitive potassium channels (K), composed of Kir6 and SUR subunits, convert the metabolic status of the cell into electrical signals. Pharmacological activation of SUR2- containing K channels by class of small molecule drugs known as K openers leads to hyperpolarization of excitable cells and to vasodilation. Thus, K openers could be used to treat cardiovascular diseases.

Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by affinity maturation and SPR assay.

The RBD (receptor binding domain) of the SARS-CoV-2 virus S (spike) protein mediates viral cell attachment and serves as a promising target for therapeutics development. Mutations on the S-RBD may alter its affinity to the cell receptor and affect the potency of vaccines and antibodies. Here we used an approach to predict how mutations on RBD affect its binding affinity to hACE2 (human angiotensin-converting enzyme2).

transmembrane domain mutation: comprehensive characteristics and real-world evidence of treatment response in Chinese lung adenocarcinoma.

Background: transmembrane domain (TMD) mutation has been reported as a rare driver mutation associated with advanced stage disease and a poor prognosis in patients with lung adenocarcinoma (LUAD). We aimed to comprehensively profile the genetic landscape and treatment response information of TMD-mutant LUAD.

Methods: An in-house database of 7,812 LUAD patients was screened for mutation prevalence.

Diffusion of Ellipsoids in Bacterial Suspensions.

Active fluids such as swarming bacteria and motile colloids exhibit exotic properties different from conventional equilibrium materials. As a peculiar example, a spherical tracer immersed inside active fluids shows an enhanced translational diffusion, orders of magnitude stronger than its intrinsic Brownian motion. Here, rather than spherical tracers, we investigate the diffusion of isolated ellipsoids in a quasi-two-dimensional bacterial bath.

Stiffening of Red Blood Cells Induced by Cytoskeleton Disorders: A Joint Theory-Experiment Study.

The functions and elasticities of the cell are largely related to the structures of the cytoskeletons underlying the lipid bilayer. Among various cell types, the red blood cell (RBC) possesses a relatively simple cytoskeletal structure. Underneath the membrane, the RBC cytoskeleton takes the form of a two-dimensional triangular network, consisting of nodes of actins (and other proteins) and edges of spectrins.

Spectrins in axonal cytoskeletons: dynamics revealed by extensions and fluctuations.

The macroscopic properties, the properties of individual components, and how those components interact with each other are three important aspects of a composited structure. An understanding of the interplay between them is essential in the study of complex systems. Using axonal cytoskeleton as an example system, here we perform a theoretical study of slender structures that can be coarse-grained as a simple smooth three-dimensional curve.

Probing the cytoadherence of malaria infected red blood cells under flow.

Malaria is one of the most widespread and deadly human parasitic diseases caused by the Plasmodium (P.) species with the P. falciparum being the most deadly.

Asymmetric disconnection of an underwater air bubble: persistent neck vibrations evolve into a smooth contact.

The disconnection of an underwater bubble illustrates how slight initial asymmetries can prevent the formation of a finite-time singularity. Creating a singularity by focusing a finite amount of energy dynamically into a vanishingly small amount of material requires that the initial condition be perfectly symmetric. In reality, imperfections are always present.