Programmable Chemoenzymatic Assembly of a Bisected and Core-Fucosylated N-Glycan Library Reveals Glycan-Binding Protein Specificity and Branch Preference.

Bisected and core-fucosylated N-glycans represent a distinct class of complex biomolecules that are implicated in diverse biological and pathological processes. The structural complexity and synthetic challenges of these glycans hinder comprehensive understanding of their biological functions due to limited access to well-defined samples. Despite advances in the complex N-glycan synthesis, the efficient preparation of bisected and core-fucosylated asymmetric N-glycans with various branches and terminal epitopes remains an unmet challenge.

A review on knowledge graphs for healthcare: Resources, applications, and promises.

Objective: This comprehensive review aims to provide an overview of the current state of Healthcare Knowledge Graphs (HKGs), including their construction, utilization models, and applications across various healthcare and biomedical research domains.

Methods: We thoroughly analyzed existing literature on HKGs, covering their construction methodologies, utilization techniques, and applications in basic science research, pharmaceutical research and development, clinical decision support, and public health. The review encompasses both model-free and model-based utilization approaches and the integration of HKGs with large language models (LLMs).

Efficacy Analysis of Arthroscopic Treatment of Synovial Chondromatosis of the Knee: A Retrospective Study of More Than Five Years.

Objective: The synovial chondromatosis is an exceptionally rare benign condition, predominantly found in the knee joint, and can result in pain, restricted mobility, and potential irreversible damage to the joint and cartilage. Despite the utilization of arthroscopic techniques in the surgical management of synovial chondromatosis, there remains a paucity of long-term assessment regarding its efficacy. The main objectives of this study include: (i) investigating the long-term efficacy of arthroscopic surgery in patients with knee synovial chondromatosis;(ii) identifying factors influencing functional improvement in patients post-surgery function.

Single-cell RNA sequencing reveals the effects of mental stress on mouse mammary tumors and the tumor microenvironment.

Mental stress has been shown to negatively impact the development and progression of human cancer, including breast cancer. However, its effects on the tumor microenvironment (TME) remain unclear. In this study, we applied single-cell sequencing analysis to tumor tissues from MMTV-PyMT transgenic mice with mammary gland tumors with or without exposure to mental stress.

DeepNanoHi-C: deep learning enables accurate single-cell nanopore long-read data analysis and 3D genome interpretation.

Single-cell long-read concatemer sequencing (scNanoHi-C) technology provides unique insights into the higher-order chromatin structure across the genome in individual cells, crucial for understanding 3D genome organization. However, the lack of specialized analytical tools for scNanoHi-C data impedes progress, as existing methods, which primarily focus on scHi-C technologies, do not fully address the specific challenges of scNanoHi-C, such as sparsity, cell-specific variability, and complex chromatin interaction networks. Here, we introduce DeepNanoHi-C, a novel deep learning framework specifically designed for scNanoHi-C data, which leverages a multistep autoencoder and a Sparse Gated Mixture of Experts (SGMoE) to accurately predict chromatin interactions by imputing sparse contact maps, thereby capturing cell-specific structural features.

Gut microbiome dysbiosis accelerates osteoarthritis progression by inducing IFP-SM inflammation in "double-hit" mice.

Background: This study investigates the complex interplay between gut microbiome dysbiosis and systemic inflammation as a critical risk factor in the pathogenesis of osteoarthritis (OA). Furthermore, it elucidates the role of gut microbiota (GMB) dysbiosis in driving OA progression.

Methods: A refined "double-hit" murine model was developed to explore this relationship.

Neuromodulatory role and therapeutic potential of N6-methyladenosine RNA methylation in neurodegenerative diseases.

N6-methyladenosine RNA methylation, an essential post-transcriptional modification, dynamically regulates RNA metabolism and plays a crucial role in neuronal function. Growing evidence suggests that dysregulated N6-methyladenosine modification contributes to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. However, the precise mechanisms by which N6-methyladenosine modification influences these conditions remain unclear.

Prognostic and immunotherapeutic significance of NCAPD2 in pan-cancer and its role in hepatocellular carcinoma progression via the AKT/GSK-3β signaling pathway.

Present studies indicated that NCAPD2 (Non-SMC condensin I complex subunit D2) has emerged as an essential participant of condensin I involved in the mitotic chromosome assembly and dissociation. However, its comprehensive role in pan-cancer and its underlying mechanisms remain underexplored. This study systematically analyzed NCAPD2's prognostic significance, functional mechanisms, and immune infiltration correlations in pan-cancer, with a focus on hepatocellular carcinoma (HCC).

Porous Co@NC Materials Obtained by Pyrolyzing Metal-Organic Framework-Supported Multinuclear Metal Clusters for the Oxygen Reduction Reaction.

The design and development of efficient oxygen reduction reaction (ORR) electrocatalysts have become a key challenge for fuel cells and metal-air batteries. As a cutting-edge field in electrocatalysis, single-atom catalysts have been widely used in ORR due to their maximum atomic utilization and tunable coordination environment. In this study, multinuclear metal clusters were selected as precursors to construct metal nanoparticles and single-atomic metal sites doped carbon materials for electrocatalytic ORR.

TORC: Target-Oriented Reference Construction for supervised cell-type identification in scRNA-seq.

Cell-type identification is a crucial step in single cell RNA-seq (scRNA-seq) data analysis, for which supervised methods are preferred due to their accuracy and efficiency. Performance is highly dependent on the quality of the reference data, but there is no method for selecting and constructing reference data. We develop Target-Oriented Reference Construction (TORC), a widely applicable strategy for constructing reference data given a target dataset for scRNA-seq supervised cell-type identification.

Activin A exacerbates neonatal necrotizing enterocolitis via ALK4-mediated apoptosis and barrier disruption.

Background: Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disorder in neonates, yet the role of Activin A (ACV A) in NEC pathogenesis remains unclear.

Methods: NEC was induced in neonatal mice through hypoxia, hypothermia, LPS, and formula feeding. An in vitro intestinal epithelial injury model was established using LPS-stimulated IEC-6 cells.

[Corrigendum] Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A.

Following the publication of the above article, the authors drew to the Editor's attention that they has misclassified some of their original data, and this led to the erroneous compilation of the cell invasion and scratch wound assay data shown in Fig. 5A and B respectively on p. 604.

Interaction of decidual macrophages and other maternal-fetal interface cells in recurrent pregnancy loss.

Recurrent Pregnancy Loss (1) is a common pregnancy complication that can have a negative impact on both the physical and mental health of pregnant women. Despite various associations, the precise etiology of RPL remains unclear, necessitating further research. Immune cells are recognized to play a pivotal role in successful pregnancy.

A CRISPR/Cas9-induced point mutation on the GABA receptor subunit RDL confers high resistance to phenylpyrazole insecticides in the rice planthopper Laodelphax striatellus.

The Delphacidae planthopper Laodelphax striatellus (Order: Hemiptera) is one of the most damaging insect pests of rice crops in Asia. The phenylpyrazole insecticide fipronil was introduced in China in the mid-1990s to control these pests, but its widespread use has led to the development of high levels of resistance. Field sampling coupled with in vitro assays indicated that an A2'N-point mutation in the gamma-aminobutyric acid receptor RDL has been linked to fipronil resistance; however, genetic evidence supporting this association has been lacking.

Gelatin-based adaptive injectable nanocomposite hydrogel for closure of irregular wounds and immunoregulation in diabetic wound healing.

Chronic wounds are a major challenge in diabetic patients, exacerbated by disorders of blood perfusion and angiogenesis, bacterial infection, oxidative stress, and inflammation and immune imbalance. Bioactive hydrogels with multifunctional immunomodulatory properties offer promising solutions for diabetic wound management. However, many hydrogels lack adaptability and rely on costly cytokines, cell therapies, or drugs with side effects.

Unveiling Multi-Scale Architectural Features in Single-Cell Hi-C Data Using scCAFE.

Single-cell Hi-C (scHi-C) has provided unprecedented insights into the heterogeneity of 3D genome organization. However, its sparse and noisy nature poses challenges for computational analyses, such as chromatin architectural feature identification. Here, scCAFE is introduced, which is a deep learning model for the multi-scale detection of architectural features at the single-cell level.

DCAF8L1 induces branching morphogenesis and hollow acinar structures remodeling of MCF10A cells in 3D culture by upregulating DDR1.

Mammary morphogenesis is a highly coordinated process involving cellular differentiation, proliferation, and organization to form a bilayered epithelial network of ducts and lobules within the stromal matrix. Here, we identified the DDB1 and CUL4 associated factor 8-like 1(DCAF8L1) as a novel regulator of mammary morphogenesis. To investigate its role, we established stable DCAF8L1-expressing MCF10A cell lines, which normally lack DCAF8L1 expression.

Different responses of phytoplankton taxa to water N and P inputs in a freshwater wetland: A mesocosm study.

The intensification of human activities has led to a large amount of nitrogen (N) and phosphorus (P) inputs into water, resulting in an increase in nutrient load and an imbalance of N and P stoichiometric ratio in wetlands. However, whether and how water eutrophication influences phytoplankton diversity, community composition, and biomass remain largely unclear. As part of a two-year (2022-2023) field experiment, this study was conducted to examine the effects of N and P inputs on phytoplankton community in a freshwater wetland in the North China Plain.

Chemoenzymatic Synthesis of Core-Fucosylated Asymmetrical N-Glycans with Different-Length Oligo-N-Acetyllactosamine Motifs and Their Sialylated Extensions.

An efficient chemoenzymatic approach for the diversity-oriented synthesis of core-fucosylated asymmetrical N-glycans bearing different lengths of oligo-N-acetyllactosamine (LacNAc) and their sialylated extensions is described. Two oligosaccharide precursors were chemically synthesized by length-controlled introduction of oligo-LacNAc motifs through stereoselectively iterative glycosylation of a common hexasaccharide intermediate. Both oligosaccharide precursors can be well recognized by α1,6-fucosyltransferase FUT8 to generate core-fucosylated N-glycans, which were subjected to divergent enzymatic extension using a galactosyltransferase module and two sialyltransferase modules to provide a wide array of core-fucosylated asymmetrical biantennary N-glycans having different-length oligo-LacNAc motifs capped by various sialic acid linkages.

Uncertainty-Aware Pre-Trained Foundation Models for Patient Risk Prediction via Gaussian Process.

Patient risk prediction models are crucial as they enable healthcare providers to proactively identify and address potential health risks. Large pre-trained foundation models offer remarkable performance in risk prediction tasks by analyzing multimodal patient data. However, a notable limitation of pre-trained foundation models lies in their deterministic predictions (, lacking the ability to acknowledge uncertainty).

Study on the Impact of Diluent Dosages on the Epoxy-Polythiol Self-Healing System.

Self-healing technology is an effective method for enhancing the crack resistance of cement-based composites. This study focuses on the impact of the environmentally friendly diluent C12-14 alkyl glycidyl ether (AGE) on the performance of the epoxy resin-polythiol (rimethylolpropane tris (3-mercaptopropionate), TMPMP) self-healing system, examining core fluidity, microcapsule properties, molecular dynamics, and the mechanical properties of cured products. The results show that as the AGE dosage increases, the particle size distribution of microcapsules becomes more concentrated, and the dispersion of particles is improved.

Precision Synthesis and Antiliver Fibrosis Activity of a Highly Branched Acidic 63-Mer Pectin Polysaccharide.

Natural polysaccharides possess various biological functions and have become increasingly important as drug candidates for biomedical development. However, the accessibility to multiple-branched and large-sized acidic polysaccharides with well-defined structures and the identification of related active glycan domains remain challenging. Here, we report the precision synthesis of a highly branched acidic pectin polysaccharide up to a 63-mer containing 10 different glycosidic linkages from .

Chemoenzymatic Synthesis of Highly O-Glycosylated MUC7 Glycopeptides for Probing Inhibitory Activity against Pseudomonas aeruginosa Biofilm Formation.

MUC7, a highly glycosylated protein in saliva and respiratory tract, plays potential roles in facilitating bacterial clearance and preventing microbial invasion. The complexity of glycan structures and multiplicity of glycosylation sites of MUC7 make it very difficult to explore accurate biofunctions against pathogens. Here, we report an efficiently convergent chemoenzymatic approach to firstly synthesize highly O-glycosylated MUC7 glycopeptides with nine glycosylation sites bearing various glycoforms via the combined use of hydrophobic tag-assisted liquid-phase peptide synthesis and enzymatic-catalyzed glycan elongation.

Whole-genome bisulfite sequencing of cell-free DNA unveils age-dependent and ALS-associated methylation alterations.

Background: Cell-free DNA (cfDNA) in plasma carries epigenetic signatures specific to tissue or cell of origin. Aberrant methylation patterns in circulating cfDNA have emerged as valuable tools for noninvasive cancer detection, prenatal diagnostics, and organ transplant assessment. Such epigenetic changes also hold significant promise for the diagnosis of neurodegenerative diseases, which often progresses slowly and has a lengthy asymptomatic period.