Oxidative stress is two-sided in the treatment of acute myeloid leukemia.

INTRODUCTION: Oxidative stress caused by elevated ROS, as a novel therapeutic mechanism, has been implicated in various tumors including AML. AML cells are chronically under oxidative stress, yet overreliance on ROS production makes tumor cells increasingly vulnerable to further damage. Reducing the cytotoxic effect of ROS on normal cells while killing leukemia stem cell (LSC) with high levels of reactive oxygen species is a new challenge for oxidative stress therapy in leukemia. METHODS: By searching literature databases, we summarized recent relevant studies. The relationship of ROS on AML genes, signaling pathways, and transcription factors, and the correlation of ROS with AML bone marrow microenvironment and autophagy were summarized. In addition, we summarize the current status of research on ROS and AML therapeutics. Finally, we discuss the research progress on redox resistance in AML. RESULTS: This review discusses the evidence showing the link between redox reactions and the progression of AML and compiles the latest research findings that will facilitate future biological studies of redox effects associated with AML treatment. CONCLUSION: We believe that exploiting this unique oxidative stress property of AML cells may provide a new way to prevent relapse and drug resistance.

Experimental and Numerical Investigation of Dynamic Damage and Load Transfer of PBX Substitute Material under Low Velocity Impact.

The accidental initiation of explosives under mechanical loads has caused numerous catastrophic events. Therefore, the dynamic damage behavior of confined polymer-bonded explosives (PBXs) must be assessed to improve their practical applicability. In this study, polymer-bonded sugar (PBS) materials were prepared using a novel agglomerate to develop a PBX substitute material with enhanced experimental safety. The mechanical properties of the PBS shell were evaluated using a dynamic compression test, which revealed that the compression response of the shell was affected by the strain rate. A low-velocity impact experiment was performed to investigate the dynamic damage and load transfer characteristics of the PBX substitute. A constitutive model was developed to characterize the mechanical response of PBS subjected to high strain rates, and implementing this model in ABAQUS ensured successful prediction of the damage evolution process associated with PBS. Simulation results indicated that the PBS specimen was primarily damaged around its center while sliding friction was dominant near the center during pressure application. Notably, different stress states result in distinct crack growth velocity histories along the axial direction, with the damage ratio progressively decreasing toward regions closer to the impact surface.

Plasma Membrane (PM) H+-ATPase Mediates Rhizosphere Acidification and Regulates Herbicide Imazethapyr Toxicity in Wheat.

The plasma membrane (PM) H+-ATPase is crucial for a plant defense system. However, there is currently no consensus on whether the PM H+-ATPase plays a role in alleviating the toxic effects of herbicides on nontarget plants. We found that under the herbicide imazethapyr (IM) exposure, PM H+-ATPase activity in wheat roots increased by approximately 69.53%, leading to rhizosphere acidification. When PM H+-ATPase activity is inhibited, the toxicity of IM significantly increases: When exposed to IM alone, the total Fe content of wheat roots decreased by 29.07%, the relative Fe2+ content increased by 27.75%, and the ROS content increased by 27.74%. When the PM H+-ATPase activity was inhibited, the corresponding data under IM exposure were 37.36%, 215%, and 57.68%, respectively. This work delves into the role of PM H+-ATPase in mediating the detoxification mechanism in plants exposed to herbicides, offering new insights into enhancing crop resistance against herbicides.

BRD4 inhibitors broadly promote erastin-induced ferroptosis in different cell lines by targeting ROS and FSP1.

Ferroptosis, an iron-dependent form of programmed cell death, is a promising strategy for cancer treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic reader and a promising target for cancer therapeutics. However, the role of BRD4 in ferroptosis is controversial and the value of the interaction between BRD4 inhibitors and ferroptosis inducers remains to be explored. Here, we found that BRD4 inhibition greatly enhanced erastin-induced ferroptosis in different types of cells, including HEK293T, HeLa, HepG2, RKO, and PC3 cell lines. Knocking down BRD4 in HEK293T and HeLa cells also promoted erastin-induced cell death. BRD4 inhibition by JQ-1 and I-BET-762 or BRD4 knockdown resulted in substantial accumulation of reactive oxygen species (ROS) in both HEK293T and HeLa cells. The effect of BRD4 inhibition on ferroptosis-associated genes varied in different cells. After using BRD4 inhibitors, the expression of FTH1, Nrf2, and GPX4 increased in HEK293T cells, while the levels of VDAC2, VDAC3, and FSP1 decreased. In HeLa cells, the expression of FTH1, VDAC2, VDAC3, Nrf2, GPX4, and FSP1 was reduced upon treatment with JQ-1 and I-BET-762. Consistently, the level of FSP1 was greatly reduced in HEK293T and HeLa cells with stable BRD4 knockdown compared to control cells. Furthermore, ChIP-sequencing data showed that BRD4 bound to the promoter of FSP1, but the BRD4 binding was greatly reduced upon JQ-1 treatment. Our results suggest that ROS accumulation and FSP1 downregulation are common mechanisms underlying increased ferroptosis with BRD4 inhibitors. Thus, BRD4 inhibitors might be more effective in combination with ferroptosis inducers, especially in FSP1-dependent cancer cells.

Identifying a locus in super-enhancer and its resident NFE2L1/MAFG as transcriptional factors that drive PD-L1 expression and immune evasion.

Although the transcriptional regulation of the programmed death ligand 1 (PD-L1) promoter has been extensively studied, the transcription factor residing in the PD-L1 super-enhancer has not been comprehensively explored. Through saturated CRISPR-Cas9 screening of the core region of the PD-L1 super-enhancer, we have identified a crucial genetic locus, referred to as locus 22, which is essential for PD-L1 expression. Locus 22 is a potential binding site for NFE2:MAF transcription factors. Although genetic silencing of NRF2 (NFE2L2) did not result in a reduction of PD-L1 expression, further analysis reveals that MAFG and NFE2L1 (NRF1) play a critical role in the expression of PD-L1. Importantly, lipopolysaccharides (LPS) as the major component of intratumoral bacteria could greatly induce PD-L1 expression, which is dependent on the PD-L1 super-enhancer, locus 22, and NFE2L1/MAFG. Mechanistically, genetic modification of locus 22 and silencing of MAFG greatly reduce BRD4 binding and loop formation but have minimal effects on H3K27Ac modification. Unlike control cells, cells with genetic modification of locus 22 and silencing of NFE2L1/MAFG failed to escape T cell-mediated killing. In breast cancer, the expression of MAFG is positively correlated with the expression of PD-L1. Taken together, our findings demonstrate the critical role of locus 22 and its associated transcription factor NFE2L1/MAFG in super-enhancer- and LPS-induced PD-L1 expression. Our findings provide new insight into understanding the regulation of PD-L1 transcription and intratumoral bacteria-mediated immune evasion.

Development and application of oncolytic viruses as the nemesis of tumor cells.

Viruses and tumors are two pathologies that negatively impact human health, but what occurs when a virus encounters a tumor? A global consensus among cancer patients suggests that surgical resection, chemotherapy, radiotherapy, and other methods are the primary means to combat cancer. However, with the innovation and development of biomedical technology, tumor biotherapy (immunotherapy, molecular targeted therapy, gene therapy, oncolytic virus therapy, etc.) has emerged as an alternative treatment for malignant tumors. Oncolytic viruses possess numerous anti-tumor properties, such as directly lysing tumor cells, activating anti-tumor immune responses, and improving the tumor microenvironment. Compared to traditional immunotherapy, oncolytic virus therapy offers advantages including high killing efficiency, precise targeting, and minimal side effects. Although oncolytic virus (OV) therapy was introduced as a novel approach to tumor treatment in the 19th century, its efficacy was suboptimal, limiting its widespread application. However, since the U.S. Food and Drug Administration (FDA) approved the first OV therapy drug, T-VEC, in 2015, interest in OV has grown significantly. In recent years, oncolytic virus therapy has shown increasingly promising application prospects and has become a major research focus in the field of cancer treatment. This article reviews the development, classification, and research progress of oncolytic viruses, as well as their mechanisms of action, therapeutic methods, and routes of administration.

Variations in surface functional groups, carbon chemical state and graphitization degree during thermal deactivation of diesel soot particles.

The thermal deactivation of diesel soot particles exerts a significant influence on the control strategy for the regeneration of diesel particulate filters (DPFs). This work focused on the changes in the surface functional groups, carbon chemical state, and graphitization degree during thermal treatment in an inert gas environment at intermediate temperatures of 600°C, 800°C, and 1000°C and explore the chemical species that were desorbed from the diesel soot surface during thermal treatment using a thermogravimetric analyser coupled with a gas-chromatograph mass spectrometer (TGA-GC/MS). The surface functional groups and carbon chemical state were characterized using Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). The graphitization degree was evaluated by means of Raman spectroscopy (RS). The concentrations of aliphatic C-H, C-OH, C=O, and O-C=O groups are reduced for diesel soot and carbon black when increasing the thermal treatment temperature, while the sp2/sp3 hybridized ratio and graphitization degree enhance. These results provide comprehensive evidence of the decreased reactivity of soot samples. Among oxygenated functional groups, the percentage reduction during thermal treatment is the largest for the O-C=O groups owing to its worst thermodynamic stability. TGA-GC/MS results show that the aliphatic and aromatic chains and oxygenated species would be desorbed from the soot surface during 1000°C thermal treatment of diesel soot.

A viscoelastic-viscoplastic constitutive model for polymer bonded explosives under low impact loading.

Viscoplastic work is very important to explosive ignition under impact loading. At present, a large number of constitutive models only consider the viscoelastic and damage behavior of explosives, ignoring the plastic effect under low impact loading. A new viscoelastic-viscoplastic (VE-VP) model was developed and studied to describe the dynamic mechanical behaviors of polymer-bonded explosives (PBXs). The total strain was assumed to be the sum of the viscoelastic (VE) and viscoplastic (VP) components. A generalized Maxwell model was used to determine the VE responses. A VP model was developed by using the classical J2 rate-dependent model with isotropic hardening. Viscoplastic flow was considered in hyperbolic sinusoidal form. The explicit algorithms of VE model were proposed and assessed by using two different integration methods. The accuracy and efficiency of these two methods are similar at high strain rates. The coupled algorithms of VE-VP model were developed by referring to the classical elasto-viscoplasticity (EVP) provided and using the expression of incremental relaxation modulus. The proposed model was implemented in the ABAQUS using a user-subroutine (VUMAT) to predict the response behaviors of PBX 9501 under low impact loading. Several numerical simulations illustrated the computational efficiency and the accuracy of the proposed methods. The model predictions were compared with experimental data, and reasonable agreement was obtained.

Study on the Performance of the Zr-Modified Cu-SSZ-13 Catalyst for Low-Temperature NH3-SCR.

Cu-SSZ-13 and Zr-modified Cu-SSZ-13 catalysts with different Zr/Cu mass ratios were prepared by ion-exchange and impregnation methods, respectively. The NH3-SCR performance tests were performed using the catalyst performance evaluation device to investigate the effects of different Zr/Cu mass ratios on the catalyst ammonia-selective catalytic reduction (NH3-SCR) performance. X-ray diffraction, ICP-OES, BET, NH3 temperature-programed desorption (NH3-TPD), H2 temperature-programmed reduction (H2-TPR), X-ray photoelectron spectrometry, and in situ diffuse reflectance infrared Fourier transform spectroscopy (in situ DRIFTS) were used to characterize the catalysts. The results show that the prepared Cu-SSZ-13 catalyst had good catalytic activity. Zr introduction was carried out on this basis. The results showed that proper Zr doping improved the catalytic activity at low temperatures and widened the high-temperature stage, with an optimal activity stage at a Zr/Cu mass ratio of 0.2. The NO x conversion efficiency was close to 100% at 200 °C and over 80% at 450 °C. The active species were well dispersed on the catalyst surface, and the metal modification did not change the crystal structure of the zeolite. The NH3-TPD results showed that the Zr-modified catalyst had more abundant acid sites, and the H2-TPR results indicated that the Cu species on the catalyst had excellent reducibility at low temperatures. The interaction between Cu and Zr could regulate the Cu+ and Cu2+ proportion on the catalyst surface, which facilitated the increase in the Cu+ for fast SCR reaction at low temperatures. With abundant acid sites and both SCR reactions following the Eley-Rideal (E-R) and Langmuir-Hinshelwood (L-H) mechanism on the catalyst surface at a low temperature of 150 °C, more abundant acid sites and reaction paths created favorable conditions for NH3-SCR reactions at low temperatures.

The relationship between serum C-reactive protein and senile hypertension.

BACKGROUND: Hypertension has become an important health risk factor in the twenty-first century, especially for the elderly. Studies have confirmed that inflammation is involved in the development of hypertension and that the inflammatory marker C-reactive protein(CRP) is significantly associated with hypertension. Therefore, in this study, we aimed to explore the CRP correlation with hypertension in the elderly. METHODS: Serum CRP levels were measured in 196 hospitalized patients, and the CRP level was used as a criterion to divide them into the group with elevated CRP (> 10 mmol/L, n = 120) and the group with normal CRP (0 < CRP ≤ 10 mmol/L, n = 76). and the patient's baseline characteristics were collected and compared between the groups, and the correlation between CRP and other factors and hypertension in the elderly was analyzed by multi-factor logistic regression. RESULTS: The prevalence of hypertension, coronary artery disease and joint reactive inflammation was significantly higher in the group with elevated CRP. There was also a significant association between the use of alcohol, low density lipoprotein cholesterol (LDL-C) and steroids and elevated CRP; logistic regression showed that elevated CRP (OR = 2.13, 95% CI: 1.14-3.99, p = 0.019), body mass index (BMI) (OR = 1.10, 95% CI:1.01-1.90, p = 0.030), diabetes (OR = 2.68, 95% CI:1.24-5.79, p = 0.012) were positively associated with hypertension, while statins use was negatively associated with hypertension (OR = 0.49, 95% CI: 0.25-0.94, p = 0.013). CONCLUSIONS: Elevated CRP, BMI, and diabetes are positively associated with hypertension in the elderly, and early screening for CRP and initiation of treatment may help prevent further inflammatory responses in hypertension.

Thermally induced variations in the nanostructure and reactivity of soot particles emitted from a diesel engine.

This work focuses on the thermally induced variation in the nanostructure, size of primary particles and oxidative reactivity of diesel soot and a commercial carbon black in an inert gas environment at temperatures ranging from 600 to 1000 °C. Soot nanostructure and size were characterized by high-resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). The soot reactivity was evaluated with respect to activation energy (Ea) and characteristic oxidation temperature, including peak temperature (TP) and burnout temperature (Tb), using thermogravimetric analysis (TGA). The mass loss of diesel soot and carbon black rises when increasing the thermal treatment temperature, especially at 1000 °C, and a significant quantity of mass loss can be observed, which is primarily due to thermal fragmentation and the desorption of chemical species on soot surfaces. The HRTEM and XRD results all indicate that the thermally treated soot samples have more ordered nanostructure than the untreated samples. There is a reduction in the size of primary particles as thermal treatment temperature increases. The soot reactivity decreases after thermal treatment, as manifested by the elevation in Ea, TP, and Tb values. Moreover, the oxidation reactivity of soot samples is closely associated with the fringe length, tortuosity, and fringe tortuosity. Compared to carbon black, diesel soot with a more disorder structure has a higher oxidative reactivity.

Combination of Pilot Injection and a NH3-SCR System To Reduce NOx Emissions of a Nonroad Compression Ignition Engine.

This study compared the NOx emissions of a nonroad compression ignition engine using pilot injection and a NH3-SCR system and revealed their effects on NOx reduction. Furthermore, the interaction of pilot injection and the NH3-SCR system on NOx reduction was also studied by simultaneously using the two technologies under broad engine operating conditions. The pilot-main interval and the rate of pilot-to-main injection used in this study are in the range of 2∼8 CA and 9.5∼58.5%, respectively. Results showed that alteration in the pilot-main injection interval and the pilot-injection fuel amount under low load conditions was prone to lead to more variation in NOx emissions in comparison with that under high-load conditions. Relative to the pilot-main injection interval, the pilot-injection fuel amount played a more important role in the NOx emission. Lower NOx emissions could be achieved when using a smaller pilot-injection amount. However, excessively advanced pilot injection and a larger pilot-injection amount would increase the NOx emissions. Under a lower engine load, the effect of pilot injection on NOx reduction enhanced, whereas the effect of the NH3-SCR system diminished. Over broad operating conditions, the NOx reduction percentage by pilot injection coupled with the SCR system was lower than the total reduction degree when separately using pilot injection and the SCR system.

Mesenchymal stem cells: ideal seeds for treating diseases.

Mesenchymal stem cells (MSCs), a kind of multipotent stem cells with self-renewal ability and multi-differentiation ability, have become the "practical stem cells" for the treatment of diseases. MSCs have immunomodulatory properties and can be used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE) and Crohn's disease. MSCs also can be used in cancer and aging. At present, many clinical experiments are using MSCs. MSCs can reduce the occurrence of inflammation and apoptosis of tissue cells, and promote the proliferation of endogenous tissue and organ cells, so as to achieve the effect of repairing tissue and organs. MSCs presumably also play an important role in Corona Virus Disease 2019 (COVID-19) infection.

Local Structures of Soft Carbon and Electrochemical Performance of Potassium-Ion Batteries.

Due to climate variation and global warming, utilization of renewable energy becomes increasingly imperative. Rechargeable potassium-ion batteries (PIBs) have lately attracted much attention due to their earth-abundance and cost-effectiveness. Because soft carbon materials are cheap, abundant, and safe, extensive feasible research studies have indicated that they could become promising anode materials for PIBs. In spite of gaining achievements, fundamental questions regarding effects of the basic structure unit inside soft carbon on potassium storage potential have not been sufficiently addressed yet. Here, a series of soft carbon pyrolyzed from 900 to 2900 °C were systematically and quantitatively characterized by combining Raman spectroscopy, near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, X-ray pair distribution function analysis, and advanced evaluation of wide-angle X-ray scattering data. All these characterizations reveal structural details of soft carbon with increasing pyrolysis temperature. Our results show that the potassium storage behavior, especially the potential plateau is closely correlated to non-uniformity in interlayer distance and defect concentration in soft carbon, which is further confirmed by reverse Monte Carlo (RMC) modeling and density functional theory calculation. On the basis of these results, optimizing strategies are discussed to design an advanced soft carbon anode. This work provides significant insights into the structure engineering of soft carbon for high-performance rechargeable PIBs.

Microbial community diversity and composition in river sediments contaminated with tetrabromobisphenol A and copper.

The microbial community composition in aquatic ecosystems have received increased attention. However, the knowledge gap relative to the responses of bacterial, archaeal and fungal communities in co-contaminated river sediments remain poorly studied. Here, we investigated the changes of tetrabromobisphenol A (TBBPA) and copper (Cu) concentrations and the responses of microbial communities in co-contaminated sediments during long-term incubation. TBBPA concentrations significantly decreased over time, whereas Cu concentrations remained relatively stable over the 60-day incubation. Abundances of the bacterial 16S rRNA, archaeal 16S rRNA and fungal ITS genes ranged from 6.53 × 106 to 1.26 × 109 copies g-1, 1.12 × 106 to 5.47 × 106 copies g-1 and 5.33 × 103 to 7.51 × 104 copies g-1 in the samples, respectively. A total of 11, 6 and 5 bacterial, archaeal and fungal phyla were identified across all samples. Bacterial, archaeal and fungal communities mainly consisted of members from the phyla Proteobacteria and Acidobacteria, Methanomicrobia and Woesearchaeia as well as Agaricales and Helotiales, respectively. Fungal communities showed a stronger response to pollutant addition after a long incubation compared with bacterial and archaeal communities. The variance analysis results revealed that the bacterial, archaeal and fungal microbial communities of all treatments were distinctly distributed into two separated clusters according to incubation time. However, the three microbial communities did not significantly change in response to pollutant types, which was consistent with variation in relative abundances of the three microbial communities. These findings improve our understanding of the ecotoxicological effects of co-exposure on sediment microbial communities.

Hard carbon spheres prepared by a modified Stöber method as anode material for high-performance potassium-ion batteries.

The Stöber method is a highly efficient synthesis strategy for homogeneous monodisperse polymer colloidal spheres and carbon spheres. This work delivers an extended Stöber method and investigates the synthesis process. By calcining the precursor under appropriate conditions, solid secondary particles of amorphous carbon (SSAC) and hollow secondary particles of graphitized carbon (HSGC) can be directly synthesized. The two materials have a nano-primary particle structure and a closely-packed sub-micron secondary particle structure, which can be used in energy storage. We find that SSAC and HSGC have high potassium-ion storage capacity with reversible capacities of 274 mA h g-1 and 283 mA h g-1 at 20 mA g-1 respectively. Significantly, SSAC has better rate performance with a specific capacity of 107 mA h g-1 at 1 A g-1.

Interaction type of tetrabromobisphenol A and copper manipulates ammonia-oxidizing archaea and bacteria communities in co-contaminated river sediments.

The combined contamination of brominated flame retardants (BFRs) and heavy metals in electronic waste (e-waste) recycling and disposal areas has been a serious concern owing to their environmental persistence and chronic toxicities. Ammonia oxidizers, e.g., ammonia-oxidizing archaea (AOA) and bacteria (AOB) play essential roles in nitrogen cycling and can serve as ideal indicators that reflect the changes in sediment health in response to environmental variables. There is currently very little information available on the combined toxic effects of BFRs and heavy metals on AOA and AOB communities. In this study, two typical e-waste pollutants, tetrabromobisphenol A (TBBPA) and copper (Cu), were selected as target contaminants to investigate the individual and combined effects of both pollutants on AOA and AOB communities in river sediments. Respective treatments of TBBPA (1, 10, and 20 mg/kg wet weight), Cu (100 mg/kg wet weight) and their combined treatments (weight ratios of 1:100, 1:10, and 1:5) were performed in laboratory experiments. High-throughput sequencing was applied to explore the response of ammonia oxidizers to TBBPA and Cu. The interaction types of TBBPA and Cu were calculated by the directional classification system to reveal the individual and combined toxicities of both contaminants to the ammonia oxidizers. On days 15 and 30, the dominant interaction type of TBBPA and Cu was synergistic (62.50%), and the combined contamination exacted selective pressure and inhibition on the AOB and AOA communities. On days 45 and 90, the interaction type shifted to be antagonistic (83.33%), with both the AOB and AOA communities gradually reaching stable population equilibria. The alteration of the interaction type is attributed to the elevated TBBPA/Cu tolerance as the incubation time increased. This study disclosed the interaction types of TBBPA and Cu in contaminated river sediments, and revealed that the combined effect could potentially manipulate AOB and AOA communities.

In†Situ Self-Assembly of Core-Shell Multimetal Prussian Blue Analogues for High-Performance Sodium-Ion Batteries.

Metal-organic frameworks (MOFs), such as Prussian blue and its analogues (PB and PBAs) with open frameworks have attracted tremendous attentions as cathode materials for sodium-ion batteries, owing to their simple method of synthesis and high theoretical specific capacity. In this study, core-shell-structured PBAs are prepared by an in situ self-assembly method. Owing to the advantages of both constituents, the as-prepared core-shell PBAs show excellent rate and cycling electrochemical properties through a dual-level-controlled charge-discharge depth mechanism. It delivers a specific capacity of 104.3 mAh g-1 at 0.1 C, as well as a remarkably enhanced cycle performance, giving 88.3 % of its initial capacity over 1000 cycles at 300 mA g-1 . In particular, the coating strategy described herein could be extended to other MOF materials, leading to wider application in energy storage.

Nitrate addition promotes the nitrogen cycling processes under the co-contaminated tetrabromobisphenol A and copper condition in river sediment.

Tetrabromobisphenol A (TBBPA) and copper (Cu) are the main pollutants at e-waste recycling sites and the effects of their biotoxicity on microorganisms have drawn extensive attention. Nitrate-based bioremediation has been applied to organic pollutant-contaminated sediments since nitrate is a favorable electron acceptor for microbes. However, the effects of TBBPA and Cu on nitrogen (N)-cycling microorganisms and bioremediation in co-contaminated sediments remain unclear. Thus, our study examined the effects of TBBPA and Cu with/without nitrate addition on the TBBPA biodegradation efficiencies, microbial activities, and N functional genes. It was found the biodegradation efficiencies of TBBPA were improved by the nitrate addition from 34.7% to 59.3% and from 22.6% to 42.8% in the TBBPA and TBBPA-Cu contaminated groups, respectively. The inhibitions of the catalase activity increased with the nitrate addition because of the anaerobic respiration of the microorganisms. In addition, the potential denitrification rate exhibited an increasing trend from 6.46 to 8.23 mg-N kg-1 dry sediment day-1 during the period of 15-90 days after adding nitrate to the co-contaminated group, whereas the potential nitrification rate exhibited an opposite trend and decreased from 4.47 to 3.19 mg-N kg-1 dry sediment day-1. The denitrification gene abundances of the N-cycling genes were 107-108 orders of magnitude higher and significantly increased in the nitrate addition groups. The amoA gene abundances were lower than the denitrification gene abundances and were 105-106 orders of magnitude in the same groups. Moreover, the interaction types of the pollutants on the gene abundances were changed from synergistic to antagonistic as nitrate addition. Our study emphasized the gap of knowledge on nitrate addition affecting N-cycling microbes in the combined pollutants exposure sediments, and will be helpful for further bioremediation in different contaminated scenarios.