Integrating Single-Cell and Spatial Transcriptomics Reveals Heterogeneity of Early Pig Skin Development and a Subpopulation with Hair Placode Formation.

The dermis and epidermis, crucial structural layers of the skin, encompass appendages, hair follicles (HFs), and intricate cellular heterogeneity. However, an integrated spatiotemporal transcriptomic atlas of embryonic skin has not yet been described and would be invaluable for studying skin-related diseases in humans. Here, single-cell and spatial transcriptomic analyses are performed on skin samples of normal and hairless fetal pigs across four developmental periods. The cross-species comparison of skin cells illustrated that the pig epidermis is more representative of the human epidermis than mice epidermis. Moreover, Phenome-wide association study analysis revealed that the conserved genes between pigs and humans are strongly associated with human skin-related diseases. In the epidermis, two lineage differentiation trajectories describe hair follicle (HF) morphogenesis and epidermal development. By comparing normal and hairless fetal pigs, it is found that the hair placode (Pc), the most characteristic initial structure in HFs, arises from progenitor-like OGN+/UCHL1+ cells. These progenitors appear earlier in development than the previously described early Pc cells and exhibit abnormal proliferation and migration during differentiation in hairless pigs. The study provides a valuable resource for in-depth insights into HF development, which may serve as a key reference atlas for studying human skin disease etiology using porcine models.

Research advancements on nerve guide conduits for nerve injury repair.

Peripheral nerve injury (PNI) is one of the most serious causes of disability and loss of work capacity of younger individuals. Although PNS has a certain degree of regeneration, there are still challenges like disordered growth, neuroma formation, and incomplete regeneration. Regarding the management of PNI, conventional methods such as surgery, pharmacotherapy, and rehabilitative therapy. Treatment strategies vary depending on the severity of the injury. While for the long nerve defect, autologous nerve grafting is commonly recognized as the preferred surgical approach. Nevertheless, due to lack of donor sources, neurological deficits and the low regeneration efficiency of grafted nerves, nerve guide conduits (NGCs) are recognized as a future promising technology in recent years. This review provides a comprehensive overview of current treatments for PNI, and discusses NGCs from different perspectives, such as material, design, fabrication process, and composite function.

Electric Field Switching of Magnon Spin Current in a Compensated Ferrimagnet.

Manipulation of directional magnon propagation, known as magnon spin current, is essential for developing magnonic devices featuring nonvolatile functionalities and ultralow power consumption. Magnon spin current can usually be modulated by magnetic field or current-induced spin torques. However, these approaches may lead to energy dissipation due to Joule heating. Electric-field switching of magnon spin current without charge current is highly preferred but challenging to realize. By integrating magnonic and piezoelectric materials, the manipulation of the magnon spin current generated by the spin Seebeck effect in the ferrimagnetic insulator Gd3 Fe5 O12 (GdIG) film on a piezoelectric substrate is demonstrated. Reversible electric-field switching of magnon polarization without applied charge current is observed. Through strain-mediated magnetoelectric coupling, the electric field induces the magnetic compensation transition between two magnetic states of the GdIG, resulting in its magnetization reversal and the simultaneous switching of magnon spin current. This work establishes a prototype material platform that paves the way for developing magnon logic devices characterized by all electric field reading and writing and reveals the underlying physics principles of their functions.

Cross-Species Comparative DNA Methylation Reveals Novel Insights into Complex Trait Genetics among Cattle, Sheep, and Goats.

The cross-species characterization of evolutionary changes in the functional genome can facilitate the translation of genetic findings across species and the interpretation of the evolutionary basis underlying complex phenotypes. Yet, this has not been fully explored between cattle, sheep, goats, and other mammals. Here, we systematically characterized the evolutionary dynamics of DNA methylation and gene expression in 3 somatic tissues (i.e. brain, liver, and skeletal muscle) and sperm across 7 mammalian species, including 3 ruminant livestock species (cattle, sheep, and goats), humans, pigs, mice, and dogs, by generating and integrating 160 DNA methylation and transcriptomic data sets. We demonstrate dynamic changes of DNA hypomethylated regions and hypermethylated regions in tissue-type manner across cattle, sheep, and goats. Specifically, based on the phylo-epigenetic model of DNA methylome, we identified a total of 25,074 hypomethylated region extension events specific to cattle, which participated in rewiring tissue-specific regulatory network. Furthermore, by integrating genome-wide association studies of 50 cattle traits, we provided novel insights into the genetic and evolutionary basis of complex phenotypes in cattle. Overall, our study provides a valuable resource for exploring the evolutionary dynamics of the functional genome and highlights the importance of cross-species characterization of multiomics data sets for the evolutionary interpretation of complex phenotypes in cattle livestock.

Polymer Additives with Gas Barrier and Anti-Aging Properties Made from Asphaltenes via Supercritical Ethanol.

Asphaltene is often regarded as an undesirable by-product of petroleum processing, possesses vast reserves with little market value. The typical routes of consuming asphaltene, namely burning and landfilling, pose significant environmental challenges. In this study, low-value asphaltene is converted into high-value ethylated carbon clusters (ECC) using a supercritical ethanol technique. The resulting ECC powder demonstrates promising properties for high density polyethylene (HDPE) composite applications. The effects of incorporating ECC on the mechanical, gas barrier, and anti-aging properties of the composite are investigated. Results show that a 1 wt.% ECC led to a 4.2% and 43.5% increase in tensile strength and elongation at break, a reduction of 45.8% and 30.7% in oxygen and carbon dioxide permeability. Furthermore, ECC exhibits effective UV spectrum absorption and conversion in the wavelength range of 400-600 nm, providing protection against UV spectrum damage to HDPE. The incorporation of ECC not only enhances the properties of polymer composites but also sequesters carbon within the polymer matrix, enabling the valorization of asphaltene while mitigating environmental impact.

Visualization of production and remediation of acetaminophen-induced liver injury by a carboxylesterase-2 enzyme-activatable near-infrared fluorescent probe.

Acetaminophen (APAP) overdose, also known as APAP poisoning, may directly result in hepatic injury, acute liver failure and even death. Nowadays, APAP-induced liver injury (AILI) has become an urgent public health issue in the developing world so the early accurate diagnosis and the revelation of underlying molecular mechanism of AILI are of great significance. As a major detoxifying organ, liver is responsible for metabolizing chemical substances, in which human carboxylesterase-2 (CES2) is present. Hence, we chose CES2 as an effective biomarker for evaluating AILI. By developing a CES2-activatable and water-soluble fluorescent probe PFQ-E with superior affinity (Km = 5.9 µM), great sensitivity (limit of detection = 1.05 ng/mL), near-infrared emission (655 nm) and large Stokes shift (135 nm), activity and distribution of CES2 in cells were determined or imaged effectively. More importantly, the APAP-induced hepatotoxicity and the underlying molecular mechanism of pathogenesis of AILI were investigated by measuring the "light-up" response of PFQ-E towards endogenous CES2 in vivo for the first time. Based on the superior performance of the probe PFQ-E for sensing CES2, we believe that it has broad potential in clinical diagnosis and therapy response evaluation of AILI.

Water-Mediated Hydrogen Bond Network Drives Highly Crystalline Structure Formation of Crown Ether-Based Covalent Organic Framework for Sr Adsorption.

Covalent organic frameworks (COFs) with crown ether units have drawn great attention due to their potential applications in adsorption, catalysis, and sensing. However, employing crown ethers to construct COFs is still challenging in light of the flexible nature of macrocycles. Here, a highly crystalline one-dimensional covalent organic framework (1D-18C6-COF) with crown ether units on the ribbon edge was synthesized. The water-mediated hydrogen bond network and π-π stacking hold the 1D COF ribbons together. The combination of experimental and DFT studies demonstrated that the hydrogen bond network plays a crucial role in the structure crystallinity. The 1D-18C6-COF was applied as an adsorbent for strontium, and it exhibited rapid kinetics with good selectivity. In the competitive adsorption experiment, a separation factor of 1900 was achieved, representing one of the largest values for cesium/strontium separation. This work provides new insights into the design and functional exploration of crystalline COFs with flexible units.

A novel intramolecular charge transfer-based near-infrared fluorescent probe with large Stokes shift for highly sensitive detection of cysteine in vivo.

Cysteine (Cys) distribute widely in organisms as the crucial components of proteins, and play important roles in pathophysiological processes of human body. Low level of Cys might induce hepatic injury, edema and growth retardation, while superfluous level of Cys is found to be closely relevant to Alzheimer's and Parkinson's diseases. In this work, a novel near-infrared (NIR) fluorescent probe PFQ-C was developed for highly selective detection of Cys in living cells and mice by utilizing the cyclization removal reaction between acrylate group and Cys. The superior sensitivity (limit of detection, 0.036 µM), NIR emission (655 nm), large Stokes shift (135 nm) and low cytotoxicity of the probe highlight its broad potential for future clinical applications. The response mechanism of the probe towards Cys was clarified by spectroscopy, chromatography and theoretical calculation. In addition, results of fluorescence imaging of cells and mice revealed the good performance of the probe for monitoring the distributions and variations of Cys activity in vivo, which is very useful for the researches on diseases associated with Cys.

Effect of Mo Oxides on the Phase Composition and Characteristics of Mo-10Re Pre-Alloyed Powders Co-Reduced with NH4ReO4.

Mo-Re pre-alloyed powders are crucial raw materials in fabricating Mo-Re alloys, and their properties can significantly impact the properties of the resulting alloys. The powders are usually produced by the co-reduction of a mixture of Mo and Re oxides. However, it remains unclear if the overall characteristics of the produced Mo-Re powders rely on the different combinations of the Mo and Re oxide precursors. Therefore, in this work, a comparative study is conducted on the co-reduction processes of different Mo oxides together with NH4ReO4, along with its influence on the size distribution and phase composition of the resulting Mo-10Re pre-alloyed powders. The results show that MoO3 is more promising than MoO2 as a precursor material. The powders fabricated using MoO3, when compared to MoO2, have a much more uniform size distribution, with a primary particle size ranging from 0.5-4 µm. In addition, it is also beneficial to achieve atomic-scale homogeneous mixing with Mo and Re elements and the formation of a solely Mo(Re) solid solution if MoO3 is used as a precursor oxide. In contrast, such desirable features were not identified when using the MoO2 route. The reason for this discrepancy may relate to whether Mo-O-Re metallurgical bonding has formed during the co-reduction process.

Morphology evolution of the aluminum surface in a fluorine-containing environment.

The interaction between aluminum (Al) and F and O atoms is essential to understand the etching process of Al and alumina (Al2O3) by fluorine-containing gases. In addition, it also has an influence on the corrosion behavior of Al devices, e.g., the Al collector in lithium-ion batteries operates in fluorine-containing electrolytes. However, the understanding of the structural evolution of the Al surface by fluorination at the atomistic level still remains elusive. Here, the thermodynamic and kinetic behaviors of F adatoms as well as co-adsorbed F and O adatoms on typical Al surfaces have been systematically investigated by combining density functional theory (DFT) calculations, canonical Monte Carlo (CMC) simulations and reactive molecular dynamics (RMD) simulations. The results of DFT calculations indicate that there is a repulsion (about 0.07 eV on Al(111) and Al(110), and 0.7 eV on Al(100)) between the first nearest neighboring (1NN) F adatoms, while an attraction of 0.14 eV on Al(111) exists within a 1NN F-O pair. CMC simulations reveal that the configurations of co-adsorbed F and O adatoms on the Al(111) surface at medium to low temperature (<600 K) and low total coverage (<0.2 monolayer, ML) have F adatoms dispersed in the hexagonal islands of O adatoms due to the attraction within the O-O and F-O pairs and the repulsion between F adatoms. As the coverage increases, the surface undergoes serious deformation. The average 1NN coordination numbers (1st CN) of O-to-O, F-to-O and F-to-F are six, three and zero, respectively. As the temperature increases, the interactions among adsorbates begin to be disrupted: the 1st CNs of O-to-O and F-to-O decrease, while that of F-to-F increases. The O-F hexagonal pattern remains until above the Al melting temperature (>1200 K). For F adatoms, both their migration on the surface and the penetration into the subsurface are easier than those of O adatoms, confirmed by both the DFT and RMD simulations. Our study on the co-adsorbates with opposite lateral interactions is instructive for understanding the thermal etching of Al and Al2O3 by fluorine-containing compounds.

Iterative multiple instance learning for weakly annotated whole slide image classification.

Objective.Whole slide images (WSIs) play a crucial role in histopathological analysis. The extremely high resolution of WSIs makes it laborious to obtain fine-grade annotations. Hence, classifying WSIs with only slide-level labels is often cast as a multiple instance learning (MIL) problem where a WSI is regarded as a bag and tiled into patches that are regarded as instances. The purpose of this study is to develop a novel MIL method for classifying WSIs with only slide-level labels in histopathology analysis.Approach.We propose a novel iterative MIL (IMIL) method for WSI classification where instance representations and bag representations are learned collaboratively. In particular, IMIL iteratively finetune the feature extractor with selected instances and corresponding pseudo labels generated by attention-based MIL pooling. Additionally, three procedures for robust training of IMIL are adopted: (1) the feature extractor is initialized by utilizing self-supervised learning methods on all instances, (2) samples for finetuning the feature extractor are selected according to the attention scores, and (3) a confidence-aware loss is applied for finetuning the feature extractor.Main results.Our proposed IMIL-SimCLR archives the optimal classification performance on Camelyon16 and KingMed-Lung. Compared with the baseline method CLAM, IMIL-SimCLR significantly outperforms it by 3.71% higher average area under curve (AUC) on Camelyon16 and 4.25% higher average AUC on KingMed-Lung. Additionally, our proposed IMIL-ImageNet achieve the optimal classification performance on TCGA-Lung with the average AUC of 96.55% and the accuracy of 96.76%, which significantly outperforms the baseline method CLAM by 1.65% higher average AUC and 2.09% higher average accuracy respectively.Significance.Experimental results on a public lymph node metastasis dataset, a public lung cancer diagnosis dataset and an in-house lung cancer diagnosis datasets show the effectiveness of our proposed IMIL method across different WSI classification tasks compared with other state-of-the-art MIL methods.

Magnetic ionic liquid-based liquid-liquid microextraction followed by ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry for simultaneous determination of neurotransmitters in human cerebrospinal fluid and plasma.

A green, efficient and easy sample pretreatment method of magnetic ionic liquid-based liquid-liquid microextraction (MIL-based LLME) combined with a sensitive, rapid and precise analytical method of ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-QqQ/MS2) was developed to simultaneously - determining of neurotransmitters (NTs) in biosamples. Two magnetic ionic liquids (MILs), [P6,6,6,14]3[GdCl6] and [P6,6,6,14]2[CoCl4] tested, and the latter was selected as the extraction solvent due to its advantages of visual recognition, paramagnetic behavior and higher extraction efficiency. Facile magnetic separation of MIL containing analytes from matrix was realized by applying external magnetic field without rather than centrifugation. Experimental parameters that would influence the extraction efficiency, including type and amount of MIL, extraction time, speed of the vortex process, salt concentration, and environmental pH, were optimized obtained. The proposed method was successfully applied to the simultaneous extraction and determination of 20 NTs in human cerebrospinal fluid and plasma samples. Excellent analytical performance indicates the broad potential of this method for clinical diagnosis and therapy of neurological diseases.

Writing-Speed Dependent Thresholds of Ferroelectric Domain Switching in Monolayer α-In2 Se3.

An electrical-biased or mechanical-loaded scanning probe written on the ferroelectric surface can generate programmable domain nanopatterns for ultra-scaled and reconfigurable nanoscale electronics. Fabricating ferroelectric domain patterns by direct-writing as quickly as possible is highly desirable for high response rate devices. Using monolayer α-In2 Se3 ferroelectric with ≈1.2 nm thickness and intrinsic out-of-plane polarization as an example, a writing-speed dependent effect on ferroelectric domain switching is discovered. The results indicate that the threshold voltages and threshold forces for domain switching can be increased from -4.2 to -5 V and from 365 to 1216 nN, respectively, as the writing-speed increases from 2.2 to 10.6 µm s-1 . The writing-speed dependent threshold voltages can be attributed to the nucleations of reoriented ferroelectric domains, in which sufficient time is needed for subsequent domain growth. The writing-speed dependent threshold forces can be attributed to the flexoelectric effect. Furthermore, the electrical-mechanical coupling can be employed to decrease the threshold force, achieving as low as ≈189±41 nN, a value smaller than those of perovskite ferroelectric films. Such findings reveal a critical issue of ferroelectric domain pattern engineering that should be carefully addressed for programmable direct-writing electronics applications.

Coal-Based Carbon Nanomaterials: En Route to Clean Coal Conversion toward Net Zero CO2.

As the world is committed to reach carbon peak by 2030 and net zero by 2050, the use of coal as an energy source is facing unprecedented challenges. According to the International Energy Agency (IEA), global annual coal demand is estimated to drop from more than 5640 million tonnes of coal equivalent (Mtce) in 2021 to 540 Mtce in 2050 under the net zero emission scenario, mostly being replaced by renewable energy such as solar and wind. Therefore, the coal industry is vigorously seeking alternative applications to keep it thriving, and nanotechnology can be one of the contributors. Herein, the challenges to coal-based carbon nanomaterials syntheses are outlined, along with a path toward commercialization. Coal-based carbon nanomaterials can be promising contributors to the concept of clean coal conversion, initiating its migration from an energy source to a high-value-added carbon source.

Coverage-dependent adsorption and dissociation of H2O on Al surfaces.

The adsorption and dissociation of H2O on Al surfaces including crystal planes and nanoparticles (ANPs) are systematically investigated by using density functional theory (DFT) calculations. H2O adsorption strength follows the order ANPs > Al(110) > Al(111) > Al(100). Due to the smaller cluster deformation caused by the moderate H2O adsorption, the relative magnitude of H2O adsorption strength on ANPs and crystal planes is opposite to the trend of adatoms like O* and/or N*. The energy barrier for the decomposition of H2O into H* and OH* is larger on ANPs than on crystal planes, and it decreases with the increasing cluster size. Due to the competition between the hydrogen (H) bonding among water molecules and the interaction between the water molecules and the substrate, the adsorption strength of H2O first increases and then decreases with the increase of water coverage. Moreover, each H2O molecule can efficiently form up to two H bonds with two H2O molecules. As a result, H2O molecules tend to aggregate into cyclic structures rather than chains on Al surfaces. Furthermore, the dissociation energy barrier of H2O drops with the increasing water coverage due to the presence of H bonds. Our results provide insight into interactions between water and Al, which can be extended to understand the interaction between water and other metal surfaces.

Genome-Wide Association Study on Reproductive Traits Using Imputation-Based Whole-Genome Sequence Data in Yorkshire Pigs.

Reproductive traits have a key impact on production efficiency in the pig industry. It is necessary to identify the genetic structure of potential genes that influence reproductive traits. In this study, a genome-wide association study (GWAS) based on chip and imputed data of five reproductive traits, namely, total number born (TNB), number born alive (NBA), litter birth weight (LBW), gestation length (GL), and number of weaned (NW), was performed in Yorkshire pigs. In total, 272 of 2844 pigs with reproductive records were genotyped using KPS Porcine Breeding SNP Chips, and then chip data were imputed to sequencing data using two online software programs: the Pig Haplotype Reference Panel (PHARP v2) and Swine Imputation Server (SWIM 1.0). After quality control, we performed GWAS based on chip data and the two different imputation databases by using fixed and random model circulating probability unification (FarmCPU) models. We discovered 71 genome-wide significant SNPs and 25 potential candidate genes (e.g., SMAD4, RPS6KA2, CAMK2A, NDST1, and ADCY5). Functional enrichment analysis revealed that these genes are mainly enriched in the calcium signaling pathway, ovarian steroidogenesis, and GnRH signaling pathways. In conclusion, our results help to clarify the genetic basis of porcine reproductive traits and provide molecular markers for genomic selection in pig breeding.

Enhanced Thermoelectric Performance and Low Thermal Conductivity in Cu2GeTe3 with Identified Localized Symmetry Breakdown.

Highly efficient and eco-friendly thermoelectric generators rely on low-cost and nontoxic semiconductors with high symmetry and ultralow lattice thermal conductivity κL. We report the rational synthesis of the novel cubic (Ag, Se)-doped Cu2GeTe3 semiconductors. A localized symmetry breakdown (LSB) was found in the composition of Cu1.9Ag0.1GeTe1.5Se1.5 (i.e., CAGTS15) with an ultralow κL of 0.37 W/mK at 723 K, the lowest value outperforming all Cu2GeCh3 (Ch = S, Se, and Te). A joint investigation of synchrotron X-ray techniques identifies the LSB embedded into the cubic CAGTS15 host matrix. This LSB is an Ångström-scale orthorhombic symmetry unit, characteristic of multiple bond lengths, large anisotropic atomic displacements, and distinct local chemical coordination of anions. Computational results highlight that such an unusual orthorhombic symmetry demonstrates low-frequency phonon modes, which become softer and more predominant with increasing temperatures. This unconventional LSB promotes bond complexity and phonon scattering, highly beneficial for extraordinarily low lattice thermal conductivity.

Lead zirconate titanate ceramics with aligned crystallite grains.

The piezoelectric properties of lead zirconate titanate [Pb(Zr,Ti)O3 or PZT] ceramics could be enhanced by fabricating textured ceramics that would align the crystal grains along specific orientations. We present a seed-passivated texturing process to fabricate textured PZT ceramics by using newly developed Ba(Zr,Ti)O3 microplatelet templates. This process not only ensures the template-induced grain growth in titanium-rich PZT layers but also facilitates desired composition through interlayer diffusion of zirconium and titanium. We successfully prepared textured PZT ceramics with outstanding properties, including Curie temperatures of 360°C, piezoelectric coefficients d33 of 760 picocoulombs per newton and g33 of 100 millivolt meters per newton, and electromechanical couplings k33 of 0.85. This study addresses the challenge of fabricating textured rhombohedral PZT ceramics by suppressing the otherwise severe chemical reaction between PZT powder and titanate templates.

Advances in biotechnology and clinical therapy in the field of peripheral nerve regeneration based on magnetism.

Peripheral nerve injury (PNI) is one of the most common neurological diseases. Recent studies on nerve cells have provided new ideas for the regeneration of peripheral nerves and treatment of physical trauma or degenerative disease-induced loss of sensory and motor neuron functions. Accumulating evidence suggested that magnetic fields might have a significant impact on the growth of nerve cells. Studies have investigated different magnetic field properties (static or pulsed magnetic field) and intensities, various magnetic nanoparticle-encapsulating cytokines based on superparamagnetism, magnetically functionalized nanofibers, and their relevant mechanisms and clinical applications. This review provides an overview of these aspects as well as their future developmental prospects in related fields.