Exploring techniques for encoding spoken instructions in working memory: a comparison of verbal rehearsal, motor imagery, self-enactment and action observation.

Encoding and recalling spoken instructions is subject to working memory capacity limits. Previous research suggests action-based encoding facilitates instruction recall, but has not directly compared benefits across different types of action-based techniques. The current study addressed this in two experiments with young adults. In Experiment 1, participants listened to instructional sequences containing four action-object pairs, and encoded these instructions using either a motor imagery or verbal rehearsal technique, followed by recall via oral repetition or enactment. Memory for instructions was better when participants used a motor imagery technique during encoding, and when recalling the instructions by enactment. The advantage of using a motor imagery technique was present in both verbal and enacted recall. In Experiment 2, participants encoded spoken instructions whilst implementing one of four techniques (verbal rehearsal, motor imagery, observation of others' actions or self-enactment), and then recalled the instructions by oral repetition or enactment. For both verbal and enacted recall, memory for instructions was least accurate in the rehearsal condition, while the other encoding conditions did not differ from each other. These novel findings indicate similar benefits of imagining, observation and execution of actions in encoding spoken instructions, and enrich current understanding of action-based benefits in working memory.

Knockdown of microRNA390 Enhances Maize Brace Root Growth.

Brace root architecture is a critical determinant of maize's stalk anchorage and nutrition uptake, influencing root lodging resistance, stress tolerance, and plant growth. To identify the key microRNAs (miRNAs) in control of maize brace root growth, we performed small RNA sequencing using brace root samples at emergence and growth stages. We focused on the genetic modulation of brace root development in maize through manipulation of miR390 and its downstream regulated auxin response factors (ARFs). In the present study, miR167, miR166, miR172, and miR390 were identified to be involved in maize brace root growth in inbred line B73. Utilizing short tandem target mimic (STTM) technology, we further developed maize lines with reduced miR390 expression and analyzed their root architecture compared to wild-type controls. Our findings show that STTM390 maize lines exhibit enhanced brace root length and increased whorl numbers. Gene expression analyses revealed that the suppression of miR390 leads to upregulation of its downstream regulated ARF genes, specifically ZmARF11 and ZmARF26, which may significantly alter root architecture. Additionally, loss-of-function mutants for ZmARF11 and ZmARF26 were characterized to further confirm the role of these genes in brace root growth. These results demonstrate that miR390, ZmARF11, and ZmARF26 play crucial roles in regulating maize brace root growth; the involved complicated molecular mechanisms need to be further explored. This study provides a genetic basis for breeding maize varieties with improved lodging resistance and adaptability to diverse agricultural environments.

LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic lung inflammation.

Pseudomonas aeruginosa causes chronic airway infections, a major determinant of lung inflammation and damage in cystic fibrosis (CF). Loss-of-function lasR mutants commonly arise during chronic CF infections, are associated with accelerated lung function decline in CF patients and induce exaggerated neutrophilic inflammation in model systems. In this study, we investigated how lasR mutants modulate airway epithelial membrane bound ICAM-1 (mICAM-1), a surface adhesion molecule, and determined its impact on neutrophilic inflammation in vitro and in vivo. We demonstrated that LasR-deficient strains induce increased mICAM-1 levels in airway epithelial cells compared to wild-type strains, an effect attributable to the loss of mICAM-1 degradation by LasR-regulated proteases and associated with enhanced neutrophil adhesion. In a subacute airway infection model, we also observed that lasR mutant-infected mice displayed greater airway epithelial ICAM-1 expression and increased neutrophilic pulmonary inflammation. Our findings provide new insights into the intricate interplay between lasR mutants, LasR-regulated proteases and airway epithelial ICAM-1 expression, and reveal a new mechanism involved in the exaggerated inflammatory response induced by lasR mutants.

Changes in the salivary metabolome in patients with chronic erosive gastritis.

INTRODUCTION: Chronic erosive gastritis (CEG) is closely related to gastric cancer, which requires early diagnosis and intervention. The invasiveness and discomfort of electronic gastroscope have limited its application in the large-scale screening of CEG. Therefore, a simple and noninvasive screening method is needed in the clinic. OBJECTIVES: The aim of this study is to screen potential biomarkers that can identify diseases from the saliva samples of CEG patients using metabolomics. METHODS: Saliva samples from 64 CEG patients and 30 healthy volunteers were collected, and metabolomic analysis was performed using UHPLC-Q-TOF/MS in the positive and negative ion modes. Statistical analysis was performed using both univariate (Student's t-test) and multivariate (orthogonal partial least squares discriminant analysis) tests. Receiver operating characteristic (ROC) analysis was conducted to determine significant predictors in the saliva of CEG patients. RESULTS: By comparing the saliva samples from CEG patients and healthy volunteers, 45 differentially expressed metabolites were identified, of which 37 were up-regulated and 8 were down-regulated. These differential metabolites were related to amino acid, lipid, phenylalanine metabolism, protein digestion and absorption, and mTOR signaling pathway. In the ROC analysis, the AUC values of 7 metabolites were greater than 0.8, among which the AUC values of 1,2-dioleoyl-sn-glycoro-3-phosphodylcholine and 1-stearoyl-2-oleoyl-sn-glycoro-3-phospholine (SOPC) were greater than 0.9. CONCLUSIONS: In summary, a total of 45 metabolites were identified in the saliva of CEG patients. Among them, 1,2-dioleoyl-sn-glycoro-3-phosphorylcholine and 1-stearoyl-2-oleoyl-sn-glycoro-3-phosphorine (SOPC) might have potential clinical application value.

Protective Effect of Cannabidiol on Hydrogen Peroxide-Induced Oxidative Damage in Human Umbilical Vein Endothelial Cells (HUVECs).

Natural antioxidants play an important role in promoting good health because of their prevention for oxidative damage. The work aimed to explore the antioxidant mechanism and activity of cannabidiol (CBD) at the cellular level. The human umbilical vein endothelial cell (HUVEC) with oxidative damage was employed as the model to study the protective capability of CBD. The results showed that CBD pre-treatment before the cells were exposed to hydrogen peroxide (H2 O2 ) resulted in an obvious increase of cell viability (about 100 %) and antioxidant related enzymes activity, and a decline of malondialdehyde (MDA) level. Besides, CBD could alleviate the increase of intracellular reactive oxygen species (ROS) content, the contraction of nucleus, and condensation of chromatin. The changes showed a dose-dependent effect. Additionally, the free radicals scavenging capacity of CBD was comparable to that of typical natural antioxidant, anthocyanidins. In summary, CBD could be employed as a potent antioxidant source for avoiding the oxidative damage. These results could provide the foundation for the development of CBD antioxidant products.

Long Non-Coding RNA Dancr Affects Myocardial Fibrosis in Atrial Fibrillation Mice via the MicroRNA-146b-5p/Smad5 Axis.

Objectives: Atrial fibrillation (AF) is the most frequent arrhythmia, and myocardial fibrosis (MF) has a close association with atrial remodeling and leads to AF. This study aimed to explore the function of the long non-coding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (Dancr)/microRNA (miR)-146b-5p/Smad5 axis on MF in AF mice. Methods: AF mouse models were established. Overexpression Dancr lentivirus was injected into AF mice to increase Dancr expression in myocardial tissues. LncRNA Dancr, miR-146b-5p, and Smad5 expression levels and inflammatory factors (IL-18 and TNF-α) in the myocardial tissues were measured. MF was measured and the expression levels of MF-related genes (COL1A1, α-SMA, and FN1) were detected. In addition, in vitro HL-1 cell rapid pacing models were constructed, and after lncRNA Dancr and miR-146b-5p-related construct transfection, cell viability and cell apoptosis were determined. Results: LncRNA Dancr up-regulation ameliorated MF in the AF mice, reduced IL-18 and TNF-α expression levels in myocardial tissues, and decreased COL1A1, α-SMA, and FN1 expression levels. The in vitro HL-1 cell rapid pacing models suggested that miR-146b-5p overexpression reversed the inhibitory effects of lncRNA Dancr overexpression on MF in HL-1 cells, and Smad5 interference reversed the ameliorative effects of miR-146b-5p interference on MF in HL-1 cells. Conclusions: LncRNA Dancr can sponge miR-146b-5p to promote Smad5 expression, thereby delaying MF in AF mice.

Minimalist Design of Wireframe DNA Nanotubes: Tunable Geometry, Size, Chirality, and Dynamics.

DNA nanotubes (NTs) have attracted extensive interest as artificial cytoskeletons for biomedical, synthetic biology, and materials applications. Here, we report the modular design and assembly of a minimalist yet robust DNA wireframe nanotube with tunable cross-sectional geometry, cavity size, chirality, and length, while using only four DNA strands. We introduce an h-motif structure incorporating double-crossover (DX) tile-like DNA edges to achieve structural rigidity and provide efficient self-assembly of h-motif-based DNA nanotube (H-NT) units, thus producing programmable, micrometer-long nanotubes. We demonstrate control of the H-NT nanotube length via short DNA modulators. Finally, we use an enzyme, RNase H, to take these structures out of equilibrium and trigger nanotube assembly at a physiologically relevant temperature, underlining future cellular applications. The minimalist H-NTs can assemble at near-physiological salt conditions and will serve as an easily synthesized, DNA-economical modular template for biosensors, plasmonics, or other functional materials and as cost-efficient drug-delivery vehicles for biomedical applications.

Improving older adults' ability to follow instructions: benefits of actions at encoding and retrieval in working memory.

The ability to follow instructions is critical for learning new skills and may support successful aging. Recent evidence indicates a close link between following instructions and working memory, and that action-based processing at encoding and retrieval can improve this ability. In this study, we examined the ability to follow instructions and the benefits of action-based processing in young and older adults. In Experiment 1, participants were presented with spoken or silent demonstrated instructions, then recalled them by oral repetition or physical enactment. Older adults produced fewer correct responses in all conditions. Both age groups were better at recalling demonstrated than spoken instructions in the verbal but not the enacted recall condition. Older adults also benefited from enacted recall relative to verbal recall, but to a smaller extent than younger adults. In Experiment 2, the additional benefit of dual modalities (spoken instructions with simultaneous demonstration) relative to single modality presentation (spoken instructions, or silent demonstration) was examined. Both age groups showed superior performance in dual modality conditions relative to spoken instructions when using verbal recall. These findings suggest that although following instruction ability appears to decline with age, older adults can still benefit from action at encoding and retrieval.

Validity and normative data of the Chinese Prospective and Retrospective Memory Questionnaire (PRMQ) across adolescence, adults and elderly people.

The Prospective and Retrospective Memory Questionnaire (PRMQ) is a widely-used questionnaire for evaluating individuals' memory failures in everyday life. However, whether the scale is valid for different age groups and gender, and how memory complaints change with age and gender remains less clear. This study aimed to validate the self-report PRMQ in a large Chinese sample across adolescence and adulthood and investigate age-related changes and gender differences in self-report prospective memory (PM) and retrospective memory (RM). A total of 2528 healthy individuals aged from 13 to 96 completed the Chinese version of the PRMQ. Results revealed that the PM-RM correlated factor model was the best fit model with satisfactory reliability and had measurement invariance across gender and adjacent age groups. Adolescents and adults reported similar memory complaints, while older people stated more memory difficulties. Female participants reported more PM errors than male participants, but this gender difference only showed in adolescents and adults. Taken together, these findings not only support the Chinese version of the PRMQ as a valid tool for evaluating prospective and retrospective memory difficulties across gender and adjacent age groups, but also reveal age-related changes and gender difference on self-report memory.

Crystal structure of a conformational antibody that binds tau oligomers and inhibits pathological seeding by extracts from donors with Alzheimer's disease.

Soluble oligomers of aggregated tau accompany the accumulation of insoluble amyloid fibrils, a histological hallmark of Alzheimer disease (AD) and two dozen related neurodegenerative diseases. Both oligomers and fibrils seed the spread of Tau pathology, and by virtue of their low molecular weight and relative solubility, oligomers may be particularly pernicious seeds. Here, we report the formation of in vitro tau oligomers formed by an ionic liquid (IL15). Using IL15-induced recombinant tau oligomers and a dot blot assay, we discovered a mAb (M204) that binds oligomeric tau, but not tau monomers or fibrils. M204 and an engineered single-chain variable fragment (scFv) inhibited seeding by IL15-induced tau oligomers and pathological extracts from donors with AD and chronic traumatic encephalopathy. This finding suggests that M204-scFv targets pathological structures that are formed by tau in neurodegenerative diseases. We found that M204-scFv itself partitions into oligomeric forms that inhibit seeding differently, and crystal structures of the M204-scFv monomer, dimer, and trimer revealed conformational differences that explain differences among these forms in binding and inhibition. The efficiency of M204-scFv antibodies to inhibit the seeding by brain tissue extracts from different donors with tauopathies varied among individuals, indicating the possible existence of distinct amyloid polymorphs. We propose that by binding to oligomers, which are hypothesized to be the earliest seeding-competent species, M204-scFv may have potential as an early-stage diagnostic for AD and tauopathies, and also could guide the development of promising therapeutic antibodies.

Dissociation of Proactive and Reactive Cognitive Control in Individuals with Schizotypy: An Event-Related Potential Study.

OBJECTIVE: Patients with schizophrenia and individuals with schizotypy, a subclinical group at risk for schizophrenia, have been found to have impairments in cognitive control. The Dual Mechanisms of Cognitive Control (DMC) framework hypothesises that cognitive control can be divided into proactive and reactive control. However, it is unclear whether individuals with schizotypy have differential behavioural impairments and neural correlates underlying these two types of cognitive control. METHOD: Twenty-five individuals with schizotypy and 26 matched healthy controls (HCs) completed both reactive and proactive control tasks with electroencephalographic data recorded. The proportion of congruent and incongruent trials was manipulated in a classic colour-word Stroop task to induce proactive or reactive control. Proactive control was induced in a context with mostly incongruent (MI) trials and reactive control in a context with mostly congruent (MC) trials. Two event-related potential (ERP) components, medial frontal negativity (MFN, associated with conflict detection) and conflict sustained potential (conflict SP, associated with conflict resolution) were examined. RESULTS: There was no significant difference between the two groups in terms of behavioural results. In terms of ERP results, in the MC context, HC exhibited significantly larger MFN (360-530 ms) and conflict SP (600-1000 ms) amplitudes than individuals with schizotypy. The two groups did not show any significant difference in MFN or conflict SP in the MI context. CONCLUSIONS: The present findings provide initial evidence for dissociation of neural activation between proactive and reactive cognitive control in individuals with schizotypy. These findings help us understand cognitive control deficits in the schizophrenia spectrum.

The benefits of emotionally salient cues on event-based prospective memory in bipolar patients and schizophrenia patients.

Prospective memory (PM) refers to the ability to remember to carry out a delayed intention in the future. Evidence suggests that emotionally salient cues can enhance PM functions in healthy population, but whether the benefit exists in schizophrenia and bipolar patients remains unclear. This study aimed to examine and compare the potential enhancement effect of emotional PM cues in schizophrenia patients and bipolar patients. Twenty-eight clinically stable schizophrenia participants, 26 euthymic bipolar participants and 29 controls completed a computerized PM task involving PM cues with different types of valences (i.e., positive, neutral and negative). All the three groups showed better PM performance when negative PM cues were presented compared with positive and neutral PM cues. The sizes of the enhancement effects of negative PM cues were large (all Cohen's d ≥ 1.00) and comparable across three groups. Our findings suggested that patients with schizophrenia and bipolar disorders could benefit from negative PM cues to an extent similar to healthy individuals, thus extended the notion of psychosis continuum to the important area of emotion-cognition interaction.

Comparing motor imagery and verbal rehearsal strategies in children's ability to follow spoken instructions.

The ability to follow spoken instructions is critical for children's learning in school and relies on the storage and processing of information in working memory. This study compared the effects of two encoding strategies (motor imagery and verbal rehearsal) on children's ability to follow spoken instructions in a working memory paradigm. A total of 146 children aged 7-12 years completed an instruction span task. In this task, children listened to a series of action-object commands and encoded them by either motor imagery or verbal rehearsal. They then attempted to recall the sequence in serial order by either enacted recall or verbal recall. Overall, children's ability to follow spoken instructions increased with age. In all age groups, children showed superior recall of instructions when they imagined the actions compared with verbal rehearsal of the actions during encoding, and this benefit of motor imagery was similar for verbal recall and enacted recall. Younger children reported motor imagery as more helpful than verbal rehearsal for remembering instructions, whereas older children considered verbal rehearsal as more useful. The study provides novel evidence for motor imagery as a superior strategy (relative to verbal rehearsal) for remembering spoken instructions in school-age children.

Structure-based inhibitors halt prion-like seeding by Alzheimer's disease-and tauopathy-derived brain tissue samples.

In Alzheimer's disease (AD) and tauopathies, tau aggregation accompanies progressive neurodegeneration. Aggregated tau appears to spread between adjacent neurons and adjacent brain regions by prion-like seeding. Hence, inhibitors of this seeding offer a possible route to managing tauopathies. Here, we report the 1.0 Å resolution micro-electron diffraction structure of an aggregation-prone segment of tau with the sequence SVQIVY, present in the cores of patient-derived fibrils from AD and tauopathies. This structure illuminates how distinct interfaces of the parent segment, containing the sequence VQIVYK, foster the formation of distinct structures. Peptide-based fibril-capping inhibitors designed to target the two VQIVYK interfaces blocked proteopathic seeding by patient-derived fibrils. These VQIVYK inhibitors add to a panel of tau-capping inhibitors that targets specific polymorphs of recombinant and patient-derived tau fibrils. Inhibition of seeding initiated by brain tissue extracts differed among donors with different tauopathies, suggesting that particular fibril polymorphs of tau are associated with certain tauopathies. Donors with progressive supranuclear palsy exhibited more variation in inhibitor sensitivity, suggesting that fibrils from these donors were more polymorphic and potentially vary within individual donor brains. Our results suggest that a subset of inhibitors from our panel could be specific for particular disease-associated polymorphs, whereas inhibitors that blocked seeding by extracts from all of the tauopathies tested could be used to broadly inhibit seeding by multiple disease-specific tau polymorphs. Moreover, we show that tau-capping inhibitors can be transiently expressed in HEK293 tau biosensor cells, indicating that nucleic acid-based vectors can be used for inhibitor delivery.

Organocatalytic Asymmetric Tandem Cyclization/Michael Addition via Oxazol-5(2H)-One Formation: Access to Perfluoroalkyl-Containing N,O-Acetal Derivatives.

Herein, we report a convenient organocatalytic asymmetric tandem cyclization/Michael addition protocol for the synthesis of diastereomerically pure and highly enantioenriched perfluoroalkyl-containing N,O-acetal derivatives starting from racemic N-perfluoroacyl amino acids under mild conditions. This efficient atom economic reaction leads to highly enantioselective and diastereoselective construction of N,O-acetal derivatives containing oxazolone and perfluoroalkyl moieties containing vicinal quaternary and tertiary stereocenters (up to 97% yield, up to 96% ee, and up to >20:1 dr).

Emotional Stop Cues Facilitate Inhibitory Control in Schizophrenia.

OBJECTIVE: Inhibitory control is a key deficit in patients with schizophrenia. This study aims to test whether emotions can facilitate inhibition in patients with schizophrenia when they increase attention to inhibitory process. METHOD: A total of 36 patients with schizophrenia and 36 healthy controls completed an emotional stop-signal task. The task involved selective responses to "Go" stimuli and stopped response when emotional or neutral stop cues occurred. RESULTS: In all conditions, patients with schizophrenia took longer time to inhibit response compared with healthy controls, indicating an overall impairment in response inhibition. Importantly, patients with schizophrenia and controls acquired similar size of benefit from the negative stop cues, showing as reduced reaction time to negative than neutral stop cues. However, the negative stop cues impaired subsequent Go performance only in patients with schizophrenia, indicating additional cost of the negative stop cues for patients with schizophrenia. In both groups, the positive stop cues did not have any significant influence on response inhibition. CONCLUSIONS: These findings provide novel evidence for the benefit of emotional stop cues on inhibitory control in patients with schizophrenia and reveal different after-effects of emotional enhancement effect in patients and healthy populations. The findings may help develop effective interventions for improving inhibitory control in patients with schizophrenia and other clinical populations.

Altered Inflammatory Pathway but Unaffected Liver Fibrosis in Mouse Models of Nonalcoholic Steatohepatitis Involving Interleukin-1 Receptor-Associated Kinase 1 Knockout.

BACKGROUND Interleukin-1 receptor-associated kinases (IRAKs) are crucial mediators in the signaling pathways of Toll-like receptors (TLRs)/IL1Rs. Targeting the IRAK4/IRAK1/TRAF6 axis and its associated pathway has therapeutic benefits in liver fibrosis. However, the function of IRAK1 itself in the development of liver fibrosis remains unknown. MATERIAL AND METHODS Irak1 global knockout (KO) mice were generated to study the functional role of Irak1 in liver fibrosis. Male Irak1 knockout and control mice were challenged with chronic carbon tetrachloride (CCl4) or fed a methionine- and choline-deficient diet (MCDD) to generate models of nonalcoholic steatohepatitis (NASH). Liver inflammation and collagen deposition were assessed by histological examination, quantitative real-time PCR (qRT-PCR), and western blotting of hepatic tissues. RESULTS The mRNA expression of the downstream inflammatory gene Il1b was significantly lower in Irak1-KO than in control mice. Irak1 ablation had little effect on inflammatory cell infiltration into livers of mice with NASH. Collagen deposition and the expression of genes related to fibrogenesis were similar in the livers of Irak1-KO and control mice exposed to CCl4 and MCDD. The loss of Irak1 did not affect lipid or glucose metabolism in these experimental models of steatohepatitis. CONCLUSIONS Irak1 knockout reduced the expression of inflammatory genes but had no effect on hepatic fibrogenesis. The Irak1-related pathway may regulate liver fibrosis via other pathways or be compensated for by other factors.

Maize microRNA166 Inactivation Confers Plant Development and Abiotic Stress Resistance.

MicroRNAs are important regulators in plant developmental processes and stress responses. In this study, we generated a series of maize STTM166 transgenic plants. Knock-down of miR166 resulted in various morphological changes, including rolled leaves, enhanced abiotic stress resistance, inferior yield-related traits, vascular pattern and epidermis structures, tassel architecture, as well as abscisic acid (ABA) level elevation and indole acetic acid (IAA) level reduction in maize. To profile miR166 regulated genes, we performed RNA-seq and qRT-PCR analysis. A total of 178 differentially expressed genes (DEGs) were identified, including 118 up-regulated and 60 down-regulated genes. These DEGs were strongly enriched in cell and intercellular components, cell membrane system components, oxidoreductase activity, single organism metabolic process, carbohydrate metabolic process, and oxidation reduction process. These results indicated that miR166 plays important roles in auxin and ABA interaction in monocots, yet the specific mechanism may differ from dicots. The enhanced abiotic stress resistance is partly caused via rolling leaves, high ABA content, modulated vascular structure, and the potential changes of cell membrane structure. The inferior yield-related traits and late flowering are partly controlled by the decreased IAA content, the interplay of miR166 with other miRNAs and AGOs. Taken together, the present study uncovered novel functions of miR166 in maize, and provide insights on applying short tandem target mimics (STTM) technology in plant breeding.

O-GlcNAc transferase activates stem-like cell potential in hepatocarcinoma through O-GlcNAcylation of eukaryotic initiation factor 4E.

O-GlcNAcylation catalysed by O-GlcNAc transferase (OGT) is a reversible post-translational modification. O-GlcNAcylation participates in transcription, epigenetic regulation, and intracellular signalling. Dysregulation of O-GlcNAcylation in response to high glucose or OGT expression has been implicated in metabolic diseases and cancer. However, the underlying mechanisms by which OGT regulates hepatoma development remain largely unknown. Here, we employed the lentiviral shRNA-based system to knockdown OGT to analyse the contribution of OGT in hepatoma cell proliferation and stem-like cell potential. The sphere-forming assay and western blot analysis of stem-related gene expression were used to evaluate stem-like cell potential of hepatoma cell. We found that the level of total O-GlcNAcylation or OGT protein was increased in hepatocellular carcinoma. OGT activated stem-like cell potential in hepatoma through eukaryotic initiation factor 4E (eIF4E) which bound to stem-related gene Sox2 5'-untranslated region. O-GlcNAcylation of eIF4E at threonine 168 and threonine 177 protected it from degradation through proteasome pathway. Expression of eIF4E in hepatoma was determined by immunostaining in 232 HCC patients, and Kaplan-Meier survival analysis was used to determine the correlation of eIF4E expression with prognosis. High glucose promoted stem-like cell potential of hepatoma cell through OGT-eIF4E axis. Collectively, our findings indicate that OGT promotes the stem-like cell potential of hepatoma cell through O-GlcNAcylation of eIF4E. These results provide a mechanism of HCC development and a cue between the pathogenesis of HCC and high glucose condition.

ß1,4-Galactosyltransferase V activates Notch1 signaling in glioma stem-like cells and promotes their transdifferentiation into endothelial cells.

Malignant glioblastoma multiforme is one of the most aggressive human cancers, with very low survival rates. Recent studies have reported that glioma stem-like cells transdifferentiate into endothelial cells, indicating a new mechanism for tumor angiogenesis and potentially providing new therapeutic options for glioblastoma treatment. Glioma malignancy is strongly associated with altered expression of N-linked oligosaccharide structures on the cell surface. We have previously reported that ß1,4-galactosyltransferase V (ß1,4GalTV), which galactosylates the GlcNAcß1-6Man arm of the branched N-glycans, is highly expressed in glioma and promotes glioma cell growth in vitro and in vivo However, the mechanism by which ß1,4GalTV stimulates glioma growth is unknown. Here we demonstrate that short hairpin RNA-mediated ß1,4GalTV knockdown inhibits the tumorigenesis of glioma stem-like cells and reduces their transdifferentiation into endothelial cells. We also found that ß1,4GalTV overexpression increased glioma stem-like cell transdifferentiation into endothelial cells and that this effect required ß1,4GalTV galactosylation activity. Moreover, ß1,4GalTV promoted ß1,4-galactosylation of Notch1 and increased Notch1 protein levels. Of note, ectopic expression of activated Notch1 rescued the inhibitory effect of ß1,4GalTV depletion on glioma stem-like cell transdifferentiation. In summary, our findings indicate that ß1,4GalTV stimulates transdifferentiation of glioma stem-like cells into endothelial cells by activating Notch1 signaling. These detailed insights shed important light on the mechanisms regulating glioma angiogenesis.