The cyclin E-cyclin-dependent kinase 2 (CDK2) complex is a component of mammalian cell-cycle machinery that drives cell division. Hyperactivation of cyclin E-CDK2 is frequent in human cancers. Small-molecule CDK2 inhibitors are tested in clinical trials for cancer patients. Here, we report that cyclin E-CDK2 has a cell-cycle-independent function in regulating the global transcriptional program of cancer cells. CDK2 phosphorylates bromodomain-containing protein-4 (BRD4) and regulates its chromatin association. Overexpression of cyclin E and the resulting activation of CDK2 in cancer cells alter the cancer cell transcriptome, repress the expression of interferon-stimulated genes, and confer resistance to immunotherapy. Conversely, CDK2 inhibition has the opposite effect and augments the efficacy of immune checkpoint blockade. CDK2 inhibition also increases tumor infiltration by dendritic cells (DCs) and enhances antigen cross-presentation to CD8 T cells. These studies reveal an additional function of cyclin E-CDK2 in tumorigenesis and identify inhibition of CDK2 with clinically available compounds as a strategy for enhancing immune checkpoint blockade.

Objective Non-small lung cancer (NSCLC) is the leading cause of death worldwide, in which lung adenocarcinoma (LUAD) is the most prevalent subtype. Epidermal growth factor receptor (EGFR) mutations are frequently found in LUAD and often lead to therapeutic resistance. This study aimed to investigate the effects of tiliacorinine (TC), a natural bisbenzylisoquinoline alkaloid from Tiliacora triandra, on LUAD cells with various EGFR statuses, including those harboring the EGFR-tyrosine kinase inhibitor (TKI) resistance. Methods TC was isolated from T. triandra using organic solvents and purified by chromatographic methods, while its structure was elucidated by 1H and 13C nuclear magnetic resonance spectroscopy. Cytotoxic effects of TC were investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was determined using annexin V-FITC staining and flow cytometry. Molecular mechanisms underlying TC-induced cell apoptosis were investigated using Western blotting and in silico molecular docking. Results TC significantly induced apoptosis in LUAD cells, regardless of EGFR mutation status. Moreover, cells harboring the EGFR T790M mutation, which exhibit EGFR-TKI resistance, also showed high sensitivity to TC. TC significantly downregulated anti-apoptotic genes, thereby activating the intrinsic apoptotic pathways. These results were consistent with downregulation of STAT3 and Akt expression, upstream activators of anti-apoptotic genes. Finally, molecular docking demonstrated TC's potential binding to the EGFR T790M mutation, with a binding energy comparable to that of osimertinib, a targeted therapy for EGFR-TKI-resistant mutations. Conclusion TC exerted pro-apoptotic effects on NSCLC cells, demonstrating promise as a therapeutic agent for NSCLC and other cancers with EGFR-TKI-resistant mutations.

Beyond their canonical role in promoting G1/S progression, the complexes formed by cyclin D and cyclin-dependent kinase (CDK) 4/6 have emerged as contributors to enhanced cell migration. However, a direct link between this complex and cytoskeletal remodeling during cell motility has remained poorly understood. Here, we show that CDK4/6 inhibition in HeLa cells disrupts lamellipodia formation and subsequent focal adhesion assembly, leading to a reduction in cell migration and invasion. Notably, CDK4, but not CDK6, in complex with cyclin D1/D2, localizes to membrane ruffles to facilitate cytoskeletal reorganization. Mechanistically, proteomic and phosphoproteomic analyses revealed that CDK4 inhibition attenuates the transforming growth factor β (TGFβ) pathway via reduced Smad3 phosphorylation at Thr8, downregulating integrin subunits (α5, α6, and β1). Furthermore, CDK4 inhibition significantly decreased focal adhesion kinase (FAK) phosphorylation at Tyr397 and Rac1-GTP levels. Importantly, the resulting migration defect was largely restored by activation of either Rac1 or FAK. Thus, our data support a model in which cyclin D1/D2-CDK4 promotes phosphorylation of Smad3, leading to upregulation of integrin subunits, activation of FAK and Rac1, and consequent lamellipodia formation and cell migration. These findings provide direct evidence that CDK4 regulates actin cytoskeletal reorganization during cell migration and suggest that CDK4/6 inhibitors may dampen cytoskeleton-dependent tumor invasion, in addition to their antiproliferative effects.

Cyclin-dependent kinases CDK8 and CDK19 together with their activating partner, cyclin C, regulate gene expression as a part of the Mediator complex and by phosphorylating DNA sequence-specific transcription factors. Here, we investigated the in vivo requirement for Cdk8 and Cdk19 in hematopoiesis by generating double knockout (DKO) mice lacking Cdk8 and Cdk19 expression in hematopoietic cells. DKO mice displayed relatively normal hematopoiesis and largely unperturbed gene expression in the bone marrow, indicating that the Mediator kinases are not essential for the regulation of gene expression during hematopoiesis. However, DKO mice showed an expansion of splenic macrophages. Bone marrow-derived DKO macrophages displayed an increased expression levels of both M1-like and M2-like markers, altered cytokine secretion, deregulated gene expression, precocious cell cycle exit and impaired Fc-mediated phagocytosis. Our findings reveal a highly cell type-specific role of Cdk8/19 in gene transcription during hematopoiesis.

CIC-rearranged sarcoma is an aggressive mesenchymal neoplasm characterized by high metastatic potential and poor clinical outcomes with median overall survival of only 12 months. The lack of effective systemic therapies highlights the urgent need to identify biologic vulnerabilities for therapeutic targeting. CIC-rearranged sarcoma shows molecular dependence on MYC, which can be targeted indirectly through cyclin-dependent kinase (CDK) 9 inhibition. In leukemia, casein kinase 1 alpha (CK1α) inhibition has been shown to have anti-tumor activity through activation of p53. We here investigated the anti-tumor effect of the CK1α/CDK7/CDK9 inhibitor BTX-A51 in preclinical models of CIC-rearranged sarcoma and determined the underlying mechanism of response. To evaluate the anti-tumor effect of BTX-A51 in vitro, we treated the CIC01, CIC02, NCC-CDS1-X1-C1 (CDS1), and NCC-CDS2-C1 (CDS2) cell lines with BTX-A51 (dose range 0.49-1000 nM) and performed BrdU cell proliferation, CellTiter-Glo cell viability, and Caspase-Glo 3/7 apoptosis assays. Daudi (MYC-driven Burkitt lymphoma) cells were used as control. IC50 values were calculated using an AAT Bioquest IC50 Calculator. We also assessed the effect of BTX-A51 on cell cycle progression using flow cytometry analysis and measured cell counts. The expression of key signaling proteins after 3, 6, 12, or 24 hours of treatment with BTX-A51 was determined through immunoblotting studies. In vivo studies assessing the anti-tumor effect of BTX-A51 in the CIC01 and CIC02 patient-derived xenografts are currently underway, and results will be reported. The CIC01, CIC02, CDS1, and CDS2 cell lines were highly sensitive to BTX-A51 with proliferation IC50 values ranging from 13-50 nM. In all 4 cell lines, BTX-A51 substantially inhibited cell viability and induced caspase 3/7-mediated apoptosis. At the same time, BTX-A51 treatment substantially inhibited expression of MYC, MCL-1, MDM2, phospho-RPB1 CTD Ser2 (a substrate of CDK9), phospho-RPB1 CTD Ser5 (a substrate of CDK7), phospho-RB1 Ser795, and RB1, and induced expression of phospho-histone H2A.X Ser13, p53, cleaved PARP (Asp214), and cleaved caspase 3. BTX-A51 treatment for 12 hours reduced the fraction of cells in S phase in cell cycle phase analysis consistent with G1 arrest and significantly reduced cell counts in all 4 cell lines (P = 0.0381 each, Wilcoxon rank-sum test). These findings demonstrate that BTX-A51 has anti-tumor activity in preclinical models of CIC-rearranged sarcoma. Treatment with BTX-A51 induces caspase 3-mediated apoptotic cell death through combined stabilization of p53 and inactivation of oncogenic drivers. Together with ongoing in vivo studies, our data will provide a compelling preclinical rationale for the evaluation of BTX-A51 in patients with CIC-rearranged sarcoma. Quentin Odom-Lewis, Samantha L. Davis, Stephan Pieper, Chen Chu, Emanuele Mazzola, Renyan Liu, Nicole Solimini, Prafulla C. Gokhale, Geoffrey I. Shapiro, George D. Demetri, Inga-Marie Schaefer. Preclinical efficacy of the CK1 alpha/CDK7/CDK9 inhibitor BTX-A51 in CIC-rearranged sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6941.

Solid tumors collectively drive the global cancer burden, with profound molecular heterogeneity demanding precision and molecularly informed management. Advances in sequencing technologies have established molecular taxonomy as a cornerstone of clinical oncology, progressively superseding traditional histopathological classifications. Sanger sequencing remains the gold standard for validating guideline mandated actionable variants. Next-generation sequencing (NGS) has revolutionized early cancer detection through liquid biopsy applications and enabled the reclassification of diagnostically challenging tumor subtypes. Emerging long-read platforms offer unique capabilities to resolve complex genomic rearrangements, structural variants, and therapy-induced epigenetic remodeling. Consequently, therapeutic strategies are shifting from organ-centric approaches to mutation-specific interventions, exemplified by non-small-cell lung cancer, where molecular stratification drives substantial improvements in treatment response. Nevertheless, temporal tumor heterogeneity, biological contamination, and computational limitations highlight the urgent need for robust, integrated verification systems. Collectively, this evolution positions sequencing as the operational backbone of adaptive precision oncology across solid tumors. Here, we synthesize our laboratory findings with the current literature to comprehensively review the diagnostic, therapeutic, and prognostic applications of first- through fourth-generation sequencing technologies and discuss future directions in this rapidly evolving field.

Extracellular vesicles (EVs) are released by nearly all types of cells, and they communicate between cells by transporting bioactive molecules, including proteins, DNA, RNA, and lipids. In recent years, RNA carried by EVs, particularly the long-chain non-coding RNA (lncRNA) and circular RNA (circRNA) subtypes, has garnered interest with respect to their role in controlling tumor progression. Among them, there are increasing reports that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) maintain a recently discovered function as transporters of lncRNAs and circRNAs. However, detailed molecular functions of lncRNAs and circRNAs contained in MSC-EVs are not presently summarized, and the efficacy of MSC-EVs as molecular carriers requires further elucidation. This review summarizes the biological characteristics of EVs and the common mechanisms of lncRNAs and circRNAs contained within them. The “double-edged sword” effect and related molecular mechanism of EV-derived lncRNAs (EV-lncRNAs) and circRNAs (EV-circRNAs) between differing tumor types and MSCs are highlighted. The potential of MSC-EVs in the field of tumor diagnosis and treatment is discussed to suggest new directions for the strategy of engineering MSC-EVs as anti-tumor drug carriers.

The endoplasmic reticulum (ER) membrane protein complex (EMC) is an ER multiprotein complex that affects a wide range of pathophysiological processes. Recently, the function of EMC6, a subunit of EMC, has been attracting attention for its role in cancers. However, research on EMC6 in the context of hepatocellular carcinoma (HCC) remains unknown. Here, we first observed the decreased EMC6 expression in human HCC tissues, and diminished expression level of EMC6 was associated with poor prognosis of HCC patients. In parallel, the knockdown of EMC6 promoted tumor progression both in HCC cell lines and in tumor-cell bearing nude mice. To delineate the in vivo roles of EMC6, we generated a hepatocyte-specific knockout of Emc6 (Emc6f/f;Alb-Cre, named Emc6 LKO) using a floxed Emc6 line. Emc6 LKO mice exhibited progressive liver dysfunction, fibrosis and spontaneous carcinogenesis phenotypes. Significant lipid metabolic disorder in the Emc6 LKO liver was revealed by combined metabolomic and proteomic analysis. Moreover, drastic elevation of 17β-Hydroxysteroid dehydrogenase type 13 (HSD17B13), a lipid droplet-associated enzyme, was identified to be involved in the process of EMC6-induced lipid metabolic disorder and HCC progression. Inhibition of HSD17B13 by a Pharmacological inhibitor BI-3231 effectively mitigated EMC6-driven HCC progression in vitro and in vivo. Taken together, these results unveiled a novel regulatory mechanism of EMC in HCC progression through lipid metabolism and may provide a new biomarker and therapeutic target for HCC.

Supplementary Figure Legends 1-5, Supplementary Table 1

Adenosine monophosphate–activated protein kinase (AMPK) activity is stimulated to promote metabolic adaptation upon energy stress. However, sustained metabolic stress may cause cell death. The mechanisms by which AMPK dictates cell death are not fully understood. We report that metabolic stress promoted receptor-interacting protein kinase 1 (RIPK1) activation mediated by TRAIL receptors, whereas AMPK inhibited RIPK1 by phosphorylation at Ser 415 to suppress energy stress–induced cell death. Inhibiting pS415-RIPK1 by Ampk deficiency or RIPK1 S415A mutation promoted RIPK1 activation. Furthermore, genetic inactivation of RIPK1 protected against ischemic injury in myeloid Ampkα1 -deficient mice. Our studies reveal that AMPK phosphorylation of RIPK1 represents a crucial metabolic checkpoint, which dictates cell fate response to metabolic stress, and highlight a previously unappreciated role for the AMPK-RIPK1 axis in integrating metabolism, cell death, and inflammation.

Abstract Although androgen deprivation treatment often effectively decreases prostate cancer, incurable metastatic castration-resistant prostate cancer (CRPC) eventually occurs. It is important to understand how CRPC metastasis progresses, which is not clearly defined. The loss of PTEN, a phosphatase to dephosphorylate phosphatidylinositol 3,4,5-trisphosphate in the PI3K pathway, occurs in up to 70% to 80% of CRPC. We generated a mouse androgen-independent prostate cancer cell line (PKO) from PTEN null and Hi-Myc transgenic mice in C57BL/6 background. We confirmed that this PKO cell line has an activated PI3K pathway and can metastasize into the femur and tibia of immunodeficient nude and immunocompetent C57BL/6 mice. In vitro, we found that androgen deprivation significantly enhanced PKO cell migration/invasion via the p110β isoform-depended PAK1-MAPK activation. Inhibition of the p110β-PAK1 axis significantly decreased prostate cancer cell migration/invasion. Of note, our analysis using clinical samples showed that PAK1 is more activated in CRPC than in advanced prostate cancer; high PAK1/phosphorylated-PAK1 levels are associated with decreased survival rates in patients with CRPC. All the information suggests that this cell line reflects the characteristics of CRPC cells and can be applied to dissect the mechanism of CRPC initiation and progression. This study also shows that PAK1 is a potential target for CRPC treatment. Implications: This study uses a newly generated PTEN null prostate cancer cell line to define a critical functional role of p110β-PAK1 in CRPC migration/invasion. This study also shows that the p110β-PAK1 axis can potentially be a therapeutic target in CRPC metastasis.

Transcriptome analysis in PKO cells vs. Myc-Cap cells.

Targeting angiotensin-converting enzyme 2 (ACE2) represents a promising and effective approach to combat not only the COVID-19 pandemic but also potential future pandemics arising from coronaviruses that depend on ACE2 for infection. Here, we report ubiquitin specific peptidase 2 (USP2) as a host-directed antiviral target; we further describe the development of MS102, an orally available USP2 inhibitor with viable antiviral activity against ACE2-dependent coronaviruses. Mechanistically, USP2 serves as a physiological deubiquitinase of ACE2, and targeted inhibition with specific small-molecule inhibitor ML364 leads to a marked and reversible reduction in ACE2 protein abundance, thereby blocking various ACE2-dependent coronaviruses tested. Using human ACE2 transgenic mouse models, we further demonstrate that ML364 efficiently controls disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as evidenced by reduced viral loads and ameliorated lung inflammation. Furthermore, we improved the in vivo performance of ML364 in terms of both pharmacokinetics and antiviral activity. The resulting lead compound, MS102, holds promise as an oral therapeutic option for treating infections with coronaviruses that are reliant on ACE2.

Activation of the cGAS/STING innate immunity pathway is essential and effective for anti-tumor immunotherapy. However, it remains largely elusive how tumor-intrinsic cGAS signaling is suppressed to facilitate tumorigenesis by escaping immune surveillance. Here, we report that the protein arginine methyltransferase, PRMT1, methylates cGAS at the conserved Arg133 residue, which prevents cGAS dimerization and suppresses the cGAS/STING signaling in cancer cells. Notably, genetic or pharmaceutical ablation of PRMT1 leads to activation of cGAS/STING-dependent DNA sensing signaling, and robustly elevates the transcription of type I and II interferon response genes. As such, PRMT1 inhibition elevates tumor-infiltrating lymphocytes in a cGAS-dependent manner, and promotes tumoral PD-L1 expression. Thus, combination therapy of PRMT1 inhibitor with anti-PD-1 antibody augments the anti-tumor therapeutic efficacy in vivo. Our study therefore defines the PRMT1/cGAS/PD-L1 regulatory axis as a critical factor in determining immune surveillance efficacy, which serves as a promising therapeutic target for boosting tumor immunity.

Background Advanced gastrointestinal stromal tumour (GIST) is characterised by genomic perturbations of key cell cycle regulators. Oncogenic activation of CDK4/6 results in RB1 inactivation and cell cycle progression. Given that single-agent CDK4/6 inhibitor therapy failed to show clinical activity in advanced GIST, we evaluated strategies for maximising response to therapeutic CDK4/6 inhibition. Methods Targeted next-generation sequencing and multiplexed protein imaging were used to detect cell cycle regulator aberrations in GIST clinical samples. The impact of inhibitors of CDK2, CDK4 and CDK2/4/6 was determined through cell proliferation and protein detection assays. CDK-inhibitor resistance mechanisms were characterised in GIST cell lines after long-term exposure. Results We identify recurrent genomic aberrations in cell cycle regulators causing co-activation of the CDK2 and CDK4/6 pathways in clinical GIST samples. Therapeutic co-targeting of CDK2 and CDK4/6 is synergistic in GIST cell lines with intact RB1, through inhibition of RB1 hyperphosphorylation and cell proliferation. Moreover, RB1 inactivation and a novel oncogenic cyclin D1 resulting from an intragenic rearrangement ( CCND1::chr11.g:70025223 ) are mechanisms of acquired CDK-inhibitor resistance in GIST. Conclusions These studies establish the biological rationale for CDK2 and CDK4/6 co-inhibition as a therapeutic strategy in patients with advanced GIST, including metastatic GIST progressing on tyrosine kinase inhibitors.

Plastics breaking down of larger plastics into smaller ones (microplastics and nanoplastic) as potential threats to the ecosystem. Previous studies demonstrate that the central nervous system (CNS) is a vulnerable target of nanoplastics. However, the potentially epigenetic biomarkers of nanoplastic neurotoxicity in rodent models are still unknown. The present research aimed to determine the role of competing endogenous RNA (ceRNA) in the process of polystyrene nanoplastics (PS NPs) exposure-induced nerve injury. The study was designed to inves-tigate whether 25 nm PS NPs could cause learning dysfunction and to elucidate the underlying mechanisms in mice. A total of 40 mice were divided into 4 groups and were exposed to PS NPs (0, 10, 25, 50 mg/kg). Chronic toxicity was introduced in mice by administration of oral gavage for 6 months. The evaluation included assessment of their behavior, pathological investigation and determination of the levels of reactive oxygen species (ROS) and DNA damage. RNA-Seq was performed to detect the expression levels of circRNAs, miRNAs and mRNAs in PFC samples of mice treated with 0 and 50 mg/kg PS NPs. The results indicated that exposure of mice to PS NPs caused a dose-dependent cognitive decline. ROS levels and DNA damage were increased in the PFC following exposure of the mice to PS NPs. A total of 987 mRNAs, 29 miRNAs and 67 circRNAs demonstrated significant differences between the 0 and 50 mg/kg PS NPs groups. Functional enrichment analyses indicated that PS NPs may induce major injury in the synaptic function. A total of 96 mRNAs, which were associated with synaptic dysfunction were identified. A competing endogenous RNA (ceRNA) network containing 27 circRNAs, 19 miRNAs and 35 synaptic dysfunction-related mRNAs was constructed. The present study provided insight into the molecular events associated with nanoplastic toxicity and induction of cognitive dysfunction.

Infertility has been reported as one of the most common reproductive impairments, affecting nearly one in six couples worldwide. A large proportion of infertility cases are diagnosed as idiopathic, signifying a deficit in information surrounding the pathology of infertility and necessity of medical intervention such as assisted reproductive therapy. Small noncoding RNAs (sncRNAs) are well-established regulators of mammalian reproduction. Advanced technologies have revealed the dynamic expression and diverse functions of sncRNAs during mammalian germ cell development. Mounting evidence indicates sncRNAs in sperm, especially microRNAs (miRNAs) and transfer RNA (tRNA)-derived small RNAs (tsRNAs), are sensitive to environmental changes and mediate the inheritance of paternally acquired metabolic and mental traits. Here, we review the critical roles of sncRNAs in mammalian germ cell development. Furthermore, we highlight the functions of sperm-borne sncRNAs in epigenetic inheritance. We also discuss evidence supporting sncRNAs as promising biomarkers for fertility and embryo quality in addition to the present limitations of using sncRNAs for infertility diagnosis and treatment.

Although inhibitors targeting CDK4/6 kinases (CDK4/6i) have shown promising clinical prospect in treating ER+/HER2- breast cancers, acquired drug resistance is frequently observed and mechanistic knowledge is needed to harness their full clinical potential. Here, we report that inhibition of CDK4/6 promotes βTrCP1-mediated ubiquitination and proteasomal degradation of RB1, and facilitates SP1-mediated CDK6 transcriptional activation. Intriguingly, suppression of CK1ε not only efficiently prevents RB1 from degradation, but also prevents CDK4/6i-induced CDK6 upregulation by modulating SP1 protein stability, thereby enhancing CDK4/6i efficacy and overcoming resistance to CDK4/6i in vitro. Using xenograft and PDX models, we further demonstrate that combined inhibition of CK1ε and CDK4/6 results in marked suppression of tumor growth in vivo. Altogether, these results uncover the molecular mechanisms by which CDK4/6i treatment alters RB1 and CDK6 protein abundance, thereby driving the acquisition of CDK4/6i resistance. Importantly, we identify CK1ε as an effective target for potentiating the therapeutic efficacy of CDK4/6 inhibitors.

[背景]环境和饮食中多种金属的暴露与抑郁、焦虑的发生有关,但血清金属元素含量与抑郁、焦虑症状的发生以及神经递质水平的关系尚不明确.[目的]分析大学生血清金属元素含量与抑郁、焦虑量表评分及血清神经递质水平的关联.[方法] 2017年12月招募河北省某医科大学86名在读本科学生,填写一般情况调查问卷、抑郁自评量表(PHQ-9)和焦虑自评量表(GAD-7).采集空腹静脉血,离心分离血清,采用电感耦合等离子体-质谱法检测血清中11种金属元素含量,采用酶联免疫吸附测定法检测血清中皮质醇(CORT)、多巴胺(DA)和5-羟色胺(5-HT)的含量.采用套索(LASSO)模型筛选与PHQ-9、GAD-7评分及神经递质相关的金属元素,采用多元线性回归分析筛选出的血清金属元素含量与抑郁和焦虑量表评分、神经递质水平的关联.采用错误发现率(FDR)控制多重假设检验造成的假阳性率.[结果]本次调查中10.465％的大学生存在抑郁症状,5.814％的大学生存在焦虑症状.LASSO模型筛选出钴(Co)、砷(As)、硒(Se)、钼(Mo)和镉(Cd)含量与PHQ-9评分相关,As和铅(Pb)含量与GAD-7评分相关,Co和Cd含量分别与CORT和DA水平相关,Mo、Cd、锡(Sn)和锑(Sb)含量与5-HT水平相关.多元线性回归模型分析显示,校正年龄、性别、体重指数(BMI)后,Cd每增加10 μg·L-1,PHQ-9量表评分增加2.180 (95％CI:1.220～3.140)分;As每增加10μg·L-1,PHQ-9量表评分增加0.010 (95％ CI:0.001～0.020)分;Se每增加10μg·L-1,PHQ-9量表评分增加0.010 (95％CI:0.001～0.010)分;Co每增加10μg·L-1,PHQ-9量表评分增加0.930(95％ CI:0.410～1.460)分,CORT水平下降2.990 (95％CI:-5.690～-0.330) ng·L1;Mo每增加10μg·L-1,PHQ-9量表评分增加0.190 (95％ CI:0.030～0.340)分,5-HT水平升高0.980 (95％CI:0.230～1.730) ng·L-1 (PFDR＜0.05).[结论]部分大学生存在抑郁、焦虑表现.血清中金属元素Cd、Co、As、Se和Mo含量与PHQ-9评分存在关联,但未见血清中金属元素与GAD-7评分的关联;Co含量与CORT水平有负向关联,Mo含量与5-HT水平有正向关联.研究结果说明血清金属元素含量与大学生抑郁情绪有关.