Research advances of nanomaterials for the acceleration of fracture healing.

The bone fracture cases have been increasing yearly, accompanied by the increased number of patients experiencing non-union or delayed union after their bone fracture. Although clinical materials facilitate fracture healing (e.g., metallic and composite materials), they cannot fulfill the requirements due to the slow degradation rate, limited osteogenic activity, inadequate osseointegration ability, and suboptimal mechanical properties. Since early 2000, nanomaterials successfully mimic the nanoscale features of bones and offer unique properties, receiving extensive attention. This paper reviews the achievements of nanomaterials in treating bone fracture (e.g., the intrinsic properties of nanomaterials, nanomaterials for bone defect filling, and nanoscale drug delivery systems in treating fracture delayed union). Furthermore, we discuss the perspectives on the challenges and future directions of developing nanomaterials to accelerate fracture healing.

Gradient-Charged Hydrogels for Highly Efficient Solar Steam Generation and Desalination.

Solar-driven interface desalination (SDID) is a promising and sustainable technology that produces freshwater from brine. Ionic hydrogels are effective evaporators, providing enhanced interaction with water and ions due to the charged groups on hydrophilic polymer networks. In this study, we developed a hydrogel-based solar steam generator with a gradient-charged (GC) structure for desalination. The gradient-charged groups' distribution on the hydrogels creates gradients of free water and osmotic pressure, realizing rapid water supplement as well as desalination of concentrated brine. Consequently, the GC hydrogel demonstrated an exceptional water evaporation rate, achieving a value as high as 2.61 kg m-2 h-1 in pure water and 1.72 kg m-2 h-1 on treating with 20 wt % NaCl solution under one sun illumination. Following the substantial solar-driven evaporation, impurities, including salt and other pollutants, were removed, thereby ensuring the purity of the condensed water. Overall, the GC hydrogel-based evaporator is a promising solution for SDID to achieve effective and sustainable water desalination.

Intrathecal drug-infusion system for treating pain in advanced cancer: New research in patient management.

Currently, the treatment of cancer pain in China mainly follows the three-step pain relief principles formulated by the World Health Organization. As research on subarachnoid drug diffusion has intensified, intrathecal drug delivery has been gradually applied in the treatment of diseases, and improved analgesia can be achieved via the continuous infusion of small doses of morphine-derived drugs. This method can not only effectively relieve pain and enhance quality of life but also significantly reduce the incidence of nausea, vomiting, constipation, and other adverse reactions caused by the long-term intensive use of drugs in patients with cancer pain. This study summarizes the development of the intrathecal drug-infusion system for treating cancer pain in patients with advanced cancer and describes the drugs used, the advantages in pain treatment, and key nursing factors before and after device placement to provide a basis for alleviating pain in patients with cancer.

An ultra-lightweight detector with high accuracy and speed for aerial images.

Aerial remote sensing images have complex backgrounds and numerous small targets compared to natural images, so detecting targets in aerial images is more difficult. Resource exploration and urban construction planning need to detect targets quickly and accurately in aerial images. High accuracy is undoubtedly the advantage for detection models in target detection. However, high accuracy often means more complex models with larger computational and parametric quantities. Lightweight models are fast to detect, but detection accuracy is much lower than conventional models. It is challenging to balance the accuracy and speed of the model in remote sensing image detection. In this paper, we proposed a new YOLO model. We incorporated the structures of YOLOX-Nano and slim-neck, then used the SPPF module and SIoU function. In addition, we designed a new upsampling paradigm that combined linear interpolation and attention mechanism, which can effectively improve the model's accuracy. Compared with the original YOLOX-Nano, our model had better accuracy and speed balance while maintaining the model's lightweight. The experimental results showed that our model achieved high accuracy and speed on NWPU VHR-10, RSOD, TGRS-HRRSD and DOTA datasets.

Investigating the Regulatory Mechanism of the Sesquiterpenol Nerolidol from a Plant on Juvenile Hormone-Related Genes in the Insect Spodoptera exigua.

Various plant species contain terpene secondary metabolites, which disrupt insect growth and development by affecting the activity of juvenile hormone-degrading enzymes, and the juvenile hormone (JH) titers maintained in insects. Nerolidol, a natural sesquiterpenol belonging to the terpenoid group, exhibits structural similarities to insect JHs. However, the impact of nerolidol on insect growth and development, as well as its underlying molecular mechanism, remains unclear. Here, the effects of nerolidol on Spodoptera exigua were investigated under treatment at various sub-lethal doses (4.0 mg/mL, 1.0 mg/mL, 0.25 mg/mL). We found that a higher dose (4.0 mg/mL) of nerolidol significantly impaired the normal growth, development, and population reproduction of S. exigua, although a relatively lower dose (0.25 mg/mL) of nerolidol had no significant effect on this growth and development. Combined transcriptome sequencing and gene family analysis further revealed that four juvenile hormone esterase (JHE)-family genes that are involved in juvenile hormone degradation were significantly altered in S. exigua larvae after nerolidol treatment (4.0 mg/mL). Interestingly, the juvenile hormone esterase-like (JHEL) gene Sexi006721, a critical element responsive to nerolidol stress, was closely linked with the significant augmentation of JHE activity and JH titer in S. exigua (R2 = 0.94, p < 0.01). Taken together, we speculate that nerolidol can function as an analog of JH by modulating the expression of the enzyme genes responsible for degrading JH, resulting in JH disorders and ultimately disrupting the development of insect larvae. This study ultimately provides a theoretical basis for the sustainable control of S. exigua in the field whilst proposing a new perspective for the development of novel biological pesticides.

SARS-CoV-2 viral genes Nsp6, Nsp8, and M compromise cellular ATP levels to impair survival and function of human pluripotent stem cell-derived cardiomyocytes.

BACKGROUND: Cardiovascular complications significantly augment the overall COVID-19 mortality, largely due to the susceptibility of human cardiomyocytes (CMs) to SARS-CoV-2 virus. SARS-CoV-2 virus encodes 27 genes, whose specific impacts on CM health are not fully understood. This study elucidates the deleterious effects of SARS-CoV-2 genes Nsp6, M, and Nsp8 on human CMs. METHODS: CMs were derived from human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, using 2D and 3D differentiation methods. We overexpressed Nsp6, M, or Nsp8 in hPSCs and then applied whole mRNA-seq and mass spectrometry for multi-omics analysis. Co-immunoprecipitation mass spectrometry was utilized to map the protein interaction networks of Nsp6, M, and Nsp8 within host hiPSC-CMs. RESULTS: Nsp6, Nsp8, and M globally perturb the transcriptome and proteome of hPSC-CMs. SARS-CoV-2 infection and the overexpression of Nsp6, Nsp8, or M coherently upregulated genes associated with apoptosis and immune/inflammation pathways, whereas downregulated genes linked to heart contraction and functions. Global interactome analysis revealed interactions between Nsp6, Nsp8, and M with ATPase subunits. Overexpression of Nsp6, Nsp8, or M significantly reduced cellular ATP levels, markedly increased apoptosis, and compromised Ca2+ handling in hPSC-CMs. Importantly, administration of FDA-approved drugs, ivermectin and meclizine, could restore ATP levels, thereby mitigating apoptosis and dysfunction in hPSC-CMs overexpressing Nsp6, Nsp8, or M. CONCLUSION: Overall, our findings uncover the extensive damaging effects of Nsp6, Nsp8, and M on hPSC-CMs, underlining the crucial role of ATP homeostasis in CM death and functional abnormalities induced by these SARS-CoV-2 genes, and reveal the potential therapeutic strategies to alleviate these detrimental effects with FDA-approved drugs.

Comparison of the effectiveness of chemotherapy combined with immunotherapy and chemotherapy alone in advanced biliary tract cancer and construction of the nomogram for survival prediction based on the inflammatory index and controlling nutritional status score.

OBJECTIVE: To analyze the effectiveness of combining immune checkpoint inhibitors (ICIs) with first-line therapy in patients with advanced biliary tract cancer (BTC) and explore the biomarkers affecting the prognosis of immunotherapy, to construct a nomogram for the prediction of survival. METHODS: A retrospective study was conducted to include a total of 209 patients with advanced BTC treated in the first line from 2018 to 2022, divided into a combination therapy group (n = 129) and a chemotherapy-only group (n = 80) according to whether ICIs were applied in combination. Univariate and multifactorial COX regression analyses were performed on variables that may affect prognosis to identify independent influences on patient prognosis, and this was used to create nomograms, which were then prospectively validated and calibrated. RESULTS: The median progression-free survival (mPFS) and median overall survival (mOS) of patients in the combination therapy group were higher than those in the chemotherapy alone group [hazard ratio (HR) = 1.152, 95% confidence interval (CI): 0.7848-1.692, p = 0.0004, and HR = 1.067, 95% CI: 0.7474-1.524, p = 0.0016]. The objective response rate (ORR) of patients in the combination therapy and chemotherapy alone groups was 39.5% (51/129) vs. 27.5% (22/80), and the disease control rate (DCR) between the two groups was 89.9% (116/129) vs. 83.8% (67/80). Univariate analysis revealed the gender, presence of long-term tobacco and alcohol, degree of histological differentiation, serum albumin level, presence of liver metastases, presence of multi-visceral metastases, response, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), glycoprotein antigen 19-9 (CA19-9), systemic inflammatory index (SII), and controlling nutritional status (CONUT) scores were statistically significant with patient prognosis (all P values < 0.05). Multi-factor COX regression analysis was continued for the above variables, and the results showed that NLR, MLR, PLR, SII, and CONUT scores were independent influences on patients' OS (all p values < 0.05). A nomogram (C-index 0.77, 95% CI: 0.71-0.84) was created based on these independent influences and later validated using a validation cohort (C-index 0.75, 95% CI: 0.68-0.81). The time-dependent receiver operator characteristic curve (ROC) showed that the area under curve (AUC) of the training cohort patients at 12, 18, and 24 months was 0.72 (95% CI: 0.63-0.81), 0.75 (95% CI: 0.67-0.85), and 0.77 (95% CI: 0.66-0.87) and the AUC of the validation cohort was 0.69 (95% CI: 0.58-0.79), 0.74 (95% CI: 0.65-0.87), and 0.71 (95% CI: 0.64-0.89), respectively. Finally, calibration was performed using calibration curves, and the results showed that nomograms based on inflammatory metrics and CONUT scores could be used to assess survival (12, 18, and 24 months) in patients with advanced BTC treated with ICIs in the first line. CONCLUSION: Patients with advanced BTC benefit more from first-line treatment with standard chemotherapy in combination with ICIs than with chemotherapy alone. In addition, nomograms based on inflammatory metrics and CONUT scores can be used to predict survival at 12, 18, and 24 months in patients with advanced BTC treated with ICIs.

Adherence to the dietary approaches to stop hypertension and bone health in the Chinese elderly.

INTRODUCTION: Many studies have demonstrated the relationship between diet and bone health, but research on the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and bone health across populations is rare. The purpose of this study was to examine associations between the DASH dietary pattern and bone health outcomes in Chinese elders, to verify whether higher adherence to the DASH was associated with better bone health in elderly populations. MATERIALS AND METHODS: A total of 839 Chinese adults aged 50 years and above participated in this cross-sectional study. Bone mineral density (BMD) at calcaneus was measured via ultrasonic bone densitometer. A semiquantitative food frequency questionnaire (FFQ) was used to assess the usual dietary intake in the past 12 months. The DASH score was calculated based on energy-adjusted intakes of nine dietary components, including whole grains, beans, vegetables, fruits, dairy, red meat, total fat, sodium, and sugar-sweetened beverages. RESULTS: In postmenopausal women, DASH score was significantly and positively correlated with BMD T-score after controlling potential covariates (ß: 0.027 ± 0.012, P = 0.031) in multivariable linear regression models. In binary logistic regression analysis, male participants in the highest tertile of DASH score had lower risk of osteoporosis than those in the lowest tertile (odds ratio = 0.499; 95% confidence interval, 0.262-0.951; P = 0.035) after adjusting potential covariates. CONCLUSION: Adherence to the DASH dietary pattern was associated with better bone health in Chinese elderly adults.

Nrf2 inhibition increases sensitivity to chemotherapy of colorectal cancer by promoting ferroptosis and pyroptosis.

Oxaliplatin is widely used in chemotherapy for colorectal cancer (CRC), but its sensitivity has become a major obstacle to limiting efficacy. Many literatures reported that Nrf2 activation promoted tumor chemoresistance. In this study, we explored the role and mechanism of Nrf2 inhibition in oxaliplatin-based chemosensitivity of CRC. In vitro experiments, we applied 4-octyl itaconate (4-OI) to activate Nrf2, and used lentivirus to knock down Nrf2 in CRC cell lines. By measuring cell viability, colony formation, apoptosis, reactive oxygen species production, and western blot, we found that oxaliplatin and lobaplatin suppressed the growth of HCT-116 and LOVO cells in a dose-dependent manner, and promoted the expression of Nrf2. 4-OI, an Nrf2 activator, reduced the sensibility of CRC cells to oxaliplatin and lobaplatin, while the knockdown of Nrf2 promoted the sensibility of CRC cells to oxaliplatin and lobaplatin. Through the public databases, we found that the expression of GPX4 in normal tissues was lower compared with cancer tissues in CRC, and the high GPX4 expression predicted a poor prognosis. Meanwhile, we found that oxaliplatin reduced the expression of GPX4 in vitro. The knockdown of Nrf2 enhanced the effects of oxaliplatin to reduce the expression of GPX4 and GSH content, and increase the MDA content, which enhanced oxaliplatin-induced ferroptosis. Subsequently, we found that oxaliplatin promoted the expression of GSDME-N, and induced LDH, IL-1ß, and TNF-a release, and the knockdown of Nrf2 aggravated the occurrence of GSMDE-mediated pyroptosis. Finally, we found that the knockdown of Nrf2 enhanced the inhibition of oxaliplatin on HCT116 xenograft tumor growth in vivo. Thus, our study showed that Nrf2 inhibition improved sensitivity to oxaliplatin of CRC cells by promoting ferroptosis and pyroptosis, which provided a new target for overcoming chemoresistance in CRC.

Structural deep clustering network for stratification of breast cancer patients through integration of somatic mutation profiles.

BACKGROUND AND OBJECTIVE: Breast cancer is among of the most malignant tumor that occurs in women and is one of the leading causes of death from gynecologic malignancy worldwide. The high degree of heterogeneity that characterizes breast cancer makes it challenging to devise effective therapeutic strategies. Accumulating evidence highlights the crucial role of stratifying breast cancer patients into clinically significant subtypes to achieve better prognoses and treatments. The structural deep clustering network is a graph convolutional network-based clustering algorithm that integrates structural information and has achieved state-of-the-art performance in various applications. METHODS: In this study, we employed structural deep clustering network to integrate somatic mutation profiles for stratifying 2526 breast cancer patients from the Memorial Sloan Kettering Cancer Center into two clinically differentiable subtypes. RESULTS: Breast cancer patients in cluster 1 exhibited better prognosis than breast cancer patients in cluster 2, and the difference between them was statistically significant. The immunogenomic landscape further demonstrated that cluster 1 was associated with remarkable infiltration of the tumor infiltrating lymphocytes. The clustering subtype could be used to evaluate the therapeutic benefit of immunotherapy and chemotherapy in breast cancer patients. Furthermore, our approach effectively classified patients from eight different cancer types, demonstrating its generalizability. CONCLUSIONS: Our study represents a step towards a generic methodology for classifying cancer patients using only somatic mutation data and structural deep clustering network approaches. Employing structural deep clustering network to identify breast cancer subtypes is promising and can inform the development of more accurate and personalized therapies.

Enhanced photo-Fenton-like performance of biotemplated manganese-doped cobalt silicate catalysts.

Cobalt-based catalysts are one of the preferred materials for effective activation of hydrogen peroxide, and metal element doping and active site dispersion are effective methods to enhance their catalytic activity. In this work, manganese-doped cobalt silicate@diatomite composites with enhanced photo-Fenton-like oxidation performance were prepared and used for degradation of methyl orange (MO) dyes. Experiments showed that manganese doping increased the specific surface area of the samples and decreased the band gap energy of the materials. Moreover, the samples doped with manganese elements had better photo-Fenton-like properties. The degradation of methyl orange by Co0.25MnSi@DE/H2O2-UV reached more than 95%. In addition, density-functional theory (DFT) calculations showed that the Mn-doped samples were more prone to activate H2O2 than non-manganese-doped samples, and the synergistic effect from using a bimetallic catalyst increased the photo-Fenton oxidation activity in the system. ESR spectroscopy and bursting tests indicated that the possible degradation mechanism consisted of hydroxyl radicals and superoxide radicals generated by the synergistic effect of cobalt ions and manganese under UV radiation. This study thus presents a feasible idea for the preparation of cobalt-based photo-Fenton catalysts that also provides a basis for understanding the catalytic mechanism analysis of other types of bimetallic catalysts.

Preparation and characterization of a modified Canna starch as a wall material for the encapsulation of methyleugenol improves its antifungal activity against Fusarium trichothecioides.

In this study, α-amylase (α-A) and 2-octenylsuccinic anhydride (OSA)-modified Canna starch (Cs) were prepared and characterized as wall materials and encapsulated with methyleugenol (α-A-OSA-Cs-methyleugenol); their in vitro antifungal activity against Fusarium trichothecioides (F. trichothecioides) was also investigated. The encapsulation efficiency under optimal encapsulation conditions was 83.98%. The results of particle size, polydispersity index (PDI), zeta potential, electron scanning microscopy and Fourier transform infrared spectroscopy showed that the modified Cs had superior physicochemical properties; it was also demonstrated that methyleugenol successfully entered the pores of Cs. The in vitro release study showed that α-A-OSA-Cs could effectively reduce their volatility under different temperature environments. α-A-OSA-Cs have excellent performance as slow-release wall materials, and after encapsulation with methyleugenol, the inhibition ability of F. trichothecioides mycelium growth was dose-dependent and improved, extending the shelf life of potatoes, which has good commercial value in the field of slow-release preservatives.

Orientin suppresses osteoclastogenesis and ameliorates ovariectomy-induced osteoporosis via suppressing ROS production.

The aberrant differentiation of osteoclasts is a key feature of the pathogenesis of osteoporosis, which has a devastating impact on human health. While the effects of Orientin (Ori) on osteoporosis, particularly on RANKL-stimulated osteoclast production and activation, remain still unclear, Ori has been found to display several biological activities, including antioxidant and anti-inflammatory. In this work, we investigated the possible pathways through which Ori suppressed RANKL-induced osteoclast development and showed for the first time that it does so. The macrophages from the bone marrow (BMMs) were cultivated and then treated with Ori after being stimulated with RANKL. Then, TRAP-positive multinucleated cells were counted, and F-actin ring analysis was used to assess Ori's impact on mature osteoclast development. In addition, dihydroethidium (DHE) staining was used to evaluate the impact of Ori on RANKL-induced reactive oxygen species (ROS). In addition, we performed western blotting and quantitative RT-PCR analysis to investigate probable causes of these downregulation effects. We discovered that Ori inhibits the creation of osteoclasts, the gene and protein expressions unique to osteoclasts, and the ROS production. By activating Nrf2 and other ROS-scavenging enzymes, Ori reduces intracellular ROS levels. The expression of the main transcription factor of osteoclast development, c-Fos, was downregulated together with NFATc1, CTSK, and NFATc2, thanks to Ori's inhibition of RANKL-induced NF-κB. Consistent with its in vitro antiosteoclastogenic action, Ori therapy in the ovariectomized (OVX) rat model was also able to restore bone mass and improve microarchitecture in the distal femurs. Together, our results demonstrate that Ori is a flavonoid molecule with therapeutic promise for bone illnesses associated with osteoclasts, such as osteoporosis.

Discovery of 2,5-diketopiperazine alkaloids with quorum sensing inhibitory activity from the marine fungus Penicillium sp. ZJUT-34.

One new 2,5-DKP derivative O-dihydroxycyclopenol (1) and seven known congeners 2-8 were isolated from the marine fungus Penicillium sp. ZJUT-34 cultured on rice medium. The planar structure of 1 was established by extensive spectroscopic analysis, including 1D, 2D NMR and HR-ESI-MS, while the relative configuration of 1 was determined by quantum chemical calculation. In the QS inhibitory assay, 1 significantly inhibited the production of violacein in Chromobacterium violaceum ATCC12472 (20.65%) at a concentration of 6.25 µg/mL without affecting the growth of the strain, as compared with norharmane (22.14%), a quorum sensing inhibitor (QSI) identified in our previous study. It represented the first report on the QS inhibitory activity of the seven-membered 2,5-DKPs. In addition, compounds 1-8 were subjected to antibacterial assay against six pathogenic bacteria Compound 8 exhibited comparable antibacterial activity against Enterococcus faecalis FA2-2 (MIC = 96 µg/mL) with the positive control gentamicin (MIC = 80 µg/mL).

Predictive value of intravascular ultrasound for the function of intermediate coronary lesions.

BACKGROUND: Intravascular ultrasound (IVUS) can provide detailed coronary anatomic parameters. The purpose of our study was to evaluate the parameters measured by IVUS for the prediction of intermediate coronary lesions function by referencing quantitative fraction ratio (QFR) ≤ 0.80 (vs. > 0.80). METHODS: Eighty four cases with 92 intermediate coronary lesions in vessels with a diameter ≥ 2.50 mm were enrolled. Paired assessment of IVUS and cQFR was available, and vessels with cQFR ≤ 0.8 were considered the positive reference standard. Logistic regression was used to select model variables by a maximum partial likelihood estimation test and receiver operating characteristic curve (ROC) analysis to evaluate the diagnostic value of different indices. RESULTS: Plaque burden (PB) and lesion length (LL) of IVUS were independent risk factors for the function of coronary lesions. The predictive probability P was derived from the combined PB and LL model. The area under the curve (AUC) of PB, (minimum lumen area) MLA, and LL and the predicted probability P are 0.789,0.732,0731, and 0.863, respectively (P < 0.01). The AUC of the predicted probability P was the biggest among them; the prediction accuracy of cQFR ≤ 0.8 was 84.8%, and the sensitivity of the diagnostic model was 0.826, specificity was 0. 725, and P < 0.01. CONCLUSION: PB and LL of IVUS were independent risk factors influencing the function of intermediate coronary lesions. The model combining the PB and LL may predict coronary artery function better than any other single parameter.

Identification and precision therapy for three maturity-onset diabetes of the young (MODY) families caused by mutations in the HNF4A gene.

Background: Heterozygous pathogenic variants in HNF4A gene cause maturity-onset diabetes of the young type 1 (MODY1). The mutation carriers for MODY1 have been reported to be relatively rare, in contrast to the most frequently reported forms of MODY2 and MODY3. Methods: Whole exome sequencing (WES) and Sanger sequencing were performed for genetic analysis of MODY pedigrees. Tertiary structures of the mutated proteins were predicted using PyMOL software. Results: Three heterozygous missense mutations in the HNF4A gene, I159T, W179C, and D260N, were identified in the probands of three unrelated MODY families using WES, one of which (W179C) was novel. Cascade genetic screening revealed that the mutations co-segregated with hyperglycemic phenotypes in their families. The molecular diagnosis of MODY1 has partly transformed its management in clinical practice and improved glycemic control. The proband in family A successfully converted to sulfonylureas and achieved good glycemic control. Proband B responded well to metformin combined with diet therapy because of his higher body mass index (BMI). The proband in family C, with paternal-derived mutations, had markedly defective pancreatic ß-cell function due to the superposition effect of T2DM susceptibility genes from the maternal grandfather, and he is currently treated with insulin. In silico analysis using PyMOL showed that the I159T and D260N mutations altered polar interactions with the surrounding residues, and W179C resulted in a smaller side chain. Discussion: We identified three heterozygous missense mutations of HNF4A from Chinese MODY families. Structural alterations in these mutations may lead to defects in protein function, further contributing to the hyperglycemic phenotype of mutation carriers.

The Effects of Early-Life Stress on Liver Transcriptomics and the Protective Role of EPA in a Mouse Model of Early-Life-Stress-Induced Adolescent Depression.

Early-life stress (ELS) was found to increase the risk of adolescent depression, and clinical evidence indicated that eicosapentaenoic acid (EPA) was decreased in patients with adolescent depression, but the underlying mechanisms are unclear. Here, we utilized an ELS model of maternal separation with early weaning to explore the protective role of EPA in adolescent depression. We found that that ELS induced depression-like behavior rather than anxiety-like behavior in adolescent mice. RNA-sequencing results showed that ELS changed the transcription pattern in the liver, including 863 upregulated genes and 971 downregulated genes, especially those related to the biosynthesis of unsaturated fatty acids metabolism in the liver. Moreover, ELS decreased the expression of the rate-limiting enzymes, fatty acid desaturases 1/2 (FADS1/2), involved in the biosynthesis of EPA in the liver. Additionally, ELS reduced the levels of EPA in the liver, serum, and hippocampus, and EPA administration improved depression-like behavior-induced by ELS. Our results provide transcriptomic evidence that ELS increases the risk of adolescent depression by reducing the synthesis of unsaturated fatty acids in the liver, especially EPA, and suggest that supplementation with EPA should be investigated as a potential treatment for adolescent depression.