Elucidating key immunological biomarkers and immune microenvironment dynamics in aging-related intracranial aneurysm through integrated multi-omics analysis.

BACKGROUND: The exact cause of intracranial aneurysms (IA) is still unclear. However, pro-inflammatory factors are known to contribute to IA progression. The specific changes in the immune microenvironment of IAs remain largely unexplored. METHODS: This study analyzed single-cell sequencing data from a male mouse model of brain aneurysm, focusing on samples before and after elastase-induced Willis aneurysms. The data helped identify eight distinct cell subpopulations: fibroblasts, macrophages, NK cells, endothelial cells, B cells, granulocytes, and monocytes. The study also involved bulk RNA sequencing of 97 IA samples, utilizing ssGSEA and CIBERSORT algorithms for analysis. Intercellular communication among these cells was inferred to understand the immune dynamics in IA. RESULTS: The study found that fibroblasts and macrophages are predominant in various disease states of IA. Notably, the onset of IA was marked by a significant increase in fibroblasts and a decrease in macrophages. There was a marked increase in cellular interactions, especially involving macrophages, at the onset of the disease. Through enrichment analysis, 12 potential immunogenic biomarkers were identified. Of these, Rgs1 emerged as a critical molecule in IA formation, confirmed through secondary validation in a single-cell sequencing dataset. CONCLUSION: This comprehensive analysis of immune cell composition and intercellular communication in IA tissues highlights the significant roles of macrophages and the molecule Rgs1. These findings shed light on the physiological and pathological conditions of IA, offering new insights into its immune microenvironment.

Anaplasma phagocytophilum Ats-1 enhances exosome secretion through Syntenin-1.

Anaplasma phagocytophilum is an intracellular obligate parasite that causes granulocytic anaplasmosis. Effector Ats-1 is an important virulence factor of A. phagocytophilum. Multiomics screening and validation has been used to determine that Ats-1 regulates host cell apoptosis and energy metabolism through the respiratory chain mPTP axis. In this study, a total of 19 potential binding proteins of Ats-1 in host cells were preliminarily screened using a yeast two-hybrid assay, and the interaction between syntenin-1 (SDCBP) and Ats-1 was identified through immunoprecipitation. Bioinformatics analysis showed that SDCBP interacted with SDC1, SDC2, and SDC4 and participated in the host exosome secretion pathway. Further studies confirmed that Ats-1 induced the expression of SDC1, SDC2, and SDC4 in HEK293T cells through SDCBP and increased the exosome secretion of these cells. This indicated that SDCBP played an important role in Ats-1 regulating the exosome secretion of the host cells. These findings expand our understanding of the intracellular regulatory mechanism of A. phagocytophilum, which may enhance its own infection and proliferation by regulating host exosome pathways.

Multiomics analyses reveals Anaplasma phagocytophilum Ats-1 induces anti-apoptosis and energy metabolism by upregulating the respiratory chain-mPTP axis in eukaryotic mitochondria.

BACKGROUND: Anaplasma translocated substrate 1 (Ats-1) is an effector of type 4 secretory systems (T4SS) and the main virulence factor of Anaplasma phagocytophilum. Ats-1 is involved in the regulation of host cell biological processes, but the specific molecular mechanism of its action is unclear. RESULTS: In this study, we identified Ats-1 as involved in mitochondrial respiratory regulation of HEK293T cells by multi-omics analysis. After intracellular expression of Ats-1, adenosine triphosphate levels and the proliferation of HEK293T cells were both up-regulated, while HEK293T cells apoptosis was inhibited. Ats-1 targeted translocation to the mitochondria where it up-regulated the expression of NDUFB5, NDUFB3, NDUFS7, COX6C, and SLC25A5, thereby enhancing energy production and inhibiting HEK293T cells apoptosis while enhancing HEK293T cells proliferation, and ultimately facilitating Anaplasma phagocytophilum replication in HEK293T cells. CONCLUSIONS: This study demonstrated that Anaplasma phagocytophilum Ats-1 induces anti-apoptosis and energy metabolism by upregulating the respiratory chain-mPTP axis in eukaryotic mitochondria. These results provide a better understanding of the pathogenic mechanism of Anaplasma phagocytophilum within host cells.

TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway.

BACKGROUND: T-cell immunoglobulin mucin-1 (TIM-1) has been reported to be associated with the biological behavior of several malignant tumors; however, it is not clear whether it has a role in cervical cancer (CC). METHODS: TIM-1 expression in cervical epithelial tumor tissues and cells was detected by immunohistochemistry or real-time quantitative-PCR and western blotting. CC cells from cell lines expressing low levels of TIM-1 were infected with lentiviral vectors encoding TIM-1. Changes in the malignant behavior of CC cells were assessed by CCK-8, wound healing, Transwell migration and invasion assays, and flow cytometry in vitro; while a xenograft tumor model was established to analyze the effects of TIM-1 on tumor growth in vivo. Changes in the levels of proteins related to the cell cycle, apoptosis, and Epithelial-mesenchymal transition (EMT) were determined by western blotting. RESULTS: TIM-1 expression was higher in CC tissues, than in high grade squamous intraepithelial lesion, low grade squamous intraepithelial lesion, or normal cervical tissues, and was also expressed in three CC cell lines. In HeLa and SiHa cells overexpressing TIM-1, proliferation, invasion, and migration increased, while whereas apoptosis was inhibited. Furthermore, TIM-1 downregulated the expression of p53, BAX, and E-cadherin, and increased cyclin D1, Bcl-2, Snail1, N-cadherin, vimentin, MMP-2, and VEGF. PI3K, p-AKT, and mTOR protein levels also increased, while total AKT protein levels remained unchanged. CONCLUSIONS: Our study indicated that TIM-1 overexpression promoted cell migration and invasion, and inhibited cell apoptosis in CC through modulation of the PI3K/AKT/p53 and PI3K/AKT/mTOR signaling pathways, and may be a candidate diagnostic biomarker of this disease.

Clinicopathological characteristics of dysplastic teratomous neuroglia with anti-N-methyl-d-aspartate receptor encephalitis.

In this study, we investigated whether unique pathological characteristics exist in teratomas that can trigger autoimmune anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. We compared a case of retroperitoneal teratoma associated with anti-NMDAR encephalitis and four control cases. The encephalitis-positive case showed that (i) more dysplastic neuroglia with higher Ki-67 labeling index values than the control cases, which met the diagnostic criteria of astrocytoma, (ii) the NMDAR subunit NR1 was expressed more abundantly in neuroglial tissue where many neuroglial cells co-expressed glial fibrillary acidic protein (GFAP) and NR1 and formed abnormally large cellular masses, (iii) intense NR1 expression occurs in squamous epithelium near neuroglial tissue and lymphocyte infiltration. This study showed that dysplastic neuroglial tissue resembling central nervous system tumors, which might promote autoimmunity, distinguished the case with NMDAR encephalitis from the controls. Additionally, abnormal expression of NR1 occurs in non-neural tissues and could be triggered by inflammation and participate in autoimmunity.

A rare case of pediatric moyamoya disease with reversible white matter lesions in a 3-year-old Chinese girl.

Moyamoya disease is a chronic cerebral vascular disease characterized by progressive occlusion of the cerebral arteries and resulting in the development of abnormal collateral circulation. We report a case of moyamoya disease in a 3-year-old Chinese girl with partly reversible white matter lesions. This case indicates that, in pediatric moyamoya disease, white matter lesions may be associated with cerebral ischemia, and they may be reversible after treatment.

Metabolism of Gallic Acid and Its Distributions in Tea (Camellia sinensis) Plants at the Tissue and Subcellular Levels.

In tea (Camellia sinensis) plants, polyphenols are the representative metabolites and play important roles during their growth. Among tea polyphenols, catechins are extensively studied, while very little attention has been paid to other polyphenols such as gallic acid (GA) that occur in tea leaves with relatively high content. In this study, GA was able to be transformed into methyl gallate (MG), suggesting that GA is not only a precursor of catechins, but also can be transformed into other metabolites in tea plants. GA content in tea leaves was higher than MG content-regardless of the cultivar, plucking month or leaf position. These two metabolites occurred with higher amounts in tender leaves. Using nonaqueous fractionation techniques, it was found that GA and MG were abundantly accumulated in peroxisome. In addition, GA and MG were found to have strong antifungal activity against two main tea plant diseases, Colletotrichum camelliae and Pseudopestalotiopsis camelliae-sinensis. The information will advance our understanding on formation and biologic functions of polyphenols in tea plants and also provide a good reference for studying in vivo occurrence of specialized metabolites in economic plants.

Clinical characteristics of anti-N-methyl-D-aspartate receptor encephalitis in children. / 儿童抗N-甲基-D-å¤©å†¬æ°¨é ¸å—ä½“è„‘ç‚Žçš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: To analyze the clinical characteristics and prognosis of children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and to provide a basis for early clinical identification of this disease. METHODS: The clinical data of 42 cases of anti-NMDAR encephalitis at Department of Pediatrics, Second Xiangya Hospital, Central South University from January 2015 to March 2018 were collected. The clinical features and followed-up outcomes were analyzed retrospectively. RESULTS: There were 15 cases (35.7%) of males and 27 cases (64.3%) of females in 42 children, with a ratio of 1꞉1.8. They were aged from 4 months to 17 years, with an average of (9.20±4.66) years. The most common initial symptoms were seizures (47.6%, 20/42) and mental behavior disorder (35.7%, 15/42). During the course of the disease, 85.7% patients(36/42) had mental and behavior disorder, 85.7% patients (36/42) had epilepsy, 76.2% (32/42) had speech disorder, 66.7% patients (28/42) had dyskinesia, 66.7% patients (28/42) had the decreased level of consciousness, 61.9% patients (26/42) had autonomic instability, and 57.1% (24/42) patients had sleep disorder. All the children had positive antibody against NMDA receptor resistance encephalitis in cerebrospinal fluid. Head MRI showed the abnormal incidence was 50.0% (21/42), and the lesions involved in parietal lobe, frontal lobe, temporal lobe, occipital lobe, midbrain, thalamus, basal ganglia and optic nerve. There was a patient with optic nerve damage combined with myelin oligodendrocyte glycoprotein (MOG) antibody positive. Forty cases were examined by electroencephalogram (EEG), 92.5% cases (37/40) were abnormal, mainly showing diffuse slow waves, and δ brushes could be seen in severe cases. And there was 1 patient (2.4%) complicated with mesenteric teratoma. The mRS score (2.14±1.46) at discharge was significantly lower than the highest mRS score (3.88±1.38) during hospitalization (P<0.05). After 3-39 months of follow-up, mRS score at 3 months after discharge was only 0.81±1.29, which was still improved compared with that at discharge, 76.2% cases (32/42) experienced complete or near-complete recovery (mRS score≤2), and 4.8% (2/42) cases relapsed. There was no mortality; the initial time of immunotherapy and the highest mRS score in the course of the disease were the factors affecting the prognosis. The earlier the starting time for immunotherapy and the lower mRS score in the course of the disease were, the better the prognosis was. CONCLUSIONS: Seizures, mental and behavior disorder, dyskinesias, speech disorder and autonomic instability are common clinical manifestations of anti-NMDAR encephalitis in children. The effect of immunotherapy is significant, and the time to start immunotherapy and the severity of the disease are important factors affecting the prognosis. Anti-NMDAR encephalitis can be combined with other autoantibodies, but its clinical significance and mechanism need further study.

Identification and functional characterization of three new terpene synthase genes involved in chemical defense and abiotic stresses in Santalum album.

BACKGROUND: It is well known that aromatic essential oils extracted from the heartwood of Santalum album L. have wide economic value. However, little is known about the role of terpenoids in response to various adverse environmental stresses as other plants do in the form of signals during plant-environment interactions. RESULTS: In this study, trace amounts of volatiles consisting of α-santalene, epi-ß-santalene, ß-santalene, α-santalol, ß-santalol, (E)-α-bergamotene, (E)-ß-farnesene and ß-bisabolene were found in the leaves of mature S. album trees. We identified more than 40 candidate terpene synthase (TPS) unigenes by mining publicly-available RNA-seq data and characterized the enzymes encoded by three cDNAs: one mono-TPS catalyzes the formation of mostly α-terpineol, and two multifunctional sesqui-TPSs, one of which produces (E)-α-bergamotene and sesquisabinene as major products and another which catalyzes the formation of (E)-ß-farnesene, (E)-nerolidol and (E,E)-farnesol as main products. Metabolite signatures and gene expression studies confirmed that santalol content is closely related with santalene synthase (SaSSY) transcripts in heartwood, which is key enzyme responsible for santalol biosynthesis. However, the expression of three new SaTPS genes differed significantly from SaSSY in the essential oil-producing heartwood. Increased activities of antioxidant enzymes, superoxide dismutase, catalase, peroxidase and ascorbate peroxidase, were detected in different tissues of S. album plants after applying 1 mM methyl jasmonate (MeJA) and 1 mM salicylic acid (SA), or exposure to 4°C, 38°C and high light intensity. MeJA and SA dramatically induced the expression of SaTPS1 and SaTPS2 in leaves. SaTPS1 to 3 transcripts were differentially activated among different tissues under adverse temperature and light stresses. In contrast, almost all SaSSY transcripts decreased in response to these environmental stresses, unlike SaTPS1 to 3. CONCLUSIONS: Multifunctional enzymes were biochemically characterized, including one chloroplastic mono-TPS and two cytosolic sesqui-TPSs in sandalwood. Our results suggest the ecological importance of these three new SaTPS genes in defensive response to biotic attack and abiotic stresses in S. album.

Comprehensive Bioinformatics Analysis and Machine Learning of TTK as a Transhepatic Arterial Chemoembolization Resistance Target in Hepatocellular Carcinoma.

Transhepatic arterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, a significant proportion of patients are non-responders or poor responders to TACE. Therefore, our aim is to identify the targets of TACE responders or non-responders. GSE104580 was utilized to identify differentially expressed genes (DEGs) in TACE responders and non-responders. Following the protein-protein interaction (PPI) analysis, hub genes were identified using the MCC and MCODE plugins in Cytoscape software, as well as LASSO regression analysis. Gene set enrichment analysis (GSEA) was performed to investigate potential mechanisms. Subsequently, the hub genes were validated using data from The Cancer Genome Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE), and The Human Protein Atlas (HPA) database. To evaluate the clinical significance of the hub genes, Kaplan-Meier (KM) survival and Cox regression analysis were employed. A total of 375 DEGs were identified, with 126 remaining following PPI analysis, and TTK, a dual-specificity protein kinase associated with cell proliferation, was ultimately identified as the hub gene through multiple screening methods. Data analysis from TCGA, CCLE, and HPA databases revealed elevated TTK expression in HCC tissues. GSEA indicated that the cell cycle, farnesoid X receptor pathway, PPAR pathway, FOXM1 pathway, E2F pathway, and ferroptosis could be potential mechanisms for TACE non-responders. Analysis of immune cell infiltration showed a significant correlation between TTK and Th2 cells. KM and Cox analysis suggested that HCC patients with high TTK expression had a worse prognosis. TTK may play a pivotal role in HCC patients' response to TACE therapy and could be linked to the prognosis of these patients.

Network Pharmacology to Reveal the Mechanism of Fufang Banmao Capsule for Treating Unresectable Primary Liver Cancer and Clinical Data Validation.

INTRODUCTION: Fufang Banmao capsules (FFBM), a traditional Chinese medicine, has been used to treat primary liver cancer (PLC) for several years. However, the bioactive ingredients, and mechanism of FFBM for treating PLC remains unclear. Our objective is to utilize network pharmacology to investigate these aspects and subsequently validate their effectiveness through clinical data. MATERIALS AND METHODS: The FFBM ingredients were obtained from the HERB database and screened for bioactive ingredients using the SwissTargetPrediction database. The PharmMapper and GEO database were used to acquire targets and differentially expressed genes (DEGs) for FFBM and PLC, respectively. Common targets were identified using Venn diagrams, followed by enrichment and protein-protein interaction (PPI) analysis. Furthermore, the Cytoscape software was utilized to identify Hub genes and construct the ingredienttarget- pathway network. Subsequently, patients diagnosed with unresectable PLC who underwent transcatheter arterial chemoembolization (TACE) at our hospital between January 2008 and December 2019 were retrospectively collected. Finally, Cox analysis was conducted to reveal the role of FFBM in the treatment of unresectable PLC. RESULTS: FFBM had 232 targets, and PLC had 1582 DEGs. HSP90AA1 and SRC were identified as crucial targets. Alpha-santalol, glycyrrhizin, and morroniside were identified as the top three bioactive ingredients. Enrichment analysis revealed a significant connection between FFBM utilization for treating PLC and multiple pathways, such as chemical carcinogenesis, PI3K-AKT, Rap1, FoxO, MAPK, and VEGF pathway. Clinic data revealed that consuming FFBM significantly improved the prognosis of unresectable PLC with a hazard ratio of 0.69. CONCLUSION: Our study identified the bioactive ingredients of FFBM and its potential mechanisms for treating PLC. Additionally, we validated the effectiveness through clinical data.

Schisandra chinensis inhibits the entry of BoHV-1 by blocking PI3K-Akt pathway and enhances the m6A methylation of gD to inhibit the entry of progeny virus.

Schisandra chinensis, a traditional Chinese medicine known for its antitussive and sedative effects, has shown promise in preventing various viral infections. Bovine herpesvirus-1 (BoHV-1) is an enveloped DNA virus that causes respiratory disease in cattle, leading to significant economic losses in the industry. Because the lack of previous reports on Schisandra chinensis resisting BoHV-1 infection, this study aimed to investigate the specific mechanisms involved. Results from TCID50, qPCR, IFA, and western blot analyses demonstrated that Schisandra chinensis could inhibit BoHV-1 entry into MDBK cells, primarily through its extract Methylgomisin O (Meth O). The specific mechanism involved Meth O blocking BoHV-1 entry into cells via clathrin- and caveolin-mediated endocytosis by suppressing the activation of PI3K-Akt signaling pathway. Additionally, findings from TCID50, qPCR, co-immunoprecipitation and western blot assays revealed that Schisandra chinensis blocked BoHV-1 gD transcription through enhancing m6A methylation of gD after virus entry, thereby hindering gD protein expression and preventing progeny virus entry into cells and ultimately inhibiting BoHV-1 replication. Overall, these results suggest that Schisandra chinensis can resist BoHV-1 infection by targeting the PI3K-Akt signaling pathway and inhibiting gD transcription.

Constructing Mal-Efferocytic Macrophage Model and Its Atherosclerotic Spheroids and Rat Model for Therapeutic Evaluation.

Efferocytosis, responsible for apoptotic cell clearance, is an essential factor against atherosclerosis. It is reported that efferocytosis is severely impaired in fibroatheroma, especially in vulnerable thin cap fibroatheroma. However, there is a shortage of studies on efferocytosis defects in cell and animal models. Here, the impacts of oxidized low density lipoprotein (ox-LDL) and glut 1 inhibitor (STF31) on efferocytosis of macrophages are studied, and an evaluation system is constructed. Through regulating the cell ratios and stimulus, three types of atherosclerotic spheroids are fabricated, and a necrotic core emerges with surrounding apoptotic cells. Rat models present a similar phenomenon in that substantial apoptotic cells are uncleared in time in vulnerable plaque, and the model period is shortened to 7 weeks. Mechanism studies reveal that ox-LDL, through mRNA and miRNA modulation, downregulates efferocytosis receptor (PPARγ/LXRα/MerTK), internalization molecule (SLC29a1), and upregulates the competitive receptor CD300a that inhibits efferocytosis receptor-ligand binding process. The foam cell differentiation has also confirmed that CD36 and Lp-PLA2 levels are significantly elevated, and macrophages present an interesting transition into prothrombic phenotype. Collectively, the atherosclerotic models featured by efferocytosis defect provide a comprehensive platform to evaluate the efficacy of medicine and biomaterials for atherosclerosis treatment.

Case Report: Evidences of myasthenia and cerebellar atrophy in a chinese patient with novel compound heterozygous MSTO1 variants.

Misato Mitochondrial Distribution and Morphology Regulator 1 (MSTO1) is a soluble cytoplasmic protein that regulates mitochondrial dynamics by promoting mitochondrial fusion. Variants in the MSTO1 gene cause a rare disease characterized by early-onset myopathy and cerebellar ataxia, with almost 30 cases reported worldwide. Here we report a case of a 3-year-old boy with novel heterozygous variants of the MSTO1 gene (c.1A>G (p.M1?) and c.727G>C(p.Ala243Pro)). Sequencing data and subsequent validation show that the two variants were inherited from the mother and father of the patient (both were heterozygous). The clinical features are infancy-onset mental and motor retardation, language disorder, dysarthria, scoliosis, cerebellar atrophy, tremor, lower-extremity muscle weakness, elevated muscle enzymes, extensive myopathy with chronic atrophy, hyperventilation lungs, and previously unreported hairy back and enlarged gastrocnemius. Finally, novel heterozygous MSTO1 variants were discovered in this case, which expands the gene spectrum and clinical phenotype of this type of disease, and provides a new direction for future treatment and research. Then we summarize the mutational spectrum, pathological, clinical features and imaging of MSTO1 variants in a cohort of reported 31 patients and discuss the pathogenesis of MSTO1 in humans.

The First Case Report of Preschool-Onset SS/SLE Coexisting With NMOSD of Chinese Origin.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease (CTD), the main features of which are multiple serum autoantibodies and extensive involvement of multiple systems. The onset age of patients varies from childhood to middle age, with nearly 1/5 in childhood. Sjogren's syndrome (SS) is also an autoimmune disease characterized by high-degree lymphocytic infiltration of exocrine glands, usually occurring in middle-aged and older women, and rarely in childhood. Neuromyelitis optica spectrum disorder (NMOSD) is an immune-mediated inflammatory demyelinating disease of the central nervous system (CNS) mainly involving the optic nerve and spinal cord. The coexistence of NMOSD and SLE and/or SS is well recognized by both neurologists and rheumatologists, but cases in children have been rarely reported. In this paper, we reported a case of a girl with onset at age 5 clinically featured by recurrent parotid gland enlargement, pancytopenia, hypocomplementemia, multiple positive serum antibodies, and cirrhosis. She was initially diagnosed with SS/SLE overlap syndrome at age 5. Four years later, the patient suffered a sudden vision loss and was examined to have positive AQP4 antibodies in serum and cerebrospinal fluid (CSF), and long segmental spinal swelling, in line with the diagnostic criteria for NMOSD. Up to now, the current patient is of the youngest onset age to develop SS/SLE coexisting with NMOSD, also with cirrhosis. It is important for clinicians to be aware of the possibility of CTDs coexisting with NMOSD in children, especially in those with positive anti-multiple autoantibodies, and to decrease the rate of missed diagnosis.

Exosome-Loaded Pro-efferocytic Vascular Stent with Lp-PLA2-Triggered Release for Preventing In-Stent Restenosis.

The efferocytosis defect is regarded as a pivotal event of atherosclerosis. The failure to clear apoptotic cells in atherosclerotic plaques under vascular stents causes a failure to resolve the inflammation underneath. However, efferocytosis repair is still confined to nonstenting therapeutics. Here, we identified a pro-efferocytotic agent and accordingly developed a bioresponsive pro-efferocytotic vascular stent aimed for poststenting healing. Exosomes derived from mesenchymal stem cells were found to be able to regulate efferocytosis via SLC2a1, STAT3/RAC1, and CD300a pathways and modulate foam cell formation processes through a CD36-mediated pathway. Pro-efferocytotic exosomes were encapsulated into liposome-based multivesicular chambers and grafted onto vascular stents. The multivesicular vesicles were able to release exosomes under the Lp-PLA2 environment. Compared to bare metal stents, exosome-stents in the presence of Lp-PLA2 enhanced the ratio of apoptotic cell clearance and reduced the neointimal thickness in the mal-efferocytotic rat model. Overall, we identified a pro-efferocytic agent─exosomes that are able to regulate target cells via multiple signaling pathways and are good candidates to serve complex pathological environments, and this bioresponsive pro-efferocytotic vascular stent is an attractive approach for prevention of poststenting complications.

Light synergistically promotes the tea green leafhopper infestation-induced accumulation of linalool oxides and their glucosides in tea (Camellia sinensis).

Linalool, which is one of the most representative aroma substances in tea, is transformed into other aroma-related compounds, including linalool 3,6-oxides and linalool 3,7-oxides. The objective of this study was to elucidate the linalool oxide synthesis pathway and its response to stress in tea. By feeding experiment, chemical synthesis, and compound analysis, it was found that linalool can be transformed to linalool oxides via 6,7-epoxylinalool. The conversion rate from 6,7-epoxylinalool to linalool oxides was relatively high under acidic conditions. Four linalool oxide glucosides obtained from tea were structurally characterized. Additionally, tea green leafhopper infestation was observed to activate the whole metabolic flow from linalool into linalool oxides and their glucosides (p < 0.01). Moreover, light treatments further increased the accumulation of linalool oxides and their glucosides (p < 0.05). These results will be useful for elucidating the mechanism mediating linalool oxides content changes in response to stress in tea.