Genome-wide association study reveals shared and distinct genetic architecture underlying fatty acid and bioactive oxylipin metabolites in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Bioactive fatty acid-derived oxylipin molecules play key roles in mediating inflammation and oxidative stress, which underlie many chronic diseases. Circulating levels of fatty acids and oxylipins are influenced by both environmental and genetic factors; characterizing the genetic architecture of bioactive lipids could yield new insights into underlying biological pathways. Thus, we performed a genome wide association study (GWAS) of n=81 fatty acids and oxylipins in n=11,584 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants with genetic and lipidomic data measured at study baseline (58.6% female, mean age = 46.1 years, standard deviation = 13.8 years). Additionally, given the effects of central obesity on inflammation, we examined interactions with waist circumference using two-degree-of-freedom joint tests. Heritability estimates ranged from 0% to 47.9%, and 48 of the 81oxylipins and fatty acids were significantly heritable. Moreover, 40 (49.4%) of the 81 oxylipins and fatty acids had at least one genome-wide significant ( p < 6.94E-11) variant resulting in 19 independent genetic loci involved in fatty acid and oxylipin synthesis, as well as downstream pathways. Four loci (lead variant minor allele frequency [MAF] range: 0.08-0.50), including the desaturase-encoding FADS and the OATP1B1 transporter protein-encoding SLCO1B1 , exhibited associations with four or more fatty acids and oxylipins. The majority of the 15 remaining loci (87.5%) (lead variant MAF range = 0.03-0.45, mean = 0.23) were only associated with one oxylipin or fatty acid, demonstrating evidence of distinct genetic effects. Finally, while most loci identified in two-degree-of-freedom tests were previously identified in our main effects analyses, we also identified an additional rare variant (MAF = 0.002) near CARS2 , a locus previously implicated in inflammation. Our analyses revealed shared and distinct genetic architecture underlying fatty acids and oxylipins, providing insights into genetic factors and motivating future multi-omics work to characterize these compounds and elucidate their roles in disease pathways.

Persulfate activation with biochar supported nanoscale zero- valent iron: Engineering application for effective degradation of NCB in soil.

Nitrochlorobenzene (NCB) is very common in pesticide and chemical industries, which has become a major problem in soil environment. However, the remediation of NCB contaminated soil is received finite concern. Using biochar as a substrate for nanoscale-zero valent iron (nZVI/p-BC) to activate peroxodisulfate (PDS), a novel heterogeneous oxidative system had been applied in the current study to remediate NCB contaminants in soil. The degradation efficiencies and kinetics of m-NCB, p-NCB, and o-NCB by various systems were contrasted in soil slurry. Key factors including the dosage of nZVI/p-BC, the molar ratio of nZVI/PDS, initial pH and temperature on degradation of NCB were further examined. The results confirmed that the nZVI/p-BC/PDS displayed the remarkable performance for removing NCB compared with other systems. Higher temperature with nZVI/PDS molar ratio of 2:1 under the acidic condition favored the reduction of NCB. The treatment for NCB with optimal conditions were evaluated for the engineering application. The mechanism of nZVI/p-BC/PDS indicated that electron transfer between p-BC and nZVI was responsible for activation of PDS, generating active species (SO4•-, •OH and 1O2) via both the free and non-free radical pathways. Experimental results revealed prominent availability of nZVI/p-BC/PDS system in remediation of actual contaminated field by NCB.

A Novel Position-Sensitive Linear Winding Silicon Drift Detector.

A novel position-sensitive linear winding silicon drift detector (LWSDD) was designed and simulated. On the frontside (anode side), the collecting anodes were set on both sides of the detector, and an S-shaped linear winding cathode strip was arranged in the middle, which can realize independent voltage division and reduce the complexity of external bias resistor chain compared with the traditional linear silicon drift detector. The detectors were arranged in a butterfly shape, which increased the effective area of the detectors and improved the collection efficiency. The linear winding silicon drift detector can obtain one-dimensional position information by measuring the drift time of electrons. The 2D position information of the incident particle is obtained from the anodes coordinates of the readout signal. One-dimensional analytically exact solutions of electric potential and field were obtained for the first time for the linear winding silicon drift detector. The simulation results show that the electric potential distribution inside the detector is uniform, and the "drift channel" inside the detector points to the collecting anodes on both sides, which proves the reasonable and feasible design of the linear winding silicon drift detector.

Characteristics and numerical simulation of chromium transportation, migration and transformation in soil-groundwater system.

Understanding chromium (Cr) migration and dispersion patterns in the soil-groundwater system is critical for the control and remediation of subsurface Cr contamination. In this study, a typical Cr-contaminated site from the Pearl River Delta (PRD) in China was simulated with a three-dimensional (3D) sandbox experiment to investigate the migration and transformation behavior of Cr. Results revealed that under the combined influence of rainfall and groundwater flow, a complex flow field favorable for 3D migration and solute dispersion was formed. The flow field characteristics were influenced by water-table depth, which in turn affected Cr behavior in the system. Moreover, downward flow field expansion under low water-table conditions led to Cr vertical migration range expansion, causing greater contamination in the deep soil. The migration process was accompanied with Cr(VI) reduction, during which approximately 75 % of the total Cr was immobilized in soils. The reactive transport model achieved a good fit for Cr retention and morphological distribution in the solid phase. The model indicates that Cr is more readily transported and dispersed with groundwater, and Cr migrated and spread downstream by 15 m during the eighth year. Therefore, managing water-table depth could be a strategy to minimize the Cr vertical migration and contamination.

Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer's disease.

JOURNAL/nrgr/04.03/01300535-202419110-00027/figure1/v/2024-03-08T184507Z/r/image-tiff Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer's disease. Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases, including Parkinson's and Huntington's diseases, however, the effect of Citri Reticulatae Semen on Alzheimer's disease remains unelucidated. In the current study, the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated. Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy. In addition, Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro, and suppress amyloid-beta-induced pathology such as paralysis, in a transgenic Caenorhabditis elegans in vivo model. Moreover, genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent. Most importantly, Citri Reticulatae Semen extract was confirmed to improve cognitive impairment, neuronal injury and amyloid-beta burden in 3×Tg Alzheimer's disease mice. As revealed by both in vitro and in vivo models, these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer's disease via its neuroprotective autophagic effects.

Design and 3D Electrical Simulations for a Controllable Equal-Gap Large-Area Silicon Drift Detector.

In this study, a controllable equal-gap large-area silicon drift detector (L-SDD) is designed. The surface leakage current is reduced by reducing the SiO2-Si interface through the new controllable equal-gap design. The design of the equal gap also solves the problem whereby the gap widens due to the larger detector size in the previous SDD design, which leads to a large invalid area of the detector. In this paper, a spiral hexagonal equal-gap L-SDD of 1 cm radius is selected for design calculation, and we implement 3D modeling and simulation of the device. The simulation results show that the internal potential gradient distribution of the L-SDD is uniform and forms a drift electric field, with the direction of electron drift pointing towards the collecting anode. The L-SDD has an excellent electron drift channel inside, and this article also analyzes the electrical performance of the drift channel to verify the correctness of the design method of the L-SDD.

Pulmonary primary oxysterol and bile acid synthesis as a predictor of outcomes in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare and fatal vascular disease with heterogeneous clinical manifestations. To date, molecular determinants underlying the development of PAH and related outcomes remain poorly understood. Herein, we identify pulmonary primary oxysterol and bile acid synthesis (PPOBAS) as a previously unrecognized pathway central to PAH pathophysiology. Mass spectrometry analysis of 2,756 individuals across five independent studies revealed 51 distinct circulating metabolites that predicted PAH-related mortality and were enriched within the PPOBAS pathway. Across independent single-center PAH studies, PPOBAS pathway metabolites were also associated with multiple cardiopulmonary measures of PAH-specific pathophysiology. Furthermore, PPOBAS metabolites were found to be increased in human and rodent PAH lung tissue and specifically produced by pulmonary endothelial cells, consistent with pulmonary origin. Finally, a poly-metabolite risk score comprising 13 PPOBAS molecules was found to not only predict PAH-related mortality but also outperform current clinical risk scores. This work identifies PPOBAS as specifically altered within PAH and establishes needed prognostic biomarkers for guiding therapy in PAH.

Comprehensive distribution characteristics and factors affecting the migration of chromium in a typical chromium slag-contaminated site with a long history in China.

The contamination of abandoned chromium slag-contaminated sites poses serious threats to human health and the environment. Therefore, improving the understanding of their distribution characteristics and health risks by multiple information is necessary. This study explored the distribution, accumulation characteristic, and the role in the migration process of chromium. The results showed that the contents of total Cr and Cr (VI) ranged from 12.00 to 7400.00 mg/kg, and 0.25 to 2160.00 mg/kg, respectively. The average contents of both total Cr and Cr (VI) reached the highest value at the depth of 7-9 m, where the silt layer retaining total Cr and Cr (VI) was. The spatial distribution analysis revealed that the total contamination area percentages of total Cr and Cr (VI) reached 7.87% and 90.02% in the mixed fill layer, and reduced to 1.21% and 34.53% in the silty layer, and the same heavily polluted areas were located in the open chromium residue storage. Soil pH and moisture content were the major factors controlling the migration of total Cr and Cr(VI) in soils. Results of probabilistic health risk assessment revealed that carcinogenic risk was negligible for adults and children, and the sensitive analysis implied that the content of Cr(VI) was the predominant contributor to carcinogenic risk. The combination of chemical reduction and microbial remediation could be the feasible remediation strategy for soil Cr(VI) pollution. Overall, this study provides scientific information into the chromium post-remediation and pollution management for various similar chromium-contaminated sites.

Functional EPAS1/HIF2A missense variant is associated with hematocrit in Andean highlanders.

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive EPAS1 variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations and validation in a lowland population. Although this genocopy of relatively lower hematocrit in Andean highlanders parallels well-replicated findings in Tibetans, it likely involves distinct pathway responses based on a protein-coding versus noncoding variants, respectively. These findings illuminate how unique variants at EPAS1 contribute to the same phenotype in Tibetans and a subset of Andean highlanders despite distinct evolutionary trajectories.

Bioaccumulation of Microcystin-LR and Induced Physio-Biochemical Changes in Rice (Oryza sativa L.) at Vegetative Stage under Hydroponic Culture Conditions.

Irrigation with water containing a variety of microcystins (MCs) may pose a potential threat to the normal growth of agricultural plants. To investigate the phytotoxicity of MC-LR at environmental concentrations on rice (Oryza sativa L.), the characteristics of uptake and accumulation in plant tissues, as well as a series of key physio-biochemical process changes in leaves of rice seedlings, were measured at concentrations of 0.10, 1.0, 10.0, and 50.0 µg·L-1 in hydroponic nutrient solutions for 7, 15, 20, and 34 days. Results showed that MC-LR could be detected in rice leaves and roots in exposure groups; however, a significant accumulation trend of MC-LR in plants (BCF > 1) was only found in the 0.10 µg·L-1 group. The time-course study revealed a biphasic response of O2•- levels in rice leaves to the exposure of MC-LR, which could be attributed to the combined effects of the antioxidant system and detoxification reaction in rice. Exposure to 1.0-50.0 µg·L-1 MC-LR resulted in significant depletion of GSH and MDA contents in rice leaves at later exposure times (15-34 days). Low MC-LR concentrations promoted nitric oxide synthase (NOS) activity, whereas high concentrations inhibited NOS activity during the later exposure times. The reduced sucrose synthase (SS) activities in rice exposed to MC-LR for 34 days indicated a decrease in the carbon accumulation ability of plants, and therefore may be directly related to the inhibition of plant growth under MC exposure. These findings indicate that the normal physiological status would be disrupted in terrestrial plants, even under exposure to low concentrations of MC-LR.

ELONGATED HYPOCOTYL 5a modulates FLOWERING LOCUS T2 and gibberellin levels to control dormancy and bud break in poplar.

Photoperiod is a crucial environmental cue for phenological responses, including growth cessation and winter dormancy in perennial woody plants. Two regulatory modules within the photoperiod pathway explain bud dormancy induction in poplar (Populus spp.): the circadian oscillator LATE ELONGATED HYPOCOTYL 2 (LHY2) and GIGANTEA-like genes (GIs) both regulate the key target for winter dormancy induction FLOWERING LOCUS T2 (FT2). However, modification of LHY2 and GIs cannot completely prevent growth cessation and bud set under short-day (SD) conditions, indicating that additional regulatory modules are likely involved. We identified PtoHY5a, an orthologs of the photomorphogenesis regulatory factor ELONGATED HYPOCOTYL 5 (HY5) in poplar (Populus tomentosa), that directly activates PtoFT2 expression and represses the circadian oscillation of LHY2, indirectly activating PtoFT2 expression. Thus, PtoHY5a suppresses SD-induced growth cessation and bud set. Accordingly, PtoHY5a knockout facilitates dormancy induction. PtoHY5a also inhibits bud-break in poplar by controlling gibberellic acid (GA) levels in apical buds. Additionally, PtoHY5a regulates the photoperiodic control of seasonal growth downstream of phytochrome PHYB2. Thus, PtoHY5a modulates seasonal growth in poplar by regulating the PtoPHYB2-PtoHY5a-PtoFT2 module to determine the onset of winter dormancy, and by fine-tuning GA levels to control bud-break.

Emulsion template fabricated gelatin-based scaffold functionalized by dialdehyde starch complex with antibacterial antioxidant properties for accelerated wound healing.

Gelatin and starch are considered as promising sustainable materials for their abundant production and good biodegradability. Efforts have been made to explore their medical application. Herein, scaffolds based on gelatin and starch with a preferred microstructure and antibacterial antioxidant property were fabricated by the emulsion template method. The dialdehyde starch was firstly combined with silver nanoparticles and curcumin to carry out the efficient hybrid antibacterial agent. Then, the gelatin microsphere of appropriate size was prepared by emulsification and gathered by the above agent to obtain gelatin-based scaffolds. The prepared scaffolds showed porous microstructures with high porosity of over 74 % and the preferred pore sizes of ∼65 µm, which is conducive to skin regeneration. Moreover, the scaffolds possessed a good swelling ability of over 640 %, good degradability of over 18 days, excellent blood compatibility, and cell compatibility. The promising antibacterial and antioxidant properties came from the hybrid antibacterial agent were affirmed. As expected, the gelatin-based scaffolds fabricated by the emulsion template method with a preferred microstructure can facilitate more adhered fibroblasts. In summary, gelatin-based scaffolds functionalized by starch-based complex expanded the application of abundant sustainable materials in the biomedical field, especially as antibacterial antioxidant wound dressings.

Overexpression of PtoMYB99 diminishes poplar tolerance to osmotic stress by suppressing ABA and JA biosynthesis.

Drought poses a serious challenge to sustained plant growth and crop yields in the context of global climate change. Drought tolerance in poplars and their underlying mechanisms still remain largely unknown. In this article, we investigated the overexpression of PtoMYB99 - both a drought and abscisic acid (ABA) induced gene constraining drought tolerance in poplars (as compared with wild type poplars). First, we found that PtoMYB99-OE lines exhibited increased stomatal opening and conductance, higher transpiration and photosynthetic rates, as well as reduced levels of ABA and jasmonic acid (JA). Second, PtoMYB99-OE lines accumulated more reactive oxygen species (ROS), including H2O2 and O2-, as well as malonaldehyde (MDA), proline, and soluble sugar under osmotic stress; conversely, the activity of antioxidant enzymes (SOD, POD, and CAT), was weakened in the PtoMYB99-OE lines. Third, the expression of ABA biosynthetic genes, PtoNCED3.1 and PtoNCED3.2, as well as JA biosynthetic genes, PtoOPR3.1 and PtoOPR3.2, was significantly reduced in the PtoMYB99-OE lines under both normal conditions and osmotic stress. Based on our results, we conclude that the overexpression of PtoMYB99 compromises tolerance to osmotic stress in poplar. These findings contribute to the understanding of the role of the MYB genes in drought stress and the biosynthesis of ABA and JA.

miR-206 alleviates LPS-induced inflammatory injury in cardiomyocytes via directly targeting USP33 to inhibit the JAK2/STAT3 signaling pathway.

Previous reports have confirmed that miR-206 participates in inflammatory cardiomyopathy, but its definite mechanism remains elusive. This study aims to elucidate the potential mechanism of miR-206 in septic cardiomyopathy (SCM). The primary mouse cardiomyocytes were isolated and exposed to lipopolysaccharides (LPS) to construct a septic injury model in vitro. Then, the gene transcripts and protein levels were detected by RT-qPCR and/or Western blot assay. Cell proliferation, apoptosis, and inflammatory responses were evaluated by CCK-8/EdU, flow cytometry, and ELISA assays, respectively. Dual luciferase assay, Co-IP, and ubiquitination experiments were carried out to validate the molecular interactions among miR-206, USP33, and JAK2/STAT3 signaling. miR-206 was significantly downregulated, but USP33 was upregulated in LPS-induced cardiomyocytes. Gain-of-function of miR-206 elevated the proliferation but suppressed the inflammatory responses and apoptosis in LPS-induced cardiomyocytes. USP33, as a member of the USP protein family, was confirmed to be a direct target of miR-206 and could catalyze deubiquitination of JAK2 to activate JAK2/STAT3 signaling. Rescue experiments presented that neither upregulation of USP33 nor JAK2/STAT3 signaling activation considerably reversed the protective effects of miR-206 upregulation in LPS-induced cardiomyocytes. The above data showed that miR-206 protected cardiomyocytes from LPS-induced inflammatory injuries by targeting the USP33/JAK2/STAT3 signaling pathway, which might be a novel target for SCM treatment.

Novel cytochrome P450s for various hydroxylation of steroids from filamentous fungi.

Hydroxylated steroids are value-added products with diverse biological activities mediated by cytochrome P450 enzymes, however, few has been thoroughly characterized in fungi. This study introduces a rapid identification strategy for filamentous fungi P450 enzymes through transcriptome and bioinformatics analysis. Five novel enzymes (CYP68J5, CYP68L10, CYP68J3, CYP68N1 and CYP68N3) were identified and characterized in Saccharomyces cerevisiae or Aspergillus oryzae. Molecular docking and dynamics simulations were employed to elucidate hydroxylation preferences of CYP68J5 (11α, 7α bihydroxylase) and CYP68N1 (11α hydroxylase). Additionally, redox partners (cytochrome P450 reductase and cytochrome b5) and ABC transporter were co-expressed with CYP68N1 to enhance 11α-OH-androstenedione (11α-OH-4AD) production. The engineered cell factory, co-expressing CPR1 and CYP68N1, achieved a significant increase of 11α-OH-4AD production, reaching 0.845 g·L-1, which increased by 14 times compared to the original strain. This study provides a comprehensive approach for identifying and implementing novel cytochrome P450 enzymes, paving the way for sustainable production of steroidal products.

Source identification and exposure risk management for soil arsenic in urban reclamation areas with high background levels: A case study in a coastal reclamation site from the Pearl River Delta, China.

Urbanization involving the excavation and reuse of arsenic-bearing geological materials may pose human health risks. We investigated the distribution and sources of soil arsenic at a coastal reclamation site in the Pearl River Delta, China, and proposed risk management strategies. Analysis of 899 soil samples revealed an average of 58.97 mg/kg arsenic, with a maximum of 1450 mg/kg, mainly in fill material obtained from a local island. Integrative analysis combining reclamation history, regional geology, and bedrock mineralogy conclusively identified hydrothermally altered arsenic-bearing sulfide minerals within extensively fractured bedrock as the primary source of arsenic. Physical weathering and anthropogenic rock blasting produced discrete arsenic-rich particles that were directly transported into soils during land reclamation and accumulated to potential hazardous levels. Oral, dermal, and inhalation pathways were identified as primary exposures for future populations. Integrated engineering and institutional controls, coupled with long-term monitoring, were recommended to mitigate risks. The results highlight the importance of identifying specific geogenic and anthropogenic sources that contribute to heavy metal enrichment of soils in reclaimed areas where native bedrock naturally contains elevated level of metals, supporting evidence-based best practices for risk management and future land use.

Machine Learning Modeling Based on Microbial Community for Prediction of Natural Attenuation in Groundwater.

Natural attenuation is widely adopted as a remediation strategy, and the attenuation potential is crucial to evaluate whether remediation goals can be achieved within the specified time. In this work, long-term monitoring of indigenous microbial communities as well as benzene, toluene, ethylbenzene, and xylene (BTEX) and chlorinated aliphatic hydrocarbons (CAHs) in groundwater was conducted at a historic pesticide manufacturing site. A machine learning approach for natural attenuation prediction was developed with random forest classification (RFC) followed by either random forest regression (RFR) or artificial neural networks (ANNs), utilizing microbiological information and contaminant attenuation rates for model training and cross-validation. Results showed that the RFC could accurately predict the feasibility of natural attenuation for both BTEX and CAHs, and it could successfully identify the key genera. The RFR model was sufficient for the BTEX natural attenuation rate prediction but unreliable for CAHs. The ANN model showed better performance in the prediction of the attenuation rates for both BTEX and CAHs. Based on the assessments, a composite modeling method of RFC and ANN was proposed, which could reduce the mean absolute percentage errors. This study reveals that the combined machine learning approach under the synergistic use of field microbial data has promising potential for predicting natural attenuation.

The Developmental Toxicity and Endocrine-Disrupting Effects of Fenpropathrin on Gobiocypris rarus during the Early Life Stage.

In the present study, the developmental toxicity and endocrine-disrupting effects of fenpropathrin on Gobiocypris rarus during the early life stage were studied using a semi-static water exposure method. The results showed that the LOEC (lowest observed effect concentration) of fenpropathrin on the incubation of rare minnow embryos was above 2.5 µg·L-1. The LOEC and NOEC (no observed effect concentration) of fenpropathrin on the developmental malformations and death indicators were 2.0 and 1.5 µg·L-1, respectively. After exposure to 1.5 µg·L-1 of fenpropathrin for 31 days, the expressions of androgen receptor genes (AR) and sex hormone-synthesis-related genes (CYP17 and CYP19a) were significantly decreased and the expressions of thyroid hormone receptor genes (TRß) and aryl hydrocarbon receptor genes (AhR1a and AhR2) were significantly increased in juvenile Gobiocypris rarus. The expression levels of the androgen receptor gene (AR), estrogen receptor gene (ER1), and the sex hormone-synthesis-related genes (HMGR, CYP17, and CYP19a) were significantly decreased, while the estrogen receptor gene (ER2a), thyroid hormone receptor gene (TRß), and aromatic hydrocarbon receptor genes (AhR1a and AhR2) were upregulated in juvenile Gobiocypris rarus under exposure to 2.0 µg·L-1 of fenpropathrin. Relatively low concentrations of fenpropathrin can affect the expression of sex hormone receptor genes, genes related to sex hormone synthesis, thyroid hormone receptor genes, and aromatic hydrocarbon receptor genes, thus interfering with the reproductive system, thyroid system, and metabolic level in Gobiocypris rarus. Therefore, more attention should be paid to the endocrine-disrupting effect caused by the pyrethroid insecticides in the water environment. Furthermore, studies on the internal mechanism of the endocrine-disrupting effect of pyrethroid insecticides on fish is needed in the future.

Significance of RNA N6-methyladenosine regulators in the diagnosis and subtype classification of coronary heart disease using the Gene Expression Omnibus database.

Background: Many investigations have revealed that alterations in m6A modification levels may be linked to coronary heart disease (CHD). However, the specific link between m6A alteration and CHD warrants further investigation. Methods: Gene expression profiles from the Gene Expression Omnibus (GEO) databases. We began by constructing a Random Forest model followed by a Nomogram model, both aimed at enhancing our predictive capabilities on specific m6A markers. We then shifted our focus to identify distinct molecular subtypes based on the key m6A regulators and to discern differentially expressed genes between the unique m6A clusters. Following this molecular exploration, we embarked on an in-depth analysis of the biological characteristics associated with each m6A cluster, revealing profound differences between them. Finally, we delved into the identification and correlation analysis of immune cell infiltration across these clusters, emphasizing the potential interplay between m6A modification and the immune system. Results: In this research, 37 important m6Aregulators were identified by comparing non-CHD and CHD patients from the GSE20680, GSE20681, and GSE71226 datasets. To predict the risk of CHD, seven candidate m6A regulators (CBLL1, HNRNPC, YTHDC2, YTHDF1, YTHDF2, YTHDF3, ZC3H13) were screened using the logistic regression model. Based on the seven possible m6A regulators, a nomogram model was constructed. An examination of decision curves revealed that CHD patients could benefit from the nomogram model. On the basis of the selected relevant m6A regulators, patients with CHD were separated into two m6A clusters (cluster1 and cluster2) using the consensus clustering approach. The Single Sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT methods were used to estimate the immunological characteristics of two separate m6A Gene Clusters; the results indicated a close association between seven candidate genes and immune cell composition. The drug sensitivity of seven candidate regulators was predicted, and these seven regulators appeared in numerous diseases as pharmacological targets while displaying strong drug sensitivity. Conclusion: m6A regulators play crucial roles in the development of CHD. Our research of m6A clusters may facilitate the development of novel molecular therapies and inform future immunotherapeutic methods for CHD.