The "depict" strategy for discovering new compounds in complex matrices: Lycibarbarspermidines as a case.

The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge. Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) is the most prominent analytical platform for the exploration of novel active compounds from complex matrices. However, the LC-HRMS-based analysis workflow suffers from several bottleneck issues, such as trace content of target compounds, limited acquisition for fragment information, and uncertainty in interpreting relevant MS2 spectra. Lycibarbarspermidines are vital antioxidant active ingredients in Lycii Fructus, while the reported structures are merely focused on dicaffeoylspermidines due to their low content. To comprehensively detect the new structures of lycibarbarspermidine derivatives, a "depict" strategy was developed in this study. First, potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway, and a comprehensive database was established, which enlarged the coverage of lycibarbarspermidine derivatives. Second, the polarity-oriented sample preparation of potential new compounds increased the concentration of the target compounds. Third, the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of identification. Finally, the weak response signals were captured by data-dependent scanning (DDA) followed by parallel reaction monitoring (PRM), and the efficiency of acquiring MS2 fragment ions of target compounds was significantly improved. Based on the integrated strategy above, 210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus, and in particular, 170 potential new compounds were structurally characterized. The integrated strategy improved the sensitivity of detection and the coverage of low-response components, and it is expected to be a promising pipeline for discovering new compounds.

Aerobic fitness as a moderator of acute aerobic exercise effects on executive function.

This study aimed to investigate the moderating role of aerobic fitness on the effect of acute exercise on improving executive function from both behavioral and cerebral aspects. Thirty-four young individuals with motor skills were divided into high- and low-fitness groups based on their maximal oxygen uptake. Both groups completed 30 min of moderate-intensity aerobic exercise on a power bike. Executive function tests (Flanker, N-back, More-odd-shifting) were performed before and after exercise and functional near-infrared spectroscopy was used to monitor prefrontal cerebral blood flow changes during the tasks. The results indicated significant differences between the two groups regarding executive function. Participants with lower aerobic fitness performed better than their higher fitness counterparts in inhibitory control and working memory, but not in cognitive flexibility. This finding suggests that the aerobic fitness may moderate the extent of cognitive benefits gained from acute aerobic exercise. Furthermore, the neuroimaging data indicated negative activation in the frontopolar area and dorsolateral prefrontal cortex in response to three complex tasks. These findings underscore the importance of considering individual aerobic fitness when assessing the cognitive benefits of exercise and could have significant implications for tailoring fitness programs to enhance cognitive performance.

Heterogeneous reaction of NO2 with hematite: The effects of UV irradiation, O2 and relative humidity.

Heterogeneous reactions on mineral dust surfaces are increasingly considered important in the removal of gaseous pollutants and the formation of secondary aerosols. Although the heterogeneous reaction of NO2 on the hematite surface has been investigated in many previous studies, little is known about the reaction of NO2 with hematite under ambient conditions. In this work, heterogeneous reactions of NO2 with hematite at 298 K were investigated via a coated-wall flow tube reactor and in situ diffuse reflectance Fourier transformed infrared spectroscopy (DRIFTS). The influence of UV illumination, relative humidity (RH) and O2 on the uptake coefficients and adsorption amount of NO2, as well as the nitrate formation on the hematite surface, has been analyzed comprehensively. UV irradiation shows a significant effect on the true uptake coefficient (γBET), which increases from 2.00 × 10-6 to 4.76 × 10-6 in the N2 stream and 1.32 × 10-6 to 4.07 × 10-6 in the air stream under dry conditions (∼0.3 % RH). RH (in the range of 0-67 %) exhibits an inhibitory effect on the adsorption of NO2 on the hematite surface because of the competition between NO2 and water molecules, that is, γBET and adsorption amount of NO2 decrease with an increase in RH under both the dark and light reaction conditions. Meanwhile, both the γBET and adsorption amount of NO2 on hematite decrease in the air stream compared to those in N2 conditions. In addition, the results from the DRIFTS experiments indicate that the presence of UV irradiation promotes the conversion of NO2 to nitrate and both the RH and O2 suppress the nitrate formation. From this research, the heterogeneous reactions between NO2 with mineral dust under ambient conditions will be better understood.

Exosomal miR-9-5p derived from iPSC-MSCs ameliorates doxorubicin-induced cardiomyopathy by inhibiting cardiomyocyte senescence.

Doxorubicin (DOX) is a chemotherapeutic agent widely used for tumor treatment. Nonetheless its clinical application is heavily limited by its cardiotoxicity. There is accumulated evidence that transplantation of mesenchymal stem cell-derived exosomes (MSC-EXOs) can protect against Dox-induced cardiomyopathy (DIC). This study aimed to examine the cardioprotective effects of EXOs isolated from human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) against DIC and explore the potential mechanisms. EXOs were isolated from the cultural supernatant of human BM-MSCs (BM-MSC-EXOs) and iPSC-MSCs (iPSC-MSC-EXOs) by ultracentrifugation. A mouse model of DIC was induced by intraperitoneal injection of Dox followed by tail vein injection of PBS, BM-MSC-EXOs, or iPSC-MSC-EXOs. Cardiac function, cardiomyocyte senescence and mitochondrial dynamics in each group were assessed. In vitro, neonatal mouse cardiomyocytes (NMCMs) were subjected to Dox and treated with BM-MSC-EXOs or iPSC-MSC-EXOs. The mitochondrial morphology and cellular senescence of NMCMs were examined by Mitotracker staining and senescence-associated-ß-galactosidase assay, respectively. Compared with BM-MSC-EXOs, mice treated with iPSC-MSC-EXOs displayed improved cardiac function and decreased cardiomyocyte mitochondrial fragmentation and senescence. In vitro, iPSC-MSC-EXOs were superior to BM-MSC-EXOs in attenuation of cardiomyocyte mitochondrial fragmentation and senescence caused by DOX. MicroRNA sequencing revealed a higher level of miR-9-5p in iPSC-MSC-EXOs than BM-MSC-EXOs. Mechanistically, iPSC-MSC-EXOs transported miR-9-5p into DOX-treated cardiomyocytes, thereby suppressing cardiomyocyte mitochondrial fragmentation and senescence via regulation of the VPO1/ERK signal pathway. These protective effects and cardioprotection against DIC were largely reversed by knockdown of miR-9-5p in iPSC-MSC-EXOs. Our results showed that miR-9-5p transferred by iPSC-MSC-EXOs protected against DIC by alleviating cardiomyocyte senescence via inhibition of the VPO1/ERK pathway. This study offers new insight into the application of iPSC-MSC-EXOs as a novel therapeutic strategy for DIC treatment.

An ARF gene mutation creates flint kernel architecture in dent maize.

Dent and flint kernel architectures are important characteristics that affect the physical properties of maize kernels and their grain end uses. The genes controlling these traits are unknown, so it is difficult to combine the advantageous kernel traits of both. We found mutation of ARFTF17 in a dent genetic background reduces IAA content in the seed pericarp, creating a flint-like kernel phenotype. ARFTF17 is highly expressed in the pericarp and encodes a protein that interacts with and inhibits MYB40, a transcription factor with the dual functions of repressing PIN1 expression and transactivating genes for flavonoid biosynthesis. Enhanced flavonoid biosynthesis could reduce the metabolic flux responsible for auxin biosynthesis. The decreased IAA content of the dent pericarp appears to reduce cell division and expansion, creating a shorter, denser kernel. Introgression of the ARFTF17 mutation into dent inbreds and hybrids improved their kernel texture, integrity, and desiccation, without affecting yield.

Scopoletin: a review of its pharmacology, pharmacokinetics, and toxicity.

Scopoletin is a coumarin synthesized by diverse medicinal and edible plants, which plays a vital role as a therapeutic and chemopreventive agent in the treatment of a variety of diseases. In this review, an overview of the pharmacology, pharmacokinetics, and toxicity of scopoletin is provided. In addition, the prospects and outlook for future studies are appraised. Scopoletin is indicated to have antimicrobial, anticancer, anti-inflammation, anti-angiogenesis, anti-oxidation, antidiabetic, antihypertensive, hepatoprotective, and neuroprotective properties and immunomodulatory effects in both in vitro and in vivo experimental trials. In addition, it is an inhibitor of various enzymes, including choline acetyltransferase, acetylcholinesterase, and monoamine oxidase. Pharmacokinetic studies have demonstrated the low bioavailability, rapid absorption, and extensive metabolism of scopoletin. These properties may be associated with its poor solubility in aqueous media. In addition, toxicity research indicates the non-toxicity of scopoletin to most cell types tested to date, suggesting that scopoletin will neither induce treatment-associated mortality nor abnormal performance with the test dose. Considering its favorable pharmacological activities, scopoletin has the potential to act as a drug candidate in the treatment of cancer, liver disease, diabetes, neurodegenerative disease, and mental disorders. In view of its merits and limitations, scopoletin is a suitable lead compound for the development of new, efficient, and low-toxicity derivatives. Additional studies are needed to explore its molecular mechanisms and targets, verify its toxicity, and promote its oral bioavailability.

Inducing aortic aneurysm/dissection in zebrafish: evaluating the efficacy of ß-Aminopropionic Nitrile as a model.

Aortic aneurysm/dissection (AAD) poses a life-threatening cardiovascular emergency with complex mechanisms and a notably high mortality rate. Zebrafish (Danio rerio) serve as valuable models for AAD due to the conservation of their three-layered arterial structure and genome with that of humans. However, the existing studies have predominantly focused on larval zebrafish, leaving a gap in our understanding of adult zebrafish. In this study, we utilized ß-Aminopropionic Nitrile (BAPN) impregnation to induce AAD in both larval and adult zebrafish. Following induction, larval zebrafish exhibited a 28% widening of the dorsal aortic diameter (p < 0.0004, n = 10) and aortic arch malformations, with a high malformation rate of 75% (6/8). Conversely, adult zebrafish showed a 41.67% (5/12) mortality rate 22 days post-induction. At this time point, the dorsal aortic area had expanded by 2.46 times (p < 0.009), and the vessel wall demonstrated significant thickening (8.22 ± 2.23 µM vs. 26.38 ± 10.74 µM, p < 0.05). Pathological analysis revealed disruptions in the smooth muscle layer, contributing to a 58.33% aneurysm rate. Moreover, the expression levels of acta2, tagln, cnn1a, and cnn1b were decreased, indicating a weakened contractile phenotype. Transcriptome sequencing showed a significant overlap between the molecular features of zebrafish tissues post-BAPN treatment and those of AAD patients. Our findings present a straightforward and practical method for generating AAD models in both larval and adult zebrafish using BAPN.

Combination of near-infrared spectroscopy with Wasserstein generative adversarial networks for rapidly detecting raw material quality for formula products.

Near-infrared spectroscopy (NIRS) has emerged as a key technique for rapid quality detection owing to its fast, non-destructive, and eco-friendly characteristics. However, its practical implementation within the formulation industry is challenging owing to insufficient data, which renders model fitting difficult. The complexity of acquiring spectra and spectral reference values results in limited spectral data, aggravating the problem of low generalization, which diminishes model performance. To address this problem, we introduce what we believe to be a novel approach combining NIRS with Wasserstein generative adversarial networks (WGANs). Specifically, spectral data are collected from representative samples of raw material provided by a formula enterprise. Then, the WGAN augments the database by generating synthetic data resembling the raw spectral data. Finally, we establish various prediction models using the PLSR, SVR, LightGBM, and XGBoost algorithms. Experimental results show the NIRS-WGAN method significantly improves the performance of prediction models, with R2 and RMSE of 0.949 and 1.415 for the chemical components of sugar, respectively, and 0.922 and 0.243 for nicotine. The proposed framework effectively enhances the predictive capabilities of various models, addressing the issue caused by limited training data in NIRS prediction tasks.

Bionic structure and biocompatibilities of long chain branched poly(L-lactic acid) oriented microcellular foaming material.

In order to solve the problem of uneven microporous structure of Poly(L-lactic acid) (PLLA) bulk orientation by using biological safety multi-functional plant oil as chain extenders (CE), multi-armed flexible chains were introduced into PLLA through reactive processing to prepare long chain branched PLLA (LCB-PLLA). When the total content of the CE was 6.15 wt%, PLLA and the CE reacted most fully, while maintaining the tensile strength of PLLA and improving toughness. After introducing the LCB structure, the presence of multi-armed flexible chains increased the mobility of the molecular chains, resulting in a significantly lower degree of crystallinity. When the draw ratio up to 900 %, the crystallinity of LCB-PLLA-F-900 % was only 45.15 %, lower than that of PLLA-F-900 %. Thanks to the mobility of polymer chains can be enhanced, which reduces the degree of crystallinity while promoting the uniform growth of oriented microporous structures. Finally, an oriented micro-porous biomimetic LCB-PLLA material with an average cell diameter of 540 nm was prepared, and the results of in vitro cell culture showed that the oriented micro-porous LCB-PLLA biomimetic material was more conducive to cell proliferation.

Magnolol extends lifespan and improves age-related neurodegeneration in Caenorhabditis elegans via increase of stress resistance.

Magnolol is a naturally occurring polyphenolic compound in many edible plants, which has various biological effects including anti-aging and alleviating neurodegenerative diseases. However, the underlying mechanism on longevity is uncertain. In this study, we investigated the effect of magnolol on the lifespan of Caenorhabditis elegans and explored the mechanism. The results showed that magnolol treatment significantly extended the  lifespan of nematode and alleviated senescence-related decline in the nematode model. Meanwhile, magnolol enhanced stress resistance to heat shock, hydrogen peroxide (H2O2), mercuric potassium chloride (MeHgCl) and paraquat (PQ) in nematode. In addition, magnolol reduced reactive oxygen species and malondialdehyde (MDA) levels, and increased superoxide dismutase and catalase (CAT) activities in nematodes. Magnolol also up-regulated gene expression of sod-3, hsp16.2, ctl-3, daf-16, skn-1, hsf-1, sir2.1, etc., down-regulated gene expression of daf-2, and promoted intranuclear translocation of daf-16 in nematodes. The lifespan-extending effect of magnolol were reversed in insulin/IGF signaling (IIS) pathway-related mutant lines, including daf-2, age-1, daf-16, skn-1, hsf-1 and sir-2.1, suggesting that IIS signaling is involved in the modulation of longevity by magnolol. Furthermore, magnolol improved the age-related neurodegeneration in PD and AD C. elegans models. These results indicate that magnolol may enhance lifespan and health span through IIS and sir-2.1 pathways. Thus, the current findings implicate magnolol as a potential candidate to ameliorate the symptoms of aging.

Targeting GRP75 with a Chlorpromazine Derivative Inhibits Endometrial Cancer Progression Through GRP75-IP3R-Ca2+-AMPK Axis.

Tumors often overexpress glucose-regulated proteins, and agents that interfere with the production or activity of these proteins may represent novel cancer treatments. The chlorpromazine derivative JX57 exhibits promising effects against endometrial cancer with minimal extrapyramidal side effects; however, its mechanisms of action are currently unknown. Here, glucose-regulated protein 75 kD (GRP75) is identified as a direct target of JX57 using activity-based protein profiling and loss-of-function experiments. The findings show that GRP75 is necessary for the biological activity of JX57, as JX57 exhibits moderate anticancer properties in GRP75-deficient cancer cells, both in vitro and in vivo. High GRP75 expression is correlated with poor differentiation and poor survival in patients with endometrial cancer, whereas the knockdown of GRP75 can significantly suppress tumor growth. Mechanistically, the direct binding of JX57 to GRP75 impairs the structure of the mitochondria-associated endoplasmic reticulum membrane and disrupts the endoplasmic reticulum-mitochondrial calcium homeostasis, resulting in a mitochondrial energy crisis and AMP-activated protein kinase activation. Taken together, these findings highlight GRP75 as a potential prognostic biomarker and direct therapeutic target in endometrial cancer and suggest that the chlorpromazine derivative JX57 can potentially be a new therapeutic option for endometrial cancer.

Integrated waveguide coupled ultralow-loss multimode waveguides based on silicon nitride resonators.

On-chip micro-ring resonators (MRRs) with low loss and large free spectral ranges (FSRs) are important for photonic devices. So far, ultra-low-loss silicon-nitride (Si3N4) waveguides are primarily fabricated in laboratories, as they often demand special processes to reduce transmission losses. While, Si3N4 waveguides fabricated by the standard multi-project wafer (MPW)-based processes often suffer from significant sidewall scattering, resulting in high scattering losses. Here, we present an innovative approach to photonics by introducing a compact and multi-mode structure. This approach significantly reduces the contact between the optical field and the rough sidewalls in the high-confinement Si3N4 waveguide. By incorporating modified Euler bends, and a weakly tapered gap directional coupler, adiabatic transmission with simultaneous ultra-low loss and compact size is achieved even in 7-µm wide waveguide. Results show that the intrinsic quality factor Qi of MRR is (6.8 ± 0.4) × 106 at the wavelength of 1550 nm, which is approximately four times higher than the previously reported by the same fabrication process. An ultra-low loss of 0.051 ± 0.003 dB/cm is achieved based on the standard LIGENTEC-AN800 technology. This accomplishment addresses a critical challenge in high-confinement waveguides. Our work provides new insights into the low propagation loss in Si3N4 waveguides and provides a broader prospect for integrated photonics in the ultra-high-Q regime.

Transcriptome analysis reveals therapeutic potential of NAMPT in protecting against abdominal aortic aneurysm in human and mouse.

Abdominal Aortic Aneurysm (AAA) is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta, which has no effective therapeutic approaches due to unclear molecular mechanisms. Using single-cell RNA sequencing, we analyzed the molecular profile of individual cells within control and AAA abdominal aortas. We found cellular heterogeneity, with increased plasmacytoid dendritic cells and reduced endothelial cells and vascular smooth muscle cells (VSMCs) in AAA. Up-regulated genes in AAA were associated with muscle tissue development and apoptosis. Genes controlling VSMCs aberrant switch from contractile to synthetic phenotype were significantly enriched in AAA. Additionally, VSMCs in AAA exhibited cell senescence and impaired oxidative phosphorylation. Similar observations were made in a mouse model of AAA induced by Angiotensin II, further affirming the relevance of our findings to human AAA. The concurrence of gene expression changes between human and mouse highlighted the impairment of oxidative phosphorylation as a potential target for intervention. Nicotinamide phosphoribosyltransferase (NAMPT, also named VISFATIN) signaling emerged as a signature event in AAA. NAMPT was significantly downregulated in AAA. NAMPT-extracellular vesicles (EVs) derived from mesenchymal stem cells restored NAMPT levels, and offered protection against AAA. Furthermore, NAMPT-EVs not only repressed injuries, such as cell senescence and DNA damage, but also rescued impairments of oxidative phosphorylation in both mouse and human AAA models, suggesting NAMPT supplementation as a potential therapeutic approach for AAA treatment. These findings shed light on the cellular heterogeneity and injuries in AAA, and offered promising therapeutic intervention for AAA treatment.

Mulberrin extends lifespan in Caenorhabditis elegans through detoxification function.

Mulberrin, a naturally occurring flavone found in mulberry and Romulus Mori, exhibits diverse biological functions. Here, we showed that mulberrin extended both the lifespan and healthspan in C. elegans. Moreover, mulberrin increased the worms' resistance to toxicants and activated the expression of detoxification genes. The longevity-promoting effect of mulberrin was attenuated in nuclear hormone receptor (NHR) homologous nhr-8 and daf-12 mutants, indicating that the lifespan extending effects of mulberrin in C. elegans may depend on nuclear hormone receptors NHR-8/DAF-12. Further analyses revealed the potential associations between the longevity effects of mulberrin and the insulin/insulin-like growth factor signaling (IIS) and adenosine 5'-monophosphate-activated protein kinase (AMPK) pathways. Together, our findings suggest that mulberrin may prolong lifespan and healthspan by activating detoxification functions mediated by nuclear receptors.

Halomonas rhizosphaerae sp. nov. and Halomonas kalidii sp. nov., two novel moderate halophilic phenolic acid-degrading species isolated from saline soil.

Four vanillic acid-degrading bacterial strains, named LR5S13T, LR5S20, and M4R5S39T and LN1S58, were isolated from Kalidium cuspidatum rhizosphere and bulk soils, respectively. Phylogenetic analysis based on 16S rRNA gene as well as core genome revealed that LR5S13T and LR5S20 clustered closely with each other and with Halomonas ventosae Al12T, and that the two strains shared the highest similarities (both 99.3 %) with H. ventosae Al12T, in contrast, M4R5S39T and LN1S58 clustered together and with Halomonas heilongjiangensis 9-2T, and the two strains shared the highest similarities (99.4 and 99.2 %, respectively) with H. heilongjiangensis 9-2T. The average nucleotides identities based on BLAST (ANIb) and digital DNA-DNA hybridization (dDDH) values of strains LR5S13T to LR5S20, and M4R5S39T to LN1S58, were both higher than the threshold values for delineation of a species. The ANIb and dDDH values of the four strains to their closely relatives were lower than the threshold values. All four strains take phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol as the major polar lipids, Summed Feature 8, Summed Feature 3, and C16:0 as the major fatty acids. Based on the phylogenetic and phenotypic results, the four strains should be classified as two novel Halomonas species. Therefore, Halomonas rhizosphaerae sp. nov. (type strain LR5S13T = KCTC 8016T = CGMCC 1.62049T) and Halomonas kalidii (type strain M4R5S39T = KCTC 8015T = CGMCC 1.62047T) are proposed. The geographical distribution analysis based on 16S rRNA gene revealed that the two novel species are widely distributed across the globe, specifically in highly saline habits, especially in Central and Eastern Asia.

Enhancing skeletal age estimation accuracy using support vector regression models.

OBJECTIVE: The objective of the study was to determine if support vector regression (SVR) models could enhance the accuracy of skeletal age estimation compared to original metrics. METHOD: The study used a dataset of 5,018 individuals from Wuhan, spanning ages 1 to 17. Optimal model parameters were found using cross-validation and grid search techniques. The study compared SVR-based bone age assessment metrics with original metrics and evaluated the performance of the SVR model across different sample sizes. RESULTS: The findings unequivocally demonstrated SVR's superior reliability over original metrics in assessing bone age among children in central China. Regardless of the training set size, constructing SVR models based on TW3, CHN05, or a combination of TW3, CHN05, and GP consistently results in top-tier predictive accuracy. CONCLUSION: This research highlights SVR's potential for accuracy improvement and robustness with limited datasets.

Gene Interaction of Dopaminergic Synaptic Pathway Genes in Attention-Deficit Hyperactivity Disorder: a Case-Control Study in Chinese Children.

Attention-deficit hyperactivity disorder is a highly inherited neurodevelopmental disorder. Previous genetic research has linked ADHD to certain genes in the dopaminergic synaptic pathway. Nonetheless, research on this relationship has produced varying results across various populations. China is a multi-ethnic country with its own unique genetic characteristics. Therefore, such a population can provide useful information about the relationship between gene polymorphisms in dopaminergic synaptic pathways and ADHD. This study looked at the genetic profiles of 284 children in China's Xinjiang. In total, 142 ADHD children and 142 control subjects were enrolled. Following the extraction of DNA from oral mucosal cells, 13 SNPs for three candidate genes (SLC6A3, DRD2, and GRIN2B) in the dopaminergic synaptic pathway of ADHD were screened. Based on the results of single nucleotide polymorphism (SNP) analyses, we found that the DRD2 gene variants rs6277 and rs6275, and the SLC6A3 gene variant rs2652511, were significantly associated with ADHD in boys and girls, respectively, after adjusting for false discovery rate (FDR) in terms of allele frequencies. Furthermore, our generalized multifactorial downscaling approach identified a significant association between rs6275 and rs1012586. These findings suggest that DRD2 and SLC6A3 genes have a crucial role in ADHD susceptibility. Additionally, we observed that the interaction between GRIN2B and DRD2 genes may contribute to the susceptibility of Chinese children with ADHD.

[Construction and application of virtual simulation teaching platform for in-hospital emergency nursing of craniofacial injury patients].

PURPOSE: To construct a virtual simulation teaching platform for in-hospital emergency nursing of craniofacial injury patients by virtual simulation technology, and to evaluate its application effect. METHODS: Through virtual reality, animation, human-computer interaction and other technologies, a 3D experiment scene based on high simulation virtual human was constructed to reproduce the virtual rescue scenes of craniofacial injury patients, such as emergency reception, first-aid cooperation, massive hemorrhage rescue cooperation, and tracheotomy cooperation in emergency rescue of sudden airway obstruction, and exercise modules and assessment modules were set. In the virtual simulation platform, the students used the holistic nursing theory and the PDCA cycle method to observe, evaluate and care for craniofacial injury patients. Preliminary evaluation of the platform was carried out in the training of 62 dental nurses. RESULTS: The virtual simulation platform could improve students' comprehensive first-aid ability for craniofacial injury patients. The item with the highest satisfaction rate for the virtual simulation platform was the consistency between the content of the virtual simulation platform and the theoretical course (the satisfaction rate was 91.9%), and the lowest satisfaction rate was the convenience of the virtual simulation platform operation and the page setting (the satisfaction rate was 80.6%). The evaluation module of the virtual simulation platform showed that the highest score of the comprehensive evaluation was 97, the lowest score was 56, and the average score was 80.2. CONCLUSIONS: The virtual simulation teaching platform for in-hospital first aid of craniofacial injury patients can create an immersive learning mode, provide an intuitive rescue experience to the students, and improve their comprehensive first-aid ability.

Involvement of plasminogen activator inhibitor-1 in p300/p53-mediated age-related atrial fibrosis.

Plasminogen activator inhibitor-1 (PAI-1), a key regulator of the fibrinolytic system, is also intimately involved in the fibrosis. Although PAI-1 may be involved in the occurrence of atrial fibrillation (AF) and thrombosis in the elderly, but whether it participated in aging-related atrial fibrosis and the detailed mechanism is still unclear. We compared the transcriptomics data of young (passage 4) versus senescent (passage 14) human atrial fibroblasts and found that PAI-1 was closely related to aging-related fibrosis. Aged mice and senescent human and mouse atrial fibroblasts underwent electrophysiological and biochemical studies. We found that p300, p53, and PAI-1 protein expressions were increased in the atrial tissue of aged mice and senescent human and mouse atrial fibroblasts. Curcumin or C646 (p300 inhibitor), or p300 knockdown inhibited the expression of PAI-1 contributing to reduced atrial fibroblasts senescence, atrial fibrosis, and the AF inducibility. Furthermore, p53 knockdown decreased the protein expression of PAI-1 and p21 in senescent human and mouse atrial fibroblasts. Our results suggest that p300/p53/PAI-1 signaling pathway participates in the mechanism of atrial fibrosis induced by aging, which provides new sights into the treatment of elderly AF.

Downregulation of ALKBH5 rejuvenates aged human mesenchymal stem cells and enhances their therapeutic efficacy in myocardial infarction.

Despite promising results in myocardial infarction (MI), mesenchymal stem cell (MSC)-based therapy is limited by cell senescence. N6-methyladenosine (m6A) messenger RNA methylation has been reported to be closely associated with cell senescence. Nonetheless, its role in the regulation of MSC senescence remains unclear. We examined the role of ALKB homolog 5 (ALKBH5) in regulating MSC senescence and determined whether ALKBH5 downregulation could rejuvenate aged MSCs (AMSCs) to improve their therapeutic efficacy for MI. RNA methylation was determined by m6A dot blotting assay. MSC senescence was evaluated by senescence-associated ß-galactosidase (SA-ß-gal) staining. A mouse model of acute MI was established by ligation of the left anterior decedent coronary artery (LAD). Compared with young MSCs (YMSCs), m6A level was significantly reduced but ALKBH5 was greatly increased in AMSCs. Overexpression of ALKBH5 reduced m6A modification and accelerated YMSC senescence. Conversely, ALKBH5 knockdown increased m6A modifications and alleviated AMSC senescence. Mechanistically, ALKBH5 regulated the m6A modification and stability of CDKN1C mRNA, which further upregulated CDKN1C expression, leading to MSC senescence. CDKN1C overexpression ameliorated the inhibition of cellular senescence of ALKBH5 siRNA-treated AMSCs. More importantly, compared with AMSCs, shALKBH5-AMSCs transplantation provided a superior cardioprotective effect against MI in mice by improving MSC survival and angiogenesis. We determined that ALKBH5 accelerated MSC senescence through m6A modification-dependent stabilization of the CDKN1C transcript, providing a potential target for MSC rejuvenation. ALKBH5 knockdown rejuvenated AMSCs and enhanced cardiac function when transplanted into the mouse heart following infarction.