Temporal resolved multi-proteomic analysis enabled the systematic characterization of N-glycosylation pattern changes during Jurkat T cell activation.

Protein glycosylation plays essential roles in regulating innate and adaptive immune response. Previous studies only focused on individual protein-glycan interactions or specific glycoform changes during T cell activation, yet the systematic characterization of protein glycosylation alterations remains insufficiently elucidated. To address these limitations, we conducted temporally resolved quantitative analysis of glycoforms, site-specific glycans, glycoproteins, and glycosylation enzymes in activated Jurkat T cells, and successfully portrayed the dynamic landscape of protein glycosylation during Jurkat T cell activation.

Self-Assembly of Human Fibrinogen into Microclot-Mimicking Antifibrinolytic Amyloid Fibrinogen Particles.

Recent clinical studies have highlighted the presence of microclots in the form of amyloid fibrinogen particles (AFPs) in plasma samples from Long COVID patients. However, the clinical significance of these abnormal, nonfibrillar self-assembly aggregates of human fibrinogen remains debated due to the limited understanding of their structural and biological characteristics. In this study, we present a method for generating mimetic microclots in vitro.

Triboelectric Nanogenerator-Embedded Intelligent Self-Aligning Roller Bearing with the Capability of Self-Sensing, Monitoring, and Fault Diagnosis.

Monitoring the dynamic behaviors of self-aligning roller bearings (SABs) is vital to guarantee the stability of various mechanical systems. This study presents a novel self-powered, intelligent, and self-aligning roller bearing (I-SAB) with which to monitor rotational speeds and bias angles; it also has an application in fault diagnosis. The designed I-SAB is compactly embedded with a novel sweep-type triboelectric nanogenerator (TENG).

A peptide-centric local stability assay enables proteome-scale identification of the protein targets and binding regions of diverse ligands.

By using a limited-proteolysis strategy that employs a large amount of trypsin to generate peptides directly from native proteins, we found that ligand-induced protein local stability shifts can be sensitively detected on a proteome-wide scale. This enabled us to develop the peptide-centric local stability assay, a modification-free approach that achieves unprecedented sensitivity in proteome-wide target identification and binding-region determination. We demonstrate the broad applications of the peptide-centric local stability assay by investigating interactions across various biological contexts.

Microparticle-assisted protein capture method facilitates proteomic and glycoproteomic analysis of urine samples.

Serum tests have become a partial alternative to renal biopsy for diagnosing primary membranous nephropathy (pMN). However, urine tests, due to their non-invasive nature and ability to more accurately reflect glomerular diseases, hold great promise for the detection of pMN. However, the low protein concentration and the time-consuming sample preparation procedure of urine samples challenges the proteomic and glycoproteomic analysis to find urine-derived signatures associated with pMN.

MCM4 Promotes the Progression of Malignant Melanoma by Activating the PI3K/AKT Pathway.

This study aims to elucidate the role of minichromosome maintenance protein 4 (MCM4) in malignant melanoma (MM) and explore the underlying mechanism. Initially, data from The Cancer Genome Atlas (TCGA) database and the Molecular Signature Database (MSigDB) were used to investigate the biological impact of MCM4 on MM. Further, a prognostic model using Cox regression analysis was developed to predict the overall survival (OS) rate in the MM patients.

GP-Plotter: Flexible Spectral Visualization for Proteomics Data with Emphasis on Glycoproteomics Analysis.

Identification evaluation and result dissemination are essential components in mass spectrometry-based proteomics analysis. The visualization of fragment ions in mass spectrum provides strong evidence for peptide identification and modification localization. Here, we present an easy-to-use tool, named GP-Plotter, for ion annotation of tandem mass spectra and corresponding image output.

GP-Marker facilitates the analysis of intact glycopeptide quantitative data at different levels.

Protein glycosylation is a highly heterogeneous post-translational modification that has been demonstrated to exhibit significant variations in various diseases. Due to the differential patterns observed in disease and healthy populations, the glycosylated proteins hold promise as early indicators for multiple diseases. With the continuous development of liquid chromatography-mass spectrometry (LC-MS) technology and spectrum analysis software, the sensitivity for the decipher of the tandem mass spectra of the glycopeptides carrying intact glycans, i.

Rational development of functional hydrophilic polymer to characterize site-specific glycan differences between bovine milk and colostrum.

As vastly modified on secreted proteins, N-glycosylation is found on milk proteins and undergo dynamic changes during lactation, characterizing milk protein glycosylation would benefit the elucidation of glycosylation pattern differences between samples. However, their low abundance required specific enrichment. Herein, through rational design and controllable synthesis, we developed a novel multi-functional polymer for the isolation of protein glycosylation.

Quantitative Characterization of Protein N-Linked Core-Fucosylation by an Efficient Glycan Truncation Strategy.

Dysregulation of protein core-fucosylation plays a pivotal role in the onset, progression, and immunosuppression of cancer. However, analyzing core-fucosylation, especially the accurate determination of the core-fucosylation (CF) site occupancy ratio, remains challenging. To address these problems, we developed a truncation strategy that efficiently converts intact glycopeptides with hundreds of different glycans into two truncated forms, i.

Transcriptomic Changes and Regulatory Networks Associated with Resistance to Mastitis in Xinjiang Brown Cattle.

Xinjiang brown cattle are highly resistant to disease and tolerant of roughage feeding. The identification of genes regulating mastitis resistance in Xinjiang brown cattle is a novel means of genetic improvement. In this study, the blood levels of IL-1β, IL-6, IL-10, TNF-α, and TGF-β in Xinjiang brown cattle with high and low somatic cell counts (SCCs) were investigated, showing that cytokine levels were higher in cattle with high SCCs.

Glycan-Imprinted Nanoparticle as Artificial Neutralizing Antibody for Efficient HIV-1 Recognition and Inhibition.

The HIV-1 envelope is a heavily glycosylated class 1 trimeric fusion protein responsible for viral entry into CD4 immune cells. Developing neutralizing antibodies against the specific envelope glycans is an alternative method for antiviral therapies. This work presents the first-ever development and characterization of artificial neutralizing antibodies using molecular imprinting technology to recognize and bind to the envelope protein of HIV-1.

Robust Glycoproteomics Platform Reveals a Tetra-Antennary Site-Specific Glycan Capping with Sialyl-Lewis Antigen for Early Detection of Gastric Cancer.

The lack of efficient biomarkers for the early detection of gastric cancer (GC) contributes to its high mortality rate, so it is crucial to discover novel diagnostic targets for GC. Recent studies have implicated the potential of site-specific glycans in cancer diagnosis, yet it is challenging to perform highly reproducible and sensitive glycoproteomics analysis on large cohorts of samples. Here, a highly robust N-glycoproteomics (HRN) platform comprising an automated enrichment method, a stable microflow LC-MS/MS system, and a sensitive glycopeptide-spectra-deciphering tool is developed for large-scale quantitative N-glycoproteome analysis.

Mitochondria-targeted pentacyclic triterpene NIR-AIE derivatives for enhanced chemotherapeutic and chemo-photodynamic combined therapy.

Complexes formed by combining pentacyclic triterpenes (PTs) with Aggregation-Induced Emission luminogens (AIEgens), termed pentacyclic triterpene-aggregation induced emission (PT-AIEgen) complexes, merge the chemotherapeutic properties of PTs with the photocytotoxicity of AIEgens. In this study, we synthesized derivatives by connecting three types of triphenylamine (TPA) pyridinium derivatives with three common pentacyclic triterpenes. Altering the connecting group between the electron donor TPA and the electron acceptor pyridinium resulted in increased production of reactive oxygen species (ROS) by PT-AIEgens and a red-shift in their fluorescence emission spectra.

Risk Factors for Postoperative Knee Stiffness in Patients with Anteromedial Knee Osteoarthritis Undergoing Unicompartmental Knee Arthroplasty with Cemented Prostheses: A Short-Term, Retrospective, Case-Control Study.

BACKGROUND The present study was performed to determine the potential risk factors for postoperative knee stiffness in patients with anteromedial knee osteoarthritis undergoing unicompartmental knee arthroplasty with cemented prostheses. MATERIAL AND METHODS This retrospective cohort study evaluated patients with anteromedial knee osteoarthritis who underwent medial unicompartmental knee arthroplasty at our hospital between May 2017 and May 2020. The patients were divided into 2 groups according to their prognosis: those who experienced knee stiffness after undergoing unicompartmental knee arthroplasty and those who did not.

Competitive binding of circCCDC6 to microRNA-128-3p activates TXNIP/NLRP3 pathway and promotes cerebral ischemia-reperfusion defects.

Objective: Circular RNAs (circRNAs) are enriched in the brain and involved in various central nervous system diseases. The potential role of circCCDC6 in cerebral ischemia-reperfusion defects was partly elucidated in the work.

Methods: A middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and an oxygen-glucose deprivation and re-oxygenation (OGD/R)-treated SH-SY5Y cell model were constructed.

The prognosis of breast cancer patients with bone metastasis could be potentially estimated based on blood routine test and biochemical examination at admission.

Purpose: Due to the poor and unpredictable prognosis of breast cancer (BC) patients with bone metastasis, it is necessary to find convenient and available prognostic predictors. This study aimed to recognize the clinical and prognostic factors related to clinical laboratory examination and to construct a prognostic nomogram for BC bone metastasis.

Methods: We retrospectively analyzed 32 candidate indicators from clinical features and laboratory examination data of 276 BC patients with bone metastasis.

Methylation Levels in the Promoter Region of and Genes Associated with Mastitis Resistance in Xinjiang Brown Cattle.

Mastitis causes serious economic losses in the dairy industry, but there are no effective treatments or preventive measures. In this study, the , , , , , and genes in Xinjiang brown cattle, which are associated with mastitis resistance, were identified using a GWAS. Pyrosequencing analysis showed that the promoter methylation levels of the and genes in the mastitis group were higher and lower, respectively, than those in the healthy group (65.

O-Glycopeptide Truncation Strategy for Heterogeneous O-GalNAc Glycoproteomics Characterization.

Mucin-type O-glycosylation (or O-GalNAcylation) takes place on most membrane and secretory proteins and is vital in regulating protein functions and many biological processes. O-GalNAcylation generally exhibits highly diverse and dense O-glycans linked to carrier proteins, which challenges the analysis of O-GalNAc glycoproteome using conventional methodologies. Here, we report an O-glycopeptide truncation strategy for the characterization of protein O-GalNAcylation in biological samples.

O-Search-Pattern: A Searching Tool Utilizing the Y-Ion Pattern to Enhance O-Glycopeptide Identification for the Analysis of O-GalNAc Glycoproteome.

Different from N-linked glycosylation, the core structures of mucin type O-glycans are much more diverse, and the sensitive interpretation of O-glycopeptide spectra remains a challenge. The Y-ion pattern, a series of Y-ions with known mass gaps derived from the penta-saccharide core structure of N-linked glycosylation, is exploited to facilitate N-glycopeptide identification from their spectra. However, the pattern of Y ions in O-glycopeptides has not been well studied.

Cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy: a propensity score-matched analysis.

Background: Cancer-related cognitive decline is a serious problem in long-term survival but no pivotal study has investigated whether checkpoint inhibitors (ICI) may be associated with cognitive adverse events.

Methods: This propensity score-matched analysis recruited non-small cell lung cancer (NSCLC) patients prescribed with or without ICI monotherapy from three Chinese tertiary hospitals. Patients were excluded from study who developed brain metastasis or had disorders severely affecting cognitive abilities.

Development of an Integrated Platform for the Simultaneous Enrichment and Characterization of N- and O-Linked Intact Glycopeptides.

Both N-linked glycosylation and O-linked glycosylation play essential roles in the onset and progression of various diseases including cancer, and N-/O-linked site-specific glycans have been proven to be promising biomarkers for the discrimination of cancer. However, the micro-heterogeneity and low abundance nature of N-/O-linked glycosylation, as well as the time-consuming and tedious procedures for the enrichment of -linked intact glycopeptides, pose great challenges for their efficient and accurate characterization. In this study, we developed an integrated platform for the simultaneous enrichment and characterization of N- and O-linked intact glycopeptides from the same serum sample.

Novel players in organogenesis and flavonoid biosynthesis in cucumber glandular trichomes.

Glandular trichomes (GTs) are outgrowths of plant epidermal cells that secrete and store specialized secondary metabolites that protect plants against biotic and abiotic stresses and have economic importance for human use. While extensive work has been done to understand the molecular mechanisms of trichome organogenesis in Arabidopsis (Arabidopsis thaliana), which forms unicellular, nonglandular trichomes (NGTs), little is known about the mechanisms of GT development or regulation of secondary metabolites in plants with multicellular GTs. Here, we identified and functionally characterized genes associated with GT organogenesis and secondary metabolism in GTs of cucumber (Cucumis sativus).