Identifying Comprehensive Genomic Alterations and Potential Neoantigens for Cervical Cancer Immunotherapy in a Cohort of Chinese Squamous Cell Carcinoma of the Cervix

Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.

Clinicopathological alterations in wild mammals from the reservoir system of Trypanosoma cruzi:a scoping review

Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as"kissing bugs").Despite the fact that hundreds of species of wild mammals are part of the reservoir system,the morphologi-cal changes and clinical manifestations resulting from the pathogenesis of the infection have been largely neglected.The aim of this review is to systematically compile the available information regarding clinicopathological altera-tions in wild mammals due to natural infection by T.cruzi.Information was obtained from six online bibliographic data search platforms,resulting in the identification of 29 publications that met the inclusion criteria.Mortality was the most common clinical manifestation,cardiac damage was the main finding at necropsy,and lymphoplas-macytic inflammation was the most frequent microscopic injury.Thus,regardless of its role as a reservoir,T.cruzi has the potential to affect the health status of wild mammals,a situation that highlights the need for further research to analyze,measure,and compare its effects at both the individual and population levels.

Application of Remote Sensing and GIS in Mineral Alteration Mapping and Lineament Extraction Case of Oudiane Elkharoub (Requibat Shield, Northern of Mauritania)

The integration of remotely sensed data allowed the successful characterization of the mineral alteration zones of the Oudiane Elkharoub area in the Northeastern part of Reguibat Shield using image transformation techniques. As both chemical and geochemical analyses showed significant Au, Ag, Cu, Pb, Mn, Cr, Ni, Th and Y anomalies, it’s very interesting to apply the remote sensing and GIS in mineral resources mapping. The remote sensing is a direct adjunct to the field, lithologic and structural mapping, and more recently, GIS has played an important role in the study of mineralization areas. The integration of several evidential maps highlighted the plausible areas with high concentrations of chlorite, epidote, kaolinite, calcite, alunite, hematite, illite and sulfur among other key mineral alterations that reflect the intensity of hydrothermal effects and the probable sites of ore bodies. The methodological approach integrates geological information acquired from Aster and Landsat 8 OLI/TIRS (Operational Land Imager/Thermal InfraRed Sensor) images and a multi-criteria GIS analysis. The superimposition of various lineament and hydrothermal alteration maps and the consideration of precious and base metal indicators allowed the zoning of sites likely to contain mineral concentrations. Remote sensing becomes an important tool for locating mineral deposits in its own right, when the primary and secondary processes of mineralization result in the formation of spectral anomalies. Reconnaissance lithological mapping is usually the first step of mineral resource mapping. This is complimented with structural mapping, as mineral deposits usually occur along or adjacent to geologic structures, and alteration mapping, as mineral deposits are commonly associated with hydrothermal alteration of the surrounding rocks. Ground truthing and laboratory studies including XRD analysis were utilized to verify the results.

Evaluation of the coupled impact of silicon oxide nanoparticles and low-salinity water on the wettability alteration of Berea sandstones

This study investigated experimentally the coupled effects of hydrophilic SiO_(2) nanoparticles(NPs)and low-salinity water(LSW)on the wettability of synthetic clay-free Berea sandstone.Capillary pressure,interfacial tension(IFT),contact angle,Zeta potential,and dynamic displacement measurements were performed at various NP mass fractions and brine salinities.The U.S.Bureau of Mines(USBM)index was used to quantify the wettability alteration.Furthermore,the NP stability and retention and the effect of enhanced oil recovery by nanofluid were examined.The results showed that LSW immiscible displacement with NPs altered the wettability toward more water wet.With the decreasing brine salinity and increasing NP mass fraction,the IFT and contact angle decreased.The wettability alteration intensified most as the brine salinity decreased to 4000 mg/L and the NP mass fraction increased to 0.075%.Under these conditions,the resulting incremental oil recovery factor was approximately 13 percentage points.When the brine salinity was 4000 mg/L and the NP mass fraction was 0.025%,the retention of NPs caused the minimum damage to permeability.

Wettability alteration of organo-vermiculites induced by layer charge and tailored bis-N-heterocyclic quaternary ammonium salts

Wettability is an important surface property that deserves to further explore the factors on its alteration.Series of bis-N-heterocyclic quaternary ammonium salts with different spacer length and N-heterocyclic headgroups(morpholinium(BMMB,BMMD and BMMH),piperidinium(BPMH)and piperazinium(BMPMH))have been synthesized and employed for altering the wettability of vermiculite and its derivates(Vts)treated by Li^(+)-saturated heating method.The results of X-ray diffraction(XRD),Fourier transform infrared spectroscopy(FT-IR),thermogravimetric analysis(TG-DTG),scanning electron microscopy(SEM)and N_(2)adsorption/desorption isotherms indicate that all of the bis-N-heterocyclic quaternary ammonium salts have been successfully inserted into the vermiculite layers,leading to the organic monolayer.The results of capillary rise tests combined with Lipophilic to Hydrophilic Ratio(LHR)values unveil the wettability alteration of the organo-Vts.As the layer charge decreases,the hydrophilicity of the organo-Vts gradually increases,which is probably caused by the decline in binding sites.As the result of the change in spacer length of modifier,the wetting properties of morpholinium-based organo-Vts change in order of BMMD-Vts>BMMH-Vts>BMMB-Vts,and difference in N-heterocyclic headgroups leads to the sequence of wettability:BMPMH-Vts>BPMH-Vts>BMMH-Vts.Layer charge of Vt,spacer length and the type of the N-heterocyclic headgroup of modifier have the synergistic effect on the regulation of the wettability.

Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

Investigation of the effect of diethylene triamine pentaacetic acid chelating agent as an enhanced oil recovery fluid on wettability alteration of sandstone rocks

This study used the diethylene triamine pentaacetic acid(DTPA)-seawater(SW)system to modify the sandstone rock wettability and enhance oil recovery.The investigation involved conducting wettability measurement,Zeta potential measurement,and spontaneous imbibition experiment.The introduction of 5%DTPA-sW solution resulted in a significant decrease in the rock-oil contact angle from 143°to 23,along with a reduction in the Zeta potential from-2.29 mV to-13.06 mV,thereby altering the rock surface charge and shifting its wettability from an oil-wet state to a strongly water-wet state.The presence or absence of potential determining ions(Ca^(2+),Mg^(2+),SO_(4)^(2-))in the solution did not impact the effectiveness of DTPA in changing the rock wettability.However,by tripling the concentration of these ions in the solution,the performance of 5%DTPA-SW solution in changing wettability was impaired.Additionally,spontaneous imbibition tests demonstrated that the 5%DTPA-SW solution led to an increase in oil recovery up to 39.6%.Thus,the optimum mass fraction of DTPA for changing sandstone wettability was determined to be5%.

Insight into the evolution of breast cancer driven by genetic alterations

Breast cancer originates primarily from the epithelial cells of the mammary gland.Repeated mammary gland expansion and degeneration are accompanied by an increased risk of genetic alterations in the breast1.These mutations in breast epithelial cells dynamically occur in response to pregnancy,labor and delivery,breastfeeding,and the menstrual cycle,with a decline in mutation rates after menopause,which may be related to a decrease in estrogen levels.The breast epithelial cell mutations are also consistent with epidemiologic observations2.

Integrating Aster Images Processing and Fieldwork for Identification of Hydrothermal Alteration Zones at the Oumjrane-Boukerzia District, Moroccan Anti-Atlas

Mapping from remote sensing has become more effective in the field of geology, mainly in lithological discrimination and identification of hydrothermal alteration zones. The use of this technique consists in obtaining information about the rock mass and the main ones existing in the inaccessible areas. Satellite data from the ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) sensor represent a favorable potential for detecting the spectral signatures of mineral zones and identifying their nature. These data are more reliable in places where the climate is arid with less abundant vegetation, as at the Oumjrane-Boukerzia mining district. This region which is part of the Eastern Anti-Atlas, is composed of several mineralized veins which still require detailed studies and exploration by the technique of remote sensing. In this work we applied several processing techniques on ASTER imagery such as Colored Composition, Principal Component Analysis and Ratio Bands. The use of the reports of the specialized Bands makes it possible to identify some hydrothermal alteration minerals within the mining district of Oumjrane Boukerzia. These minerals are represented mainly by iron oxides and hydroxides (Hematite, jarosite, limonite and goethite), carbonate minerals (dolomite, calcite), clay minerals (Illite, kaolinite and chlorite) and quartz minerals. This work allows us to produce a map of hydrothermal alteration zones which can be used as a valuable reference in the strategy of mining exploration for the base metals (Cu, Pb, Zn and Ba), in the mining district of Oumjrane-Boukerzia and in the entire Eastern Anti-Atlas.

ASTER Data Processing by Discrete Wavelets Transform and Band Ratio Techniques for the Identification of Lineaments and Hydrothermal Alteration Zones in Poli, North Cameroon

The aim of this study is to carry out hydrothermal alteration mapping and structural mapping using ASTER images in order to identify indices that could guide mining exploration work in the Poli area and its surroundings. To achieve this, the ASTER images were first preprocessed to correct atmospheric effects and remove vegetation influence. Secondly, a lineament mapping was conducted by applying Discrete Wavelet Transform (DWT) algorithms to the First Principal Component Analysis (PCA1) of Visible Near-Infrared (VNIR) and Shortwave Infrared (SWIR) bands. Lastly, band ratio methods were applied to the VNIR, SWIR, and Thermal Infrared (TIR) bands to determine indices of iron oxides/hydroxides (hematite and limonite), hydroxyl-bearing minerals (chlorite, epidote, and muscovite), and the quartz index. The results obtained showed that the lineaments were mainly oriented NE-SW, ENE-WSW, and E-W, with NE-SW being the most predominant direction. Concerning hydrothermal alteration, the identified indices covered almost the entire study area and showed a strong correlation with lithological data. Overlaying the obtained lineaments with the hydrothermal alteration indices revealed a significant correlation between existing mining indices and those observed in the field. Mineralized zones generally coincided with areas of high lineament density exhibiting significant hydrothermal alteration. Based on the correlation between existing mining indices and the results of hydrothermal and structural mapping, the results obtained can then be used as a reference document for any mining exploration in the study area.

Alteration Typology and Geochemical Signatures of the Napélépéra Gold-Bearing Granodiorite in South-West Burkina Faso (West Africa)

The characterization of the relationships between mineralization and hydrothermal alteration is an essential element in understanding gold deposits. In south-west Burkina Faso, the Napélépéra mineralisation, the mobility of chemical elements and alteration-mineralization relationships were studied by means of selected core drilling and geochemical analyses using ICP-MS (Inductively Coupled Plasma Mass Spectrometry) and ICP-AES (Inductively coupled plasma atomic emission spectroscopy). The mineralised granodiorite is grey porphyroid with quartz, plagioclase, biotite and amphibole. It is metaluminous and located in the tholeiitic series. The Na2O + CaO versus Fe2O3 + MgO alteration diagram divides the samples according to alteration dominance. Chloritisation and carbonation are the main alterations. There is a relationship between gold mineralisation at Napélépéra and alteration, and the paragenesis of gold + pyrite ± carbonate ± silica ± sericite is the main characteristic. Carbonation is the result of fluid input in the shear corridor of the mineralised zone. The mass balance of comparative metals in the proximal and distal zones of the mineralisation shows the absence of metals, while As, Hg, Ag and Bi are strongly enriched from the distal zone to the mineralised zone. The oxides associated with the mineralisation are mainly NaO, SrO and CaO.

Hydro-uvarovite from Mantle Peridotites of Naga Hills Ophiolite: A Mineral Tracer for Neo-Tethyan Mantle Wedge Metasomatism

Hydrous Cr-bearing uvarovite garnets are rare in natural occurrences and belong to the ugrandite series and exist in binary solid solutions with grossular and andradite garnets. Here, we report the occurrence of hydrous uvarovite garnet having Cr_(2)O_(3) upto 19.66 wt% and CaO of 32.12–35.14 wt% in the serpentinized mantle peridotites of Naga Hills Ophiolite(NHO), India. They occur in association with low-Cr diopsides. They are enriched in LILE(Ba, Sr), LREEs, with fractionating LREE-MREE [avg.(La/Sm)_(N) = 2.16] with flat MREE/HREE patterns [avg.(Sm/Yb)_(N) = 0.95]. Raman spectra indicate the presence of hydroxyl(OH^(–)) peaks from 3500 to 3700 cm^(-1). Relative abundances in fluid mobile elements and their close association with clinopyroxenes are suggestive of the formation of uvarovite garnets through low temperature metasomatic alteration of low-Cr diopsides by hydrothermal slab fluids. The high LREE concentration and absence of Eu anomaly in the garnet further attest to alkaline nature of the transporting slab dehydrated fluid rather the involvement of low-p H solution. The chemical characteristics of the hydroxyl bearing uvarovite hosted by the mantle peridotite of NHO deviate from the classical features of uvarovite garnet, and their origin is attributed to the fluid-induced metasomatism of the sub arc mantle wedge in a suprasubduction zone regime.

New insights into the effects of APP gene dose on synapse in Down syndrome

Synaptic dysfunction:Alzheimer’s disease(AD)is a prevalent form of dementia,affecting over 35 million people worldwide(Tzioras et al.,2023).A synapse serves as the connection point between neurons,facilitating the transmission of information from one neuron to another.Dynamic alterations in synapses,known as synaptic plasticity,play a pivotal role in cognitive processes such as learning and memory.Synaptic loss has been identified as a key contributor to cognitive decline in AD patients.Studies have shown that the soluble forms of amyloid-beta(Aβ)and tau proteins are toxic to synapses,leading to cognitive impairment in animal models(Spires-Jones and Hyman,2014).Additionally,the formation of oligomers of tau and Aβcan spread pathology through synaptic connections in the brain,emphasizing the vital role of synapses in disease progression.

Geology and mineralization of the Dongping supergiant alkalic-hosted Au-Te deposit(>100 t Au)in Northern Hebei Province,China:A review

The Dongping deposit is the largest alkalic-hosted gold deposit in China containing>100 t of Au.This paper presents a new understanding for Dongping ore system,based on the previous studies.The mineralization originally occurred at 400-380 Ma,simultaneous with emplacement of the Shuiquangou alkaline complex,and was overprinted by the hydrothermal activity in the Yanshanian.Isotope compositions of ores indicate metals of the deposit are mainly provided by the Shuiquangou complex.Ore-forming fluids are characterized by increasing oxygen fugacity and decreasing sulfur fugacity,while tellurium fugacity increased in the Stage II-2 and decreased in Stage II-3.These systematic changes are closely related to the processes of mineral precipitation and fluid evolution.Sulfide precipitation from Stage Ⅰ to Stage Ⅱ was triggered by fluid boiling,which leads to the precipitation of Pb-Bi-Te,due to decrement of sulfur fugacity.Condensation of gas phase containing high concentration of H_2Te leads to precipitation of Te-Au-Ag minerals and native tellurium.Based on these hypotheses,this paper present a polyphase metallogenic model as follow.During the Devonian,fluids were released from alkaline magmas,which carried ore-forming materials form the surrounding rocks and precipitate the early ores.During the Jurassic-Cretaceous,fluorine-rich fluids exsolved from highly factionated Shangshuiquan granite,which extracted and concentrated Au from the Shuiquangou complex and the Sanggan Group metamorphic rocks,and finally formed the Dongping gold deposit.

Genomic alterations in oral multiple primary cancers

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs.Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

Activity-dependent mechanisms of neuroprotection:promising avenues against dementia

The study of the brain and its complex functions is highly fascinating and,at the same time,extremely important.Indeed,furthering our understanding of the biology of neurons and synapses is a prerequisite to uncover the mechanisms involved in memory formation and the coordination of movement as well as their alterations occurring in several neurological disorders.

Sex-dependent alterations in extracellular vesicles linking chronic spinal cord injury to brain neuroinflammation and neurodegeneration

Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.

Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

Calcium-sensitive protein MLC1 as a possible modulator of the astrocyte functional state

Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult life.To maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.

Plasma metabolites and risk of myocardial infarction:a bidirectional Mendelian randomization study

BACKGROUND Myocardial infarction(MI)is a critical cardiovascular event with multifaceted etiology,involving several genetic and environmental factors.It is essential to understand the function of plasma metabolites in the development of MI and unravel its complex pathogenesis.METHODS This study employed a bidirectional Mendelian randomization(MR)approach to investigate the causal relationships between plasma metabolites and MI risk.We used genetic instruments as proxies for plasma metabolites and MI and conducted MR analyses in both directions to assess the impact of metabolites on MI risk and vice versa.In addition,the large-scale genome-wide association studies datasets was used to identify genetic variants associated with plasma metabolite(1400 metabolites)and MI(20,917 individuals with MI and 440,906 individuals without MI)susceptibility.Inverse variance weighted was the primary method for estimating causal effects.MR estimates are expressed as beta coefficients or odds ratio(OR)with 95%CI.RESULTS We identified 14 plasma metabolites associated with the occurrence of MI(P<0.05),among which 8 plasma metabolites[propionylglycine levels(OR=0.922,95%CI:0.881–0.965,P<0.001),gamma-glutamylglycine levels(OR=0.903,95%CI:0.861–0.948,P<0.001),hexadecanedioate(C16-DC)levels(OR=0.941,95%CI:0.911–0.973,P<0.001),pentose acid levels(OR=0.923,95%CI:0.877–0.972,P=0.002),X-24546 levels(OR=0.936,95%CI:0.902–0.971,P<0.001),glycine levels(OR=0.936,95%CI:0.909–0.964,P<0.001),glycine to serine ratio(OR=0.930,95%CI:0.888–0.974,P=0.002),and mannose to trans-4-hydroxyproline ratio(OR=0.912,95%CI:0.869–0.958,P<0.001)]were correlated with a decreased risk of MI,whereas the remaining 6 plasma metabolites[1-palmitoyl-2-arachidonoyl-GPE(16:0/20:4)levels(OR=1.051,95%CI:1.018–1.084,P=0.002),behenoyl dihydrosphingomyelin(d18:0/22:0)levels(OR=1.076,95%CI:1.027–1.128,P=0.002),1-stearoyl-2-docosahexaenoyl-GPE(18:0/22:6)levels(OR=1.067,95%CI:1.027–1.109,P=0.001),alpha-ketobutyrate levels(OR=1.108,95%CI:1.041–1.180,P=0.001),5-acetylamino-6-formylamino-3-methyluracil levels(OR=1.047,95%CI:1.019–1.076,P<0.001),and N-acetylputrescine to(N(1)+N(8))-acetylspermidine ratio(OR=1.045,95%CI:1.018–1.073,P<0.001)]were associated with an increased risk of MI.Furthermore,we also observed that the mentioned relationships were unaffected by horizontal pleiotropy(P>0.05).On the contrary,MI did not lead to significant alterations in the levels of the aforementioned 14 plasma metabolites(P>0.05 for each comparison).CONCLUSIONS Our bidirectional MR study identified 14 plasma metabolites associated with the occurrence of MI,among which 13 plasma metabolites have not been reported previously.These findings provide valuable insights for the early diagnosis of MI and potential therapeutic targets.