A Natural Casein-Based Separator with Brick-and-Mortar Structure for Stable, High-Rate Proton Batteries.

Rechargeable aqueous proton batteries with small organic molecule anodes are currently considered promising candidates for large-scale energy storage due to their low cost, stable safety, and environmental friendliness. However, the practical application is limited by the poor cycling stability caused by the shuttling of soluble organic molecules between electrodes. Herein, a cell separator is modified by a GO-casein-Cu2+ layer with a brick-and-mortar structure to inhibit the shuttling of small organic molecules. Experimental and calculation results indicate that, attributed to the synergistic effect of physical blocking of casein molecular chains and electrostatic and coordination interactions of Cu2+, bulk dissolution and shuttling of multiple small molecules can be inhibited simultaneously, while H+ transfer across the separators is not almost affected. With the protection of the GO-casein-Cu2+ separator, soluble small molecules, such as diquinoxalino[2,3-a:2',3'-c]phenazine,2,3,8,9,14,15-hexacyano (6CN-DQPZ) exhibit a high reversible capacity of 262.6 mA h g-1 and amazing stability (capacity retention of 92.9% after 1000 cycles at 1 A g-1). In addition, this strategy is also proved available to other active conjugated small molecules, such as indanthrone (IDT), providing a general green sustainable strategy for advancing the use of small organic molecule electrodes in proton cells.

Developing an abnormal high-Na-content P2-type layered oxide cathode with near-zero-strain for high-performance sodium-ion batteries.

Layered transition metal oxides (NaxTMO2) possess attractive features such as large specific capacity, high ionic conductivity, and a scalable synthesis process, making them a promising cathode candidate for sodium-ion batteries (SIBs). However, NaxTMO2 suffer from multiple phase transitions and Na+/vacancy ordering upon Na+ insertion/extraction, which is detrimental to their electrochemical performance. Herein, we developed a novel cathode material that exhibits an abnormal P2-type structure at a stoichiometric content of Na up to 1. The cathode material delivers a reversible capacity of 108 mA h g-1 at 0.2C and 97 mA h g-1 at 2C, retaining a capacity retention of 76.15% after 200 cycles within 2.0-4.3 V. In situ diffraction studies demonstrated that this material exhibits an absolute solid-solution reaction with a low volume change of 0.8% during cycling. This near-zero-strain characteristic enables a highly stabilized crystal structure for Na+ storage, contributing to a significant improvement in battery performance. Overall, this work presents a simple yet effective approach to realizing high Na content in P2-type layered oxides, offering new opportunities for high-performance SIB cathode materials.

Enhancing endometrial receptivity: the roles of human chorionic gonadotropin in autophagy and apoptosis regulation in endometrial stromal cells.

Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted during early embryonic development, which regulates embryonic maternal interface signaling and promotes embryo implantation. This study aimed to examine the impact of hCG on endometrial receptivity and its underlying mechanisms. An exploratory study was designed, and endometrial samples were obtained from women diagnosed with simple tubal infertility or male factor infertile (n = 12) and recurrent implantation failure (RIF, n = 10). Using reverse transcription-quantitative PCR and western blotting, luteinizing hormone (LH)/hCG receptor (LHCGR) levels and autophagy were detected in the endometrial tissues. Subsequently, primary endometrial stromal cells (ESCs) were isolated from these control groups and treated with hCG to examine the presence of LHCGR and markers of endometrial receptivity (HOXA10, ITGB3, FOXO1, LIF, and L-selectin ligand) and autophagy-related factors (Beclin1, LC3, and P62). The findings revealed that the expressions of receptivity factors, LHCGR, and LC3 were reduced in the endometrial tissues of women with RIF compared with the control group, whereas the expression of P62 was elevated. The administration of hCG to ESCs specifically activated LHCGR, stimulating an increase in the endometrial production of HOXA10, ITGB3, FOXO1, LIF and L-selectin ligands. Furthermore, when ESCs were exposed to 0.1 IU/mL hCG for 72 h, the autophagy factors Beclin1 and LC3 increased within the cells and P62 decreased. Moreover, the apoptotic factor Bax increased and Bcl-2 declined. However, when small interfering RNA was used to knock down LHCGR, hCG was less capable of controlling endometrial receptivity and autophagy molecules in ESCs. In addition, hCG stimulation enhanced the phosphorylation of ERK1/2 and mTOR proteins. These results suggest that women with RIF exhibit lower levels of LHCGR and compromised autophagy function in their endometrial tissues. Thus, hCG/LHCGR could potentially improve endometrial receptivity by modulating autophagy and apoptosis.

Ag(I) Ion-Concentration-Dependent Dynamic Mechanism of Thiolactic-Acid-Capped Gold Nanoclusters Revealed by Fluorescence Spectra and Two-Dimensional Correlation Spectroscopy.

Based on fluorescence spectroscopy, being combined with several spectral analysis techniques including principal component analysis (PCA), two-dimensional correlation spectroscopy (2D-COS), and moving window 2D-COS, the study disclosed the structural variations of gold nanoclusters capped by thiolactic acid (AuNCs@TLA) induced by Ag(I) ions. Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) were applied to monitor the morphology evolution of the surface and composition of the nanoclusters induced by Ag(I) ions. Several spectral components, centered at (790, 607) nm, (670, 590) nm, and (740, 670) nm were revealed by 2D-COS analysis, suggesting new luminescent species or groups were generated with the introduction of Ag(I) ions. A two-stage mechanism was revealed for the photoluminescence variations of AuNCs@TLA induced by Ag(I) ion. The first stage was characterized by the emission quench of 790 nm followed by the emerging emission of 607 nm, which was attributed to the anti-galvanic reaction; and the second stage featured by the noticeable growth of the emission's intensity around 670 nm as result of the AuNCs' size effect. The present study will attract more focuses on near-infrared (NIR)-emitted metal nanoclusters and promote their synthesis and utilities.

EEG analysis in patients with schizophrenia based on microstate semantic modeling method.

Introduction: Microstate analysis enables the characterization of quasi-stable scalp potential fields on a sub-second timescale, preserving the temporal dynamics of EEG and spatial information of scalp potential distributions. Owing to its capacity to provide comprehensive pathological insights, it has been widely applied in the investigation of schizophrenia (SCZ). Nevertheless, previous research has primarily concentrated on differences in individual microstate temporal characteristics, neglecting potential distinctions in microstate semantic sequences and not fully considering the issue of the universality of microstate templates between SCZ patients and healthy individuals. Methods: This study introduced a microstate semantic modeling analysis method aimed at schizophrenia recognition. Firstly, microstate templates corresponding to both SCZ patients and healthy individuals were extracted from resting-state EEG data. The introduction of a dual-template strategy makes a difference in the quality of microstate sequences. Quality features of microstate sequences were then extracted from four dimensions: Correlation, Explanation, Residual, and Dispersion. Subsequently, the concept of microstate semantic features was proposed, decomposing the microstate sequence into continuous sub-sequences. Specific semantic sub-sequences were identified by comparing the time parameters of sub-sequences. Results: The SCZ recognition test was performed on the public dataset for both the quality features and semantic features of microstate sequences, yielding an impressive accuracy of 97.2%. Furthermore, cross-subject experimental validation was conducted, demonstrating that the method proposed in this paper achieves a recognition rate of 96.4% between different subjects. Discussion: This research offers valuable insights for the clinical diagnosis of schizophrenia. In the future, further studies will seek to augment the sample size to enhance the effectiveness and reliability of this method.

Multi-Mode Damage and Fracture Mechanisms of Thin-Walled Tubular Parts with Cross Inner Ribs Manufactured via Flow Forming.

In order to study the multi-mode damage and fracture mechanisms of thin-walled tubular parts with cross inner ribs (longitudinal and transverse inner ribs, LTIRs), the Gurson-Tvergaard-Needleman (GTN) model was modified with a newly proposed stress state function. Thus, tension damage and shear damage were unified by the new stress state function, which was asymmetric with respect to stress triaxiality. Tension damage dominated the modification, which coupled with the shear damage variable, ensured the optimal prediction of fractures of thin-walled tubular parts with LTIRs by the modified GTN model. This included fractures occurring at the non-rib zone (NRZ), the longitudinal rib (LIR) and the interface between the transverse rib (TIR) and the NRZ. Among them, the stripping of material from the outer surface of the tubular part was mainly caused by the shearing of built-up material in front of the rollers under a large wall thickness reduction (ΔT). Shear and tension deformation were the causes of fractures occurring at the NRZ, while axial tension under a large TIR interval (l) mainly resulted in fractures on LIRs. Fractures at the interface between the TIR and NRZ were due to the shearing applied by rib grooves and radial tension during the formation of ribs. This study can provide guidance for the manufacturing of high-performance aluminum alloy thin-walled tubular components with complex inner ribs.

Revealing brain's cognitive process deeply: a study of the consistent EEG patterns of audio-visual perceptual holistic.

Introduction: To investigate the brain's cognitive process and perceptual holistic, we have developed a novel method that focuses on the informational attributes of stimuli. Methods: We recorded EEG signals during visual and auditory perceptual cognition experiments and conducted ERP analyses to observe specific positive and negative components occurring after 400ms during both visual and auditory perceptual processes. These ERP components represent the brain's perceptual holistic processing activities, which we have named Information-Related Potentials (IRPs). We combined IRPs with machine learning methods to decode cognitive processes in the brain. Results: Our experimental results indicate that IRPs can better characterize information processing, particularly perceptual holism. Additionally, we conducted a brain network analysis and found that visual and auditory perceptual holistic processing share consistent neural pathways. Discussion: Our efforts not only demonstrate the specificity, significance, and reliability of IRPs but also reveal their great potential for future brain mechanism research and BCI applications.

Effect of radiation cross-linked collagen scaffold in alveolar ridge preservation of extraction socket.

This study aimed to evaluate the properties of radiation cross-linked collagen scaffold (RCS) and its efficacy for alveolar ridge preservation (ARP). RCS was prepared from collagen dispersion by electron beam irradiation and freeze-drying. The microstructure, swelling ratio, area alteration and mechanical properties of RCS were characterized. Fifty-four New Zealand rabbits performing incisor extraction on maxilla and mandible were randomly assigned into positive, sham operation or treatment groups. Micro-computed tomography (micro-CT) scans, performed after 1, 4, and 12 weeks of surgery, were to assess changes in ridge height at buccal and palatal side, in ridge width and in micromorphological parameters. Histological analysis accessed socket microarchitecture. The results showed that RCS had stable mechanical properties and morphologic features that provided a reliable physical support for ARP. Dimensional changes in treatment group revealed significantly greater vertical height at buccal (5.32 [3.37, 7.26] mm, p < .0001) and palatal (4.37 [2.66, 6.09] mm, p < .0001) side, and horizontal width at the maxilla (0.16 [0.04, 0.28] mm, p < .01) and mandible (0.33 [0.11, 0.54] mm, p < .01) than those in sham operation group after 12 weeks. The treatment group had advantage than positive group in vertical height preservation, quantitatively. The order and density of bone trabeculae were improved in treatment group. These findings indicated that RCS had the potential to serve as an effective scaffold for ARP.

Integrated single-cell transcriptome and T cell receptor profiling reveals defects of T cell exhaustion in pulmonary tuberculosis.

Tuberculosis-affected lungs with chronic inflammation harbor abundant immunosuppressive immune cells but the nature of such inflammation is unclear. Dysfunction in T cell exhaustion, while implicated in chronic inflammatory diseases, remains unexplored in tuberculosis. Given that immunotherapy targeting exhaustion checkpoints exacerbates tuberculosis, we speculate that T cell exhaustion is dysfunctional in tuberculosis. Using integrated single-cell RNA sequencing and T cell receptor profiling we reported defects in exhaustion responses within inflamed tuberculosis-affected lungs. Tuberculosis lungs demonstrated significantly reduced levels of exhausted CD8+ T cells and exhibited diminished expression of exhaustion-related transcripts among clonally expanded CD4+ and CD8+ T cells. Additionally, clonal expansion of CD4+ and CD8+ T cells bearing T cell receptors specific for CMV was observed. Expanded CD8+ T cells expressed the cytolytic marker GZMK. Hence, inflamed tuberculosis-affected lungs displayed dysfunction in T cell exhaustion. Our findings likely hold implications for understanding the reactivation of tuberculosis observed in patients undergoing immunotherapy targeting the exhaustion checkpoint.

A novel variant in a Chinese boy with lysinuric protein intolerance: A case report and literature review.

We report a case of a 4-year-old boy with lysinuric protein intolerance in China. The patient presented with interstitial lung disease with obvious clubbing of the fingers and toes. During the course of diagnosis and treatment, we found he was averse to a high-protein diet, intolerant to activity, and had a history of diarrhea and fractures. Physical examination revealed hepatosplenomegaly and clubbing of the fingers and toes. Next-generation sequencing revealed compound heterozygous mutations (c.1387delG, c.958T > C) in SLC7A7, which was confirmed as a disease-causing gene for lysinuric protein intolerance. After a literature review, we found that c.958T > C had not been previously reported, and summarized the clinical and genetic characteristics of patients from different continents. His symptoms improved significantly after 3 months of being on a low-protein diet, supplementation with lysine, citrulline, carnitine, and trace elements, and oral corticosteroid treatment for 2 months. The patient is still under follow-up.

The Protein Acetylation after Traumatic Spinal Cord Injury: Mechanisms and Therapeutic Opportunities.

Spinal cord injury (SCI) leads to deficits of various normal functions and is difficult to return to a normal state. Histone and non-histone protein acetylation after SCI is well documented and regulates spinal cord plasticity, axonal growth, and sensory axon regeneration. However, our understanding of protein acetylation after SCI is still limited. In this review, we summarize current research on the role of acetylation of histone and non-histone proteins in regulating neuron growth and axonal regeneration in SCI. Furthermore, we discuss inhibitors and activators targeting acetylation-related enzymes, such as α-tubulin acetyltransferase 1 (αTAT1), histone deacetylase 6 (HDAC6), and sirtuin 2 (SIRT2), to provide promising opportunities for recovery from SCI. In conclusion, a comprehensive understanding of protein acetylation and deacetylation in SCI may contribute to the development of SCI treatment.

Analyses of plasma metabolites using a high performance four-channel CIL LC-MS method and identification of metabolites associated with enteric methane emissions in beef cattle.

Reducing enteric methane (one greenhouse gas) emissions from beef cattle not only can be beneficial in reducing global warming, but also improve efficiency of nutrient utilization in the production system. However, direct measurement of enteric methane emissions on individual cattle is difficult and expensive. The objective of this study was to detect plasma metabolites that are associated with enteric methane emissions in beef cattle. Average enteric methane emissions (CH4) per day (AVG_DAILYCH4) for each individual cattle were measured using the GreenFeed emission monitoring (GEM) unit system, and beef cattle with divergent AVG_DAILYCH4 from Angus (n = 10 for the low CH4 group and 9 for the high CH4 group), Charolais (n = 10 for low and 10 for = high), and Kinsella Composite (n = 10 for low and 10 for high) populations were used for plasma metabolite quantification and metabolite-CH4 association analyses. Blood samples of these cattle were collected near the end of the GEM system tests and a high performance four-channel chemical isotope labeling (CIL) liquid chromatography (LC) mass spectrometer (MS) method was applied to identify and quantify concentrations of metabolites. The four-channel CIL LC-MS method detected 4235 metabolites, of which 1105 were found to be significantly associated with AVG_DAILYCH4 by a t-test, while 1305 were significantly associated with AVG_DAILYCH4 by a regression analysis at p<0.05. Both the results of the t-test and regression analysis revealed that metabolites that were associated with enteric methane emissions in beef cattle were largely breed-specific whereas 4.29% to 6.39% CH4 associated metabolites were common across the three breed populations and 11.07% to 19.08% were common between two breed populations. Pathway analyses of the CH4 associated metabolites identified top enriched molecular processes for each breed population, including arginine and proline metabolism, arginine biosynthesis, butanoate metabolism, and glutathione metabolism for Angus; beta-alanine metabolism, pyruvate metabolism, glycolysis / gluconeogenesis, and citrate cycle (TCA cycle) for Charolais; phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arginine biosynthesis, and arginine and proline metabolism for Kinsella Composite. The detected CH4 associated metabolites and enriched molecular processes will help understand biological mechanisms of enteric methane emissions in beef cattle. The detected CH4 associated plasma metabolites will also provide valuable resources to further characterize the metabolites and verify their utility as biomarkers for selection of cattle with reduced methane emissions.

Steric hindrance modulation of hexaazatribenzanthraquinone isomers for high-capacity and wide-temperature-range aqueous proton battery.

Organic materials with rich active sites are good candidates of high-capacity anodes in aqueous batteries, but commonly low utilization of active sites limits their capacity. Herein, two isomers, symmetric and asymmetric hexaazatribenzanthraquinone (s-HATBAQ and a-HATBAQ), with rich active sites have been synthesized in a controllable manner. It has been revealed for the first time that a sulfuric acid catalyst can facilitate the stereoselective formation of s-HATBAQ. Attributed to the reduced steric hindrance in favor of proton insertion as well as the amorphous structure conducive to electrochemical dynamics, s-HATBAQ exhibits 1.5 times larger specific capacity than a-HATBAQ. Consequently, the electrode of s-HATBAQ with 50% reduced graphene oxide (s-HATBAQ-50%rGO) delivers a record high specific capacity of 405 mAh g-1 in H2SO4 electrolyte. Moreover, the assembled MnO2//s-HATBAQ-50%rGO aqueous proton full batteries show an exceptional cycling stability at 25°C and can maintain ∼92% capacity after 1000 cycles at 0.5 A g-1 at -80°C. This work demonstrates the controllable synthesis of isomers, showcases a wide-temperature-range prototype proton battery and highlights the significance of precise molecular structure modulation in organic energy storage.

Emotion recognition based on microstate analysis from temporal and spatial patterns of electroencephalogram.

Introduction: Recently, the microstate analysis method has been widely used to investigate the temporal and spatial dynamics of electroencephalogram (EEG) signals. However, most studies have focused on EEG at resting state, and few use microstate analysis to study emotional EEG. This paper aims to investigate the temporal and spatial patterns of EEG in emotional states, and the specific neurophysiological significance of microstates during the emotion cognitive process, and further explore the feasibility and effectiveness of applying the microstate analysis to emotion recognition. Methods: We proposed a KLGEV-criterion-based microstate analysis method, which can automatically and adaptively identify the optimal number of microstates in emotional EEG. The extracted temporal and spatial microstate features then served as novel feature sets to improve the performance of EEG emotion recognition. We evaluated the proposed method on two publicly available emotional EEG datasets: the SJTU Emotion EEG Dataset (SEED) and the Database for Emotion Analysis using Physiological Signals (DEAP). Results: For the SEED dataset, 10 microstates were identified using the proposed method. These temporal and spatial features were fed into AutoGluon, an open-source automatic machine learning model, yielding an average three-class accuracy of 70.38% (±8.03%) in subject-dependent emotion recognition. For the DEAP dataset, the method identified 9 microstates. The average accuracy in the arousal dimension was 74.33% (±5.17%) and 75.49% (±5.70%) in the valence dimension, which were competitive performance compared to some previous machine-learning-based studies. Based on these results, we further discussed the neurophysiological relationship between specific microstates and emotions, which broaden our knowledge of the interpretability of EEG microstates. In particular, we found that arousal ratings were positively correlated with the activity of microstate C (anterior regions of default mode network) and negatively correlated with the activity of microstate D (dorsal attention network), while valence ratings were positively correlated with the activity of microstate B (visual network) and negatively correlated with the activity of microstate D (dorsal attention network). Discussion: In summary, the findings in this paper indicate that the proposed KLGEV-criterion-based method can be employed to research emotional EEG signals effectively, and the microstate features are promising feature sets for EEG-based emotion recognition.

Molecular mechanism of miRNA mediated biosynthesis of secondary metabolites in medicinal plants.

Plant secondary metabolites are important raw materials for the pharmaceutical industry, and their biosynthetic processes are subject to diverse and precise regulation by miRNA. The identification of miRNA molecules in medicinal plants and exploration of their mechanisms not only contribute to a deeper understanding of the molecular genetic mechanisms of plant growth, development and resistance to stress, but also provide a theoretical basis for elucidating the pharmacological effects of authentic medicinal materials and constructing bioreactors for the synthesis of medicinal secondary metabolite components. This paper summarizes the research reports on the discovery of miRNA in medicinal plants and their regulatory mechanisms on the synthesis of secondary metabolites by searching the relevant literature in public databases. It summarizes the currently discovered miRNA and their functions in medicinal plants, and summarizes the molecular mechanisms regulating the synthesis and degradation of secondary metabolites. Furthermore, it provides a prospect for the research and development of medicinal plant miRNA. The compiled information contributes to a comprehensive understanding of the research progress on miRNA in medicinal plants and provides a reference for the industrial development of related secondary metabolite biosynthesis.

Transfer learning from rating prediction to Top-k recommendation.

Recommender system has made great strides in two major research fields, rating prediction and Top-k recommendation. In essence, rating prediction is a regression task, which aims to predict users scores on other items, while Top-k is a classification task selecting the items that users have the most potential to interact with. Both characterize users and items, but the optimization of parameters varies widely for their respective tasks. Inspired by the idea of transfer learning, we consider extracting the information learned from rating prediction models for serving for Top-k tasks. To this end, we propose a universal transfer model for recommender systems. The transfer model consists of two sub-components: quadruple-based Bayesian Converter (BC) and Prediction-based Multi-Layer Perceptron (PMLP). As the main part, BC is responsible for transforming the feature vectors extracted from the rating prediction model. Meanwhile, PMLP extracts the prediction ratings, constructs the prediction rating matrix, and uses multi-layer perceptron to enhance the final performance. On four benchmark datasets, we use the information extracted from the singular value decomposition plus plus (SVD++) model to demonstrate the effectiveness of BC-PMLP, comparing to classical and state-of-the-art baselines. We also conduct extra experiments to verify the utility of BC, and performance within different parameter values.

Enhancing Electron/Ion Transport in SnO2 Quantum Dots Decorated Polyaniline/Graphene Hybrid Fibers for Wearable Supercapacitors with High Energy Density.

Fiber-based supercapacitors are the potential power sources in the field of wearable electronics and energy storage textiles due to their unique advantages of electrochemical properties and mechanical flexibility, but achieving high energy density and practical energy supply still presents some challenges. In this study, we reported an approach of microfluidic assisted wet-spinning to fabricate SnO2 quantum dots encapsulated polyaniline/graphene hybrid fibers (SnO2 QDs@PGF) by incorporating uniformly polyaniline into graphene fibers and covalently bridging SnO2 quantum dots. The assembled SnO2 QDs@PGF fiber-typed flexible supercapacitors exhibit an ultralarge specific areal capacitance of 925 mF cm-2 in PVA/H2SO4, superior rate capabilities, and capacitance retention of 88% after 8000 cycles, indicating that the SnO2 QDs@PGF possess near-ideal capacitance properties, efficient ion transfer rate, and good cycling stability. In the EMITFSI/PVDF-HFP electrolyte system, SnO2 QDs@PGF realize a wide operating potential window of 2.5 V, a specific areal capacitance of 678.4 mF cm-2, and an energy density of 147.2 µWh cm-2 at 500 µW cm-2, which can be utilized to power an alarm clock, an electronic timer, and a desk lamp with a requirement of a 3 V battery. The exceptional performance of the SnO2 QDs@PGF can be attributed to the molecular-level homogeneous composite of granular polyaniline and graphene nanosheets and the interfacial C-O-Sn covalent coupling strategy employed between SnO2 QDs and PGF. These avenues not only effectively prevent the undesirable restacking of graphene nanosheets but also increase the interlayer electroactive sites, ordered ion diffusion channels, and strong interfacial charge transfer.

Recombinant human collagen I/carboxymethyl chitosan hydrogel loaded with long-term released hUCMSCs derived exosomes promotes skin wound repair.

BACKGROUND: Stem cell exosomes are beneficial in accelerating wound repair. However, the therapeutic function is limited due to its rapid clearance in vivo. To improve the functionality of exosomes in cutaneous wound healing, a novel hydrogel was designed and fabricated by recombinant human collagen I and carboxymethyl chitosan loaded with exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs), named as the rhCol I/CMC-Exos hydrogel. METHODS: Exosomes were extracted from hUCMSCs and were characterizated by TEM (Transmission Electron Microscopy), and biomarker detection. The rhCol I hydrogel, rhCol I/carboxymethyl chitosan (rhCol I/CMC) hydrogel and the rhCol I/CMC-Exos hydrogel composites were cross-linked by genipin. These materials were assessed and compared for their physical characteristics, including cross-sectional morphology, porosity, pore distribution, and hydrophilicity. Cell biocompatibility on biomaterials was investigated using scanning electron microscopy and CFDA staining, as well as assessed in vivo through histological examination of major organs in mice. Effects of the hydrogel composite on wound healing were further evaluated by using the full-thickness skin defect mice model. RESULTS: Successful extraction of hUCMSCs-derived exosomes was confirmed by TEM，Western Blotting and flow cytometry. The synthesized rhCol I/CMC-Exos hydrogel composite exhibited cytocompatibility and promoted cell growth in vitro. The rhCol I/CMC-Exos hydrogel showed sustained release of exosomes. In the mice full skin-defects model, the rhCol I/CMC-Exos-treated group showed superior wound healing efficiency, with 15 % faster wound closure compared to controls. Histological examinations revealed thicker dermis formation and more balanced collagen deposition in wounds treated with rhCol I/CMC-Exos hydrogel. Mechanistically, the application of rhCol I/CMC-Exos hydrogel increased fibroblasts proliferation, alleviated inflammation responses as well as promoted angiogenesis, thereby was beneficial in promoting skin wound healing and regeneration. CONCLUSION: Our study, for the first time, introduced recombinant human Collagen I in fabricating a novel hydrogel loaded with hUCMSCs-derived exosomes, which effectively promoted skin wound closure and regeneration, demonstrating a great potential in severe skin wound healing treatment.

Discovery of benzoheterocyclic-substituted amide derivatives as apoptosis signal-regulating kinase 1 (ASK1) inhibitors.

Three series of benzoheterocyclic-substituted amide derivatives were designed and synthesized as potent ASK1 inhibitors in this work. After undergoing continuous structural optimization, compound 17a was discovered to be a novel inhibitor of ASK1 with good potency (kinase, IC50 = 26 nM), noteworthy liver microsomal stability (human, T1/2 = 340.4 min), good pharmacokinetic parameters (rat, T1/2 p.o. = 2.11 h, AUClast p.o. = 10 900 h ng mL-1) and high oral bioavailability (rat, F = 97.9%), while also being inactive towards hERG (IC50 > 10 µM).

Integration of scRNA-seq data by disentangled representation learning with condition domain adaptation.

BACKGROUND: The integration of single-cell RNA sequencing data from multiple experimental batches and diverse biological conditions holds significant importance in the study of cellular heterogeneity. RESULTS: To expedite the exploration of systematic disparities under various biological contexts, we propose a scRNA-seq integration method called scDisco, which involves a domain-adaptive decoupling representation learning strategy for the integration of dissimilar single-cell RNA data. It constructs a condition-specific domain-adaptive network founded on variational autoencoders. scDisco not only effectively reduces batch effects but also successfully disentangles biological effects and condition-specific effects, and further augmenting condition-specific representations through the utilization of condition-specific Domain-Specific Batch Normalization layers. This enhancement enables the identification of genes specific to particular conditions. The effectiveness and robustness of scDisco as an integration method were analyzed using both simulated and real datasets, and the results demonstrate that scDisco can yield high-quality visualizations and quantitative outcomes. Furthermore, scDisco has been validated using real datasets, affirming its proficiency in cell clustering quality, retaining batch-specific cell types and identifying condition-specific genes. CONCLUSION: scDisco is an effective integration method based on variational autoencoders, which improves analytical tasks of reducing batch effects, cell clustering, retaining batch-specific cell types and identifying condition-specific genes.