Drug discovery and mechanism prediction with explainable graph neural networks.

Apprehension of drug action mechanism is paramount for drug response prediction and precision medicine. The unprecedented development of machine learning and deep learning algorithms has expedited the drug response prediction research. However, existing methods mainly focus on forward encoding of drugs, which is to obtain an accurate prediction of the response levels, but omitted to decipher the reaction mechanism between drug molecules and genes.

Reconfigurable and nonvolatile ferroelectric bulk photovoltaics based on 3R-WS for machine vision.

Hardware implementation of reconfigurable and nonvolatile photoresponsivity is essential for advancing in-sensor computing for machine vision applications. However, existing reconfigurable photoresponsivity essentially depends on the photovoltaic effect of p-n junctions, which photoelectric efficiency is constrained by Shockley-Queisser limit and hinders the achievement of high-performance nonvolatile photoresponsivity. Here, we employ bulk photovoltaic effect of rhombohedral (3R) stacked/interlayer sliding tungsten disulfide (WS) to surpass this limit and realize highly reconfigurable, nonvolatile photoresponsivity with a retinomorphic photovoltaic device.

Hypoxia-tolerant polymeric photosensitizer prodrug for cancer photo-immunotherapy.

Although photodynamic immunotherapy represents a promising therapeutic approach against malignant tumors, its efficacy is often hampered by the hypoxia and immunosuppressive conditions within the tumor microenvironment (TME) following photodynamic therapy (PDT). In this study, we report the design guidelines towards efficient Type-I semiconducting polymer photosensitizer and modify the best-performing polymer into a hypoxia-tolerant polymeric photosensitizer prodrug (HTPS) for cancer photo-immunotherapy. HTPS not only performs Type-I PDT process to partially overcome the limitation of hypoxic tumors in PDT by recycling oxygen but also specifically releases a Signal Transducer and Activator of Transcription-3 (STAT3) inhibitor (Niclosamide) in response to a cancer biomarker in the TME.

Plasma fibronectin is a prognostic biomarker of disability in Parkinson's disease: a prospective, multicenter cohort study.

In a prospective longitudinal study with 218 Parkinson's disease (PD) patients in the discovery cohort and 84 in the validation cohort, we aimed to identify novel blood biomarkers predicting disability milestones in PD. Through Least Absolute Shrinkage and Selection Operator-Cox (Lasso-Cox) regression, developed nomogram predictive model and Linear mixed-effects models, we identified low level of plasma fibronectin (pFN) as one of the best-performing risk markers in predicting disability milestones. A low level of pFN was associated with a short milestone-free survival period in PD.

Chemical looping synthesis of amines from N via iron nitride as a mediator.

Amines are commonly synthesized through the amination of organooxygenates using ammonia, frequently involving the use of noble metal catalysts. In this study, we present an alternative route to make amines using iron nitride (FeN) as the nitrogen source. Without any additional catalyst, FeN reacts with a range of alcohols at 250 °C under 1 or 10 bar H to produce amines as major products.

Predicting thermodynamic stability of inorganic compounds using ensemble machine learning based on electron configuration.

Machine learning offers a promising avenue for expediting the discovery of new compounds by accurately predicting their thermodynamic stability. This approach provides significant advantages in terms of time and resource efficiency compared to traditional experimental and modeling methods. However, most existing models are constructed based on specific domain knowledge, potentially introducing biases that impact their performance.

Pt/IrO enables selective electrochemical C-H chlorination at high current.

Employing electrochemistry for the selective functionalization of liquid alkanes allows for sustainable and efficient production of high-value chemicals. However, the large potentials required for C(sp)-H bond functionalization and low water solubility of such alkanes make it challenging. Here we discover that a Pt/IrO electrocatalyst with optimized Cl binding energy enables selective generation of Cl free radicals for C-H chlorination of alkanes.

Carbene-catalyzed chirality-controlled site-selective acylation of saccharides.

Acylation stands as a fundamental process in both biological pathways and synthetic chemical reactions, with acylated saccharides and their derivatives holding diverse applications ranging from bioactive agents to synthetic building blocks. A longstanding objective in organic synthesis has been the site-selective acylation of saccharides without extensive pre-protection of alcohol units. In this study, we demonstrate that by simply altering the chirality of N-heterocyclic carbene (NHC) organic catalysts, the site-selectivity of saccharide acylation reactions can be effectively modulated.

More than just a name? From magnetic to optical skyrmions and the topology of light.

Topology is usually perceived intrinsically immutable for a given object. We argue that optical topologies do not immediately enjoy such benefits. Using 'optical skyrmions' as an example, we show that they will exhibit varying textures and topological invariants (skyrmion numbers), depending on how to construct the skyrmion vector when projecting from real to parameter space.

Structurally Transformable and Reconfigurable Hydrogel-Based Mechanical Metamaterials and Their Application in Biomedical Stents.

Mechanical metamaterials exhibit several unusual mechanical properties, such as a negative Poisson's ratio, which impart additional capabilities to materials. Recently, hydrogels have emerged as exceptional candidates for fabricating mechanical metamaterials that offer enhanced functionality and expanded applications due to their unique responsive characteristics. However, the adaptability of these metamaterials remains constrained and underutilized, as they lack integration of the hydrogels' soft and responsive characteristics with the metamaterial design.

Impact of selenium supplementation on antioxidant enzyme activity and liver gene expression in juvenile pangasius catfish (Pangasius pangasius).

This study examined the effect of dietary selenium (Se) fortification on growth efficiency, antioxidant status, and liver gene expression in juvenile pangasius catfish. Sodium selenite was incorporated into a basal diet at incremental levels of 0-2.0 mg Se/kg.

Quantitative comparison of vascular characteristics of plus disease images published over time: International Classification of Retinopathy of Prematurity.

Plus disease was first defined in the original International Classification of retinopathy of prematurity (ICROP) publication in 1984. Over time, the definition of plus disease has evolved, and each ensuing ICROP publication has included example plus disease images. Because plus disease is often present when treatment is indicated, it is important to evaluate whether the retinal vascular characteristics (ie, dilation and tortuosity) depicted in these example images have remained the same or changed over time.

The Physical Activity at Work (PAW) Program in Thai Office Workers: Mixed Methods Process Evaluation Study.

Background: An increasing number of multicomponent workplace interventions are being developed to reduce sedentary time and promote physical activity among office workers. The Physical Activity at Work (PAW) trial was one of these interventions, but it yielded an inconclusive effect on sedentary time after 6 months, with a low uptake of movement breaks, the main intervention component.

Objective: This study investigates the factors contributing to the outcomes of the PAW cluster randomized trial.

Dropping the baton: Cognitive biases in emergency physicians.

Introduction: Clinical medicine is becoming more complex and increasingly requires a team-based approach to deliver healthcare needs. This dispersion of cognitive reasoning across individuals, teams and systems (termed "distributed cognition") means that our understanding of cognitive biases and errors must expand beyond traditional "in-the-head" individual mental models and focus on a broader "out-in-the-world" context instead. To our knowledge, no qualitative studies thus far have examined cognitive biases in clinical settings from a team-based sociocultural perspective.

Structural Basis of High-Precision Protein Ligation and Its Application.

Enzyme-catalyzed protein modifications have become invaluable in diverse applications, outperforming chemical methods in terms of precision, conjugation efficiency, and biological compatibility. Despite significant advances in ligases, such as sortase A and OaAEP1, their use in heterogeneous biological environments remains constrained by limited target sequence specificity. In 2021, Lupas' group introduced Connectase, a family of repurposed archaeal proteases for protein ligations, but its low processivity and lack of structural information have impeded further engineering for practical biological and biophysical applications.

Direct Synthesis of Unprotected C-Glycosides via Photoredox Activation of Glycosyl Ester.

Synthetic C-glycosides play a crucial role in molecular biology and medicine. With the surge of interest in C-glycosides and the demand to provide efforts with sufficient feedstock, it is highly significant to pursue novel methodologies to access C-glycosides in a concise and efficient manner. Here, we disclose an attractive strategy that diverges itself from conventional multistep reaction sequences involving the manipulations of protecting groups.

Whole-exome sequencing association study reveals genetic effects on tumor microenvironment components in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) presents a substantial clinical challenge due to the limited understanding of its genetic underpinnings. Here we conduct the largest scale whole-exome sequencing association study of NPC to date, encompassing 6,969 NPC cases and 7,100 controls. We unveil 3 germline genetic variants linked to NPC susceptibility: a common rs2276868 in RPL14, a rare rs5361 in SELE, and a common rs1050462 in HLA-B.

Self-assembled eumelanin nanoparticles enhance IFN-I activation and cilia-driven intercellular communication to defend against Tulane virus, a human norovirus surrogate.

Norovirus (NoV) infection is a leading cause of gastroenteritis and poses global health threats, with increasing incidence reported in immunocompromised individuals, which is further exacerbated by the globalization of the food industry. Eumelanin has demonstrated its potential in antiviral treatments, but its role in preventing viral infections remains underexplored. Therefore, in this study, we investigated the antiviral properties and potential mechanisms of self-assembled eumelanin nanoparticles (EmNPs) against Tulane virus (TuV), a surrogate with a similar infection mechanism to NoVs.

Antigen-antibody complex density and antibody-induced HLA protein unfolding influence Fc-mediated antibody effector function.

Donor-specific antibodies (DSAs) targeting mismatched human leukocyte antigen (HLA) molecules are one of the principal threats to long-term graft survival in solid organ transplantation. However, many patients with long-term circulating DSAs do not manifest rejection responses, suggesting a degree of heterogeneity in their pathogenicity and related functional activity. Immunologic risk stratification of transplant recipients is complicated by challenges intrinsic to defining alloantibody responses that are potentially pathogenic versus those that are not.