Prediction of cellular morphology changes under perturbations with a transcriptome-guided diffusion model.

Investigating cell morphology changes after perturbations using high-throughput image-based profiling is increasingly important for phenotypic drug discovery, including predicting mechanisms of action (MOA) and compound bioactivity. The vast space of chemical and genetic perturbations makes it impractical to explore all possibilities using conventional methods. Here we propose MorphDiff, a transcriptome-guided latent diffusion model that simulates high-fidelity cell morphological responses to perturbations.

Feature fusion based on global-local weighted attention model for automatic epileptic seizure detection.

Objective: Epilepsy is a neurological disorder characterized by recurrent seizures, which present significant challenges in both diagnosis and treatment. Despite advances in seizure detection, existing methods often struggle with accurately capturing the complex and dynamic interactions between temporal, spatial, and spectral features of EEG signals. This leads to limitations in the detection accuracy and generalization across different datasets.

Fostering social-emotional competence in early childhood: EmoCog Play Integration Programme.

Background: Developing social-emotional competence and executive function is essential to children's long-term success. While their interconnection is well-established, limited evidence exists on interventions that systematically integrate both domains.

Aims: To address this, this study developed the EmoCog Play Integration (EPI) Programme, a pioneering initiative designed to systematically integrate social-emotional competence and executive function through structured, game-based activities.

The underexplored pulmonary toxicity of pyrrolizidine alkaloids: Emerging hazard from food contamination.

Pyrrolizidine alkaloids (PAs) are the most widespread plant-derived toxins globally. Humans are frequently exposed to PAs through ingestion of PA-contaminated food products, with chronic dietary exposure estimated at up to 48.4 ng/kg body weight/day, posing a significant global health threat.

Achieving controllable packing mode and broad colour-tunable emission the end group effect in pyrene-based aggregation-induced emission luminogens.

To clarify the impact of the end groups on aggregation behaviour and emission properties, a series of α-cyanostilbene pyrene-based compounds (Py-R and Py-PR) were synthesized. These compounds display aggregation-induced emission characteristics with broad colour-tunable solid-state emission with the colour ranging from cyan to deep red (500-667 nm), achieved by modulating their end groups. The electronic effect of these end groups plays a key role in regulating the emission and the aggregation mode, demonstrating a strong correlation with Hammett constants.

Sunlight-driven photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer polymerization at a large scale.

Photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization is a sustainable and powerful tool to synthesize polymers and copolymers. However, the development of large-scale production and polymerizations using sunlight irradiation remain top challenges for PET-RAFT polymerizations. In this study, conjugated cross-linked phosphine (PPh-CHCP) was explored as a heterogeneous photocatalyst for efficient PET-RAFT polymerization.

Ru@NiMoS aggregate with boosted electrochemical catalysis for enhanced electrochemiluminescence and lidocaine detection.

A binder-free Ru@NiMoS electrode was engineered by in situ growth of two-dimensional NiMoS nanosheets on nickel foam. This process effectively promoted the electrostatic-driven aggregation of Ru(bpy) , harnessing the synergistic effect to enhance electrochemiluminescence (ECL) performance. The integration (Ru@NiMoS) achieved an impressive ECL efficiency of 70.

Insights into anti-tuberculosis drug design on the scaffold of nitroimidazole derivatives using structure-based computer-aided approaches.

Deazaflavin-dependent nitroreductase (Ddn) is a crucial enzyme involved in mycolic acid biosynthesis, a vital component of the cell wall in (MTB)-the bacterial pathogen responsible for tuberculosis. Over the past two decades, nitroimidazole oxazine scaffold (NOS) derivatives have been investigated as potential therapeutic agents targeting Ddn in MTB, with a focus on enhancing drug efficacy, minimizing toxicity, and combating drug resistance. In this study, we performed an extensive theoretical investigation combining three-dimensional quantitative structure-activity relationship (3D-QSAR) studies, all-atom molecular docking, and atomic-level molecular dynamics (MD) simulations.

Integrative analysis of high-dimensional quantile regression with contrasted penalization.

In the era of big data, the simultaneous analysis of multiple high-dimensional, heavy-tailed datasets has become essential. Integrative analysis offers a powerful approach to combine and synthesize information from these various datasets, and often outperforming traditional meta-analysis and single-dataset analysis. In this paper, we introduce a novel high-dimensional integrative quantile regression that can accommodate the complexities inherent in multi-dataset analysis.

THRUST: translesion synthesis-driven hierarchical regulation using a template-activator construct for Cas12a activity.

The CRISPR/Cas12a system has demonstrated extraordinary capabilities in biosensing and molecular diagnostics, owing to its precise recognition and efficient -cleavage ability. However, current crRNA-based Cas12a regulation is relatively crude, requiring costly modifications and multiple components, increasing system complexity. Here, we develop translesion synthesis-driven hierarchical regulation using a template-activator construct for Cas12a activity (THRUST), a powerful and economical Cas12a regulation strategy.

Reversible surface reconstruction of metal-organic frameworks for durable oxygen evolution reaction.

Metal-organic frameworks (MOFs) are regarded as prospective electrocatalysts for the oxygen evolution reaction (OER). Nevertheless, controllably reversible reconstruction of MOFs, yielding highly active catalytic sites for durable OER, has not been extensively studied. Herein, Ni-BPM (BPM = 4,4'-dihydroxybiphenyl-3,3'-dicarboxylic acid) equipped with open metal sites was selected as a potential electrocatalyst, and orientated MOF electrodes were fabricated a sacrificial lattice-matched-template method.

Excessive Existence of Positively Charged Amino Acids Caused Off-Target Recognition in the Seed Region of Argonaute.

Argonaute (Ago) can achieve DNA-guided DNA recognition and cleavage at physiological temperatures (~37 °C), making it a promising tool for gene editing. However, its significant off-target effects, particularly associated with the seed region (sites 2-8), pose challenges for precise gene therapy. This study focuses on enhancing the specificity of the seed region recognition to mitigate these off-target effects.

Intention to disclose maternal HIV status to children among Chinese mothers: association with outcome expectations and moderation by perceived health.

Background: Disclosure of maternal HIV status to children can be beneficial for both mother and children. Few studies have examined factors and moderators of HIV disclosure among mothers living with HIV.

Objective: The present study examined the association of outcome expectations and perceived health on intention to disclose maternal HIV status to children, and the moderating role of perceived health among women living with HIV in China.

Thermodynamics of Spin-Imbalanced Fermi Gases with SU(N)-Symmetric Interaction.

Thermodynamics of degenerate Fermi gases has been extensively studied through various aspects such as Pauli blocking effects, collective modes, BCS superfluidity, and more. Despite this, multicomponent fermions with imbalanced spin configurations remain largely unexplored, particularly beyond the two-component scenario. In this Letter, we generalize the thermodynamic study of SU(N) fermions to spin-imbalanced configurations based on density fluctuations.

Towards global reaction feasibility and robustness prediction with high throughput data and bayesian deep learning.

Predicting organic reaction feasibility and robustness against environmental factors is challenging. We address this issue by integrating high throughput experimentation (HTE) and Bayesian deep learning. Diverging from existing HTE studies focused on niche chemical spaces, in this work, our in-house HTE platform conducted 11,669 distinct acid amine coupling reactions in 156 working hours, yielding the most extensive single HTE dataset at a volumetric scale for industrial delivery.

Target Recognition Mechanism of Argonaute at the Supplementary Site.

Argonaute (Ago) utilizes a guide DNA strand to cleave foreign DNA, defending the bacteria against invasive genetic elements and thus offering potential as a gene-editing tool. However, the underlying mechanism for target recognition remains underexplored. For example, the necessity of guide-target complementarity at the supplementary site (positions g13-16) for target cleavage has been debated for years.

Fate of Thermalization of Ultracold Fermions with Two-Body Dissipation.

Two-body inelastic collisions arising from chemical reactions are prevalent in ultracold fermionic and bosonic molecular gases. Although recent advancements have achieved quantum degeneracy in these systems, loss dynamics are typically modeled phenomenologically using rate equations that often assume thermalization during chemical reactions. In this study, we employ the inelastic quantum Boltzmann equation to analyze particle loss, temperature evolution, and momentum distributions in single-component Fermi gases from first principles.

PDGF-BB improves cortical bone quality through restoring the osteogenic microenvironment in the steroid-associated osteonecrosis of rabbits.

Objective: Steroid-associated osteonecrosis of the femoral head (SONFH) is a refractory disease characterized by progressive bone destruction. Clinical evidence suggests that SONFH may extend beyond the intra-capital region to the femoral neck, metaphysis, and even diaphysis, increasing the risk of subtrochanteric fractures and implant loosening post-surgery. While our previous study demonstrated that platelet-derived growth factor-BB (PDGF-BB) promotes reparative osteogenesis in the femoral head, its effects on cortical bone quality in the extended diaphyseal regions under steroid-associated osteonecrosis (SAON) remain unclear.

An interpretable artificial intelligence approach to differentiate between blastocysts with similar or same morphological grades.

Study Question: Can a quantitative method be developed to differentiate between blastocysts with similar or same inner cell mass (ICM) and trophectoderm (TE) grades, while also reflecting their potential for live birth?

Summary Answer: We developed BlastScoringNet, an interpretable deep-learning model that quantifies blastocyst ICM and TE morphology with continuous scores, enabling finer differentiation between blastocysts with similar or same grades, with higher scores significantly correlating with higher live birth rates.

What Is Known Already: While the Gardner grading system is widely used by embryologists worldwide, blastocysts having similar or same ICM and TE grades cause challenges for embryologists in decision-making. Furthermore, human assessment is subjective and inconsistent in predicting which blastocysts have higher potential to result in live birth.

Robust Spatial Cell-Type Deconvolution with Qualitative Reference for Spatial Transcriptomics.

Many spatially resolved transcriptomic technologies have been developed to provide gene expression profiles for spots that may contain heterogeneous mixtures of cells. To decompose cellular composition and expression levels, various deconvolution methods have been developed using single-cell RNA sequencing (scRNA-seq) data with known cell-type labels as a reference. However, in the absence of a reliable reference dataset or in the presence of heterogeneous batch effects, these methods may introduce bias.

Electrochemical Biosensors for the Detection of Exosomal microRNA Biomarkers for Early Diagnosis of Neurodegenerative Diseases.

Early and precise diagnosis of neurodegenerative disorders like Alzheimer's (AD) and Parkinson's (PD) is crucial for slowing their progression and enhancing patient outcomes. Exosomal microRNAs (miRNAs) are emerging as promising biomarkers due to their ability to reflect the diseases' pathology, yet their low abundance poses significant detection hurdles. This review article delves into the burgeoning field of electrochemical biosensors, designed for the precise detection of exosomal miRNA biomarkers.

Tuning the Near-Infrared Aggregate of a Multicationic Photosensitizer through Molecular Coassembly for Symbiotic Photothermal Therapy and Chemotherapy.

Cationic photosensitizers (PSs) offer many intriguing advantages, in addition to generating heat or reactive oxygen species for cancer phototherapy. However, the preparation of cationic PSs with enhanced near-infrared (NIR) absorption remains a significant challenge. In this work, we have synthesized a PS TPBBT, which incorporates a strong electron-withdrawing unit, benzobisthiadiazole, and four terminal pyridinium groups.

Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis.

Direct reprogramming has garnered considerable attention due to its capacity to directly convert differentiated cells into desired cells. Fibroblasts are frequently employed in reprogramming studies due to their abundance and accessibility. However, they are also the key drivers in the progression of fibrosis, a pathological condition characterized by excessive extracellular matrix deposition and tissue scarring.

Infrapatellar branch of saphenous nerve: from anatomy, sonoanatomy to its clinical implications.

The infrapatellar branch of the saphenous nerve (IPBSN) is implicated in nerve injury from different knee surgeries because of its intimate course relative to the knee joint capsule. Pain physicians encounter patients in their practice for the management of neuralgia of this nerve or in the context of advanced management of knee osteoarthritis. This article aims to provide a comprehensive review of the anatomy, sonoanatomy, and the intervention of the IPBSN in pain management of infrapatellar neuralgia and chronic knee pain.