The m6A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN.

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear. METHODS: The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT-PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1. RESULTS: The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m6A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells. CONCLUSIONS: Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC.

Mendelian randomization analyses reveal causal relationship between liver volume and stroke.

BACKGROUND: Observational studies have suggested a potential association between abdominal viscera volume and increased risk of stroke. However, the causal relationship remains unclear. This study aims to utilize Mendelian randomization (MR) to explore the genetic causal relationship between them. METHODS: We conducted MR analysis to study the causal effects of five abdominal viscera volumes on stroke. The genetic variations of abdominal viscera volume were obtained from the UK Biobank, and the summary data for stroke and ischemic stroke were acquired from the MEGASTROKE consortium. This study employed inverse variance weighting (IVW), MR Egger, and weighted median methods. IVW served as the primary MR analysis method, supplemented by other sensitivity analyses to validate the robustness of the results. RESULTS: We found that liver volume can causally increase the risk of stroke [odds ratio (OR): 1.13, 95 % confidence interval (CI): 1.03-1.25, P = 0.013] and ischemic stroke (OR: 1.14, 95 % CI: 1.03-1.26, P = 0.012). No causal relationships between other abdominal viscera volumes and stroke and ischemic stroke appeared to be present (P > 0.05). Sensitivity analyses confirmed the robustness of the results. CONCLUSION: Our research findings indicate a causal relationship between liver volume and stroke, highlighting the potential role of liver volume in the onset of stroke. However, further basic and clinical research is needed to delve into the specific mechanisms underlying the relationship between liver volume and stroke, and to implement interventions aimed at reducing the impact of liver volume on stroke risk.

YTHDF1's Regulatory Involvement in Breast Cancer Prognosis, Immunity, and the ceRNA Network.

YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), an m6A reader, has a role in the development and progression of breast cancer as well as the immunological microenvironment. The networks of competing endogenous RNA in cancer have received much attention in research. In tumor gene therapy, the regulatory networks of m6A and competing endogenous RNA are increasingly emerging as a new route. We evaluated the relationship between the YTHDF1 expression, overall survival, and clinicopathology of breast cancer using TCGA, PrognoScan, and other datasets. We used Western blot to demonstrate that YTHDF1 is substantially expressed in breast cancer tissues. Furthermore, we explored YTHDF1's functions in the tumor mutational burden, microsatellite instability, and tumor microenvironment. Our findings indicate that YTHDF1 is a critical component of the m6A regulatory proteins in breast cancer and may have a particular function in the immunological microenvironment. Crucially, we investigated the relationship between YTHDF1 and the associated competitive endogenous RNA regulatory networks, innovatively creating three such networks (Dehydrogenase/Reductase 4-Antisense RNA 1-miR-378g-YTHDF1, HLA Complex Group 9-miR-378g-YTHDF1, Taurine Up-regulated 1-miR-378g-YTHDF1). Furthermore, we showed that miR-378g could inhibit the expression of YTHDF1, and that miR-378g/YTHDF1 could impact MDA-MB-231 proliferation. We speculate that YTHDF1 may serve as a biomarker for poor prognosis and differential diagnosis, impact the growth of breast cancer cells via the ceRNA network axis, and be a target for immunotherapy against breast cancer.

Genome-wide association study on resistance of cultivated soybean to Fusarium oxysporum root rot in Northeast China.

BACKGROUND: Fusarium oxysporum is a prevalent fungal pathogen that diminishes soybean yield through seedling disease and root rot. Preventing Fusarium oxysporum root rot (FORR) damage entails on the identification of resistance genes and developing resistant cultivars. Therefore, conducting fine mapping and marker development for FORR resistance genes is of great significance for fostering the cultivation of resistant varieties. In this study, 350 soybean germplasm accessions, mainly from Northeast China, underwent genotyping using the SoySNP50K Illumina BeadChip, which includes 52,041 single nucleotide polymorphisms (SNPs). Their resistance to FORR was assessed in a greenhouse. Genome-wide association studies utilizing the general linear model, mixed linear model, compressed mixed linear model, and settlement of MLM under progressively exclusive relationship models were conducted to identify marker-trait associations while effectively controlling for population structure. RESULTS: The results demonstrated that these models effectively managed population structure. Eight SNP loci significantly associated with FORR resistance in soybean were detected, primarily located on Chromosome 6. Notably, there was a strong linkage disequilibrium between the large-effect SNPs ss715595462 and ss715595463, contributing substantially to phenotypic variation. Within the genetic interval encompassing these loci, 28 genes were present, with one gene Glyma.06G088400 encoding a protein kinase family protein containing a leucine-rich repeat domain identified as a potential candidate gene in the reference genome of Williams82. Additionally, quantitative real-time reverse transcription polymerase chain reaction analysis evaluated the gene expression levels between highly resistant and susceptible accessions, focusing on primary root tissues collected at different time points after F. oxysporum inoculation. Among the examined genes, only this gene emerged as the strongest candidate associated with FORR resistance. CONCLUSIONS: The identification of this candidate gene Glyma.06G088400 improves our understanding of soybean resistance to FORR and the markers strongly linked to resistance can be beneficial for molecular marker-assisted selection in breeding resistant soybean accessions against F. oxysporum.

Major genetic locus with pleiotropism determined seed-related traits in cultivated and wild soybeans.

KEY MESSAGE: Here, a novel pleiotropic QTL qSS14 simultaneously regulating four seed size traits and two consistently detected QTLs qSW17 and qSLW02 were identified across multiple years. Seed-related traits were the key agronomic traits that have been artificially selected during the domestication of wild soybean. Identifying the genetic loci and genes that regulate seed size could clarify the genetic variations in seed-related traits and provide novel insights into high-yield soybean breeding. In this study, we used a high-density genetic map constructed by F10 RIL populations from a cross between Glycine max and Glycine soja to detect additive QTLs for seven seed-related traits over the last three years. As a result, we identified one novel pleiotropic QTL, qSS14, that simultaneously controlled four seed size traits (100-seed weight, seed length, seed width, and seed thickness) and two consistently detected QTLs, qSW17, and qSLW02, in multiple years of phenotypic data. Furthermore, we predicted two, two and three candidate genes within these three critical loci based on the parental resequencing data and gene function annotations. And the relative expression of four candidate genes GLYMA_14G155100, GLYMA_17G061000, GLYMA_02G273100, and GLYMA_02G273300 showed significant differences among parents and the extreme materials through qRT-PCR analysis. These findings could facilitate the determination of beneficial genes in wild soybean and contribute to our understanding of the soybean domestication process.

Serum metabolomics probes the molecular mechanism of action of acupuncture on metabolic pathways related to glucose metabolism in patients with polycystic ovary syndrome-related obesity.

Polycystic ovary syndrome (PCOS) is a common endocrine syndrome, and obesity is the most common clinical manifestation. Acupuncture is effective in treating PCOS, but the differences in the biological mechanisms of acupuncture therapy and Western medicine treatment have not been determined. Thus, the purpose of this study was to find glucose metabolism-related pathways in acupuncture treatment and differentiate them from Western medical treatment. Sixty patients with PCOS-related obesity were randomly distributed into three groups: patients receiving (1) acupuncture treatment alone, (2) conventional Western medicine treatment, and (3) acupuncture combined with Western medicine treatment. A targeted metabolomics approach was used to identify small molecules and metabolites related to glucose metabolism in the serum of each group, and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to analyze different metabolic fractions. The results showed acupuncture treatment modulates the activity of citric and succinic acids in the tricarboxylic acid cycle, regulates glycolytic and gluconeogenesis pathways, and improves the levels of sex hormones and energy metabolism. The intervention effects on the metabolic pathways were different between patients receiving combination therapy and patients receiving acupuncture therapy alone, suggesting that the dominant modulatory effect of Western drugs may largely conceal the efficacy of acupuncture intervention.

Molecular Networking Accelerated Discovery of Biflavonoid Alkaloids from Cephalotaxus sinensis.

Four undescribed biflavonoid alkaloids, sinenbiflavones A-D, were isolated from Cephalotaxus sinensis using a MS/MS-based molecular networking guided strategy. Their structures were elucidated by series of spectroscopic methods (HR-ESI-MS, UV, IR, 1D, and 2D NMR). Sinenbiflavones A-D are the first examples of amentoflavone-type (C-3'-C-8'') biflavonoid alkaloids. Meanwhile, sinenbiflavones B and D are the unique C-6-methylated amentoflavone-type biflavonoid alkaloids. Sinenbiflavone D showed weak SARS-CoV-2 3CLpro inhibitory activity with 43 % inhibition rate at 40 µM.

HOTAIR/miR-203/CAV1 Crosstalk Influences Proliferation, Migration, and Invasion in the Breast Cancer Cell.

In recent years, malignant breast cancer metastasis has caused a great increase in mortality. Research on the genetic and molecular mechanisms of malignant breast cancer has continued to deepen, and targeted therapy has become the general trend. Among them, competing endogenous RNA (ceRNA)-related molecules have received much attention. Homeobox transcript antisense RNA (HOTAIR) has been reported to function extensively as a ceRNA in breast cancer. Notably, miR-203 and Caveolin 1 (CAV1) have also been found to play a role in breast cancer. However, the relationship between the three remains unclear. In this study, we present a new mechanic through bioinformatics tool and basic experiments: the HOTAIR/miR-203/CAV1 axis, which complemented the role network of HOTAIR as a ceRNA, thus, it will provide a novel potential idea for breast cancer research and therapy.

Feasibility and efficacy of left bundle branch area pacing in patients indicated for cardiac resynchronization therapy.

AIMS: The present study was to evaluate the feasibility and clinical outcomes of left bundle branch area pacing (LBBAP) in cardiac resynchronization therapy (CRT)-indicated patients. METHODS AND RESULTS: LBBAP was performed via transventricular septal approach in 25 patients as a rescue strategy in 5 patients with failed left ventricular (LV) lead placement and as a primary strategy in the remaining 20 patients. Pacing parameters, procedural characteristics, electrocardiographic, and echocardiographic data were assessed at implantation and follow-up. Of 25 enrolled CRT-indicated patients, 14 had left bundle branch block (LBBB, 56.0%), 3 right bundle branch block (RBBB, 12.0%), 4 intraventricular conduction delay (IVCD, 16.0%), and 4 ventricular pacing dependence (16.0%). The QRS duration (QRSd) was significantly shortened by LBBAP (intrinsic 163.6 ± 29.4 ms vs. LBBAP 123.0 ± 10.8 ms, P < 0.001). During the mean follow-up of 9.1 months, New York Heart Association functional class was improved to 1.4 ± 0.6 from baseline 2.6 ± 0.6 (P < 0.001), left ventricular ejection fraction (LVEF) increased to 46.9 ± 10.2% from baseline 35.2 ± 7.0% (P < 0.001), and LV end-diastolic dimensions (LVEDD) decreased to 56.8 ± 9.7 mm from baseline 64.1 ± 9.9 mm (P < 0.001). There was a significant improvement (34.1 ± 7.4% vs. 50.0 ± 12.2%, P < 0.001) in LVEF in patients with LBBB. CONCLUSION: The present study demonstrates the clinical feasibility of LBBAP in CRT-indicated patients. Left bundle branch area pacing generated narrow QRSd and led to reversal remodelling of LV with improvement in cardiac function. LBBAP may be an alternative to CRT in patients with failure of LV lead placement and a first-line option in selected patients such as those with LBBB and heart failure.

How to implant left bundle branch pacing lead in routine clinical practice.

INTRODUCTION: Left bundle branch pacing (LBBP) is characterized with a low and stable pacing capture threshold, relatively narrow QRS duration due to fast left ventricular activation, and direct excitation of the diseased left bundle branch. This report aims to describe the methods, procedural skills, and clinical implications of performing LBBP implantation. METHODS AND RESULTS: LBBP is achieved by transventricular-septal approach. There are two methods to identify the location for LBBP lead placement: the single-lead method and the dual-lead method. During implantation, the unique transition of the paced QRS morphology and pacing parameter changes are important for guiding the lead - advancement to the left side of the interventricular septum. In our experience, LBBP can be safely performed in most patients requiring pacemaker therapy. CONCLUSION: Clinical development of LBBP is at an early but encouraging phase with increasing clinical use, and a standardized procedure with improved delivery tools and pacing leads is needed, as well as long-term efficacy and safety.

Recovery of complete left bundle branch block following heart failure improvement by left bundle branch pacing in a patient.

A 57-year-old male presented with symptomatic systolic heart failure and complete left bundle branch block (LBBB). Left bundle branch pacing corrected LBBB at a low capture threshold (0.5V @0.4ms) with right bundle branch conduction delay and paced QRS morphology changed to near-normal by adjusting AV delay with diminished RBBD. At 1-year follow-up, the patient had a significant improvement in heart failure and LBBB automatically resolved with a rate-dependent pattern. LBBP may be an alternative to conventional cardiac resynchronization therapy with the likelihood of recovery of LBBB. More research is needed to evaluate the potential use of this pacing strategy in patients with LBBB and heart failure.

Comparison of electrocardiogram characteristics and pacing parameters between left bundle branch pacing and right ventricular pacing in patients receiving pacemaker therapy.

AIMS: This study explores the feasibility of left bundle branch pacing (LBBP) and characterizes electrocardiogram (ECG) patterns during the pacing in comparison with conventional right ventricular pacing (RVP). METHODS AND RESULTS: Forty pacing-indicated patients were prospectively enrolled. Twenty patients underwent LBBP (the LBBP group), and 20 patients underwent RVP (the RVP group). Left bundle branch pacing was achieved by transseptal method in the basal ventricular septum. Electrocardiogram characteristics, pacing parameters, pacing sites, and safety events were assessed at implantation and 3-month follow-up. In the LBBP group, the pacing lead was successfully placed near the endocardium of the left side of the septum. Electrocardiogram pattern during LBBP showed right bundle branch conduction delay. Left bundle branch block (LBBB) in two patients was corrected by LBBP. Post-implantation 3D echocardiography confirmed the pacing location. In the RVP group, ECG showed LBBB pattern. The paced QRS duration was 111.85 ± 10.77 ms in LBBP group and 160.15 ± 15.04 ms in the RVP group (P < 0.001). Pacing thresholds (at implantation: 0.73 ± 0.20 V in the LBBP group and 0.61 ± 0.23 V in the RVP group) remained low and stable at 3-month follow-up. No adverse event was observed during 3-month follow-up. CONCLUSION: This study demonstrates the clinical feasibility of LBBP. Left bundle branch pacing that has a low pacing threshold and produces narrow ECG QRS duration may be a new pacing strategy for patients in need of ventricular pacing.

Role of leptin in allergic rhinitis during sublingual immunotherapy.

OBJECTIVE: Increasing evidence suggests that leptin is upregulated during allergic reactions in the airway and related to the severity of disease in allergic rhinitis (AR). In this study, we aimed to investigate the expression of leptin during sublingual immunotherapy (SLIT) in AR patients. METHODS: Forty AR patients without obesity were recruited in this study. Twenty patients received house dust mite (HDM) allergen extract for SLIT and twenty patients received placebo randomly. Protein expression of leptin in serum and nasal lavage was tested by enzyme-linked immuno sorbent assay (ELISA) 1 and 2 years after SLIT treatment, respectively. Peripheral blood mononuclear cells (PBMCs) and human nasal epithelial cell were prepared and stimulated by recombinant leptin after 24 months' SLIT treatment and the induction of Th2 cytokines (IL-4/IL-5/IL-13) were detected by ELISA. RESULTS: SLIT treatment decreased the expression of leptin protein in serum and nasal lavage significantly compared with placebo group 1 and 2 years after SLIT treatment. Nasal leptin level was correlated to decreased Th2 response (IL-4/IL-5/IL-13) and enhanced Treg (IL-10/TGF-beat) response after 2 years' SLIT. We also found that SLIT decreased the ability of leptin in promoting Th2 cytokines expression by PBMCs and human nasal epithelial cell after 2 years' SLIT treatment. CONCLUSION: Changes of leptin expression in serum and nasal lavage may be correlated with Th2/Treg regulation during SLIT. Our results suggested that leptin served as an important biomarker during SLIT.

Association of angiotensin II receptor 1 and lectin-like oxidized low-density lipoprotein receptor-1 mediates the cardiac hypertrophy induced by oxidized low-density lipoprotein.

To date the molecular mechanism of cardiac hypertrophy has not been completely elucidated. Since oxidized low-density lipoprotein (ox-LDL) is considered a risk marker for early ventricular remodeling, we speculated that ox-LDL may be related to cardiac hypertrophy. We observed the significantly upregulation of plasma ox-LDL and hypertrophic responses, such as cardiomyocyte size and specific gene expressions in Apo E-/- mice fed with high fat diet, accompanied by the upregulation of AT1-R and lectin-like oxidized low-density protein receptor 1 (LOX-1). Ox-LDL treatment with neonatal rat cardiomyocyte for 24 h significantly induced similar hypertrophic responses and also upregulation of AT1-R and LOX-1. The analysis of co-immunoprecipitation and the bimolecular fluorescence complementation assay proved that LOX-1 and AT1-R could directly bind together in the presence of ox-LDL, suggesting a critical role of the association between LOX-1 and AT1-R in ox-LDL-induced cardiac hypertrophy. Furthermore, we found that the AT1-R blocker Losartan and LOX-1 neutralizing antibody through inhibiting AT1-R or LOX-1 could both decline ox-LDL-induced hypertrophic responses whereas angiotensin converting enzyme inhibitor Enalapril only partially inhibited the responses stimulated by ox-LDL. These findings suggested that ox-LDL could induce cardiac hypertrophy through the direct association of AT1-R and LOX-1.

Anti-Inflammatory Effects of a Mytilus coruscus α-d-Glucan (MP-A) in Activated Macrophage Cells via TLR4/NF-κB/MAPK Pathway Inhibition.

The hard-shelled mussel (Mytilus coruscus) has been used as Chinese traditional medicine for thousands of years; however, to date the ingredients responsible for the various beneficial health outcomes attributed to Mytilus coruscus are still unclear. An α-d-Glucan, called MP-A, was isolated from Mytilus coruscus, and observed to exert anti-inflammatory activity in THP-1 human macrophage cells. Specifically, we showed that MP-A treatment inhibited the production of inflammatory markers, including TNF-α, NO, and PGE2, inducible NOS (iNOS), and cyclooxygenase-2 (COX-2), in LPS-activated THP-1 cells. It was also shown to enhance phagocytosis in the analyzed cells, but to severely inhibit the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear translocation of NF-κB P65. Finally, MP-A was found to exhibit a high binding affinity for the cell surface receptor TLR4, but a low affinity for TLR2 and dectin-1, via surface plasmon resonance (SPR) analysis. The study indicates that MP-A suppresses LPS-induced TNF-α, NO and PEG2 production via TLR4/NF-κB/MAPK pathway inhibition, and suggests that MP-A may be a promising therapeutic candidate for diseases associated with TNF-α, NO, and/or PEG2 overproduction.

Risk factors for ventricular arrhythmias after emergency percutaneous coronary intervention in elderly patients with acute myocardial infarction.

OBJECTIVE: To explore the risk factors for ventricular arrhythmia after percutaneous coronary intervention (PCI) in elderly patients with acute myocardial infarction (AMI). METHODS: A retrospective cohort of 201 elderly AMI patients who underwent PCI in the emergency department of No. 215 Hospital of Shaanxi Nuclear Industry from April 2020 to January 2023 was analyzed. The patients were randomly divided into a training set (n=134) for model development and a test set (n=67) for model validation. The training set was divided into a ventricular arrhythmia group (n=51) and a non-ventricular arrhythmia group (n=83), based on the occurrence of ventricular arrhythmia post-PCI. The factors affecting ventricular arrhythmias were analyzed by logistic regression and Lasso regression models. RESULTS: Lasso regression screened 12 characteristic factors at λ=0.1 se. In the training set, the area under the ROC curve (AUC) of the Lasso model for predicting ventricular arrhythmia was 0.954, which was significantly higher than 0.826 for the Logistic model (P < 0.001). In the test set, the AUC of the Lasso model was 0.962, which was also significantly higher than 0.825 for the Logistic model (P=0.003). CONCLUSION: Compared to the logistic regression model, the Lasso regression model can more accurately predict the occurrence of ventricular arrhythmia after PCI in elderly AMI patients. The Lasso regression model constructed in this study can provide a reference for the clinical identification of high-risk elderly AMI patients and the development of targeted monitoring and treatment.

Pre-metastatic niche: from revealing the molecular and cellular mechanisms to the clinical applications in breast cancer metastasis.

Breast cancer (BC) is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths in women worldwide. Metastasis is a major contributor to high cancer mortality and is usually the endpoint of a series of sequential and dynamic events. One of the critical events is forming a pre-metastatic niche (PMN) that occurs before macroscopic tumor cell invasion and provides a suitable environment for tumor cells to colonize and progress into metastases. Due to the unique characteristics of PMN in cancer metastasis, developing therapies to target PMN may bring new advantages in preventing cancer metastasis at an early stage. Various biological molecules, cells, and signaling pathways are altered in BC, regulating the functions of distinctive immune cells and stromal remodeling, inducing angiogenesis, and effect metabolic reprogramming and organotropism to promote PMN formation. In this review, we elucidate the multifaceted mechanisms contributing to the development of PMN in BC, discuss the characteristics of PMN, and highlight the significance of PMN in providing potential diagnostic and therapeutic strategies for BC metastasis, which may bring promising insights and foundations for future studies.

Exosomal miRNAs assist in the crosstalk between tumor cells and immune cells and its potential therapeutics.

Exosomes are small extracellular vesicles that carry active substances (including proteins, lipids, and nucleic acids) and are essential for homeostasis and signal transmission. Recent studies have focused on the function of exosomal miRNAs in tumor progression. Researchers have expanded the use of exosomes and miRNAs as potential therapeutic tools and biomarkers to detect tumor progression. Immune cells, as an important part of the tumor microenvironment (TME), secrete a majority of exosome-derived miRNAs involved in the biological processes of malignancies. However, the underlying mechanisms remain unclear. Currently, there is no literature that systematically summarizes the communication of exosome-derived miRNAs between tumor cells and immune cells. Based on the cell specificity of exosome-derived miRNAs, this review provides the first comprehensive summary of the significant miRNAs from the standpoint of exosome sources, which are tumor cells and immune cells. Furthermore, we elaborated on the potential clinical applications of these miRNAs, attempting to propose existing difficulties and future possibilities in tumor diagnostics and therapy.

Untargeted metabolomics analysis of serum and follicular fluid samples from women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with well-established metabolic abnormalities. In the present study, untargeted metabolomics technology was applied to analyze the serum and follicular fluid samples from women with polycystic ovary syndrome and healthy controls using 1H nuclear magnetic resonance (NMR). METHODS: Seventy samples for PCOS analysis were collected in hospital of Shandong University of Traditional Chinese Medicine (Jinan, China), NMR was used as analytical technology and multivariate analysis was applied to analyze metabolomics difference in PCOS and healthy controls. RESULTS: Significant metabolic differences were found in both serum and follicular fluid samples with orthogonal partial least-squares discriminant analysis (OPLS-DA). Three discriminated metabolites (1-Methylhistidine, threonine and Citrate) in both serum and follicular fluid were altered in PCOS patients. Abnormal energy metabolism, lipid metabolism and amino acid metabolism were detected in PCOS patients. Furthermore, more significantly changed amino acids were discovered in follicular fluid samples. CONCLUSIONS: Our findings would provide a resource for further investigations on metabolic disturbance in PCOS patients.