Development of a dual-layer silica fume-epoxy resin composite coating to enhance durability and interfacial bond for FRP bars in alkaline concrete environments

Construction and Building Materials · 2025-06-04 · 8 citations

The susceptibility of fiber reinforced polymer (FRP) bars to alkaline degradation in concrete environments remains a critical durability challenge. This study develops an innovative dual-layer silica fume-epoxy resin composite coating (SF-ERC), comprising an inner epoxy/silica fume hybrid layer (SF+ER) and outer layer of silica fume (SFC). The influence of the inner SF+ER layer on the durability of FRP bars was investigated, and the optimal mix proportion of this layer was determined. Subsequently, the effect of the complete SF-ERC on the bond strength at the FRP bar-concrete interface was investigated. The results indicate that the silica fume dispersed in the inner layer can consume alkaline substances through the pozzolanic reaction. This provides a spatial corrosion-inhibition effect, thereby effectively enhancing the durability of FRP bars. After 180 days of immersion corrosion, the water absorption, dissolved resin, and mechanical property loss rate of the optimal inner SF+ER layer coated specimens were only 16.59 %, 15.96 %, and 31.51 % of those of the uncoated specimens, respectively. The outer SFC layer not only serves as an additional corrosion-inhibition barrier, but also promotes the formation of a new C-S-H gel protective layer through the pozzolanic reaction. Moreover, the SF-ERC alleviates the problem of bond weakening typically linked to conventional single epoxy coatings and further enhances the bond strength. After 90 days of immersion in seawater, the interfacial bond strength of FRP bars coated with SF-ERC increased by 18.32 % compared to those coated solely with epoxy resin. • Dual-layer coating enhances durability and interfacial bond of FRP bar in concrete. • Inner layer provides a spatial corrosion-inhibition effect. • Outer layer provides additional barrier while enhancing interfacial bond. • The working mechanism of the dual-layer coating was elucidated.

From seq-ing to modeling: towards a molecular understanding of special properties of immature neurons in the human hippocampus

Life Medicine · 2025-09-28

2 32 New neurons arising from adult neurogenesis represent a striking manifestation of neural 33 cell plasticity that persists throughout adulthood 1 .These immature dentate granule cells 34 (imGCs) exhibit distinct cellular and physiological properties compared to their mature 35 counterparts and execute the function of adult neurogenesis, making them an important 36 focus for analysis 1 .They play pivotal roles in modulating learning and memory, affective 37 behaviors, and cognition, whereas dysregulation of imGCs has been associated with 38 various human neurological disorders 1 .These intrinsic adult-born neurons offer potential 39 for developing new strategies to alleviate brain disorders, stroke and injury 1 .However, our 40 understanding of imGCs is largely based on studies involving mouse models 2 .The 41 molecular features and regulatory mechanisms of imGCs in humans and non-human 42 primates (NHPs) remain elusive, and their existence in adult humans was debated 2-4 .This 43 is largely attributed to the common assumption that imGCs in different species share vast 44 similarities.There is a lack of cross-species comparative studies and human cell-based 45 modeling for mechanistic investigation to directly examine human imGCs.Therefore, the 46 lack of a consistent method for identifying human and NHP imGCs and elucidating their 47 human-specific features impedes molecular targeting and therapeutic applications of 48 immature neurons in the human hippocampus. 49Recent efforts have utilized single-cell and single-nucleus RNA sequencing (scRNA-50 seq) to explore cell heterogeneity in the hippocampus of humans and NHPs (summarized 51 in references [ [5][6][7]).However, the DCX + PROX1 + imGCs are interspersed among other cells 52 within the dentate granule cell (GC) cluster using unsupervised clustering, even during 53 perinatal stages 5 .Consequently, these studies have yielded inconsistent cell-typing 54 outcomes of imGCs.Most studies have relied on prior knowledge from mouse models and 55 have adopted study-specific criteria for cell definition, such as using various combinationsPage 3 of 11 https://mc.manuscriptcentral.com/lifemed

Cross-species analysis of adult hippocampal neurogenesis reveals human-specific gene expression but convergent biological processes

Nature Neuroscience · 2025-08-11 · 13 citations

Resveratrol induces ferroptosis in triple-negative breast cancer through NEDD4L-mediated GPX4 ubiquitination and degradation

Free Radical Biology and Medicine · 2025-05-01 · 13 citations

Shikimic Acid Mitigates Deoxynivalenol-Induced Jejunal Barrier Injury in Mice via Activation of the Nrf-2/HO-1/NQO1 Pathway and Modulation of Gut Microbiota

Antioxidants · 2025-09-23 · 3 citations

Deoxynivalenol (DON), a mycotoxin from Fusarium that contaminates cereals, can also induce intestinal injury. However, the mechanisms underlying DON-induced jejunal barrier injury remain unclear. This study demonstrates that shikimic acid (SA) alleviates DON-induced jejunal barrier damage and dysbiosis via antioxidant pathways. Fifty 5-week-aged male KM mice were divided into control (CON), model (MOD, 2.4 mg/kg bw DON), and SA-treated groups (LDG/MDG/HDG: 25/50/100 mg/kg bw SA + DON). After SA treatment, notably MDG, reversed DON-induced weight loss and jejunal hyperemia; ameliorated villus atrophy, crypt deepening and goblet cell loss, increasing villus/crypt ratio; reduced gut permeability markers (D-LA/DAO) and pro-inflammatory cytokines (TNF-α/IL-6/IL-1β); and dose-dependently upregulated tight junction proteins (ZO-1/Occludin/Claudin1). Mechanistically, SA activated the Nrf2/HO-1/NQO1 pathway, elevating antioxidants (GSH/SOD/AOC) while reducing MDA, with MDG showing optimal efficacy. 16S rRNA sequencing revealed MDG counteracted DON-induced dysbiosis by enriching beneficial bacteria (e.g., Bacteroidota at phylum level; Muribaculaceae at family level) and suppressing pathogens (Staphylococcaceae) (LDA score > 4.0). Thus, SA mitigates DON toxicity via Nrf2-mediated barrier restoration, anti-inflammation, and microbiota modulation. This research provides new insights for the further development of Shikimic Acid and the treatment of DON-induced jejunal barrier injury.

Comparative molecular landscapes of immature neurons in the mammalian dentate gyrus across species reveal special features in humans

bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-17

Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity, learning and memory, but their evolutionary changes across species and specialized features in humans remain poorly understood. Here we performed machine learning-augmented analysis of published single-cell RNA-sequencing datasets and identified macaque imGCs with transcriptome-wide immature neuronal characteristics. Our cross-species comparisons among humans, monkeys, pigs, and mice showed few shared (such as DPYSL5), but mostly species-specific gene expression in imGCs that converged onto common biological processes regulating neuronal development. We further identified human-specific transcriptomic features of imGCs and demonstrated functional roles of human imGC-enriched expression of a family of proton-transporting vacuolar-type ATPase subtypes in development of imGCs derived from human pluripotent stem cells. Our study reveals divergent gene expression patterns but convergent biological processes in the molecular characteristics of imGCs across species, highlighting the importance of conducting independent molecular and functional analyses for adult neurogenesis in different species.

The effect of the pericardial patching exclusion technique for left atrial appendage closure on postoperative reopening rate

BMC Cardiovascular Disorders · 2025-12-08

BACKGROUND: The left atrial appendage (LAA) is the primary source of cardiogenic embolism in atrial fibrillation patients. Traditional LAA closure methods have shown suboptimal clinical outcomes. In recent years, some surgeons have proposed employing a autologous pericardial patch for suturing the LAA. METHODS: This study included 104 patients undergoing mitral valve surgery with concomitant LAA closure at our center between January 2019 and December 2021. Two surgical methods for LAA closure were compared. A transesophageal echocardiogram performed 6 months after surgery was used to verify the success of left atrial appendage closure. Left atrial appendage closure failure was defined as reopening of the left atrial appendage or persistent blood flow into the left atrial appendage. RESULTS: Among the 104 patients included (mean age: 65.0 ± 7.58 years, male: 52.50%), 7 patients were found to have a reopened left atrial appendage; 5 patients (5 of 32,15.6%) were in the suture closure group, and 2 patients (2 of 72,2.8%) were in the pericardial patch exclusion (PPE; defined as closure of the LAA orifice via sutured autologous pericardium) group (15.6% vs. 2.8%, P = 0.047). CONCLUSIONS: The pericardial patch exclusion technique is a reliable technique for closing the left atrial appendage in patients with atrial fibrillation and can effectively reduce the possibility of reopening the left atrial appendage.

Transcription Factor-Wide Association Studies to Identify Functional SNPs in Alzheimer's Disease

Journal of Neuroscience · 2024-12-02 · 3 citations

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with profound global impact. While genome-wide association studies (GWAS) have revealed genomic variants linked to AD, their translational impact has been limited due to challenges in interpreting the identified genetic associations. To address this challenge, we have devised a novel approach termed transcription factor-wide association studies (TF-WAS). By integrating the GWAS, expression quantitative trait loci, and transcriptome analyses, we selected 30 AD single nucleotide polymorphisms (SNPs) in noncoding regions that are likely to be functional. Using human transcription factor (TF) microarrays, we have identified 90 allele-specific TF interactions with 53 unique TFs. We then focused on several interactions involving SMAD4 and further validated them using electrophoretic mobility shift assay, luciferase, and chromatin immunoprecipitation on engineered genetic backgrounds (female cells). This approach holds promise for unraveling the intricacies of not just AD, but any complex disease with available GWAS data, providing insight into underlying molecular mechanisms and clues toward potential therapeutic targets.

Leveraging deep single-soma RNA sequencing to explore the neural basis of human somatosensation

Nature Neuroscience · 2024-11-04 · 69 citations

The versatility of somatosensation arises from heterogeneous dorsal root ganglion (DRG) neurons. However, soma transcriptomes of individual human (h)DRG neurons-critical information to decipher their functions-are lacking due to technical difficulties. In this study, we isolated somata from individual hDRG neurons and conducted deep RNA sequencing (RNA-seq) to detect, on average, over 9,000 unique genes per neuron, and we identified 16 neuronal types. These results were corroborated and validated by spatial transcriptomics and RNAscope in situ hybridization. Cross-species analyses revealed divergence among potential pain-sensing neurons and the likely existence of human-specific neuronal types. Molecular-profile-informed microneurography recordings revealed temperature-sensing properties across human sensory afferent types. In summary, by employing single-soma deep RNA-seq and spatial transcriptomics, we generated an hDRG neuron atlas, which provides insights into human somatosensory physiology and serves as a foundation for translational work.

GABAergic neuron dysregulation in a human neurodevelopmental model for major psychiatric disorders

bioRxiv (Cold Spring Harbor Laboratory) · 2024-09-23 · 1 citations

Abstract “GABA dysfunction” is a major hypothesis for the biological basis of schizophrenia with indirect supporting evidence from human post-mortem brain and genetic studies. Patient-derived induced pluripotent stem cells (iPSCs) have emerged as a valuable platform for modeling psychiatric disorders, and previous modeling has revealed glutamatergic synapse deficits. Whether GABAergic synapse properties are affected in patient-derived human neurons and how this impacts neuronal network activity remain poorly understood. Here we optimized a protocol to differentiate iPSCs into highly enriched ganglionic eminence-like neural progenitors and GABAergic neurons. Using a collection of iPSCs derived from patients of psychiatric disorders carrying a Disrupted-in-Schizophrenia 1 ( DISC1 ) mutation and their unaffected family member, together with respective isogenic lines, we identified mutation-dependent deficits in GABAergic synapse formation and function, a phenotype similar to that of mutant glutamatergic neurons. However, mutant glutamatergic and GABAergic neurons contribute differentially to neuronal network excitability and synchrony deficits. Finally, we showed that GABAergic synaptic transmission is also defective in neurons derived from several idiopathic schizophrenia patient iPSCs. Transcriptome analysis further showed some shared gene expression dysregulation, which is more prominent in DISC1 mutant neurons. Together, our study supports a functional GABAergic synaptic deficit in major psychiatric disorders.