ADAR1-regulated miR-142-3p/RIG-I axis suppresses antitumor immunity in nasopharyngeal carcinoma.

Following the initial treatment of nasopharyngeal carcinoma (NPC), tumor progression often portends an adverse prognosis for these patients. MicroRNAs (miRNAs) have emerged as critical regulators of tumor immunity, yet their intricate mechanisms in NPC remain elusive. Through comprehensive miRNA sequencing, tumor tissue microarrays and tissue samples analysis, we identified miR-142-3p as a significantly upregulated miRNA that is strongly associated with poor prognosis in recurrent NPC patients. To elucidate the underlying molecular mechanism, we employed RNA sequencing, coupled with cellular and tissue assays, to identify the downstream targets and associated signaling pathways of miR-142-3p. Our findings revealed two potential targets, CFL2 and WASL, which are directly targeted by miR-142-3p. Functionally, overexpressing CFL2 or WASL significantly reversed the malignant phenotypes induced by miR-142-3p both in vitro and in vivo. Furthermore, signaling pathway analysis revealed that miR-142-3p repressed the RIG-I-mediated immune defense response in NPC by inhibiting the nuclear translocation of IRF3, IRF7 and p65. Moreover, we discovered that ADAR1 physically interacted with Dicer and promoted the formation of mature miR-142-3p in a dose-dependent manner. Collectively, ADAR1-mediated miR-142-3p processing promotes tumor progression and suppresses antitumor immunity, indicating that miR-142-3p may serve as a promising prognostic biomarker and therapeutic target for NPC patients.

Corrigendum: Alterations in cellular metabolism under different grades of glioma staging identified based on a multi-omics analysis strategy.

[This corrects the article DOI: 10.3389/fendo.2023.1292944.].

Molecular mechanisms and diagnostic model of glioma-related epilepsy.

Epilepsy is one of the most common symptoms in patients with gliomas; however, the mechanisms underlying its interaction are not yet clear. Moreover, epidemiological studies have not accurately identified patients with glioma-related epilepsy (GRE), and there is an urgent need to identify the molecular mechanisms and markers of its occurrence. We analyzed the demographics, transcriptome, whole-genome, and methylation sequences of 997 patients with glioma, to determine the genetic differences between glioma and GRE patients and to determine the upregulated molecular function, cellular composition, biological processes involved, signaling pathways, and immune cell infiltration. Twelve machine learning algorithms were refined into 113 combinatorial algorithms for building diagnostic recognition models. A total of 342 patients with GRE were identified with WHO grade 2 (174), grade 3 (107), and grade 4 (61). The mean age of the patients with GREs, with IDH mutations (n = 217 [63%]) and 1p19q non-codeletion (n = 169 [49%]), was 38 years old. GRE molecular functions were mainly passive transmembrane transporter protein activity, ion channel activity, and gated channel activity. Cellular components were enriched in the cation-channel and transmembrane transporter complexes. Cerebral cortical development regulates the membrane potential and synaptic organization as major biological processes. The signaling pathways mainly focused on cholinergic, GABAergic, and glutamatergic synapses. LASSO, combined with Random Forest, was the best diagnostic model and identified nine diagnostic genes. This study provides new insights and future perspectives for resolving the molecular mechanisms of GRE.

Sinonasal adenoid cystic carcinoma: preoperative apparent diffusion coefficient histogram analysis in prediction of prognosis and Ki-67 proliferation status.

PURPOSE: To investigate the value of preoperative apparent diffusion coefficient (ADC) histogram analysis in predicting the prognosis of patients with sinonasal adenoid cystic carcinoma (ACC) and the correlation between ADC histogram parameters and Ki-67 labeling index (LI). MATERIALS AND METHODS: The study enrolled 66 patients with sinonasal ACC who were surgically resected and confirmed by histopathology. The disease-free survival (DFS) was evaluated with clinical-pathologic and radiologic characteristics using the Cox proportion hazard model. Spearman correlation analysis was used to evaluate the correlation between ADC histogram parameters and Ki-67 LI. The predictive performance of ADC histogram parameters for Ki-67 LI was assessed using the receiver operating characteristic (ROC) curve. RESULTS: Multivariable analysis showed Ki-67 LI (hazard ratio: 9.279; 95% confidence interval 1.099-78.338; P = 0.041) and ADCskewness (hazard ratio: 5.942; 95% confidence interval 1.832-19.268; P = 0.003) were significant independent predictors of DFS. The combination of these two variables achieved the predictive ability with a C-index of 0.717 (95% confidence interval 0.607-0.826). ADCmean and all ADC percentiles (10th, 50th, and 90th) significantly and inversely correlated with Ki-67 LI of ACC (Correlation coefficients = - 0.574 to - 0.591, Ps < 0.001). Among the ADC histogram parameters, the ADC50th showed superior performance for the differentiation of the high from low Ki-67 LI groups with an area under the curve (AUC) of 0.834 and an accuracy of 80.30%. CONCLUSION: ADC histogram analysis had predictive value for DFS and Ki-67 LI, which may be a valuable biomarker for prognosis and proliferation status for ACC in clinical practice.

Massive chest wall bleeding 3 days after lung wedge resection caused by a protruding staple.

We report a case of massive chest wall bleeding after lung wedge resection caused by a protruding staple. On the third postoperative day, the patient experienced sudden left posterior back pain without any apparent trigger, accompanied by signs of shock. Computed tomography imaging revealed a significant accumulation of blood in the pleural cavity on the side of the surgery. A reoperation was performed, during which we identified active arterial bleeding from a small vessel at the second intercostal space on the posterior chest wall. Hemostasis was achieved using electrocautery. Further examination revealed a protruding staple at the left upper lobe resection margin, which we speculated was likely causing abrasion against the chest wall and leading to the bleeding. This case reveals the potential risk posed by protruding staples. Appropriate precautions should be taken to prevent this rare but dangerous occurrence.

Dexmedetomidine and Dexamethasone as Adjuvants to the Local Anesthetic Mixture in Rhomboid Intercostal and Sub-Serratus Block for Video-Assisted Thoracoscopic Surgery: A Randomized, Double-Blind, Controlled Trial.

Background: The utilization of adjuvants such as dexamethasone and dexmedetomidine in combination with local anesthetics has proven effective in extending analgesia duration. We aimed to investigate the potential efficacy of combining dexmedetomidine and dexamethasone in rhomboid intercostal and sub-serratus (RISS) block for prolonging postoperative analgesia in patients undergoing video-assisted thoracoscopic surgery (VATS). Methods: We did this randomized, double-blind, controlled trial in two tertiary-care hospitals. A total of eighty-eight patients undergoing VATS under general anesthesia were enrolled in this study. They were randomly assigned into four groups: ropivacaine (R) group, ropivacaine + dexmedetomidine (RM) group, ropivacaine + dexamethasone (RS) group, or ropivacaine + dexmedetomidine + dexamethasone (RSM) group. The primary outcome measure was the duration of analgesia. Secondary outcomes included Numeric Rating Scale (NRS) scores, cumulative oxycodone consumption, and adverse effects. Results: The RSM group exhibited a significantly prolonged duration of analgesia at 1073.5 min (932.0-1283.3) compared to the R group with a duration of 154.5 min (80.5-199.3) and the RS group with a duration of 282.0 min (195.3-350.0, P < 0 0.001). The cumulative oxycodone consumption during the 0-12 hours and 0-24-hours period was significantly reduced in the RSM group compared to the R group (P < 0.05). There was also a lower incidence of nausea at 48 hours postoperatively in the RSM group compared to the RM group. However, there were no significant differences between the four groups regarding NRS pain scores. Conclusion: The combination of ropivacaine, dexmedetomidine, and dexamethasone in RISS block significantly prolongs the duration of postoperative analgesia following VATS.

EEG spatial inter-channel connectivity analysis: A GCN-based dual stream approach to distinguish mental fatigue status.

Mental fatigue is defined as a decline in the ability and efficiency of mental activities. A lot of research suggests that the transition from alertness to fatigue is accompanied by alterations in correlation patterns among various brain regions. However, conventional methods for detecting mental fatigue seldom emphases inter-channel connectivity in the spatial domain. To fill this gap, this paper explores the spatial inter-channel connectivity in alertness and fatigue, employing spectral graph convolutional networks (GCN) for mental fatigue detection. We utilized Pearson correlation coefficients (PCC) to establish temporal connections and magnitude-squared coherence (MSC) for spectral connections. Topological features of the brain network were then analysed. To enhance the learning of spatial inter-channel connectivity, a dual-graph strategy transforms edge features into node features, serving as inputs to the spectral GCN. By simultaneously learning PCC and MSC features, the model results indicate significant differences in some brain network characteristics between alert and fatigue states. It confirms that the synchronicity of brain operations differs in the alert state compared to mental fatigue, and indicates that fatigue states can influence correlation patterns among different brain regions. Our approach is evaluated on a self-designed experimental dataset containing 7 subjects, demonstrating a classification accuracy of 89.59 % in group-level experiments and 95.24 % at the subject level. Additionally, on the public dataset SEED-VIG containing 23 subjects, our method achieves an accuracy of 86.58 %. In summary, this paper proposes a neural network approach based on a dynamic functional connectivity network. The network integrates both temporal and spectral connections with the goal of simultaneously learning spatial inter-channel connectivity in time and frequency domains. This effectively accomplishes fatigue state detection, highlighting that fatigue significantly influences correlations among different brain regions.

Thioredoxin C of Streptococcus suis serotype 2 contributes to virulence by inducing antioxidative stress and inhibiting autophagy via the MSR1/PI3K-Akt-mTOR pathway in macrophages.

The thioredoxin (Trx) system plays a vital role in protecting against oxidative stress and ensures correct disulfide bonding to maintain protein function. Our previous research demonstrated that TrxA of Streptococcus suis Serotype 2 (SS2), a clinical strain from the lung of a diseased pig, contributes to virulence but is not involved in antioxidative stress. In this study, we identified another gene in the Trx family, TrxC, which encodes a protein of 104 amino acids with a CGDC active motif and 22.4 % amino acid sequence homology with TrxA. Unlike the TrxA, TrxC mutant strains were more susceptible to oxidative stresses induced by hydrogen peroxide and paraquat. In vitro experiments, the survival rate of the TrxC deletion mutant in RAW264.7 macrophages was only one-eighth of that of TrxA mutant strains. Transcriptome analysis revealed that autophagy-related genes were significantly upregulated in the TrxC mutant compared to those in the wild-type or TrxA mutant strains. Co-localization of LC3 puncta with TrxC was confirmed using laser confocal microscopy, and autophagy-related indicators were quantified using western blotting. Autophagy deficiency induced by ATG5 knockout significantly increased SS2 survival rate, especially in TrxC mutant strains. For the upstream signal regulation pathways, we found ΔTrxC strains regulate autophagy by activation of PI3K/Akt/mTOR signaling in RAW264.7 macrophages. In the Akt1-overexpressing cell line, ΔTrxC infection significantly decreased the autophagic response and promoted ΔTrxC mutant strain survival, while inhibition of Akt with MK2206 resulted in reduced ΔTrxC mutant strain survival and enhance the autophagic response. Furthermore, loss of TrxC increased the activity of MSR1, thereby inducing cellular autophagy and phagocytosis. Our data demonstrate that TrxC of SS2 contributes to virulence by inducing antioxidative stress and inhibits autophagy via the PI3K-Akt-mTOR pathway in macrophages, with MSR1 acting as a key factor in controlling infection.

Discovery of novel fructose-1,6-bisphosphatase inhibitors bearing benzimidazole scaffold using a dual-ligand molecular docking model.

Fructose-1,6-bisphosphatase (FBPase) is an emerging target in gluconeogenesis, inhibitors of which would be an effective treatment for elevated fasting blood glucose in patients with type 2 diabetes. Based on the lead compound G-1 (FBPase 10 µM inhibition = 64.3 %) and according to the X-ray crystal structure of FBPase, we designed and validated an innovative molecular docking method based on the dual-ligand model to explore the interactions between two identical ligands in neighboring targets. Based on the dual-ligand molecular docking model, a novel compound 45 bearing a benzimidazole scaffold was identified to show increased inhibitory activity against FBPase (IC50, 2.08 µM). An oral pyruvate tolerance test in ICR mice showed that 45 had a potent inhibitory effect on gluconeogenesis similar to that of metformin when administered as a single dose in vivo. Compound 45 did not inhibit the common subtypes of the human cytochrome P450 system, indicating that it may have a reduced propensity for drug-drug interactions. The findings of this study may pave the way for further development of FBPase inhibitors with novel structural features, improved activity, and good druggability.

Maltol Improves Peripheral Nerve Function by Inhibiting Schwann Cell Apoptosis via the PERK/eIF2α/CHOP Pathway and MME Upregulation in Diabetic Peripheral Neuropathy.

Diabetic peripheral neuropathy (DPN) is the most prevalent chronic complication among diabetic patients and a primary risk factor contributing to the deterioration of diabetic foot conditions. The pathogenesis of DPN remains complex and not fully understood, and there are hardly any effective treatment drugs. Maltol (3-hydroxy-2-methyl-4-pyranone) has demonstrated antioxidant and anti-inflammatory properties. However, the potential role of maltol in the treatment of DPN remains unclear. This study aimed to assess maltol's effects on DPN rats and high glucose (HG)/palmitic acid (PA)-induced rat Schwann cells (RSC96). The results indicated maltol's capacity to enhance peripheral nerve function in DPN rats. In RSC96 cells stimulated with high HG and PA, maltol treatment reduced DPN markers and apoptosis-related proteins. Functional enrichment analysis of differentially expressed genes revealed that endoplasmic reticulum (ER) stress pathways were involved in this process. Western blot results demonstrated the activation of ER stress pathway in HG/PA-induced RSC96 cells, with maltol attenuating ER stress-related protein expression. Furthermore, the knockdown of Membrane metallo-endopeptidase (MME) reversed maltol's effects on apoptosis-related protein expression, suggesting a potential therapeutic role for maltol via MME in treating DPN. These findings indicate that maltol may hold promise as a therapeutic agent for DPN treatment.

Identification and characterization of Jingmen tick virus from Rhipicephalus microplus in Hunan, China.

Jingmen tick virus (JMTV) is a tick-borne pathogen known to affect human beings, characterized by a segmented genome structure that defies the conventional understanding of the Flaviviridae family. In the present study, we employed metagenomic analysis to screen for tick-borne viruses in Hunan Province, China, and identified five JMTV variants with complete genomes from Rhipicephalus microplus ticks sampled from cattle. These viral strains exhibited the highest sequence similarity to JMTV isolates previously reported in Hubei Province, China. However, evidence of genomic reassortment was detected, particularly with the S2 segment showing greater similarity to the strains from Japan. Phylogenetic analysis demonstrated that JMTV strains cluster predominantly based on their geographic origin. In agreement with the homology data, the S1, S3, and S4 segments of the strains identified in this study grouped with those from Hubei Province, while the S2 segment displayed a distinct topological structure. Moreover, JMTV displayed limited replication in mammal-derived cells, but thrived in tick-derived cell lines. In addition to the commonly used R. microplus-derived BME/CTVM23 cells, we found that JMTV also proliferated robustly in both Ixodes scapularis-derived ISE6 and Ixodes ricinus-derived IRE/CTVM19 cells, offering new avenues for in vitro production of the virus. In summary, this study expands the known geographic distribution and genetic diversity of JMTV, providing valuable insights into its epidemiology and potential for in vitro cultivation.

Calcium enrichment activity initiates extracellular calcium influx-dependent inflammatory response of biologically-derived hydroxyapatite.

Biologically-derived hydroxyapatite is a widely used biomaterial in various clinical applications including bone augmentation. However, the osteogenic application of biological hydroxyapatite is limited by inflammatory responses, and the underlying mechanism remains unknown. The current study aimed to elucidate the molecular mechanisms underlying the inflammatory response to biological hydroxyapatite. Porcine-derived hydroxyapatite (PHA) with two sintering temperatures (800 and 1600 °C), PHA800 and PHA1600, respectively, were prepared. A PHA/macrophage co-culture model was established. Transcriptome, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) analyses were used to determine the inflammatory effects and the main pathways activated by PHA800 and PHA1600. Intracellular calcium level, PHA-induced calcium enrichment, and related biological effects were used to determine the molecular mechanism at the PHA-cell interface. PHA800 significantly upregulated a TLR4 mediated inflammatory pathway in a calcium influx-dependent manner, and the calcium enrichment activity on the surface of PHA800 promoted calcium influx. In contrast, the calcium enrichment activity on the surfaces of the PHA1600 and PHA800 pretreated groups was attenuated, resulting in decreased calcium influx and mild inflammatory effects. Our results provide a fundamental basis for the development of novel bone substitutes that elicit low levels of inflammation response.

An imine-functionalized silicone-based epoxy coating with stable adhesion and controllable degradation for enhanced marine antifouling and anticorrosion properties.

Biofouling and corrosion of submerged equipment caused by marine organisms severely restrict the rapid development of the marine industry. Traditional antifouling or anticorrosion coatings typically serve a sole purpose and exhibit limited degradability upon failure, rendering them inadequate for current demands. Herein, a novel imine-functionalized command-degradable bio-based epoxy coating (SAHPEP-DDM) with enhanced integrated antifouling and anticorrosion performances was synthesized utilizing 1,3-bis (3-aminopropyl)-1,1,3,3-tetramethyldisiloxane and syringaldehyde. Compared with commercial epoxy resins (E51-DDM) and polydimethylsiloxanes (PDMS), the SAHPEP-DDM coating exhibits superior antifouling and anticorrosion properties due to the existence of -C=N- and Si-O-Si chain segments in the cross-linking network. The coating shows promising resistance against bacteria, algae and proteins, as well as excellent corrosion resistance in artificial seawater. The coating also exhibits excellent chemical resistance in organic solvents as well as neutral and alkaline environments. Moreover, its controlled degradation after failure can be achieved in acid aqueous solutions through temperature and acidity adjustments, facilitated by the presence of -C=N-. This work presents a novel degradable coating successfully coupled the dual functions of antifouling and anticorrosion coatings, avoiding the employment of intermediate coat, indicating vast potential for application in marine engineering fields.

[Retracted] SOX2 knockdown inhibits the migration and invasion of basal cell carcinoma cells by targeting the SRPK1­mediated PI3K/AKT signaling pathway.

[This retracts the article DOI: 10.3892/ol.2018.9810.].

Age affects the association of red blood cell indices with efficacy of remote ischemic conditioning in patients with acute moderate ischemic stroke.

We conducted a post hoc analysis of Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS) to investigate whether red blood cell (RBC) indices are associated with efficacy of remote ischemic conditioning (RIC), and whether the association is affected by age. In this post hoc analysis, patients with RBC indices at admission were enrolled. RBC indices including RBC count, hematocrit (HCT), mean corpuscular volume (MCV), hemoglobin (HB), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were analyzed. According to the median of these RBC indices, eligible patients were divided into high and low groups, which were further subdivided into RIC and control subgroups. Primary endpoint was excellent functional outcome defined as a modified Rankin Scale score of 0-1 at 90 days, which was used to evaluate RIC efficacy. RIC efficacy as well as effect of age on RIC efficacy were analyzed across the high and low groups of different RBC indices, and the interaction effects of RBC indices on RIC efficacy were evaluated. A total of 1640 patients were enrolled in the final analysis. In overall patients, no significant interaction effects of RIC intervention by all RBC indices were found, although there was a trend in interaction effect of RIC intervention by MCH (p = 0.116). However, we found an effect of age on the association of MCH with RIC efficacy. In patients over 60 years old, MCH significantly affected RIC efficacy (p = 0.006) and RIC significantly produced a higher proportion of primary outcome in high MCH (72.6% vs. 59.1%, P < 0.001) vs. low MCH group (61.2% vs. 62%, P = 0.829), which was not identified in patients under 60 years old. Furthermore, RIC efficacy decreased with increasing age in patients with low MCH with significant interaction effect (p = 0.012), while RIC efficacy increased with increasing age in patients with high MCH although no significant interaction (p = 0.126). No significant interaction effects of RIC intervention by RBC count, HCT, MCV, HB, and MCHC were found regardless of age. This secondary analysis of RICAMIS suggested that RIC exhibited more obvious benefit in AIS patients over 60 years old with high MCH compared with those with low MCH group, but RBC count, HCT, MCV, HB, and MCHC were not associated with the efficacy of RIC treatment regardless of age.

Real-time quantitative reverse transcription PCR assay for the detection of Nuomin virus - An emerging tick-borne virus.

Nuomin virus (NOMV), an emerging tick-borne virus (TBVs) identified in 2020, has been associated with fever, headache, and potential liver dysfunction in infected individuals. This study presents a novel TaqMan real-time quantitative PCR method designed for the rapid, sensitive, and specific detection of NOMV, facilitating early diagnosis. Utilizing Beacon Designer software 8.0, we optimized the PCR assay including the development of primers and probes to precisely target the conserved region of the NOMV genome, followed by optimization of primer and probe concentrations and annealing temperature. The resulting assay demonstrated robust performance, with standard curve represented by the equation y=-3.29x+39.42, a high correlation coefficient (R2 = 0.995) and an efficiency 99.53 %. Importantly, the method exhibited exceptional specificity, which did not yield cross-reacting signals from other TBVs, including Songling virus (SGLV), Beiji virus (BJNV), tick-borne encephalitis virus (TBEV), Yezo virus (YEZV), Alongshan virus (ALSV), and severe fever with thrombocytopenia syndrome bunyavirus (SFTSV). The assay's detection limit was remarkably low, reaching 10 copies/µL, representing a 100-fold increase compared to semi-nested RT-PCR. Additionally, it demonstrated excellent repeatability, with coefficients of variation for intra- and inter-group tests consistently below 3 %. Clinical evaluations confirmed the assay's superior performance, highlighting its high specificity, sensitivity, and reproducibility for NOMV detection. In conclusion, the method developed in this study provides a valuable tool to support timely management of NOMV infections, with significant implications for clinical practice.

Identification of SNHG11 as a Therapeutic Target in Pulmonary Hypertension.

Pulmonary hypertension (PH) is a life-threatening condition characterized by pulmonary vascular remodeling and endothelial dysfunction. Current therapies primarily target vasoactive imbalances but often fail to address adverse vascular remodeling. Long non-coding RNA (lncRNA), which are key regulators of various cellular processes, remain underexplored in the context of PH. To investigate the role of lncRNA in PH, we performed a comprehensive analysis using Weighted Gene Co-expression Network Analysis (WGCNA) on the GSE113439 dataset, comprising human lung tissue samples from different PH subtypes. Our analysis identified the lncRNA SNHG11 as consistently downregulated in PH. Functional assays in human pulmonary artery endothelial cells (HPAECs) demonstrated that SNHG11 plays a critical role in modulating inflammation, cell proliferation, apoptosis, and the JAK/STAT and MAPK signaling pathways. Mechanistically, SNHG11 influences the stability of PRPF8, a crucial mRNA spliceosome component, thereby affecting multiple cellular functions beyond splicing. In vivo experiments using a hypoxic rat model showed that knockdown of SNHG11 alleviates PH development and improves right ventricular function. These findings highlight SNHG11 as a key regulator in PH pathogenesis and suggest it as a potential therapeutic target.

Bioinspired Functional Composites for Enhanced Thermally Conductivity via Fractal-Growth CuNP Fillers.

Thermal conduction for electronic devices has attracted extensive attention in light of the development of 5G communication. Thermally conductive materials with high thermal conductivity and extensive mechanical flexibility are extremely desirable in practical applications. However, the construction of efficient interconnected conductive pathways and continuous conductive networks is inadequate for either processing or actual usage in existing technologies. In this work, spherical copper nanoparticles (S-CuNPs) and urchin-inspired fractal-growth CuNPs (U-CuNPs), thermally conductive metal fillers induced by ionic liquids, were fabricated successfully through the electrochemical deposition method. Compared to S-CuNPs, the U-CuNPs shows larger specific surface contact area, thus making it easier to build a continuous conductive pathway network in the corresponding U-CuNPs/liquid silicone rubber (LSR) thermally conductive composites. The optimal loading of CuNP fillers was determined by evaluating the rheological performance of the prepolymer and the mechanical properties and thermal conductivity performances of the composites. When the filler loading is 150 phr, the U-CuNPs/LSR produces optimal mechanical properties (e.g., tensile strength and modulus), thermal conductivity (above 1000% improvement compared to pure LSR), and heating/cooling efficiency. The enhanced thermal conductivity of U-CuNPs/LSR was also confirmed through the finite element analysis (FEA) overall temperature distribution, indicating that U-CuNPs with larger specific surface contact areas exhibit more advantages in forming a continuous network in composites than S-CuNPs, making U-CuNPs/LSR a promising and competitive alternative to traditional flexible thermally interface materials.

Dual Antiplatelet Therapy and Outcomes in Acute Mild to Moderate Stroke With Versus Without Large-Artery Atherosclerosis Post Hoc Analysis of ATAMIS.

BACKGROUND: We conducted a post hoc analysis of the ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial to investigate whether the priority of clopidogrel plus aspirin to aspirin alone was consistent between patients with and without stroke pathogenesis of large-artery atherosclerosis (LAA). METHODS AND RESULTS: Patients with stroke classification randomized to a clopidogrel-plus-aspirin group and aspirin-alone group in a modified intention-to-treat analysis set of ATAMIS were classified into LAA and non-LAA subtypes. The primary outcome was early neurologic deterioration at 7 days, defined as a >2-point increase in National Institutes of Health Stroke Scale score compared with baseline, and safety outcomes were bleeding events and intracranial hemorrhage. We compared treatment effects in each stroke subtype and investigated the interaction. Among 2910 patients, 225 were assigned into the LAA subtype (119 in the clopidogrel-plus-aspirin group and 106 in the aspirin-alone group) and 2685 into the non-LAA subtype (1380 in the clopidogrel-plus-aspirin group and 1305 in the aspirin-alone group). Median age was 66 years, and 35% were women. A lower proportion of early neurologic deterioration was found to be associated with dual antiplatelet therapy in the LAA subtype (adjusted risk difference, -10.4% [95% CI, -16.2% to -4.7%]; P=0.001) but not in the non-LAA subtype (adjusted risk difference, -1.4% [95% CI, -2.6% to 0.1%]; P=0.06). No significant interaction was found (P=0.11). CONCLUSIONS: Compared with the non-LAA subtype, patients with stroke of the LAA subtype may get more benefit from dual antiplatelet therapy with clopidogrel plus aspirin with respect to early neurologic deterioration at 7 days. REGISTRATION: URL: clinicaltrials.gov; UnIque identifier: NCT02869009.

Deciphering the cellular and molecular landscapes of Wnt/ß-catenin signaling in mouse embryonic kidney development.

Background: The Wnt/ß-catenin signaling pathway is critical in kidney development, yet its specific effects on gene expression in different embryonic kidney cell types are not fully understood. Methods: Wnt/ß-catenin signaling was activated in mouse E12.5 kidneys in vitro using CHIR99021, with RNA sequencing performed afterward, and the results were compared to DMSO controls (dataset GSE131240). Differential gene expression in ureteric buds and cap mesenchyme following pathway activation (datasets GSE20325 and GSE39583) was analyzed. Single-cell RNA-seq data from the Mouse Cell Atlas was used to link differentially expressed genes (DEGs) with kidney cell types. ß-catenin ChIP-seq data (GSE39837) identified direct transcriptional targets. Results: Activation of Wnt/ß-catenin signaling led to 917 significant DEGs, including the upregulation of Notum and Apcdd1 and the downregulation of Crym and Six2. These DEGs were involved in kidney development and immune response. Single-cell analysis identified 787 DEGs across nineteen cell subtypes, with Macrophage_Apoe high cells showing the most pronounced enrichment of Wnt/ß-catenin-activated genes. Gene expression profiles in ureteric buds and cap mesenchyme differed significantly upon ß-catenin manipulation, with cap mesenchyme showing a unique set of DEGs. Analysis of ß-catenin ChIP-seq data revealed 221 potential direct targets, including Dpp6 and Fgf12. Conclusion: This study maps the complex gene expression driven by Wnt/ß-catenin signaling in embryonic kidney cell types. The identified DEGs and ß-catenin targets elucidate the molecular details of kidney development and the pathway's role in immune processes, providing a foundation for further research into Wnt/ß-catenin signaling in kidney development and disease.