Unveiling the molecular mechanisms of Dendrobium officinale polysaccharides on intestinal immunity: An integrated study of network pharmacology, molecular dynamics and in vivo experiments.

Intestinal immunity plays a pivotal role in overall immunological defenses, constructing mechanisms against pathogens while maintaining balance with commensal microbial communities. Existing therapeutic interventions may lead to drug resistance and potential toxicity when immune capacity is compromised. Dendrobium officinale, a traditional Chinese medicine, contains components identified to bolster immunity. Employing network pharmacology strategies, this study identified constituents of Dendrobium officinale and their action targets in the TCMSP and Swiss Target Prediction databases, and compared them with intestinal immunity-related targets. Protein-protein interaction networks revealed the core targets of Dendrobium officinale polysaccharides, encompassing key pathways such as cell proliferation, inflammatory response, and immune reactions, particularly in association with the Toll-like receptor 4. Molecular docking and molecular dynamics simulation further confirmed the high affinity and stability between Dendrobium officinale polysaccharides and Toll-like receptor 4. In vivo experiments demonstrated that Dendrobium officinale polysaccharides modulates the expression of Toll-like receptor 4 and its downstream key proteins in the colonic mucosa of mice. Consequently, these findings suggest that Dendrobium officinale polysaccharides may serve as a potential modulator for intestinal immune functions, with its mechanism potentially related to the Toll-like receptor 4.

Fluorinated Titanium Oxide (TiO2-xFx) Nanospindles as Ultrasound-Triggered Pyroptosis Inducers to Boost Sonodynamic Immunotherapy.

Pyroptosis is an inflammatory form of programmed cell death associated with the immune system that can be induced by reactive oxygen species (ROS). As a therapeutic strategy with better penetration depth, sonodynamic therapy (SDT) is expected to induce pyroptosis of cancer cells and boost the immune response. However, it is still a limited problem to precisely adjust the structure of sonosensitizers to exhibit satisfactory sono-catalytic properties. Herein, fluorinated titanium oxide (TiO2-xFx) sonosensitizers were developed to induce pyroptosis under ultrasound (US) to boost antitumor immune responses, enabling highly effective SDT. On the one hand, the introduction of F atoms significantly reduced the adsorption energy of TiO2-xFx for oxygen and water, which is conducive to the occurrence of sono-catalytic reactions. On the other hand, the process of F replacing O increased the oxygen vacancies of the sonosensitizer and shortened the band gap, which enabled powerful ROS generation ability under US stimulation. In this case, large amounts of ROS could effectively kill cancer cells by inducing mitochondrial damage and disrupting oxidative homeostasis, leading to significant cell pyroptosis. Moreover, SDT treatment with TiO2-xFx not only suppressed tumor proliferation but also elicited robust immune memory effects and hindered tumor recurrence. This work highlighted the importance of precisely regulating the structure of sonosensitizers to achieve efficient ROS generation for inducing pyroptosis, which sets the stage for the further development of SDT-immunotherapy.

The jasmonate pathway promotes nodule symbiosis and suppresses host plant defense in Medicago truncatula.

Root nodule symbiosis (RNS) between legume and rhizobia is a major source of nitrogen in agricultural systems. Effective symbiosis requires precise regulation of plant defense responses. The role of the defense hormone jasmonic acid in the immune response has been extensively studied. The current research shows that JA can play either a positive or negative regulatory role in RNS depending on its concentration, while the molecular mechanisms remain to be elucidated. Here, we found that inoculation with rhizobia Sm1021 induced the JA pathway response in Medicago truncatula, and blocking JA pathway significantly reduced the number of infection threads. Mutations in the MtMYC2 gene, a JA signaling master transcription factor, significantly inhibited rhizobia infection, terminal differentiation, and symbiotic cell formation. Combining RNA-seq and ChIP-seq, we discovered that MtMYC2 regulates the expression of nodule-specific MtDNF2, MtNAD1, and MtSymCRK to suppress host defense. MtMYC2 activates MtDNF1 expression to regulate the maturation of MtNCRs, which in turn promotes bacteroid formation. More importantly, MtMYC2 promotes the expression of MtIPD3 to participate in symbiotic signaling transduction. Notably, the MtMYC2-MtIPD3 transcriptional regulation module is specifically present in legumes. Additionally, The Mtmyc2 mutants exhibits a susceptible phenotype to Rhizoctonia solani. Collectively, our findings reveal the molecular mechanisms of the JA pathway in RNS and further broaden the understanding of JA in the plant-microbe interaction network.

Reliability and validity of the Chinese version of the Information Security Attitude Questionnaire for nurses.

AIM: Nurses play a crucial role within medical institutions, maintaining direct interaction with patient data. Despite this, there is a scarcity of tools for evaluating nurses' perspectives on patient information security. This study aimed to translate the Information Security Attitude Questionnaire into Chinese and validate its reliability and validity among clinical nurses. DESIGN: A cross-sectional design. METHODS: A total of 728 clinical nurses from three hospitals in China participated in this study. The Information Security Attitude Questionnaire (ISA-Q) was translated into Chinese utilizing the Brislin two-way translation method. The reliability was assessed through internal consistency coefficient and test-retest reliability. The validity was determined through the Delphi expert consultation method and factor analysis. RESULTS: The Chinese version of ISA-Q consists of 30 items. Cronbach's α coefficient of the questionnaire was 0.930, and Cronbach's α coefficient of the six dimensions ranged from 0.781 to 0.938. The split-half reliability and test-retest reliability were 0.797 and 0.848, respectively. The content validity index (S-CVI) was 0.962. Exploratory factor analysis revealed a 6-factor structure supported by eigenvalues, total variance interpretation, and scree plots, accounting for a cumulative variance contribution rate of 69.436%. Confirmatory factor analysis further validated the 6-factor structure, demonstrating an appropriate model fit. CONCLUSION: The robust reliability and validity exhibited by the Chinese version of ISA-Q establish it as a dependable tool for evaluating the information security attitudes of clinical nurses. IMPLICATIONS FOR NURSING PRACTICE: The Chinese iteration of the ISA-Q questionnaire offers a profound insight into the information security attitudes held by clinical nurses. This understanding serves as a foundation for nursing managers to develop targeted intervention strategies aimed at fortifying nurses' information security attitudes, thereby enhancing patient safety.

2D Hybrid Perovskites: From Static and Dynamic Structures to Potential Applications.

2D perovskites have received great attention recently due to their structural tunability and environmental stability, making them highly promising candidates for various applications by breaking property bottlenecks that affect established materials. However, in 2D perovskites, the complicated interplay between organic spacers and inorganic slabs makes structural analysis challenging to interpret. A deeper understanding of the structure-property relationship in these systems is urgently needed to enable high-performance tunable optoelectronic devices. Herein, this study examines how structural changes, from constant lattice distortion and variable structural evolution, modeled with both static and dynamic structural descriptors, affect macroscopic properties and ultimately device performance. The effect of chemical composition, crystallographic inhomogeneity, and mechanical-stress-induced static structural changes and corresponding electronic band variations is reported. In addition, the structure dynamics are described from the viewpoint of anharmonic vibrations, which impact electron-phonon coupling and the carriers' dynamic processes. Correlated carrier-matter interactions, known as polarons and acting on fine electronic structures, are then discussed. Finally, reliable guidelines to facilitate design to exploit structural features and rationally achieve breakthroughs in 2D perovskite applications are proposed. This review provides a global structural landscape of 2D perovskites, expected to promote the prosperity of these materials in emerging device applications.

Long, short, and medium terms wind speed prediction model based on LSTM optimized by improved moth flame optimization algorithm.

Time series prediction of wind speed has been widely used in wind power generation. The volatility and instability of wind speed have a large negative impact on wind turbines and power systems, which can lead to grid collapse in severe cases. Therefore, accurate wind speed prediction is crucial for wind power generation. In this paper, considering the influence of different parameters on algorithm training and prediction, an improved moth flame optimization algorithm is constructed to optimize the LSTM wind energy prediction system to obtain better performance. The system consists of three modules: data preprocessing, optimization, and prediction. The data preprocessing module uses fuzzy information granulation to blur the input data. On this basis, the combination of swarm intelligent optimization algorithm and prediction model can effectively predict wind speed time series. Taking the California wind farm as an example, the MAPE of the experiment in the short-term forecast is 3.15%, the MAPE of the medium-term forecast is 4.38%, and the MAPE of the long-term forecast is 18.28%. The experimental results show that the proposed model has obvious advantages over the previous model.

Manganese-Doped Potassium Chloride Nanoelectrodes to Potentiate Electrochemical Immunotherapy.

Hypochlorous acid (HClO), as a powerful oxidizer, is obtained from the oxidation of Cl- ions during the electrochemical therapy (EChT) process for cancer therapy. However, the extracellular generated HClO is inadequate to inhibit effective tumor cell death. Herein, manganese-doped potassium chloride nanocubes (MPC NCs) fabricated and modified with amphipathic polymer PEG (PMPC NCs) to function as massive three-dimensional nanoelectrodes (NEs) were developed to enhance the generation of HClO for electrochemical immunotherapy under an alternating electric field. Under an square-wave alternating current (AC) electric field, the generation of HClO was boosted by PMPC NEs due to the enlarged active surface area, enhanced mass transfer rate, and improved electrocatalytic activity. Notably, PMPC NEs upregulated the intracellular HClO concentration to induce robust immunogenic cell death (ICD) under an AC electric field. Meanwhile, the electric-triggered release of Mn2+ effectively stimulated dendritic cells (DCs) maturation. In vivo results illustrated that PMPC-mediated EChT inhibited tumor growth and triggered the promotion of the immune response to regulate the tumor immune microenvironment. Based on the potent antitumor immunity, PMPC-mediated EChT was further combined with an immune checkpoint inhibitor (αCTLA-4) to realize combined EChT-immunotherapy, which demonstrated enhanced tumor inhibition of the primary tumors and an abscopal effect on distant tumors. To summarize, our work highlights the application of electrochemical-immunotherapy technology in tumor therapy.

LaMYC7, a positive regulator of linalool and caryophyllene biosynthesis, confers plant resistance to Pseudomonas syringae.

Linalool and caryophyllene are the main monoterpene and sesquiterpene compounds in lavender; however, the genes regulating their biosynthesis still remain many unknowns. Here, we identified LaMYC7, a positive regulator of linalool and caryophyllene biosynthesis, confers plant resistance to Pseudomonas syringae. LaMYC7 was highly expressed in glandular trichomes, and LaMYC7 overexpression could significantly increase the linalool and caryophyllene contents and reduce susceptibility to P. syringae in Nicotiana. In addition, the linalool possessed antimicrobial activity against P. syringae growth and acted dose-dependently. Further analysis demonstrated that LaMYC7 directly bound to the promoter region of LaTPS76, which encodes the terpene synthase (TPS) for caryophyllene biosynthesis, and that LaTPS76 was highly expressed in glandular trichomes. Notably, the LaMYC7 promoter contained hormone and stress-responsive regulatory elements and responded to various treatments, including ultraviolet, low temperature, salt, drought, methyl jasmonate, and P. syringae infection treatments. Under these treatments, the changes in the linalool and caryophyllene contents were similar to those in LaMYC7 transcript abundance. Based on the results, LaMYC7 could respond to P. syringae infection in addition to being involved in linalool and caryophyllene biosynthesis. Thus, the MYC transcription factor gene LaMYC7 can be used in the breeding of high-yielding linalool and caryophyllene lavender varieties with pathogen resistance.

A Modified Tridecapeptide Probe for Imaging Cell Junction.

Cell junctions, which are typically associated with dynamic cytoskeletons, are essential for a wide range of cellular activities, including cell migration, cell communication, barrier function and signal transduction. Observing cell junctions in real-time can help us understand the mechanisms by which they regulate these cellular activities. This study examined the binding capacity of a modified tridecapeptide from Connexin 43 (Cx43) to the cell junction protein zonula occludens-1 (ZO-1). The goal was to create a fluorescent peptide that can label cell junctions. A cell-penetrating peptide was linked to the modified tridecapeptide. The heterotrimeric peptide molecule was then synthesized. The binding of the modified tridecapeptide was tested using pulldown and immunoprecipitation assays. The ability of the peptide to label cell junctions was assessed by adding it to fixed or live Caco-2 cells. The testing assays revealed that the Cx43-derived peptide can bind to ZO-1. Additionally, the peptide was able to label cell junctions of fixed cells, although no obvious cell junction labeling was observed clearly in live cells, probably due to the inadequate affinity. These findings suggest that labeling cell junctions using a peptide-based strategy is feasible. Further efforts to improve its affinity are warranted in the future.

Research progress of procyanidins in repairing cartilage injury after anterior cruciate ligament tear.

Anterior cruciate ligament (ACL) tear is a common sports-related injury, and cartilage injury always emerges as a serious complication following ACL tear, significantly impacting the physical and psychological well-being of affected individuals. Over the years, efforts have been directed toward finding strategies to repair cartilage injury after ACL tear. In recent times, procyanidins, known for their anti-inflammatory and antioxidant properties, have emerged as potential key players in addressing this concern. This article focuses on summarizing the research progress of procyanidins in repairing cartilage injury after ACL tear. It covers the roles, mechanisms, and clinical significance of procyanidins in repairing cartilage injury following ACL tear and explores the future prospects of procyanidins in this domain. This review provides novel insights and hope for the repair of cartilage injury following ACL tear.

Antimicrobial Nonisocyanate Polyurethane Foam Derived from Lignin for Wound Healing.

Medical dressings, as a cover for wounds, can replace damaged skin in the wound healing process to play a temporary barrier role, avoid or control wound infection, and provide a favorable environment for wound healing. Therefore, there is an urgent need for medical antimicrobial dressings for the treatment of chronic wounds. Although traditional polyurethane foam has been widely used in medical dressings, conventional polyurethane foams are primarily prepared using nonbiocompatible isocyanate-based compounds, which are potentially hazardous for both operators and applications in the medical field. Here, we propose nonisocyanate polyurethane foams naturally derived from lignin by enzymatic lignin alkylation, cyclic carbonation modification, and polymerization with diamine and the addition of a blowing agent. Silver nanoparticle solution was added during foaming to confer antimicrobial properties. This lignin-based nonisocyanate polyurethane/silver composite foam (named NIPU foam-silver) using a green synthesis method has good mechanical properties, which can be used to manufacture polyurethane/silver foams, and thermal and antimicrobial properties. Notably, NIPU foam-Ag showed more than 95% bactericidal efficacy against both Escherichia coli and Staphylococcus aureus within 4 h. Evaluation of in vitro wounds in mice showed that this antimicrobial composite foam rapidly promotes wound healing and repairs damaged tissue. This suggests that this biobased biodegradable antimicrobial foam has significant scope for clinical applications in wound management.

Genome-wide identification and expression of BAHD acyltransferase gene family shed novel insights into the regulation of linalyl acetate and lavandulyl acetate in lavender.

The BAHD acyltransferase superfamily has a variety of biological functions, especially in catalyzing the synthesis of ester compounds and improving plant stress resistance. Linalyl acetate and lavandulyl acetate, the most important volatile esters in lavender, are generated by LaBAHDs. However, the systematic identification, expression characteristics of LaBAHD genes and their correlations with ester formation remain elusive. Here, 166 LaBAHD genes were identified from the lavender genome. Based on detailed phylogenetic analysis, the LaBAHD family genes were divided into five groups, among which the LaBAHDs involved in volatile ester biosynthesis belong to the IIIa and Va clades. Whole-genome duplications (WGDs) and tandem duplications (TDs) jointly drive the expansion of LaBAHD superfamily. The promoter regions of LaBAHDs contained a variety of stress- and hormone-related motifs, as well as binding sites with five types of transcription factors (TFs). Then, linalyl acetate- and lavandulyl acetate-regulated coexpression modules were established and some candidate TFs that may function in inducing ester formation were identified. Based on the correlation analysis between the ester contents and expression profiles of BAHD genes in different tissues, five candidate genes were screened for further examination. Drought, salt and MeJA treatments increased the accumulation of linalyl acetate and lavandulyl acetate, and induced the expression of LaBAHDs. Our results indicated that LaBAHD57, LaBAHD63, LaBAHD104, LaBAHD105 and LaBAHD119 are crucial candidate genes involved in linalyl acetate and lavandulyl acetate biosynthesis. Our findings offer a theoretical foundation for further studying the specific biological functions of LaBAHD family and improving the quality of lavender essential oil.

Optimizing the Buried Interface in Flexible Perovskite Solar Cells to Achieve Over 24% Efficiency and Long-Term Stability.

The buried interface of the perovskite layer has a profound influence on its film morphology, defect formation, and aging resistance from the outset, therefore, significantly affects the film quality and device performance of derived perovskite solar cells. Especially for FAPbI3 , although it has excellent optoelectronic properties, the spontaneous transition from the black perovskite phase to nonperovskite phase tends to start from the buried interface at the early stage of film formation then further propagate to degrade the whole perovskite. In this work, by introducing ─NH3 + rich proline hydrochloride (PF) with a conjugated rigid structure as a versatile medium for buried interface, it not only provides a solid α-phase FAPbI3 template, but also prevents the phase transition induced degradation. PF also acts as an effective interfacial stress reliever to enhance both efficiency and stability of flexible solar cells. Consequently, a champion efficiency of 24.61% (certified 23.51%) can be achieved, which is the highest efficiency among all reported values for flexible perovskite solar cells. Besides, devices demonstrate excellent shelf-life/light soaking stability (advanced level of ISOS stability protocols) and mechanical stability.

The SALT OVERLY SENSITIVE 2-CONSTITUTIVE TRIPLE RESPONSE1 module coordinates plant growth and salt tolerance in Arabidopsis.

High salinity stress promotes plant ethylene biosynthesis and triggers the ethylene signalling response. However, the precise mechanism underlying how plants transduce ethylene signalling in response to salt stress remains largely unknown. In this study, we discovered that SALT OVERLY SENSITIVE 2 (SOS2) inhibits the kinase activity of CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) by phosphorylating the 87th serine (S87). This phosphorylation event activates the ethylene signalling response, leading to enhanced plant salt resistance. Furthermore, through genetic analysis, we determined that the loss of CTR1 or the gain of SOS2-mediated CTR1 phosphorylation both contribute to improved plant salt tolerance. Additionally, in the sos2 mutant, we observed compromised proteolytic processing of ETHYLENE INSENSITIVE 2 (EIN2) and reduced nuclear localization of EIN2 C-terminal fragments (EIN2-C), which correlate with decreased accumulation of ETHYLENE INSENSITIVE 3 (EIN3). Collectively, our findings unveil the role of the SOS2-CTR1 regulatory module in promoting the activation of the ethylene signalling pathway and enhancing plant salt tolerance.

ZmELP1, an Elongator complex subunit, is required for the maintenance of histone acetylation and RNA Pol II phosphorylation in maize kernels.

The Elongator complex was originally identified as an interactor of hyperphosphorylated RNA polymerase II (RNAPII) in yeast and has histone acetyltransferase (HAT) activity. However, the genome-wide regulatory roles of Elongator on transcriptional elongation and histone acetylation remain unclear. We characterized a maize miniature seed mutant, mn7 and map-based cloning revealed that Mn7 encodes one of the subunits of the Elongator complex, ZmELP1. ZmELP1 deficiency causes marked reductions in the kernel size and weight. Molecular analyses showed that ZmELP1 interacts with ZmELP3, which is required for H3K14 acetylation (H3K14ac), and Elongator complex subunits interact with RNA polymerase II (RNAPII) C-terminal domain (CTD). Genome-wide analyses indicated that loss of ZmELP1 leads to a significant decrease in the deposition of H3K14ac and the CTD of phosphorylated RNAPII on Ser2 (Ser2P). These chromatin changes positively correlate with global transcriptomic changes. ZmELP1 mutation alters the expression of genes involved in transcriptional regulation and kernel development. We also showed that the decrease of Ser2P depends on the deposition of Elongator complex-mediated H3K14ac. Taken together, our results reveal an important role of ZmELP1 in the H3K14ac-dependent transcriptional elongation, which is critical for kernel development.

Correction to "Screening Mixed-Metal Sn2M(III)Ch2X3 Chalcohalides for Photovoltaic Applications".

[This corrects the article DOI: 10.1021/acs.chemmater.3c01629.].

Drought resistance index screening and evaluation of lettuce under water deficit conditions on the basis of morphological and physiological differences.

Introduction: Water is one of the important factors affecting the yield of leafy vegetables. Lettuce, as a widely planted vegetable, requires frequent irrigation due to its shallow taproot and high leaf evaporation rate. Therefore, screening drought-resistant genotypes is of great significance for lettuce production. Methods: In the present study, significant variations were observed among 13 morphological and physiological traits of 42 lettuce genotypes under normal irrigation and water-deficient conditions. Results: Frequency analysis showed that soluble protein (SP) was evenly distributed across six intervals. Principal component analysis (PCA) was conducted to transform the 13 indexes into four independent comprehensive indicators with a cumulative contribution ratio of 94.83%. The stepwise regression analysis showed that root surface area (RSA), root volume (RV), belowground dry weight (BDW), soluble sugar (SS), SP, and leaf relative water content (RWC) could be used to evaluate and predict the drought resistance of lettuce genotypes. Furthermore, the drought resistance ranks of the genotypes were similar according to the drought resistance comprehensive evaluation value (D value), comprehensive drought resistance coefficient (CDC), and weight drought resistance coefficient (WDC). The cluster analysis enabled the division of the 42 genotypes into five drought resistance groups; among them, variety Yidali151 was divided into group I as a strongly drought-resistant variety, group II included 6 drought-resistant genotypes, group III included 16 moderately drought-resistant genotypes, group IV included 12 drought-sensitive genotypes, and group V included 7 highly drought-sensitive genotypes. Moreover, a representative lettuce variety was selected from each of the five groups to verify its water resistance ability under water deficit conditions. In the drought-resistant variety, it was observed that stomatal density, superoxide anion (O2.-wfi2) production rate, and malondialdehyde (MDA) content exhibited a low increase rate, while catalase (CAT), superoxide dismutase (SOD), and that peroxidase (POD) activity exhibited a higher increase than in the drought-sensitive variety. Discussion: In summary, the identified genotypes are important because their drought-resistant traits can be used in future drought-resistant lettuce breeding programs and water-efficient cultivation.

Terpene produced by coexpression of the TPS and P450 genes from Lavandula angustifolia protects plants from herbivore attacks during budding stages.

To deter herbivore attacks, plants employ a diverse array of volatile compounds, particularly during the early developmental stages. The highly expressed genes LaTPS7, LaTPS8, and LaCYP71D582 were identified during the budding phases of Lavandula angustifolia. In vitro studies revealed that LaTPS7 generated nine distinct compounds, including camphene, myrcene, and limonene. LaTPS8 enzymatically converted eight volatiles by utilizing geranyl diphosphate and nerolidyl diphosphate as substrates. Overexpression of plastid-localized LaTPS7 in Nicotiana benthamiana resulted in the production of limonene. Furthermore, the endoplasmic reticulum-associated enzyme LaCYP71D582 potentially converted limonene into carveol. In N. benthamiana, LaTPS8 is responsible for the synthesis of α-pinene and sylvestrene. Furthermore, leaves transfected with LaTPS7 and leaves cotransfected with LaTPS7 and LaCYP71D582 exhibited a repellent effect on aphids, with an approximate rate of 70%. In comparison, leaves with an empty vector displayed a repellent rate of approximately 20%. Conversely, tobacco leaves expressing LaTPS7 attracted ladybugs at a rate of 48.33%, while leaves coexpressing LaTPS7 and LaCYP71D582 attracted ladybugs at a slightly higher rate of 58.33%. Subsequent authentic standard tests confirmed that limonene and carveol repel Myzus persicae while attracting Harmonia axyridis. The promoter activity of LaTPS7 and LaCYP71D582 was evaluated in Arabidopsis thaliana using GUS staining, and it was observed that wounding stimulated the expression of LaTPS7. The volatile compounds produced by LaTPS7, LaTPS8, and LaCYP71D582 play a crucial role in plant defence mechanisms. In practical applications, employing biological control measures based on plant-based approaches can promote human and environmental health.

Identification of Molecular Markers Predicting the Outcome of Anti-thrombotic Therapy After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome and Atrial fibrillation: Evidence from a Meta-analysis and Experimental Study.

Acute coronary syndrome (ACS) and atrial fibrillation (AF) often coexist in clinical practice, and patients with these conditions often have a critical illness with high risk of both ischemia and bleeding. This study aims to report potential molecular markers for predicting the efficacy based on a meta-analysis of microarray data from the GEO database. In 40 patients with acute coronary syndrome (ACS) and atrial fibrillation (AF) treated with PCI, P2RX1's effects on platelet aggregation, medication resistance, and predictive value were examined. Twenty up-regulated genes in peripheral blood samples of ACS and AF patients were down-regulated after PCI, while 7 down-regulated genes were up-regulated. ACS affected eight potential genes. P2RX1, one of the four LASSO analysis-retrieved disease characteristic genes, accurately predicted AF patients' thrombosis risk and PCI's anti-thrombotic impact. Therefore, P2RX1 may be a molecular marker to predict the effect of anti-thrombotic therapy in patients with ACS and AF after PCI.

Persistent Hypoxia with Intermittent Aggravation Causes Imbalance in Smad3/Myocardin-Related Transcription Factor Signaling with Consequent Endothelial Senescence and Pulmonary Arterial Remodeling.

Loss of Smad3 and the consequent activation of myocardin-related transcription factor (MRTF) are associated with vascular pathologies. This study aimed to examine the impact of persistent hypoxia with intermittent aggravation (PI hypoxia) on cellular senescence and pulmonary arterial remodeling mediated by the Smad3/MRTF imbalance. We examined the effects of PI hypoxia on the Smad3/MRTF pathway and cellular senescence using human pulmonary artery endothelial cells (HPAECs) and in vivo studies in rats. The senescent degree was evaluated using ß-galactosidase staining, p16 quantitation and the measurement of senescence-associated secretory phenotype. Structural data in the pathological analysis of pulmonary artery remodeling were collected. Compared to the control, HPAECs and pulmonary tissue from rats exposed to PI hypoxia showed a significantly higher senescent degree, lower expression of Smad3, and higher MRTF levels. The overexpression of Smad3 significantly mitigated HPAECs senescence in vitro. Further, treatment with CCG-203971, which inhibits MRTF, increased Smad3 levels and reduced ß-galactosidase positive cells in rat lung tissue. This intervention also alleviated PI hypoxia-induced pathological changes, including remodeling indices of pulmonary arterial thickening, muscularization, and collagen formation. In conclusion, imbalanced Smad3/MRTF signaling is linked to PI hypoxia-induced senescence and pulmonary arterial remodeling, making it a potential therapeutic target for patients with sleep apnea and chronic obstructive pulmonary disease.