CD20highCD138low tumor-infiltrating lymphocytes predominantly related to cytokine‒cytokine receptor interactions are associated with favorable outcomes in neuroblastoma patients.

Recent advances have revealed that the role of the immune system is prominent in the antitumor response. In the present study, it is aimed to provide an expression profile of tumor-infiltrating lymphocytes (TILs), including mature B cells, plasma cells, and their clinical relevance in neuroblastoma. The expression of CD20 and CD138 was analyzed in the Cangelosi786 dataset (n = 769) as a training dataset and in our cohort (n = 120) as a validation cohort. CD20 high expression was positively associated with favorable overall survival (OS) and event-free survival (EFS) (OS: P < 0.001; EFS: P < 0.001) in the training dataset, whereas CD138 high expression was associated with poor OS and EFS (OS: P < 0.001; EFS: P < 0.001) in both the training and validation datasets. Accordingly, a combined pattern of CD20 and CD138 expression was developed, whereby neuroblastoma patients with CD20highCD138low expression had a consistently favorable OS and EFS compared with those with CD20lowCD138high expression in both the training and validation cohorts (P < 0.0001 and P < 0.01, respectively). Examination of potential molecular functions revealed that signaling pathways, including cytokine‒cytokine receptor interactions, chemokine, and the NF-kappa B signaling pathways, were involved. Differentially expressed genes, such as BMP7, IL7R, BIRC3, CCR7, CXCR5, CCL21, and CCL19, predominantly play important roles in predicting the survival of neuroblastoma patients. Our study proposes that a new combination of CD20 and CD138 signatures is associated with neuroblastoma patient survival. The related signaling pathways reflect the close associations among the number of TILs, cytokine abundance and patient outcomes and provide therapeutic insights into neuroblastoma.

Comparison of falls and risk factors among older adults in urban villages, urban and rural areas of Shantou, China.

Objective: To investigate and compare the differences between the incidence of falls, balance and living environment among older persons in urban villages and other types of residential areas. Methods: We surveyed 580 older adults living in different types of residential areas in Shantou, China, surveying basic information, fall incidence, balance ability testing of older persons, home environment safety assessment. Results: The incidence of falls among older people in urban villages (19.54 %) was between urban areas(26.63 %) and rural areas(16.91 %). The influencing factors of falls in different residential types were different. Near-fall, abnormal bowel movement, and impaired balance ability were the risk factors of falls among older persons in urban villages. Divorce/single, fair and poor hearing loss and near-fall were the risk factors of falls in urban older adults. Frailty and impaired balance ability were the risk factors of falls in rural older people. Conclusions: Risk factors for falls in older people vary according to the characteristics of their living areas and relevant interventions should be targeted according to the characteristics of falls occurring in different residential areas.

Research on the trajectory and influential factors of poly-victimization: A longitudinal study of Chinese adolescents.

BACKGROUND: Poly-victimization is more detrimental to adolescents' physical and mental health than is a single type of victimization. However, there has been limited research on the trajectory of poly-victimization among Chinese adolescents. OBJECTIVE: Identify the different developmental trajectories of poly-victimization among Chinese adolescents over time and examine the influencing factors of poly-victimization trajectories. METHODS: Data from four surveys conducted between 2020 and 2022, encompassing a cohort of 319 adolescents who had experienced poly-victimization, were utilized to identify their developmental trajectories via group-based trajectory modeling. Potential influencing factors were screened and compared using ANOVA or chi-square tests, while factors affecting the developmental trajectories of poly-victimization were analyzed through multinomial logistic regression. RESULTS: We identified three poly-victimization trajectories among adolescents: increasing poly-victimization (n = 39, 12.2 %), relieved poly-victimization (n = 228, 71.5 %), and fluctuating poly-victimization (n = 52, 16.3 %). Our findings indicate that boys, and those with poor class grade ranking, a lower level of parental education, lower household economy, smoking, drinking, suicide attempts, and suicide ideation, constitute the primary focus for the prevention and treatment of poly-victimization. CONCLUSION: We identified three poly-victimization trajectories, highlighting a significant heterogeneity in poly-victimization development. Understanding the characteristics of these developmental trajectories is crucial for realizing the dynamics of different poly-victimization subgroups and informing effective interventions.

Releasing characteristics of toxic chemicals from polystyrene microplastics in the aqueous environment during photoaging process.

Microplastics (MPs) are pervasive in the environment and inevitably undergo photoaging due to UV irradiation. This study delved into the dynamic releasing and transformation process of toxic chemicals from polystyrene microplastics (PS MPs) during photoaging, a subject that remains underexplored. It was revealed that photoaging led to substantial alterations in the physicochemical properties of PS MPs, initiating polymer chain scission and facilitating the release of a large number of toxic chemicals, including numerous organic compounds and several inorganic compounds. The kinetic analysis revealed a dynamic release pattern for PS MPs, where under varying UV intensities (2, 5, and 10 mW/cm2), the release rate (kDOC) initially increased and then decreased, peaking at a total irradiation energy of approximately 7 kW·h/m2. Furthermore, chemicals in leachate were transformed into compounds with smaller molecular weight, higher oxidized and greater unsaturated state over the prolonged photoaging. This transformation was primarily attributed to two reasons. Firstly, the aged PS MPs released chemicals with higher oxidized state compared to the pristine MPs. Secondly, the chemicals previously released underwent further reactions. Besides, among the complex leachate generated by aged PS MPs, the organic chemicals characterized by small molecular weight and high oxidized state exhibited notable acute toxicity, whereas heavy metal ions showed lesser toxicity, and anions were non-toxic. This study shed more light on the photoaging process of PS MPs, releasing characteristics of organic chemicals, and the potential environmental risks associated with plastic wastes.

The development of probiotics and prebiotics therapy to ulcerative colitis: a therapy that has gained considerable momentum.

Ulcerative colitis (UC) is increasingly common, and it is gradually become a kind of global epidemic. UC is a type of inflammatory bowel disease (IBD), and it is a lifetime recurrent disease. UC as a common disease has become a financial burden for many people and has the potential to develop into cancer if not prevented or treated. There are multiple factors such as genetic factors, host immune system disorders, and environmental factors to cause UC. A growing body of research have suggested that intestinal microbiota as an environmental factor play an important role in the occurrence and development of UC. Meanwhile, evidence to date suggests that manipulating the gut microbiome may represent effective treatment for the prevention or management of UC. In addition, the main clinical drugs to treat UC are amino salicylate and corticosteroid. These clinical drugs always have some side effects and low success rate when treating patients with UC. Therefore, there is an urgent need for safe and efficient methods to treat UC. Based on this, probiotics and prebiotics may be a valuable treatment for UC. In order to promote the wide clinical application of probiotics and prebiotics in the treatment of UC. This review aims to summarize the recent literature as an aid to better understanding how the probiotics and prebiotics contributes to UC while evaluating and prospecting the therapeutic effect of the probiotics and prebiotics in the treatment of UC based on previous publications.

LINC01605 promotes malignant phenotypes of cervical cancer via miR-149-3p/WNT7B axis.

BACKGROUND: Long non-coding RNAs (LncRNA) play a pivotal role in the progression of various malignancies. Despite recent identification as an oncogene associated with tumorigenesis. The precise role of LINC01605 in cervical cancer (CC) remains unclear. Therefore, the objective of this study was to investigate the influence of LINC01605 on proliferation and invasion of CC cells, while also exploring its potential underlying mechanisms. METHODS: The expression of LINC01605 in CC cell lines was analyzed using the TCGA database and qRT-PCR. Various assays, including CCK-8 and transwell analysis, were conducted on CC cells to assess the influence of LINC01605 on their proliferation, migration, and invasion capabilities. Bioinformatics and dual luciferase reporter gene assays were employed to analyze the target genes of LINC01605 and miR-149-3p. To further investigate the mechanism of action, transfection and investigation were performed using specific siRNA, miRNA mimics, or inhibitors. RESULTS: The expression of LINC01605 exhibited a significant increase in CC cell lines, and this upregulation was associated with an unfavorable prognosis. Modulating the expression of LINC01605, either by down-regulating or up-regulating it, exerted suppressive or stimulatory effects on the growth and invasion of HeLa and Siha cells. LINC01605 functioned as a competitive endogenous RNA (ceRNA) for miR-149-3p, with WNT7B being identified as a target gene of miR-149-3p. The involvement of LINC01605 in CC development is facilitated by its ability to regulate the expression of WNT7B through sequestering miR-149-3p. CONCLUSION: Our study demonstrates that LINC01605 acts as a competitive endogenous RNA in modulating the effects of WNT7B on the proliferation and invasion of CC cells by sequestering miR-149-3p. This research provides novel insights into the involvement of LINC01605 in the advancement of CC.

An Unexpected Decrease in Vibrational Entropy of Multicomponent Rutile Oxides.

High-entropy oxides (HEOs), featuring infinite chemical composition and exceptional physicochemical properties, are attracting much attention. The configurational entropy caused by a component disorder of HEOs is popularly believed to be the main driving force for thermal stability, while the role of vibrational entropy in the thermodynamic landscape has been neglected. In this study, we systematically investigated the vibrational entropy of multicomponent rutile oxides (including Fe0.5Ta0.5O2, Fe0.333Ti0.333Ta0.333O2, Fe0.25Ti0.25Ta0.25Sn0.25O2, and Fe0.21Ti0.21Ta0.21Sn0.21Ge0.16O2) by precise heat capacity measurements. It is found that vibrational entropy gradually decreases with increasing component disorder, beyond what one could expect from an equilibrium thermodynamics perspective. Moreover, all multicomponent rutile oxides exhibit a positive excess vibrational entropy at 298.15 K. Upon examinations of configuration disorder, size mismatch, phase transition, and polyhedral distortions, we demonstrate that the excess vibrational entropy plays a pivotal role in lowering the crystallization temperature of multicomponent rutile oxides. These findings represent the first experimental confirmation of the role of lattice vibrations in the thermodynamic landscape of rutile HEOs. In particular, vibrational entropy could serve as a novel descriptor to guide the predictive design of multicomponent oxide materials.

Corrigendum: Establishment of noncycloplegic methods for screening myopia and pre-myopia in preschool children.

[This corrects the article DOI: 10.3389/fmed.2023.1291387.].

Luminescence-Monitored Progressive Chemical Pressure Implementation Realized through Successive Y3+ and Mg2+ Doping into Ca10.5(PO4)7:Eu2.

Chemical pressure generated through ion doping into crystal lattices has been proven to be conducive to exploration of new matter, development of novel functionalities, and realization of unprecedented performances. However, studies are focusing on one-time doping, and there is a lack of both advanced investigations for multiple doping and sophisticated strategies to precisely and quantitatively track the gradual functionality evolution along with progressive chemical pressure implementation. Herein, high-valent Y3+ and equal-valent Mg2+ is successively doped to replace multiple Ca sites in Ca10.5(PO4)7:Eu2+. The luminescence evolution of Eu2+ serves as an optical probe, allowing step-by-step and atomic-level tracking of the site occupation of Y3+ and Mg2+, interassociation of Ca sites, and ultimately functionality improvement. The resulting Ca8MgY(PO4)7:Eu2+ displays a record-high relative sensitivity for optical thermometry. Utilization of the environment-sensitive emission of Eu2+ as a luminescent probe has offered a unique approach to monitoring structure-functionality evolution in vivo with atomic precision, which shall also be extended to optimization of other functionalities such as ferroelectricity, conductivity, thermoelectricity, and catalytic activity through precise control over atomic diffusion in other types of substances.

Thiostrepton suppresses triple-negative breast cancer through downregulating c-FLIP/SMAD2/3 signaling pathway.

Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis of breast cancer. Thiostrepton exerts anti-tumor activities against several cancers including TNBC. Herein we discussed the new molecular mechanisms of thiostrepton in TNBC. Thiostrepton inhibited MDA-MB-231 cell viability, accompanied by a decrease of c-FLIP and p-SMAD2/3. c-FLIP overexpression reduced the sensitivity of MDA-MB-231 cells to thiostrepton, while SMAD2/3 knockdown increased the sensitivity of MDA-MB-231 cells to thiostrepton. Moreover, c-FLIP overexpression significantly increased the expression and phosphorylation of SMAD2/3 proteins and vice versa. In conclusion, our study reveals c-FLIP/SMAD2/3 signaling pathway as a novel mechanism of antitumor activity of thiostrepton.

Identification of a circulating three-miRNA panel for the diagnosis of primary open angle glaucoma.

PURPOSE: Conventional diagnosis of primary open angle glaucoma (POAG) needs a combination of ophthalmic examinations. An efficient assay is urgently needed for a timely POAG diagnosis. We aim to explore differential expressions of circulating microRNAs (miRNA) and provide novel miRNA biomarkers for POAG diagnosis. METHODS: A total of 180 POAG patients and 210 age-related cataract (ARC) patients were enrolled. We collected aqueous humor (AH) and plasma samples from the recruited patients. The expressions of candidate miRNAs were measured using quantitative real time polymerase chain reaction. The diagnostic ability of candidate miRNAs was analyzed by receiver operating characteristic curve. RESULTS: The expressions of miR-21-5p and miR-29b-3p were downregulated significantly in AH and plasma of POAG and miR-24-3p expression was significantly increased in AH and plasma of POAG, comparing with those of ARC. A three-miRNA panel was constructed by a binary logistic regression. And the panel could differentiate between POAG and ARC with an area under the curve of 0.8867 (sensitivity = 78.0%, specificity = 83.3%) in aqueous humor and 0.7547 (sensitivity = 73.8%, specificity = 81.2%) in plasma. Next, we verified the three-miRNA panel working as a potential diagnostic biomarker stable and reliable. At last, we identified related function and regulation pathways in vitro. CONCLUSIONS: In conclusion, we built and identified a circulating three-miRNA panel as a potential diagnostic biomarker for POAG. It may be developed into an efficient assay and help improve the POAG diagnosis in the future.

Application of interpretable machine learning algorithms to predict distant metastasis in ovarian clear cell carcinoma.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. METHODS: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). RESULTS: In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762-0.823), 0.904 (0.835-0.973), 0.759 (0.731-0.787), 0.221 (0.186-0.256), 0.974 (0.967-0.982), 0.353 (0.306-0.399), and 0.834 (0.696-0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753-0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. CONCLUSIONS: This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.

Discovery of a Novel Potent Tetrazole Antifungal Candidate with High Selectivity and Broad Spectrum.

Thirty-one novel albaconazole derivatives were designed and synthesized based on our previous work. All compounds exhibited potent in vitro antifungal activities against seven pathogenic fungi. Among them, tetrazole compound D2 was the most potent antifungal with MIC values of <0.008, <0.008, and 2 µg/mL against Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus, respectively, the three most common and critical priority pathogenic fungi. In addition, compound D2 also exhibited potent activity against fluconazole-resistant C. auris isolates. Notably, compound D2 showed a lower inhibitory activity in vitro against human CYP450 enzymes as well as a lower inhibitory effect on the hERG K+ channel, indicating a low risk of drug-drug interactions and QT prolongation. Moreover, with improved pharmacokinetic profiles, compound D2 showed better in vivo efficacy than albaconazole at reducing fungal burden and extending the survival of C. albicans-infected mice. Taken together, compound D2 will be further investigated as a promising candidate.

IMPDH2 Positively Impacts the Proliferation Potential of Hepatoblastoma Cells by Activating JunB Signaling Pathway.

BACKGROUND: Amplification of inosine monophosphate dehydrogenase II, EC 1,1,1,205 (IMPDH2) has been reported in various cancers, which results in transformation and tumorigenicity. In our current work, we have explored the oncogenic properties and the underlying pathophysiology of IMPDH2 in hepatoblastoma (HB). METHODS: To investigate IMPDH2 expression in HB tissues and prognostic significance in HB patients, gene expression profiling interactive analysis (GEPIA) has been adopted. Immunohistochemistry has also helped to validate the protein expression of IMPDH2 in HB tissues. The effect of IMPDH2 overexpression or depletion on the proliferation of Hepatoblastoma cells in vitro has been evaluated by CCK8 assays and colony formation assays. Xenograft tumor growth of mice has been detected. Luciferase reporter assays have been conducted to determine the interaction of IMPDH2 and JunB, which was further asserted by pharmacological inhibition of JunB. RESULTS: IMPDH2 was highly expressed in HB tissues. Experimentally, the proliferation and colony formation of HuH6 cells were increased by IMPDH2 overexpression. Conversely, genetic inactivation of IMPDH2 impaired the proliferative efficiency and colony-forming rate of HepG2 cells. Besides, the luciferase reporter assay validated IMPDH2 overexpression to be associated with enhanced JunB transcriptional activity, while its activity was diminished in the case of IMPDH2 depletion. JunB inhibitor neutralized the IMPDH2-mediated increased phosphorylation of JunB. CONCLUSION: Our findings, thus, suggest that IMPDH2 exhibits its oncogenic role in HB partially via JunB-dependent proliferation.

The associated factors for physical activity-related injuries among first-year university students in southern China from a biopsychosocial perspective.

Background: Understanding the diverse factors influencing physical activity-related injuries is crucial for developing effective interventions that enable individuals to participate in physical activity (PA) while minimizing injury risk. Currently, research evidence on the multiple factors associated with PA-related injuries is inadequate. This study aimed to examine the associations between PA-related injuries and various biological, psychological, and social factors among first-year university students in China. Methods: We recruited first-year university students from Shantou University in Guangdong Province, China, to participate in our study. Data collection employed a structured self-administered questionnaire, gathering information on PA-related injuries, as well as relevant biological, psychological, and social factors. Binary logistic regression, using a stepwise modeling approach, was employed for the data analysis. Results: Among 1,051 first-year university students, 28.16% reported having experienced PA-related injuries in the past year. Most of the injuries reported were minor, with the knee or lower leg being the most frequently injured part of the body. Improper posture, environmental conditions, and excessive physical load were the leading causes of PA-related injuries. Multiple logistic regression analysis revealed that female students (OR = 0.67, 95% CI: 0.47-0.94, p = 0.022) had reduced odds of PA-related injuries. Conversely, high neuroticism (OR = 1.61, 95% CI: 1.07-2.41, p = 0.022), being a member of a sports team (OR = 2.09, 95% CI: 1.34-3.27, p < 0.001), PA on the wet ground (OR = 1.73, 95% CI: 1.18-2.54, p = 0.005) increased the odds of PA-related injuries. Conclusion: Our findings underscore the intricate interplay of various factors contributing to PA-related injuries. Identifying high-risk individuals based on physiological and psychological characteristics, coupled with targeted interventions addressing modifiable risk factors, is crucial for effective prevention.

Validation of the Mindray VS9 Vital Signs Monitor in a combined adult and pediatric population according to ISO Standard 81060-2:2018.

We aimed to validate the accuracy of the Mindray VS9 Vital Signs Monitor, which features the Mindray TrueBP inflation algorithm for oscillometric blood pressure (BP) measurement, to check if it complies with the International Organization for Standardization Standard (ISO 81060-2:2018) in a combined adult and pediatric population. A total of 86 participants, including both adult and pediatric subjects, were recruited. The distribution of their ages, gender, BPs and limb sizes all complied with the requirement of the ISO standard. The inflation and deflation algorithms were validated independently using the same-arm sequential BP measurement method. For each subject, the BP was first determined by two independent observers using a mercury sphygmomanometer (R1). The BP of the subject was then determined by the third observer using the test equipment (T1). Then, using a mercury sphygmomanometer, two independent observers were asked to determine the subject's BP (R2) again. R1-T1-R2 were considered a valid pair of data. This cycle continued until 3 pairs of valid data were achieved. We collected 258 pairs of valid BP data for the validation of the inflation and deflation algorithms respectively. For validation Criterion 1, the mean ± SD of the differences between the readings obtained from the test device and reference BP was 0.0 ±â€…6.6/-1.8 ±â€…7.1 mmHg (systolic/diastolic) when the deflation algorithm was used, and 2.4 ±â€…6.3/ 0.3 ±â€…6.9 mmHg (systolic/diastolic) when the inflation algorithm was used. For validation Criterion 2, the SD of the averaged BP differences between the test device and the reference BP per subject was 5.35/6.33 mmHg (systolic/diastolic) when the deflation algorithm was used, and 5.17/5.75 mmHg (systolic/diastolic) when the inflation algorithm was used. The VS9 Vital Signs Monitor fulfilled all the criteria in the ISO Standard. Moreover, the inflation algorithm had a shorter Measure Time (by 7-21 s) and lower maximum inflation pressure (by 9.7-22 mmHg). The VS9 Vital Signs Monitor fulfilled all the requirements of the ISO Standard (ISO 81060-2:2018) in a combined adult and pediatric population and is recommended for clinical use.

Genome-Wide Analysis of C-Repeat Binding Factor Gene Family in Capsicum baccatum and Functional Exploration in Low-Temperature Response.

Capsicum baccatum is a close relative of edible chili peppers (Capsicum annuum) with high economic value. The CBF gene family plays an important role in plant stress resistance physiology. We detected a total of five CBF genes in the C. baccatum genome-wide sequencing data. These genes were scattered irregularly across four chromosomes. The genes were categorized into three groupings according to their evolutionary relationships, with genes in the same category showing comparable principles for motif composition. The 2000 bp upstream of CbCBF contains many resistance-responsive elements, hormone-responsive elements, and transcription factor binding sites. These findings emphasize the crucial functions of these genes in responding to challenging conditions and physiological regulation. Analysis of tissue-specific expression revealed that CbCBF3 exhibited the greatest level of expression among all tissues. Under conditions of low-temperature stress, all CbCBF genes exhibited different levels of responsiveness, with CbCBF3 showing a considerable up-regulation after 0.25 h of cold stress, indicating a high sensitivity to low-temperature response. The importance of the CbCBF3 gene in the cold response of C. baccatum was confirmed by the use of virus-induced gene silencing (VIGS) technology, as well as the prediction of its protein interaction network. To summarize, this study conducts a thorough bioinformatics investigation of the CbCBF gene family, showcases the practicality of employing VIGS technology in C. baccatum, and confirms the significance of the CbCBF3 gene in response to low temperatures. These findings provide significant references for future research on the adaptation of C. baccatum to low temperatures.

Antiviral memory B cells exhibit enhanced innate immune response facilitated by epigenetic memory.

The long-lasting humoral immunity induced by viral infections or vaccinations depends on memory B cells with greatly increased affinity to viral antigens, which are evolved from germinal center (GC) responses. However, it is unclear whether antiviral memory B cells represent a distinct subset among the highly heterogeneous memory B cell population. Here, we examined memory B cells induced by a virus-mimicking antigen at both transcriptome and epigenetic levels and found unexpectedly that antiviral memory B cells exhibit an enhanced innate immune response, which appeared to be facilitated by the epigenetic memory that is established through the memory B cell development. In addition, T-bet is associated with the altered chromatin architecture and is required for the formation of the antiviral memory B cells. Thus, antiviral memory B cells are distinct from other GC-derived memory B cells in both physiological functions and epigenetic landmarks.

Combined effects of copper and cadmium exposure on ovarian function and structure in Nile Tilapia (Oreochromis niloticus).

With the rapid development of industrialization and urbanization, the issue of copper (Cu) and cadmium (Cd) pollution in aquatic ecosystems has become increasingly severe, posing threats to the ovarian tissue and reproductive capacity of aquatic organisms. However, the combined effects of Cu and Cd on the ovarian development of fish and other aquatic species remain unclear. In this study, female Nile tilapia (Oreochromis niloticus) were individually or co-exposed to Cu and/or Cd in water. Ovarian and serum samples were collected at 15, 30, 60, 90, and 120 days, and the bioaccumulation, ovarian development, and hormone secretion were analyzed. Results showed that both single and combined exposure significantly reduced the gonadosomatic index and serum hormone levels, upregulated estrogen receptor (er) and progesterone receptor (pr) gene transcription levels, and markedly affected ovarian metabolite levels. Combined exposure led to more adverse effects than single exposure. The data demonstrate that the Cu and Cd exposure can impair ovarian function and structure, with more pronounced adverse effects under Cu and Cd co-exposure. The Cu and Cd affect the metabolic pathways of nucleotides and amino acids, leading to ovarian damage. This study highlights the importance of considering combined toxicant exposure in aquatic toxicology research and provides insights into the potential mechanisms underlying heavy metal-induced reproductive toxicity in fish.