Cholecystokinin neurons in the spinal trigeminal nucleus interpolaris regulate mechanically evoked predatory hunting in male mice.

Predatory hunting plays a critical role in animal survival. Motion-related vibrissal somatosensory signaling is essential for prey detection and hunting in mice. However, little is known about the neural circuits that convert vibrissal somatosensory cues to trigger predatory hunting.

Meta Learning Task Representation in Multiagent Reinforcement Learning: From Global Inference to Local Inference.

Multiagent meta reinforcement learning (MAMRL) enables multiagent systems (MASs) to adapt to multiple tasks. However, partial observability poses a significant challenge by hindering efficient task inference from agents' limited local experiences. To address this, we propose MG2L, a novel algorithm featuring a global-to-local (G2L) training scheme based on mutual information optimization (MIO).

Two multifunctional zero-dimensional Gd(III) complexes: magnetocaloric effect and anticancer mechanisms for lung cancer.

Two Gd(III) complexes [GdL(HO)(NO)(CHOH)(CHCHOH)] (Gd1) and [Gd(OOCCH)L(HO)]•2(HO) (Gd2) (HL = 2-pyridylcarboxaldehyde isonicotinoylhydrazone) were synthesized with a Schiff base ligand. Crystallographic study reveals both Gd1 and Gd2 have a zero-dimensional mononuclear or binuclear structure. Magnetic investigations demonstrate that Gd1 and Gd2 exhibit potential magnetocaloric effects due to Gd(III) ions, which provide negligible magnetic anisotropy, and possess low-lying excited spin states.

Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humans.

Non-contact anterior cruciate ligament (ACL) rupture is a common serious orthopaedic disease in humans and dogs. Familial risk has been recognized in both species but interactions between genetic effects and environmental risk are not understood. We investigated ACL rupture heritability, genetic architecture, selection pressure, sharing of risk genes and biological pathways, and polygenic risk score (PRS) prediction of disease risk.

Modulating Oxygen Reduction Activity in Chalcogenophene-Incorporated Organic Electrocatalysts through Main-Group Element Engineering.

Organic small molecules (OSMs) with well-defined structures are crucial integral components of cathode catalysts for fuel cells. Despite the acknowledged potential of heteroatom doping to enhance the catalytic performance of metal-free carbon-based catalysts, there exists a notable gap in conducting molecular structure and catalytic activity, particularly under the premise of maintaining a constant molecular skeleton and with a clear molecular structure. Herein, the charge distribution is modulated by introducing different chalcogens into the same molecular skeleton through main-group engineering.

One score to rule them all: regularized ensemble polygenic risk prediction with GWAS summary statistics.

Ensemble learning has been increasingly popular for boosting the predictive power of polygenic risk scores (PRS), with almost every recent multi-ancestry PRS approach employing ensemble learning as a final step. Existing ensemble approaches rely on individual-level data for model training, which severely limits their real-world applications, especially in non-European populations without sufficient genomic samples. Here, we introduce a statistical framework to construct regularized ensemble PRS, which allows us to combine a large number of candidate PRS models using only summary statistics from genome-wide association studies.

GlutaR: A High-Performance Fluorescent Protein-Based Sensor for Spatiotemporal Monitoring of Glutamine Dynamics In Vivo.

Glutamine is the most abundant amino acid in human blood and muscle, and is integral to a wide variety of functions in cancer cells. However, the inability to monitor the subcellular distribution of glutamine in real-time has obscured understanding of glutamine metabolism under physiological and pathological conditions. Here, we report the development of a genetically encoded fluorescent sensor and demonstrate how this GlnBP-cpYFP fusion "GlutaR sensor" undergoes glutamine-induced conformational changes reflected in detectable fluorescence responses.

Controlling for polygenic genetic confounding in epidemiologic association studies.

Epidemiologic associations estimated from observational data are often confounded by genetics due to pervasive pleiotropy among complex traits. Many studies either neglect genetic confounding altogether or rely on adjusting for polygenic scores (PGS) in regression analysis. In this study, we unveil that the commonly employed PGS approach is inadequate for removing genetic confounding due to measurement error and model misspecification.

Polystyrene nanoplastics enhance thrombosis through adsorption of plasma proteins.

Plastic products offer remarkable convenience for modern life. However, growing concerns are emerging regarding the potential health hazards posed by nanoplastics, which formed as plastics break down. Currently, the biological effects and mechanisms induced by nanoplastics are largely underexplored.

Optimizing and benchmarking polygenic risk scores with GWAS summary statistics.

Background: Polygenic risk score (PRS) is a major research topic in human genetics. However, a significant gap exists between PRS methodology and applications in practice due to often unavailable individual-level data for various PRS tasks including model fine-tuning, benchmarking, and ensemble learning.

Results: We introduce an innovative statistical framework to optimize and benchmark PRS models using summary statistics of genome-wide association studies.

Abnormal circadian rhythms exacerbate dilated cardiomyopathy by reducing the ventricular mechanical strength.

Aims: Dilated cardiomyopathy (DCM) has etiological and pathophysiological heterogeneity. Abnormal circadian rhythm (ACR) is related to the development of DCM in animal models, but exploration based on clinical samples is lacking. Sleep apnea (SA) is the most common disease related to ACR, and we chose SA as the study object to explore ACR-DCM.

Structural Health Monitoring of Glass Fiber-Reinforced Polymer Laminates with Carbon Nanotube-Coated Glass Fiber Sensing Layer after Low-Velocity Impact Using Electrical Resistance Tomography.

Structural health monitoring (SHM) of composite materials is of great significance in various practical applications. However, it is a challenge to accurately monitor the damage of composites without affecting their mechanical properties. In this paper, an embedded sensing layer based on carbon nanotube-coated glass fiber is designed, combined with electrical resistance tomography (ERT) for in situ damage monitoring.

A low-voltage-driven MEMS ultrasonic phased-array transducer for fast 3D volumetric imaging.

Wearable ultrasound imaging technology has become an emerging modality for the continuous monitoring of deep-tissue physiology, providing crucial health and disease information. Fast volumetric imaging that can provide a full spatiotemporal view of intrinsic 3D targets is desirable for interpreting internal organ dynamics. However, existing 1D ultrasound transducer arrays provide 2D images, making it challenging to overcome the trade-off between the temporal resolution and volumetric coverage.

Curved and Annular Diaphragm Coupled Piezoelectric Micromachined Ultrasonic Transducers for High Transmit Biomedical Applications.

In this paper, we present a novel three-dimensional (3D) coupled configuration of piezoelectric micromachined ultrasound transducers (pMUTs) by combing a curved and an annular diaphragm for transmit performance optimization in biomedical applications. An analytical equivalent circuit model (EQC) is developed with varied excitation methods to incorporate the acoustic-structure coupling of the curved and annular diaphragm-coupled pMUTs (CAC-pMUTs). The model-derived results align well with the reference simulated by the finite element method (FEM).

Additive Manufacturing of Micro-Architected Copper based on an Ion-Exchangeable Hydrogel.

Additive manufacturing (AM) of copper through laser-based processes poses challenges, primarily attributed to the high thermal conductivity and low laser absorptivity of copper powder or wire as the feedstock. Although the use of copper salts in vat photopolymerization-based AM techniques has garnered recent attention, achieving micro-architected copper with high conductivity and density has remained elusive. In this study, we present a facile and efficient process to create complex 3D micro-architected copper structures with superior electrical conductivity and hardness.

Controlling for polygenic genetic confounding in epidemiologic association studies.

Epidemiologic associations estimated from observational data are often confounded by genetics due to pervasive pleiotropy among complex traits. Many studies either neglect genetic confounding altogether or rely on adjusting for polygenic scores (PGS) in regression analysis. In this study, we unveil that the commonly employed PGS approach is inadequate for removing genetic confounding due to measurement error and model misspecification.

Vitamin D status and variable responses to supplements depend in part on genetic factors in adults with cystic fibrosis.

Vitamin D sufficiency has been difficult to achieve consistently in patients with cystic fibrosis (CF), even with robust oral supplements. To assess vitamin D status and resistance to supplementation, we studied 80 adults using 25-hydroxyvitamin D (25OHD) determinations and whole genome sequencing to construct polygenic risk scores (PRS) that aggregate variants associated with vitamin D status. The results revealed that 30 % of patients were below the threshold of 30 ng/mL and thus should be regarded as insufficient despite normal vitamin E status, a reflection of adherence to fat soluble vitamin supplementation.

Impact of intrinsic and extrinsic risk factors on early-onset lung disease in cystic fibrosis.

Background: Although respiratory pathology is known to develop in young children with cystic fibrosis (CF), the determinants of early-onset lung disease have not been elucidated.

Objective: We aimed to determine the impact of potential intrinsic and extrinsic risk factors during the first 3 years of life, testing the hypothesis that both contribute significantly to early-onset CF lung disease.

Design: We studied 104 infants born during 2012-2017, diagnosed through newborn screening by age 3 months, and evaluated comprehensively to 36 months of age.

Synthesis and Characterization of an Environmentally Friendly Phenol-Formaldehyde Resin Modified with Waste Plant Protein.

To develop a lower-cost, excellent-performance, and environmentally friendly phenol-formaldehyde (PF) resin, soybean meal was used to modify PF resin, and soybean meal-phenol-formaldehyde (SMPF) resins were prepared. This reveals the effect of soybean meal on the structural, bonding, and curing properties of PF resin, which are very important for its applications in the wood industry. The resins' physicochemical properties and curing performance were investigated, showing that SMPF resins have higher curing temperatures than PF resin.

Photoacoustic testing of shear viscoelastic properties of soft tissues using annular beam illumination.

This Letter reports a new, to the best of our knowledge, photoacoustic excitation method for evaluating the shear viscoelastic properties of soft tissues. By illuminating the target surface with an annular pulsed laser beam, circularly converging surface acoustic waves (SAWs) are generated, focused, and detected at the center of the annular beam. The shear elasticity and shear viscosity of the target are extracted from the dispersive phase velocity of the SAWs based on the Kelvin-Voigt model and nonlinear regression fitting.

The production of within-family inequality: Insights and implications of integrating genetic data.

The integration of genetic data within large-scale social and health surveys provides new opportunities to test long-standing theories of parental investments in children and within-family inequality. Genetic predictors, called polygenic scores, allow novel assessments of young children's abilities that are uncontaminated by parental investments, and family-based samples allow indirect tests of whether children's abilities are reinforced or compensated. We use over 16,000 sibling pairs from the UK Biobank to test whether the relative ranking of siblings' polygenic scores for educational attainment is consequential for actual attainments.

Quantifying portable genetic effects and improving cross-ancestry genetic prediction with GWAS summary statistics.

Polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of Europeans are known to have substantially reduced predictive accuracy in non-European populations, limiting their clinical utility and raising concerns about health disparities across ancestral populations. Here, we introduce a statistical framework named X-Wing to improve predictive performance in ancestrally diverse populations. X-Wing quantifies local genetic correlations for complex traits between populations, employs an annotation-dependent estimation procedure to amplify correlated genetic effects between populations, and combines multiple population-specific PRS into a unified score with GWAS summary statistics alone as input.

Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1.

As a terpenoids natural product isolated from the plant Thunder God Vine, Celastrol is widely studied for its pharmacological activities, including anti-tumor activities. The clinical application of Celastrol is strictly limited due to its severe side effects, whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization. Target identification has a far-reaching influence on the development of innovative drugs, and omics data has been widely used for unbiased target prediction.

Heterocyclic Modulated Electronic States of Alkynyl-Containing Conjugated Microporous Polymers for Efficient Oxygen Reduction.

The oxygen reduction reaction (ORR) is a key process in green energy conversion technology. Heteroatom doping has been proven to be a prospective strategy to prepare metal-free carbon-based electrocatalysts, but such methods often suffer from uncontrollable catalyst frameworks and imprecise active sites. Herein, an organic heterocyclic strategy is adopted to modulate the charge redistribution of alkynyl-containing conjugated microporous polymers (CMPs) by introducing varied five-membered heterocyclic structures.