Interaction between macrophages and ferroptosis: Metabolism, function, and diseases.

ABSTRACT: Ferroptosis, an iron-dependent programmed cell death process driven by reactive oxygen species-mediated lipid peroxidation, is regulated by several metabolic processes, including iron metabolism, lipid metabolism, and redox system. Macrophages are a group of innate immune cells that are widely distributed throughout the body, and play pivotal roles in maintaining metabolic balance by its phagocytic and efferocytotic effects. There is a profound association between the biological functions of macrophage and ferroptosis. Therefore, this review aims to elucidate three key aspects of the unique relationship between macrophages and ferroptosis, including macrophage metabolism and their regulation of cellular ferroptosis; ferroptotic stress that modulates functions of macrophage and promotion of inflammation; and the effects of macrophage ferroptosis and its role in diseases. Finally, we also summarize the possible mechanisms of macrophages in regulating the ferroptosis process at the global and local levels, as well as the role of ferroptosis in the macrophage-mediated inflammatory process, to provide new therapeutic insights for a variety of diseases.

Nanoneedle Array-Electroporation Facilitates Intranuclear Ribonucleoprotein Delivery and High Throughput Gene Editing.

Dendritic cells (DCs) are critical regulators of T cell immunity, with immense therapeutic potential against tumors and autoimmune diseases. Efficient gene editing in DCs is crucial for understanding their regulatory mechanisms and maximizing their therapeutic efficacy. However, DCs are notoriously difficult to transfect, posing a major bottleneck for conventional DNA and RNA-based editing approaches. Microneedle-mediated injection of Cas9/sgRNA ribonucleoprotein (RNP) directly into the nucleus, akin to gene editing in reproductive cells, offers promise but suffers from limitations in scalability. Here, an intranuclear delivery system using a hollow nanoneedle array (HNA) combined with nano-electroporation is developed. The 2 µm-high HNA physically reaches the nucleus, positioning the nuclear envelope and plasma membrane in close proximity at the tip. Transient electronic pulses then induce simultaneous perforations across all 3 membranes, enabling direct RNP delivery into the nucleus. This HNA-based system achieves efficient knockout of genes like PD-L1 in primary DCs, demonstrating its potential as a powerful tool for gene editing in DCs and other hard-to-transfect cells.

Cucurbitacin B Inhibits the Proliferation of WPMY-1 Cells and HPRF Cells via the p53/MDM2 Axis.

Modern research has shown that Cucurbitacin B (Cu B) possesses various biological activities such as liver protection, anti-inflammatory, and anti-tumor effects. However, the majority of research has primarily concentrated on its hepatoprotective effects, with limited attention devoted to exploring its potential impact on the prostate. Our research indicates that Cu B effectively inhibits the proliferation of human prostate stromal cells (WPMY-1) and fibroblasts (HPRF), while triggering apoptosis in prostate cells. When treated with 100 nM Cu B, the apoptosis rates of WPMY-1 and HPRF cells reached 51.73 ± 5.38% and 26.83 ± 0.40%, respectively. In addition, the cell cycle assay showed that Cu B had a G2/M phase cycle arrest effect on WPMY-1 cells. Based on RNA-sequencing analysis, Cu B might inhibit prostate cell proliferation via the p53 signaling pathway. Subsequently, the related gene and protein expression levels were measured using quantitative real-time PCR (RT-qPCR), immunocytochemistry (ICC), and enzyme-linked immunosorbent assays (ELISA). Our results mirrored the regulation of tumor protein p53 (TP53), mouse double minute-2 (MDM2), cyclin D1 (CCND1), and thrombospondin 1 (THBS1) in Cu B-induced prostate cell apoptosis. Altogether, Cu B may inhibit prostate cell proliferation and correlate to the modulation of the p53/MDM2 signaling cascade.

TRPM2-AS promotes ovarian cancer cell proliferation and inhibits cell apoptosis by upregulating the nearby gene TRPM2 via miR-6764-5p.

Ovarian cancer (OC) becomes a fatal gynecologic malignant cancer in females worldwide. Target therapy is a promising therapeutical choice for patients with OC, and identifying biomarkers and exploring molecular mechanisms are necessary. In this study, the functions and mechanism of long noncoding RNA transient receptor potential cation channel subfamily M member 2 antisense RNA (TRPM2-AS) in OC were explored. TRPM2-AS expression in OC cells was analyzed utilizing reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 (CCK-8) and colony forming assays were carried out to explore the influence of TRPM2-AS on OC cell viability and proliferation. Cell apoptosis was detected using TdT-mediated dUTP Nick-End labeling (TUNEL) and flow cytometry analysis. Protein expression of apoptotic markers was subjected to western blotting. RNA pulldown or luciferase reporter assays were applied to explore the interaction between TRPM2-AS and miR-6764-5p or the binding of miR-6764-5p and TRPM2. The results showed that TRPM2-AS is highly expressed in OC cells and was mainly localized in cytoplasm. TRPM2-AS depletion suppressed OC cell viability and proliferation while increasing cell apoptotic rate. TRPM2 displayed a high level in OC cells and was positively regulated by TRPM2-AS. TRPM2-AS interacted with miR-6764-5p and thereby upregulated TRPM2 expression. In addition, TRPM2 overexpression reversed the repressive impact of TRPM2-AS depletion on malignant OC cellular process. In conclusion, TRPM2-AS promotes OC cell viability and proliferation while enhancing cell apoptosis through interaction with miR-6764-5p to regulate TRPM2 level.

Flexible Pressure Sensors Based on P(VDF-TrFE) Films Incorporated with Ag@PDA@PZT Particles.

Films of piezoelectric poly(vinylidene fluoride) (PVDF) and its copolymer P(VDF-TrFE) have been studied intensively for their potential application in piezoelectric sensing devices. The present work focuses on tuning the piezoelectric properties of P(VDF-TrFE) films via incorporating Ag and polydopamine co-decorated PZT (Ag@PDA@PZT) particles. Ag@PDA@PZT particles can effectively improve the ß-phase content and piezoelectric properties of P(VDF-TrFE) films. The highest open-circuit voltage and short-circuit current of P(VDF-TrFE)-based flexible pressure sensors incorporating Ag@PDA@PZT particles are ~30 V and ~2.4 µA, respectively. The flexible sensors exhibit a response to different body movements, providing a practical and potentially useful basis for human-machine interface applications.

The neurotransmitter calcitonin gene-related peptide shapes an immunosuppressive microenvironment in medullary thyroid cancer.

Neurotransmitters are key modulators in neuro-immune circuits and have been linked to tumor progression. Medullary thyroid cancer (MTC), an aggressive neuroendocrine tumor, expresses neurotransmitter calcitonin gene-related peptide (CGRP), is insensitive to chemo- and radiotherapies, and the effectiveness of immunotherapies remains unknown. Thus, a comprehensive analysis of the tumor microenvironment would facilitate effective therapies and provide evidence on CGRP's function outside the nervous system. Here, we compare the single-cell landscape of MTC and papillary thyroid cancer (PTC) and find that expression of CGRP in MTC is associated with dendritic cell (DC) abnormal development characterized by activation of cAMP related pathways and high levels of Kruppel Like Factor 2 (KLF2), correlated with an impaired activity of tumor infiltrating T cells. A CGRP receptor antagonist could offset CGRP detrimental impact on DC development in vitro. Our study provides insights of the MTC immunosuppressive microenvironment, and proposes CGRP receptor as a potential therapeutic target.

Evidence of electron interaction with an unidentified bosonic mode in superconductor CsCa2Fe4As4F2.

The kink structure in band dispersion usually refers to a certain electron-boson interaction, which is crucial in understanding the pairing in unconventional superconductors. Here we report the evidence of the observation of a kink structure in Fe-based superconductor CsCa2Fe4As4F2 using angle-resolved photoemission spectroscopy. The kink shows an orbital selective and momentum dependent behavior, which is located at 15 meV below Fermi level along the Γ - M direction at the band with dxz orbital character and vanishes when approaching the Γ - X direction, correlated with a slight decrease of the superconducting gap. Most importantly, this kink structure disappears when the superconducting gap closes, indicating that the corresponding bosonic mode (~ 9 ± 1 meV) is closely related to superconductivity. However, the origin of this mode remains unidentified, since it cannot be related to phonons or the spin resonance mode (~15 meV) observed by inelastic neutron scattering. The behavior of this mode is rather unique and challenges our present understanding of the superconducting paring mechanism of the bilayer FeAs-based superconductors.

Complete mitochondrial genome of Melia azedarach L., reveals two conformations generated by the repeat sequence mediated recombination.

Melia azedarach is a species of enormous value of pharmaceutical industries. Although the chloroplast genome of M. azedarach has been explored, the information of mitochondrial genome (Mt genome) remains surprisingly limited. In this study, we used a hybrid assembly strategy of BGI short-reads and Nanopore long-reads to assemble the Mt genome of M. azedarach. The Mt genome of M. azedarach is characterized by two circular chromosomes with 350,142 bp and 290,387 bp in length, respectively, which encodes 35 protein-coding genes (PCGs), 23 tRNA genes, and 3 rRNA genes. A pair of direct repeats (R1 and R2) were associated with genome recombination, resulting in two conformations based on the Sanger sequencing and Oxford Nanopore sequencing. Comparative analysis identified 19 homologous fragments between Mt and chloroplast genome, with the longest fragment of 12,142 bp. The phylogenetic analysis based on PCGs were consist with the latest classification of the Angiosperm Phylogeny Group. Notably, a total of 356 potential RNA editing sites were predicted based on 35 PCGs, and the editing events lead to the formation of the stop codon in the rps10 gene and the start codons in the nad4L and atp9 genes, which were verified by PCR amplification and Sanger sequencing. Taken together, the exploration of M. azedarach gap-free Mt genome provides a new insight into the evolution research and complex mitogenome architecture.

The predictors of fungal infections after liver transplantation and the influence of fungal infections on outcomes.

The primary objective of this study was to assess the incidence, timing, risk factors of fungal infections (FIs) within 3 months after liver transplantation (LT). The secondary objective was to evaluate the impact of FIs on outcomes. Four hundred and ten patients undergoing LT from January 2015 until January 2023 in a tertiary university hospital were included in the present retrospective cohort study to investigate the risk factors of FIs and to assess the impacts of FIs on the prognosis of LT recipients using logistic regression. The incidence of FIs was 12.4% (51/410), and median time from LT to the onset of FIs was 3 days. By univariate analysis, advanced recipient age, prolonged hospital stay prior to LT, high Model for End Stage Liver Disease (MELD) score, use of broad-spectrum antibiotics, and elevated white blood cell (WBC) count, increased operating time, massive blood loss and red blood cell transfusion, elevated alanine aminotransferase on day 1 and creatinine on day 3 after LT, prolonged duration of urethral catheter, prophylactic antifungal therapy, the need for mechanical ventilation and renal replacement therapy were identified as factors of increased post-LT FIs risk. Multivariate logistic regression analysis identified that recipient age ≥ 55 years[OR = 2.669, 95%CI: 1.292-5.513, P = 0.008], MELD score at LT ≥ 22[OR = 2.747, 95%CI: 1.274-5.922, P = 0.010], pre-LT WBC count ≥ 10 × 109/L[OR = 2.522, 95%CI: 1.117-5.692, P = 0.026], intraoperative blood loss ≥ 3000 ml [OR = 2.691, 95%CI: 1.262-5.738, P = 0.010], post-LT duration of urethral catheter > 4 d [OR = 3.202, 95%CI: 1.553-6.602, P = 0.002], and post-LT renal replacement therapy [OR = 5.768, 95%CI: 1.822-18.263, P = 0.003] were independently associated with the development of post-LT FIs. Post-LT prophylactic antifungal therapy ≥ 3 days was associated with a lower risk of the development of FIs [OR = 0.157, 95%CI: 0.073-0.340, P < 0.001]. As for clinical outcomes, FIs had a negative impact on intensive care unit (ICU) length of stay ≥ 7 days than those without FIs [OR = 3.027, 95% CI: 1.558-5.878, P = 0.001] but had no impact on hospital length of stay and 1-month all-cause mortality after LT. FIs are frequent complications after LT and the interval between the onset of FIs and LT was short. Risk factors for post-LT FIs included high MELD score at LT, advanced recipient age, pre-LT WBC count, massive intraoperative blood loss, prolonged post-LT duration of urethral catheter, and the need for post-LT renal replacement therapy. However, post-LT prophylactic antifungal therapy was independently associated with the reduction in the risk of FIs. FIs had a significant negative impact on ICU length of stay.

[Retracted] MicroRNA­126 exerts antitumor functions in ovarian cancer by targeting EGFL7 and affecting epithelial­to­mesenchymal transition and ERK/MAPK signaling pathway.

[This retracts the article DOI: 10.3892/ol.2020.11687.].

Infliximab inhibits TNF-α-dependent activation of the NLRP3/IL-1ß pathway in acne inversa.

Background: Acne inversa (AI) is a refractory inflammatory skin disease, and TNF-α plays an important role in the pathogenesis of AI. By blocking TNF-α, infliximab (IFX) has been proven to be a promising method. Objectives: To explore the underlying mechanisms of IFX treatment in AI patients. Methods: In this research, we integrated transcriptome sequencing data from the samples of our patients with AI and the GEO database. Ex vivo skin culture of AI patients was conducted to evaluate the efficacy of IFX treatment. Animal studies and cell experiments were used to explore the therapeutic effect and mechanism of IFX treatment. Results: Both TNF-α and NLRP3 inflammasome-related pathways were enriched in skin lesions of AI patients and murine AI models. After IFX treatment, the NLRP3 inflammasome-related pathway was effectively blocked, and the IL-1ß level was normalized in ex vivo AI skin explants and murine AI models. Mechanistically, IFX suppressed the NF-κB signaling pathway to lower the expression of NLRP3 and IL-1ß in keratinocytes. Conclusions: IFX treatment alleviated skin lesions in murine AI models and downregulated NLRP3 and IL-1ß expression levels by inhibiting the NF-κB signaling pathway, which was helpful for understanding the mechanism of IFX therapy.

Associations between different anatomical types of chronic rhinosinusitis and anxiety and depression.

Aims/Background Patients with chronic rhinosinusitis often have a higher incidence of anxiety and depression. Nevertheless, the impact of specific chronic rhinosinusitis types (chronic anterior/posterior/anterior and posterior rhinosinusitis) on anxiety and depression remains unexplored. Methods From January 2022 to July 2023, we employed various assessment scales to gauge the severity of chronic rhinosinusitis and anxiety and depression among Chinese patients with chronic rhinosinusitis. Statistical analysis involved non-parametric tests and binary logistic regression. Results In total, 123 patients with chronic rhinosinusitis were enrolled. The number of patients with anxiety and depression in the chronic posterior rhinosinusitis and chronic anterior and posterior rhinosinusitis groups (p=0.022), the nasal symptom subdomain scores of the chronic anterior rhinosinusitis and chronic anterior and posterior rhinosinusitis (p=0.011) groups and the chronic posterior rhinosinusitis and chronic anterior and posterior rhinosinusitis (p=0.008) groups, and the Lund-Kennedy score of the three groups (all p < 0.05) were significantly different. Binary logistic regression analysis revealed that chronic rhinosinusitis type (p=0.035) was a risk factor for anxiety and depression. Conclusion Anatomical chronic rhinosinusitis type was a risk factor for anxiety and depression in patients with chronic rhinosinusitis.

Early use of oral antiviral drugs and the risk of post COVID-19 syndrome: A systematic review and network meta-analysis.

OBJECTIVES: This study aimed to determine the association of early use of oral antiviral drugs (including nirmatrelvir-ritonavir and molnupiravir) with the risk of post COVID-19 condition (PCC) and compare the possible efficacy of nirmatrelvir-ritonavir and molnupiravir. METHODS: PubMed, Web of Science, Embase, Cochrane, MedRxiv, and Psycinfo were searched from inception until November 1, 2023. We included studies that assessed the effect of oral antiviral drugs on the incidence of PCC. Pairwise and network meta-analyses were conducted using a random-effects model. Risk ratios (RRs) for oral antiviral drugs were calculated with a confidence interval (CI). RESULTS: Nine observational studies containing 866,066 patients were included. Nirmatrelvir-ritonavir and molnupiravir were evaluated in eight and two studies respectively, with both drugs evaluated in one study. Pair-wise meta-analysis showed that early oral antiviral drugs reduced PCC risk (RR 0.77, 95% CI 0.68-0.88). Network meta-analysis showed that nirmatrelvir-ritonavir may perform better than molnupiravir (surface under the cumulative ranking curve: 95.5% vs. 31.6%) at reducing PCC risk. CONCLUSIONS: Early use of oral antiviral drugs may potentially protect against developing PCC in non-hospitalized patients with COVID-19. These findings support the standardized administration of oral antiviral drugs in patients during the acute phase of COVID-19 according to the guidelines.

Principles and research progress of physical prevention and control technologies for algae in eutrophic water.

The abnormal reproduction of algae in water worldwide is prominent in the context of human interference and global climate change. This study first thoroughly analyzed the effects of physical factors, such as light, temperature, hydrodynamics, and operational strategies, on algal growth and their mechanisms. Physical control techniques are safe and have great potential for preventing abnormal algal blooms in the absence of chemical reagents. The focus was on the principles and possible engineering applications of physical shading, ultrasound, micro-current, and ultraviolet (UV) technologies, in controlling abnormal algal reproduction. Physical shading can inhibit or weaken photosynthesis in algae, thereby inhibiting their growth. Ultrasound mainly affects the physiological and biochemical activities of cells by destroying the cell walls, air cells, and active enzymes. Micro-currents destroy the algal cell structure through direct and indirect oxidation, leading to algal cell death. UV irradiation can damage DNA, causing organisms to be unable to reproduce or algal cells to die directly. This article comprehensively summarizes and analyzes the advantages of physical prevention and control technologies for the abnormal reproduction of algae, providing a scientific basis for future research. In the future, attempts will be made toward appropriately and comprehensively utilizing various physical technologies to control algal blooms. The establishment of an intelligent, comprehensive physical prevention and control system to achieve environmentally friendly, economical, and effective physical prevention and control of algae, such as the South-to-North Water Diversion Project in China, is of great importance for specific waters.

MiR-3074-5p suppresses non-small cell lung cancer progression by targeting the YWHAZ/Hsp27 axis.

Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases, and the 5-year survival rate of patients remains unsatisfactory. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that are considered essential posttranscriptional regulators of tumorigenesis, including NSCLC. In this study, we aimed to investigate the biological role of miR-3074-5p in NSCLC cells and the underlying molecular mechanisms. We showed that miR-3074-5p expression was decreased in human NSCLC specimens and cell lines. Moreover, miR-3074-5p overexpression inhibited cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. In addition, miR-3074-5p overexpression not only suppressed tumor growth but also enhanced the antitumor effect of paclitaxel (PTX) on NSCLC cells in vitro and in vivo. A transcriptome sequencing assay revealed genes that were differentially expressed after miR-3074-5p overexpression, and among the genes whose expression levels were most significantly decreased, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) was a target of miR-3074-5p. The regulatory effect of miR-3074-5p on YWHAZ expression was verified by Western blotting and dual-luciferase reporter assays. The inhibition of A549 cell growth, migration and invasion was reversed by YWHAZ overexpression. Furthermore, we showed that PTX stimulated the expression of the YWHAZ and Hsp27 proteins and promoted the phosphorylation of Hsp27 (at S15 and S78). YWHAZ was confirmed to interact with Hsp27 in A549 cells, and downregulating YWHAZ expression promoted the degradation of the Hsp27 protein. Taken together, these results suggest that the miR-3074-5p/YWHAZ/Hsp27 axis may be a novel therapeutic target for NSCLC treatment.

Impact of soil physicochemical factors and heavy metals on co-occurrence pattern of bacterial in rural simple garbage dumping site.

Rural waste accumulation leads to heavy metal soil pollution, impacting microbial communities. However, knowledge gaps exist regarding the distribution and occurrence patterns of bacterial communities in multi-metal contaminated soil profiles. In this study, high-throughput 16 S rRNA gene sequencing technology was used to explore the response of soil bacterial communities to various heavy metal pollution in rural simple waste dumps in karst areas of Southwest China. The study selected three habitats in the center, edge, and uncontaminated areas of the waste dump to evaluate the main factors driving the change in bacterial community composition. Pollution indices reveal severe contamination across all elements, except for moderately polluted lead (Pb); contamination severity ranks as follows: Mn > Cd > Zn > Cr > Sb > V > Cu > As > Pb. Proteobacteria, Actinobacteria, Chloroflexi, and Acidobacteriota predominate, collectively constituting over 60% of the relative abundance. Analysis of Chao and Shannon indices demonstrated that the waste dump center boasted the greatest bacterial richness and diversity. Correlation data indicated a predominant synergistic interaction among the landfill's bacterial community, with a higher number of positive associations (76.4%) compared to negative ones (26.3%). Network complexity was minimal at the dump's edge. RDA analysis showed that Pb(explained:46%) and Mn(explained:21%) were the key factors causing the difference in bacterial community composition in the edge area of the waste dump, and AK(explained:42.1%) and Cd(explained:35.2%) were the key factors in the center of the waste dump. This study provides important information for understanding the distribution patterns, co-occurrence networks, and environmental response mechanisms of bacterial communities in landfill soils under heavy metal stress, which helps guide the formulation of rural waste treatment and soil remediation strategies.

Signatures of Adaptation and Purifying Selection in Highland Populations of Dasiphora fruticosa.

High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.

Relationship between abnormal pelvic floor electromyography and obstetric factors in postpartum women: a cross-sectional study.

OBJECTIVE: To evaluate the surface electromyography (sEMG) of pelvic floor muscles (PFMs), compare between vaginal birth and cesarean section and correlate with maternity and obstetrics characteristics in primiparous 6-8 weeks postpartum. METHODS: PFMs surface electromyography screening data of primiparous postpartum women in our hospital at 6-8 weeks postpartum from 2018 to 2021 were selected and analyzed. The study collected data on delivery activities of 543 postpartum women totally. RESULTS: In general, the abnormal incidence of pelvic floor electromyography in postpartum women mainly occurred in slow muscle (type I fiber) stage and endurance testing stage. Compared to vaginal birth postpartum women, the incidence of abnormal pelvic floor electromyography in cesarean section postpartum women is lower. There were statistical differences in measurement values of pelvic floor electromyography in several different stages between cesarean section and vaginal birth (P < 0.005). Regarding the influence on pelvic floor electromyography, there were more influencing factors on vaginal birth postpartum women including age, height, weight, weight gain during pregnancy, gestational week, and first and second stage of labor than on cesarean section postpartum women whose influencing factors included age, weight gain during pregnancy, and newborn weight. CONCLUSION: Effects on surface electromyography (sEMG) of pelvic floor muscles (PFMs) at 6-8 weeks postpartum differed based on the different modes of delivery. The high-risk obstetric factors closely related to abnormal surface electromyography (sEMG) of pelvic floor muscles (PFMs) were maternal age, height, weight, and second stage of labor.

Characteristics of DOM and Their Relationships with Potentially Toxic Elements in the Inner Mongolia Section of the Yellow River, China.

The characterization of dissolved organic matter (DOM) is important for better understanding of the migration and transformation mechanisms of DOM in water bodies and its interaction with other contaminants. In this work, fluorescence characteristics and molecular compositions of the DOM samples collected from the mainstream, tributary, and sewage outfall of the Inner Mongolia section of the Yellow River (IMYR) were determined by using fluorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). In addition, concentrations of potentially toxic elements (PTEs) in the relevant surface water and their potential relationships with DOM were investigated. The results showed that the abundance of tyrosine-like components increased significantly in downstream waters impacted by outfall effluents and was negatively correlated with the humification index (HIX). Compared to the mainstream, outfall and tributaries have a high number of molecular formulas and a higher proportion of CHOS molecular formulas. In particular, the O5S class has a relative intensity of 41.6% and the O5-7S class has more than 70%. Thirty-eight PTEs were measured in the surface water samples, and 12 found above their detective levels at all sampling sites. Protein-like components are positively correlated with Cu, which is likely indicating the source of Cu in the aquatic environment of the IMYR. Our results demonstrated that urban wastewater discharges significantly alter characteristics and compositions of DOM in the mainstream of IMYR with strongly anthropogenic features. These results and conclusions are important for understanding the role and sources of DOM in the Yellow River aquatic environment.