Exploring the role of CBLB in acute myocardial infarction: transcriptomic, microbiomic, and metabolomic analyses.

BACKGROUND: Specific alterations in gut microbiota and metabolites have been linked to AMI, with CBLB potentially playing an essential role. However, the precise interactions remain understudied, creating a significant gap in our understanding. This study aims to address this by exploring these interactions in CBLB-intervened AMI mice using transcriptome sequencing, 16 S rDNA, and non-targeted metabolite analysis. METHODS: To probe the therapeutic potential and mechanistic underpinnings of CBLB overexpression in AMI, we utilized an integrative multi-omics strategy encompassing transcriptomics, metabolomics, and 16s rDNA sequencing. We selected these particular methods as they facilitate a holistic comprehension of the intricate interplay between the host and its microbiota, and the potential effects on the host's metabolic and gene expression profiles. The uniqueness of our investigation stems from utilizing a multi-omics approach to illuminate the role of CBLB in AMI, an approach yet unreported to the best of our knowledge. Our experimental protocol encompassed transfection of CBLB lentivirus-packaged vectors into 293T cells, followed by subsequent intervention in AMI mice. Subsequently, we conducted pathological staining, fecal 16s rDNA sequencing, and serum non-targeted metabolome sequencing. We applied differential expression analysis to discern differentially expressed genes (DEGs), differential metabolites, and differential microbiota. We performed protein-protein interaction analysis to identify core genes, and conducted correlation studies to clarify the relationships amongst these core genes, paramount metabolites, and key microbiota. RESULTS: Following the intervention of CBLB in AMI, we observed a significant decrease in inflammatory cell infiltration and collagen fiber formation in the infarcted region of mice hearts. We identified key changes in microbiota, metabolites, and DEGs that were associated with this intervention. The findings revealed that CBLB has a significant correlation with DEGs, differential metabolites and microbiota, respectively. This suggests it could play a pivotal role in the regulation of AMI. CONCLUSION: This study confirmed the potential of differentially expressed genes, metabolites, and microbiota in AMI regulation post-CBLB intervention. Our findings lay groundwork for future exploration of CBLB's role in AMI, suggesting potential therapeutic applications and novel research directions in AMI treatment strategies.

Remote Raman Detection of Trace Explosives by Laser Beam Focusing and Plasmonic Spray Enhancement Methods.

Remote Raman spectroscopy is a technique that can detect and identify different target molecules through Raman vibrational modes from a remote distance. However, the current remote Raman technique is restricted by poor detection sensitivity, and it is still extremely challenging for trace explosive detection. Here, in order to achieve trace explosive detection from a remote distance, we innovatively propose two enhanced Raman spectroscopy methods by using a plasmonic spray and a laser beam focusing/Raman signal collecting instrument. In brief, a facile convex lens can converge the laser beam and collect Raman scattering signals, and a plasmonic spray can be used for surface-enhanced Raman scattering. Under the combination of the above enhancement methods, we achieve remote Raman detection of a variety of trace explosives with a concentration of ∼1 µg/cm2 from a distance of 30 m. These novel methods demonstrate a simple approach that significantly improves the capability of remote detection of trace chemicals for further applications.

Solution-Based SERS Detection of Weak Surficial Affinity Molecules Using Cysteamine-Modified Au Bipyramids.

To achieve ultrasensitive detection of trace targets through solution-based surface-enhanced Raman spectroscopy (SERS), direct adsorption of the target molecules on a SERS-active surface is vital. In this work, cetyltrimethylammonium bromide (CTAB)-capped gold nano-bipyramids (Au BPs) with different aspect ratios (ARs) are prepared and the surface is successfully modified by a simple ligand exchange method. Cysteamine-capped gold nano-bipyramids (cyst-Au BPs) are obtained by means of replacement of CTAB by cysteamine using Au-S covalent bonding and applied in the solution-based SERS detection of different pigment molecules, which always have weak affinity to the gold surface. The hydrogen bonding between the pigment molecule and cysteamine causes the aggregation of Au BPs to generate local electromagnetic field enhancement. The influence of the AR and concentration of Au BPs on SERS properties is investigated. The SERS detection of weak-affinity molecules to an extremely low limit shows that the cyst-Au BPs are highly sensitive compared to CTAB-capped Au BPs. The limit of detection (LOD) of allura red as low as 0.1 ppb and that of sunset yellow as low as 1 ppb show that the proposed strategy has many advantages due to its simplicity and fast and rapid detection for the sensitivity analysis of weak-affinity molecules.

Rosmarinic acid ameliorated cardiac dysfunction and mitochondrial injury in diabetic cardiomyopathy mice via activation of the SIRT1/PGC-1α pathway.

Mitochondrial injury plays an essential role in the pathogenesis of diabetic cardiomyopathy (DCM). Previous studies demonstrated that rosmarinic acid (RA) treatment prevented high glucose-induced mitochondrial injury in vitro. However, whether RA can ameliorate cardiac function by preventing mitochondrial injury in DCM is unknown. The SIRT1/PGC-1α pathway has emerged as an important regulator of metabolic control and other mitochondrial functions. The present study was undertaken to determine the effects of RA on mitochondrial and cardiac function in DCM as well as the involvement of the SIRT1/PGC-1α pathway. Our results revealed that RA improved cardiac systolic and diastolic function and prevented mitochondrial injury in DCM, as shown by the reduced blood glucose and lipid levels, increased mitochondrial membrane potential levels, improved adenosine triphosphate synthesis, and inhibited apoptosis (P < 0.05). Moreover, RA upregulated the expression of SIRT1 and PGC-1α in DCM mice and high glucose-treated H9c2 cardiomyocytes (P < 0.05). Further mechanistic studies in H9c2 cardiomyocytes revealed that suppression of SIRT1 by Sh-SIRT1 counteracted the effects of RA on high glucose-induced abnormal metabolism of glucose and lipids, oxidative stress and apoptosis (P < 0.05). Taken together, these data indicate that RA prevented mitochondrial injury and cardiac dysfunction in DCM mice, and the SIRT1/PGC-1α pathway mediated the protective effects of RA.

Facile Surface Modification of Mesoporous Au Nanoparticles for Highly Sensitive SERS Detection.

The stability, dispersity, and surface chemical properties of colloidal nanoparticles are crucial for the reliable and desired chemical sensing in various applications. Here, we report an effective strategy to engineer the surface properties of mesoporous Au nanoparticles (meso-Au NPs) via PVP ligand modification, template removal, and surface purification. Monodispersed 3D meso-Au NPs with well-defined sizes and shapes were obtained using a general soft-enveloping strategy. During surface modification, the addition of PVP ligands and the concentration of HF solutions play key roles in the stability, shape, and size distributions of ordered Au networks. In order to obtain an improved sensing performance, the morphologies of meso-Au NPs were optimized with smaller mesopore size, and NaBH4 solution was used to efficiently remove the adsorbed PVP ligands. Due to the characteristics of high-density porosities and large surface area, the purified meso-Au NPs could be a kind of promising plasmonic-enhanced nanomaterial and provide abundant "hot spots." Combined with the enrichment effect using a slippery liquid-infused porous surface, the lowest detection limits of crystal violet molecule could be down to 0.1 pM, demonstrating an excellent SERS sensitivity. Moreover, a realistic illegal drug containing aspirin could be sensitively detected with a limit of 2.8 × 10-6 M, showing great potential for practical molecular sensing and applications.

Shape-Controlled Hierarchical Flowerlike Au Nanostructure Microarrays by Electrochemical Growth for Surface-Enhanced Raman Spectroscopy Application.

How to fabricate Au nanostructures conveniently on microstructured/nanostructured arrays surface with low cost has become a crucial and urgent challenge. In this study, we demonstrate hierarchical flowerlike Au nanostructures with rich nanothorns (HF-AuNTs) through one-step electrochemical deposition. The morphology of the HF-AuNTs is easily manipulated by controlling the applied potential or precursor solution concentration of electrodeposition. The as-prepared HF-AuNTs possessing unique local morphology of thin petals and dense thorns are further applied in the Si micropit arrays to acquire HF-AuNTs microarrays. As an initial detection, these HF-AuNTs microarrays exhibit a fascinating surface-enhanced Raman spectroscopy consistency (relative standard deviation is 7.17%) and sensitivity with the limitation of crystal violet reaching to 10-10 M, and Rhodamine 6G reaching to 10-11 M. The HF-AuNTs microarrays with well-defined shape and elaborate structure may be applicated in SERS substrates, superhydrophobic materials, and so on.

Ratiometric Sensing of Polycyclic Aromatic Hydrocarbons Using Capturing Ligand Functionalized Mesoporous Au Nanoparticles as a Surface-Enhanced Raman Scattering Substrate.

The absorption behavior between plasmonic nanostructures and a target molecule plays key roles in effective surface-enhanced Raman scattering (SERS) detection. However, for analytes with low surface affinity to the metallic surface, e.g., polycyclic aromatic hydrocarbons (PAHs), it remains challenging to observe the enhanced Raman signal. In this work, we reported a ratiometric SERS strategy for sensitive PAH detection through the surface functionalization of 3D ordered mesoporous Au nanoparticles (meso-Au NPs). By employing mono-6-thio-ß-cyclodextrin (HS-ß-CD) as capture ligands, the hydrophobic molecules, e.g., anthracene, could be effectively absorbed on the meso-Au NP surface via a host-guest interaction. Besides, a hydrophobic slippery surface is used as a concentrator to deliver and enrich the Au/analyte droplets into a small area. Consequently, the detection limits of anthracene and naphthalene are down to 1 and 10 ppb. The improved SERS enhancement is mainly ascribed to the host-guest effect of HS-ß-CD ligands, large surface area and high-density of sub-10 nm mesopores of Au networks, as well as the enrichment effect of hydrophobic slippery surface. Moreover, the HS-ß-CD (480 cm-1 band) could serve as an internal standard, leading to the ratiometric determination of anthracene ranging from 1 ppm to 1 ppb. The proposed surface modification strategy in combination with the hydrophobic slippery surface shows great potential for active capture and trace detection of persistent organic pollutants in real-world SERS applications.

Catalytic function of ferric oxide and effect of water on the formation of sulfur trioxide.

Sulfur trioxide (SO3) is not only environmentally harmful but also highly corrosive, taking a great threat to the safe operation of coal-fired power plants. A dominant pathway of SO3 formation in coal-fired power plant is through the catalytic oxidation of SO2 (SO2+1/2O2→SO3) on the surfaces of ash particles containing Fe2O3. The catalytic formation of SO3 could be affected by complex atmosphere, where the effect from H2O is still debatable. In this paper, density functional theory (DFT) is employed to explore the reaction pathway of SO3 formation catalyzed by α-Fe2O3 in complex atmosphere containing O, O2, SO2 and H2O. In order to get the stable adsorption sites of these species, the adsorption energy of potential adsorption configurations on the α-Fe2O3 (001) surface is calculated. The dissociations of O2 molecule on complete and defect α-Fe2O3 (001) surfaces with O vacancy are calculated, and the Langmuir-Hinshelwood and Eley-Rideal mechanisms for the O(ads) reaction with SO2(ads) or SO2 are compared. The effect of H2O besides of SO2 and O2 on the formation of SO3 is especially discussed. The DFT calculation results show that for the formation of SO3 in gas phase, the energy barrier of 'SO2+1/2O2→SO3' is 436.75 kJ mol-1, in contrast, for the catalytic formation of SO3 on α-Fe2O3 surfaces, this energy barrier becomes an order of magnitude smaller, 24.82 kJ mol-1. O2 molecules can dissociate on the defect α-Fe2O3 (001) surface with O vacancy spontaneously, indicating that the defect α-Fe2O3 is favorable for the dissociation of O2, thereby promotes the formation of SO3. The energy barrier of 'SO2(ads)+O(ads)→SO3(ads)' through Langmuir-Hinshelwood mechanism is much higher than that of 'SO2+O(ads)→SO3(ads)' through Eley-Rideal mechanism. The adsorption energy on the α-Fe2O3 (001) surface of H2O is much smaller than that of SO2 and O2, indicating that H2O has little effect on the adsorption of O, O2, SO2 and eventually the heterogeneous formation of SO3. The DFT analysis results in this study provide a deep understanding on the reaction pathway of SO3 catalytic formation by Fe2O3.

Hydrophobic Slippery Surface-Based Surface-Enhanced Raman Spectroscopy Platform for Ultrasensitive Detection in Food Safety Applications.

Collecting highly diluted target analytes into specific hot spot regions is vital for ultrasensitive surface-enhanced Raman spectroscopy (SERS) applications. In this work, a hydrophobic slippery platform was employed as a concentrator to construct colloidal SERS-active substrates regardless of the diffusion limits during droplet evaporation. Within only 140 s, sufficient absorption between the analytes and colloidal Au nanoparticles (Au NPs) was observed by fluorescence imaging. This effect resulted in excellent SERS sensitivity and stability. Compared with the common metal colloid-based SERS substrates, e.g., drying on a silicon wafer or detection in colloidal solutions, this preconcentrated method showed lower detection limits and the lowest detection concentration of crystal violet molecule down to 10-12 M with a portable Raman spectrometer. Such high signal enhancement was mainly ascribed to the condensation effect of Au colloids/analytes on the hydrophobic slippery substrate, by which almost all probe molecules were guided into the "hot spot" regions of aggregated Au NPs. Using the SERS platform, various illegal additives in realistic food and health-care products, for example, malachite green (1 ppb) added in fish and morphine (0.1 ppm) added in a chafing dish, could be sensitively detected. Therefore, our protocol is a general SERS platform that may provide a simple, fast, and cost-effective approach for trace molecular sensing.

Designing Novel Nonsymmetric Ag/AgI Nanoplates for Superior Photocatalytic Activity.

Precisely engineering the decoration of metal nanoparticles on the special surface of semiconductor represents a promising strategy to design efficient metal-semiconductor heterostructured photocatalysts. This study demonstrates a versatile soft-template method to fabricate a novel nonsymmetrical heterostructured Ag/AgI nanoplate, in which only one side surface of the nanoplate is covered with uniform 2D Ag nanoweb. Compared with symmetrical heterostructure, the nonsymmetrical heterostructure may further facilitate the separation of photogenerated electron-hole pairs and shows a greatly enhanced photocatalytic activity. This study may open up a new way to improve the photocatalytic property by synthesizing nonsymmetrical metal-semiconductor composites.

In Situ Probing of the Particle-Mediated Mechanism of WO3 -Networked Structures Grown inside Confined Mesoporous Channels.

Nanocasting, using ordered mesoporous silica or carbon as a hard template, has enormous potential for preparing novel mesoporous materials with new structures and compositions. Although a variety of mesoporous materials have been synthesized in recent years, the growth mechanism of nanostructures in a confined space, such as mesoporous channels, is not well understood, which hampers the controlled synthesis and further application of mesoporous materials. Here, the nucleation and growth of WO3 -networked mesostructures within an ordered mesoporous matrix, using an in situ transmission electron microscopy heating technique and in situ synchrotron small-angle X-ray scattering spectroscopy, are probed. It is found that the formation of WO3 mesostructures involves a particle-mediated transformation and coalescence mechanism. The liquid-like particle-mediated aggregation and mesoscale transformation process can occur in ≈10 nm confined mesoporous channels, which is completely unexpected. The detailed mechanistic study will be of great help for experimental design and to exploit a variety of mesoporous materials for diverse applications, such as catalysis, absorption, separation, energy storage, biomedicine, and nanooptics.

IFN-γ aggravates neointimal hyperplasia by inducing endoplasmic reticulum stress and apoptosis in macrophages by promoting ubiquitin-dependent liver X receptor-α degradation.

Neointimal hyperplasia is the main cause of restenosis after percutaneous coronary interventions (PCIs). Both IFN-γ and macrophages play nonredundant roles in the pathogenesis of vascular intimal hyperplasia; however, the underlying mechanisms remain elusive and must be further investigated. In mouse peritoneal macrophages, IFN-γ significantly accelerated degradation and up-regulated polyubiquitination of liver X receptor (LXR)-α. Signal transducer and activator of transcription 1 (STAT1) inhibitor, fludarabine, and PIAS1 knockdown reduced ubiquitination and increased the expression of LXR-α in IFN-γ-treated macrophages. IFN-γ also increased the expression of endoplasmic reticulum (ER) stress-related proteins, including p-PERK, p-eIIF2α, and CCAAT-enhancer-binding protein homologous protein (CHOP), as well as apoptosis of macrophages. Treatment with ER stress inhibitor, 4-phenylbutyric acid (4-PBA), and LXR agonist, T0901317 (T0), alleviated IFN-γ-induced apoptosis in macrophages. Neointimal hyperplasia was significant after carotid ligation for 4 wk in ApoE-/- mice. IFN-γ mAb, T0, and 4-PBA treatment not only significantly attenuated neointimal hyperplasia but also decreased CD68+TUNEL+ double-positive macrophages in the hyperplastic neointima. Moreover, after 4-PBA or T0 administration, the number of CD68+p-eIIF2α+ and CD68+CHOP+ double-positive cells in neointimal was also apparently decreased. Taken together, these results defined an unexpected role of IFN-γ and LXR-α in the development of neointimal hyperplasia. The PIAS1/STAT1-dependent LXR-α degradation induced by IFN-γ promoted ER stress and apoptosis in macrophages, which leads to aggravated neointimal hyperplasia. LXR agonist efficiently improved neointimal hyperplasia, which may be a promising new strategy to ameliorate restenosis and vascular remodeling after PCI.-Zhao, Q., Zhou, D., You, H., Lou, B., Zhang, Y., Tian, Y., Guo, N., Chen, X., Liu, Y., Wu, Y., Yuan, Z., Zhou, J. IFN-γ aggravates neointimal hyperplasia by inducing endoplasmic reticulum stress and apoptosis in macrophages by promoting ubiquitin-dependent liver X receptor-α degradation.

Insight of holey-graphene in the enhancing of electrocatalytic activity as supporting material.

An ideal supporting material improves both activity and durability of noble metal nanoparticles in electrocatalytic reactions. Graphene possesses a high transport rate of electrons in-plane, a low cost, and stability, but, the restacking of graphene layers trap noble metal nanoparticles and make them inaccessible to reactants and results in reduced catalytic activity. Here, holey-graphene as the supporting materials for Pt nanoparticle catalysts is deeply investigated in the electrocatalytic reaction of methanol oxidation. The holey-graphene can be scalable to synthesize using our simple method described herein. The holes on the holey-graphene layer promote the access of reactants with Pt nanoparticle catalysts compared with carbon black and graphene when used as supporting materials. Density functional theory calculations and molecule dynamic simulation further explain the function of holey-graphene in the promotion of electrocatalytic activity. Holey-graphene may open extraordinary possibilities as a supporting material for electrocatalysts.

Synthesis of colloidal metal and metal alloy nanoparticles for electrochemical energy applications.

This Review is focused on the recent progresses in the synthetic approaches to the precise control of structure, size, shape, composition and multi-functionality of metal and metal alloy nanoparticles. Many of these strategies have been developed based on colloidal methods, and to limited extent, the galvanic and other methods. The shape, size and composition often govern the chemical and catalytic properties that are important for electrochemical energy applications. The structure-property relationship and the design in controllable structures and morphologies for specific reactions such as oxygen reduction reaction (ORR) are emphasized.

Identification of necroptosis-related diagnostic biomarkers in coronary heart disease.

Background: The implication of necroptosis in cardiovascular disease was already recognized. However, the molecular mechanism of necroptosis has not been extensively studied in coronary heart disease (CHD). Methods: The differentially expressed genes (DEGs) between CHD and control samples were acquired in the GSE20681 dataset downloaded from the GEO database. Key necroptosis-related DEGs were captured and ascertained by bioinformatics analysis techniques, including weighted gene co-expression network analysis (WGCNA) and two machine learning algorithms, while single-gene gene set enrichment analysis (GSEA) revealed their molecular mechanisms. The diagnostic biomarkers were selected via receiver operating characteristic (ROC) analysis. Moreover, an analysis of immune elements infiltration degree was carried out. Authentication of pivotal gene expression at the mRNA level was investigated in vitro utilizing quantitative real-time PCR (qRT-PCR). Results: A total of 94 DE-NRGs were recognized here, among which, FAM166B, NEFL, POLDIP3, PRSS37, and ZNF594 were authenticated as necroptosis-related biomarkers, and the linear regression model based on them presented an acceptable ability to different sample types. Following regulatory analysis, the ascertained biomarkers were markedly abundant in functions pertinent to blood circulation, calcium ion homeostasis, and the MAPK/cAMP/Ras signaling pathway. Single-sample GSEA exhibited that APC co-stimulation and CCR were more abundant, and aDCs and B cells were relatively scarce in CHD patients. Consistent findings from bioinformatics and qRT-PCR analyses confirmed the upregulation of NEFL and the downregulation of FAM166B, POLDIP3, and PRSS37 in CHD. Conclusion: Our current investigation identified 5 necroptosis-related genes that could be diagnostic markers for CHD and brought a novel comprehension of the latent molecular mechanisms of necroptosis in CHD.

Effective enrichment of trace exosomes for the label-free SERS detection via low-cost thermophoretic profiling.

Exosome-based liquid biopsies possess great potential in monitoring cancer development However, current exosome detection biosensors require large exosome volumes, showing the weak detection sensitivity. Besides, these methods pay little attention to in situ analysis of exosomes, hence limiting the provision of more accurate clinically-relevant information. Herein, we develop an innovative label-free biosensor combining the low-cost thermophoretic enrichment method with the surface-enhanced Raman spectroscopy (SERS) detection. Based on the thermophoretic enrichment strategy, exosomes and gold nanoparticles can be enriched together into a small area with a scale of 500 µm within 10 min. The Raman signals of various exosomes derived from normal, cancerous cell lines and human serum are dynamically monitored in situ, with the limit of detection of 102-103 particles per microliter, presenting higher sensitivity compared with the similar label-free SERS detection. The spectral data set of different exosomes is applied to train for multivariate classification of cell types and to estimate how the normal exosome data resemble cancer cell exosome. The reliable classification and identification of different exosomes can be realized. The current biosensor is convenient, low-cost and requires small exosome volumes (∼3 µL), and if validated in larger cohorts may contribute to the tumor prediction and diagnosis.

Observation of the photorefractive effects in bent-core liquid crystals.

We present a new observation of photorefractive (PR) effects in bent-core nematic (BCN) liquid crystal (LC) materials, where two kinds of optical-induced gratings are demonstrated and compared in pure and surface-doped BCN systems. The experimental results showed that these two kinds of gratings exhibit distinctive different polarization-dependent and angular-dependent behaviors, respectively. Furthermore, we supplied the pure and surface-doped rodlike LC systems for comparison, which revealed that V shape molecular structure of BCN can produce charge carrier more efficiently than rodlike molecular structure does. Thus BCN materials can offer an exciting potential for optical information processing.

Prediction of diagnostic gene biomarkers for hypertrophic cardiomyopathy by integrated machine learning.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM), a leading cause of heart failure and sudden death, requires early diagnosis and treatment. This study investigated the underlying pathogenesis and explored potential diagnostic gene biomarkers for HCM. METHODS: Transcriptional profiles of myocardial tissues from patients with HCM (dataset GSE36961) were downloaded from the Gene Expression Omnibus database and subjected to bioinformatics analyses, including differentially expressed gene (DEG) identification, enrichment analyses, and protein-protein interaction (PPI) network analysis. Least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination were performed to identify candidate diagnostic gene biomarkers. mRNA expression levels of candidate biomarkers were tested in an external dataset (GSE141910); area under the receiver operating characteristic curve (AUC) values were obtained to validate diagnostic efficacy. RESULTS: Overall, 156 DEGs (109 downregulated, 47 upregulated) were identified. Enrichment and PPI network analyses indicated that the DEGs were involved in biological functions and molecular pathways including inflammatory response, platelet activity, complement and coagulation cascades, extracellular matrix organization, phagosome, apoptosis, and VEGFA-VEGFR2 signaling. RASD1, CDC42EP4, MYH6, and FCN3 were identified as diagnostic biomarkers for HCM. CONCLUSIONS: RASD1, CDC42EP4, MYH6, and FCN3 might be diagnostic gene biomarkers for HCM and can provide insights concerning HCM pathogenesis.

Identification of Immuno-Inflammation-Related Biomarkers for Acute Myocardial Infarction Based on Bioinformatics.

Purpose: Previous studies have confirmed that inflammation and immunity are involved in the pathogenesis of acute myocardial infarction (AMI). However, only few related genes are identified as biomarkers for the diagnosis and treatment of AMI. Patients and Methods: GSE48060 and GSE60993 datasets were retrieved from Gene Expression Omnibus. The differentially expressed immuno-inflammation-related genes (DEIIRGs) were obtained from GSE48060, and the biomarkers for AMI were screened and validated using the "Neuralnet" package and GSE60993 dataset. Further, the biomarker-based nomogram was constructed, and miRNAs, transcription factors (TFs), and potential drugs targeting the biomarkers were explored. Furthermore, immune infiltration analysis was analyzed in AMI. Finally, the biomarkers were verified by assessing their mRNA levels using real-time quantitative PCR (RT-qPCR). Results: First, eight biomarkers were screened via bioinformatics, and the artificial neural network model indicated a higher prediction accuracy for AMI even in the validation dataset. Nomogram had accurate forecasting ability for AMI as well. The TFs GTF2I, PHOX2B, RUNX1, and FOS targeting hsa-miR-1297 could regulate the expressions of ADM and CBLB, and RORA could effectively interact with melatonin and citalopram. RT-qPCR results for ADM, PI3, MMP9, NRG1 and CBLB were consistent with those of bioinformatic analysis. Conclusion: In conclusion, eight key immuno-inflammation-related genes, namely, SH2D1B, ADM, PI3, MMP9, NRG1, CBLB, RORA, and FASLG, may serve as the potential biomarkers for AMI, in which the downregulation of CBLB and upregulation of ADM, PI3, and NRG1 in AMI was detected for the first time, providing a new strategy for the diagnosis and treatment of AMI.

Diagnostic potential of energy metabolism-related genes in heart failure with preserved ejection fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with changes in cardiac metabolism that affect energy supply in the heart. However, there is limited research on energy metabolism-related genes (EMRGs) in HFpEF. Methods: The HFpEF mouse dataset (GSE180065, containing heart tissues from 10 HFpEF and five control samples) was sourced from the Gene Expression Omnibus database. Gene expression profiles in HFpEF and control groups were compared to identify differentially expressed EMRGs (DE-EMRGs), and the diagnostic biomarkers with diagnostic value were screened using machine learning algorithms. Meanwhile, we constructed a biomarker-based nomogram model for its predictive power, and functionality of diagnostic biomarkers were conducted using single-gene gene set enrichment analysis, drug prediction, and regulatory network analysis. Additionally, consensus clustering analysis based on the expression of diagnostic biomarkers was utilized to identify differential HFpEF-related genes (HFpEF-RGs). Immune microenvironment analysis in HFpEF and subtypes were performed for analyzing correlations between immune cells and diagnostic biomarkers as well as HFpEF-RGs. Finally, qRT-PCR analysis on the HFpEF mouse model was used to validate the expression levels of diagnostic biomarkers. Results: We selected 5 biomarkers (Chrna2, Gnb3, Gng7, Ddit4l, and Prss55) that showed excellent diagnostic performance. The nomogram model we constructed demonstrated high predictive power. Single-gene gene set enrichment analysis revealed enrichment in aerobic respiration and energy derivation. Further, various miRNAs and TFs were predicted by Gng7, such as Gng7-mmu-miR-6921-5p, ETS1-Gng7. A lot of potential therapeutic targets were predicted as well. Consensus clustering identified two distinct subtypes of HFpEF. Functional enrichment analysis highlighted the involvement of DEGs-cluster in protein amino acid modification and so on. Additionally, we identified five HFpEF-RGs (Kcnt1, Acot1, Kcnc4, Scn3a, and Gpam). Immune analysis revealed correlations between Macrophage M2, T cell CD4+ Th1 and diagnostic biomarkers, as well as an association between Macrophage and HFpEF-RGs. We further validated the expression trends of the selected biomarkers through experimental validation. Conclusion: Our study identified 5 diagnostic biomarkers and provided insights into the prediction and treatment of HFpEF through drug predictions and network analysis. These findings contribute to a better understanding of HFpEF and may guide future research and therapy development.