Increased PD-1+ NK Cell Subset in the Older Population.

Background: The aging of the immune system is associated with various diseases. It is worth exploring the changes of the immune system in aging. Previous studies have shown that aged T cells have enhanced expression of co-inhibitory molecules. However, it remains unclear whether aged NK cells exhibit similar characteristics to aged T cells. The objective of our research was to clarify this aspect. Patients and Methods: This study included 98 adults aged 24-90 years (50 males and 48 females). We detected the subset of peripheral blood NK cells and the expression of various receptors on NK cells among donors of different age groups by flow cytometry. Immune subsets were initially defined by forward and side-scatter characteristics and then staining with the appropriate marker. Results: The absolute number and subset distribution of NK cells were not associated with age. However, CD57 expression and CD69 expression were correlated with age. Furthermore, we found that PD-1 was up-regulated on NK cells in older people, associated with aging, while no such change was observed in other co-inhibitory molecules, including 2B4, CTLA-4, TIM-3, BTLA, CD70, CD39, CD160, and TIGIT. PD-1+ NK cells expressed high levels of CD57 and CD69, indicating PD-1+ NK cells displayed a phenotype of over-activation and aging. Discussion: This study indicated that PD-1+ NK cells were one of the characteristics of NK cells in older people. Conclusion: This study indicated that PD-1+ NK cells were one of the characteristics of NK cells in older people. Those findings provided new ideas to explore the underlying drivers of NK aging.

A new phenolic compound from Persicaria capitata.

Persicaria capitata was a frequently used Hmong medicinal flora in China. In this study, one new phenolic compound, capitaone A (1) together with 20 known ones, were isolated from the whole herb of P. capitata. Among them, 7 components (4, 9-11, 15-16, 20-21) were discovered from P. capitata for the first time. Their chemical structures were elucidated on the basis of extensive NMR and MS spectrum. Furthermore, three compounds (15, 20, 21) displayed remarkable cytotoxic activities against two human cancer cell lines (A549 and HepG2).

Comparison of Short-Term Surgery Outcomes and Clinical Characteristics Between Elderly and Non-Elderly Patients with Middle Third Parasagittal and Parafalcine Meningiomas.

Purpose: This study aims to compare the short-term surgery outcomes of the resection of meningiomas and clinical characteristics between elderly and non-elderly patients. Patients and Methods: This retrospective study included patients who underwent a resection of middle third parasagittal and parafalcine meningiomas between January 2011 and December 2020. All lesions arise from the middle third of the parafalcine or infiltrate superior sagittal sinus (SSS). The clinical characteristics studied included neurological deficit, peritumoral brain edema (PTBE), SSS invasion, tumor size, and symptoms; perioperative complications, and short-term surgery outcomes including neurological deficit, operative blood loss, postoperative hospitalization duration, and WHO classification were compared. Results: A total of 43 elderly patients and 63 non-elderly patients were included. Compared with non-elderly patients, elderly patients had larger lesions (P = 0.013) and presented with a larger PTBE (P = 0.019). SSS blockage was identified in 28.57% of elderly patients and 19.57% of non-elderly patients. Compared with non-elderly patients, elderly patients tended to suffer from more aggressive lesions (WHO II/III meningioma 6 vs 3, P = 0.154) and presented with longer postoperative hospital stays (17.25 ± 5.8 vs 13.50 ± 3.8, P = 0.009); conversely, while the non-elderly patients experienced more blood loss (P = 0.022) and had more perioperative reoperations (3 vs 1). No significant difference in neurological deficit was detected between the two groups (P = 0.97). After total tumor resection, patients with neurological deficits in both groups can recover during the follow-up period. Conclusion: Among the 106 patients with middle third parasagittal and falx meningiomas in our hospital, elderly patients had larger lesions, presented with more severe PTBE, and had longer postoperative hospital stays than younger patients. Conversely, younger patients had more blood loss and serious complications than elderly patients. Postoperative neurological dysfunction in elderly patients was similar to that in middle-aged and young patients.

The Effect of Pretreatment Potential Resistance to NNRTIs on Antiviral Therapy in Patients With HIV/AIDS.

BACKGROUND: With the increasing coverage of antiretroviral therapy, concerns for the emergence and transmission of HIV drug resistance (HIVDR) are arising. HIVDR was divided into 5 levels: sensitive, potentially resistant, low resistant, intermediate resistant, and high resistant. Most of the articles on HIVDR involved low-level, intermediate-level, and high-level drug resistance to antiretroviral drug, and few articles deal with potential drug resistance. Treatment failure associated with the level of low-level, intermediate-level, and high-level resistance to antiretroviral drug has been reported. However, whether virological failure (VF) is related to potential resistance remains unclear. In this study, we aimed to describe the situation of potential resistance to antiretroviral drug and whether it is related to VF. METHODS: We analyzed the demographic, behavioral information, medical history, and drug resistance-associated mutation data from subjects. Drug resistance mutations at baseline and time of failure in patients suffering VF were detected by using the Vela automated next-generation sequencing platform. The χ2 test or Fisher exact test and logistic regression were used to assess the risk factors that contribute to VF in the potential drug-resistant people. RESULTS: The prevalence of overall pretreatment drug resistance was 7.06% (233/3300), and the prevalence of pretreatment potential resistance was 8.79% (290/3300). All these patients with pretreatment potential first-line drugs resistance showed potential resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), and some of them had potential drug resistance to NNRTIs and NRTIs or NNRTIs and PIs; among these patients, 94.71% (179/189) had V179 D/E mutations. The VF rate of first-line treatment for potentially resistant people is 17.99%. CD4+ T-cell count ≤200 cells/L at antiretroviral therapy initiation are risk factors for the failure of first-line treatment. CONCLUSIONS: The prevalence of potential drug resistance among individuals with HIV and the VF rate of first-line treatment for potential drug-resistant people were high. To better optimize clinical management, prevention, and control of HIV, attention should be devoted to the potential resistance of nonnucleoside drugs.

Clinical predictors for nondiabetic kidney diseases in patients with type 2 diabetes mellitus: a retrospective study from 2017 to 2021.

BACKGROUND: Nondiabetic kidney disease (NDKD), which is prevalent among patients with diabetes mellitus (DM), is considerably different from diabetic kidney disease (DKD) in terms of the pathological features, treatment strategy and prognosis. Although renal biopsy is the current gold-standard diagnostic method, it cannot be routinely performed due to a range of risks. The aim of this study was to explore the predictors for differentiating NDKD from DKD to meet the urgent medical needs of patients who cannot afford kidney biopsy. METHODS: This is a retrospective study conducted by reviewing the medical records of patients with type 2 DM who underwent percutaneous renal biopsy at the Affiliated Hospital of Guizhou Medical University between January 2017 and May 2021. The demographic data, clinical data, blood test results, and pathological examination results of the patients were obtained from their medical records. Multivariate regression analysis was performed to evaluate the predictive factors for NDKD. RESULTS: A total of 244 patients were analyzed. The median age at biopsy was 55 (46, 62) years. Patients diagnosed with true DKD, those diagnosed with NDKD and those diagnosed with NDKD superimposed DKD represented 48.36% (118/244), 45.9% (112/244) and 5.74% (14/244), respectively, of the patient population. Immunoglobulin A nephropathy was the most common type of lesion in those with NDKD (59, 52.68%) and NDKD superimposed DKD (10, 71.43%). Independent predictive indicators for diagnosing NDKD included a DM duration of less than 5 years (odds ratio [OR] = 4.476; 95% confidence interval [CI]: 2.257-8.877; P < 0.001), an absence of diabetic retinopathy (OR = 4.174; 95% CI: 2.049-8.502; P < 0.001), a high RBC count (OR = 1.901; 95% CI: 1.251-2.889; P = 0.003), and a negative of urinary glucose excretion test result (OR = 2.985; 95% CI: 1.474-6.044; P = 0.002).. CONCLUSIONS: A DM duration less than 5 years, an absence of retinopathy, a high RBC count and an absence of urinary glucose excretion were independent indicators for the diagnosis of NDKD, suggesting that patients with NDKD may require a different treatment regimen than those with DKD.

High Levels of CD244 Rather Than CD160 Associate With CD8+ T-Cell Aging.

Aging leads to functional dysregulation of the immune system, especially T cell defects. Previous studies have shown that the accumulation of co-inhibitory molecules plays an essential role in both T cell exhaustion and aging. In the present study, we showed that CD244 and CD160 were both up-regulated on CD8+ T cells of elderly individuals. CD244+CD160- CD8+ T cells displayed the increased activity of ß-GAL, higher production of cytokines, and severe metabolic disorders, which were characteristics of immune aging. Notably, the functional dysregulation associated with aging was reversed by blocking CD244 instead of CD160. Meanwhile, CD244+CD160+ CD8+ T cells exhibited features of exhaustion, including lower levels of cytokine, impaired proliferation, and intrinsic transcriptional regulation, compared to CD244+CD160- population. Collectively, our findings demonstrated that CD244 rather than CD160 acts as a prominent regulator involved in T cell aging, providing a solid therapeutic target to improve disorders and comorbidities correlated to immune system aging.

Non-linear relationship between basal serum albumin concentration and cardiac arrest in critically ill patients with end-stage renal disease: a cross-sectional study.

OBJECTIVES: The aim of our study was to investigate the association between serum albumin concentration and the risk of cardiac arrest in critically ill patients with end-stage renal disease in the intensive care unit (ICU). DESIGN: This was a secondary analysis. SETTING: The Phillip electronic-ICU collaborative database from 2014 to 2015. PARTICIPANTS: This study included 4990 critically ill patients diagnosed with end-stage renal disease. PRIMARY AND SECONDARY OUTCOME MEASURES: The exposure of interest was serum albumin concentration. The outcome variable was cardiac arrest. RESULTS: A non-linear relationship was observed between serum albumin concentration and risk of cardiac arrest, with an inflection point of 3.26 g/dL after adjusting for potential confounders. The effect sizes and the CIs on the left and right sides of the inflection point were 0.88 (0.65 to 1.19) and 0.32 (0.16 to 0.64), respectively. CONCLUSIONS: Within an albumin range of 3.26-5.6 g/dL, each 1 g/dL increase in serum levels is associated with a 68% decrease of the risk of cardiac arrest in critically ill patients with end-stage renal disease.

Altered T-Cell Subsets are Associated with Dysregulated Cytokine Secretion of CD4+ T Cells During HIV Infection.

BACKGROUND: CD4+ T cells play a critical role in the regulation of immunopathogenesis in HIV infection. Previous studies have shown contradictory results of the CD4+ T-cell responses in people living with HIV (PLHIV). METHODS: A cross-sectional study was performed on 40 healthy controls, 134 ART-naïve PLHIV, and 34 individuals who experienced 3-year ART with low baseline CD4 count from 4 August 2016 to 23 January 2019. We determined the frequencies of CD4+ T-cell subsets and described the cytokine secretion pattern of total and subsets of CD4+ T cells in these individuals. RESULTS: We found that CD4+ T cells in PLHIV displayed enhanced secretion of pro-inflammation cytokines and polyfunctionality due to HIV disease progression (r = -0.282, P = 0.0035 for IFN-γ; r = -0.412, P = 0.0002 for TNF-α; r = -0.243, P < 0.0001 for GM-CSF; r = -0.252, P = 0.0093 for IFN-γ+ TNF-α+ cells). However, the altered T-cell subsets, as presented by the loss of naïve cells and expansion of memory/effector population in PLHIV, were associated with discordant results in total and subsets of CD4+ T cells. As major cytokine-producing T subsets, effector/memory CD4 subsets showed impaired cytokine production (P < 0.05). We further demonstrated that 3-year ART treatment could improve CD4 counts by increasing the pool of naïve T cells but could not restore cytokine secretion in CD4+ T-cell subsets (P < 0.05). CONCLUSION: These data identified the impaired capacity of cytokine secretion in CD4+ T-cell subsets due to HIV disease progression, and the altered T-cell subsets were associated with pseudo-elevation of cytokine production in total CD4+ T cells. This study collectively suggested the importance of therapies that can preserve and/or enhance the function of CD4+ T cells in strategies of HIV remission.

Natural killer cell­based immunotherapy for lung cancer: Challenges and perspectives (Review).

Despite the marked success of molecular targeted therapy in lung cancer in this era of personalized medicine, its efficacy has been limited by the presence of resistance mechanisms. The prognosis of patients with lung cancer remains poor, and there is an unmet need to develop more effective therapies to improve clinical outcomes. The increasing insight into the human immune system has led to breakthroughs in immunotherapy and has prompted research interest in employing immunotherapy to treat lung cancer. Natural killer (NK) cells, which serve as the first line of defense against tumors, can induce the innate and adaptive immune responses. Therefore, the use of NK cells for the development of novel lung­cancer immunotherapy strategies is promising. A growing number of novel approaches that boost NK cell antitumor immunity and expand NK cell populations ex vivo now provide a platform for the development of antitumor immunotherapy. The present review outlined the biology of NK cells, summarized the role of NK cells in lung cancer and the effect of the tumor microenvironment on NK cells, highlighted the potential of NK cell­based immunotherapy as an effective therapeutic strategy for lung cancer and discussed future directions.

Partial recovery of disturbed V-J pairing profiles of T-cell receptor in people living with HIV receiving long-term antiretroviral therapy.

Chronic human immunodeficiency virus (HIV) infection not only causes a gradual loss of CD4+ T cells but also leads to a disturbance of the T cell receptor (TCR) repertoire. In people living with HIV (PLWH), monitoring TCR repertoire is challenged by the inconsistency of complementarity determining region 3 (CDR3) and limited cell numbers in clinical samples. Thus, a quantitative method is necessary for monitoring the TCR repertoire in PLWH. We characterized the TCR V-J pairing profile of naïve and memory CD4+ T cells in healthy donors, HIV-infected antiretroviral therapy (ART)-naïve patients and long-term (over 5 years) ART-experienced patients by performing TCR sequencing. We developed a V-J index with 18 parameters which were subdivided into five categories (expression coverage, cumulative percentage of the top tenth percentile, diversity, intra-individual similarity and inter-individual similarity). In ART-naïve patients, 14 of the 18 parameters were significantly altered. Long-term ART recovered ten parameters. The four unrecovered parameters were related to inter-individual similarity. Therefore, these findings indicate that long-term ART could only partially recover TCR V-J pairs and introduce newly impacted V-J pairs. Moreover, these results provide new insights into the V-J pairing of the TCR and into the disturbance of TCR repertoire in HIV infection.

Prevalence and risk factors for bone mineral density changes in antiretroviral therapy-naive human immunodeficiency virus-infected adults: a Chinese cohort study.

BACKGROUND: Studies have reported that low bone mineral density (BMD) is prevalent in human immunodeficiency virus (HIV)-infected patients; however, the factors that contribute to HIV-related BMD changes are yet to be fully understood. Due to the application of dual X-ray absorptiometry (DXA) among a select group of hospitals only, the prevalence and risk factors of low BMD in HIV-infected populations have not been intensively investigated in China. Thus, the aim of our study was to investigate the prevalence of and risk factors associated with BMD changes among antiretroviral therapy (ART)-naive HIV-positive patients in China. METHODS: The assessment of the prevalence of and risk factors associated with BMD changes was conducted among 156 ART-naive HIV-infected patients. Demographic and clinical data, as well as results of fasting blood tests were obtained from patients. Further, all patients underwent DXA scans to determine BMD, which was then used to classify patients with osteopenia/osteoporosis. The risk factors of reduced BMD were then evaluated using binary logistic regression. RESULTS: Among the 156 ART-naive HIV-infected participants, osteopenia and osteoporosis were diagnosed in 48.7% (76/156) and 4.5% (7/156) of patients, respectively. The lumbar spine was most likely to have reduced BMD (49.4% [77/156]), and the proportion of osteopenia in the left hip (32.7% [51/156]) was higher than in the right hip (24.4% [38/156]). In the lumbar spine, bone loss rate in the L1 section (60.9% [95/156]) was the most significant (L2, 53.2% [83/156]; L3, 45.5% [71/156]; L4, 52.6% [82/156]). Further analysis showed that, compared with the neck (26.9% [42/156] in the left, 18.6% [29/156] in the right) and the interior (15.4% [24/156] in the left, 13.5% [21/156] in the right), the trochanter had the greatest probability of reduced BMD (46.2% [72/156] in the left, 28.8% [45/156] in the right). In the risk factor analysis, low body mass index (BMI: <18.5 kg/m2) was positively associated with reduced BMD (Exp (B) = 39.743, 95% confidence interval: 3.234-488.399, P = 0.004), and was specifically positively correlated with BMD values at three sites (r = 0.335 at right hip, r = 0.327 at left hip, r = 0.311 at lumbar spine). CONCLUSION: Reduced BMD was found in the majority of ART-naive HIV-infected patients and BMI was identified as an additional risk factor for reduced BMD. Our results show that BMD reduction was simultaneously present in the left hip, right hip, and lumbar spine among nearly one fifth of patients. Our work highlights the importance of closely monitoring BMD in ART-naive patients and provides a foundation for the clinical intervention of bone demineralization in them.

CD70 contributes to age-associated T cell defects and overwhelming inflammatory responses.

Aging is associated with immune dysregulation, especially T cell disorders, which result in increased susceptibility to various diseases. Previous studies have shown that loss of co-stimulatory receptors or accumulation of co-inhibitory molecules play important roles in T cell aging. In the present study, CD70, which was generally regarded as a costimulatory molecule, was found to be upregulated on CD4+ and CD8+ T cells of elderly individuals. Aged CD70+ T cells displayed a phenotype of over-activation, and expressed enhanced levels of numerous inhibitory receptors including PD-1, 2B4 and LAG-3. CD70+ T cells from elderly individuals exhibited increased susceptibility to apoptosis and high levels of inflammatory cytokines. Importantly, the functional dysregulation of CD70+ T cells associated with aging was reversed by blocking CD70. Collectively, this study demonstrated CD70 as a prominent regulator involved in immunosenescence, which led to defects and overwhelming inflammatory responses of T cells during aging. These findings provide a strong rationale for targeting CD70 to prevent dysregulation related to immunosenescence.

The stage-specific impairment of granulopoiesis in people living with HIV/AIDS (PLWHA) with neutropenia.

Neutropenia and impaired functions were common manifestation in antiretroviral therapy (ART) in both naïve and experienced PLWHA. Granulopoiesis can be divided into two phases: lineage determination and committed granulopoiesis. However, stage-specific impairment of granulopoiesis in PLWHA with neutropenia remains unclear. A total of 48 ART-naïve and 49 ART-experienced PLWHA from 2016 to 2018 were recruited and divided into non-, mild-, and moderate-to-severe-neutropenia groups according to their neutrophil counts. The bone marrow aspirates and peripheral blood were collected and analyzed by multicolor flow cytometry for granulocyte subsets, hematopoietic stem/progenitor cells (HSPC), apoptosis, and emigration and retention of different subsets. Compared with healthy donors, the percentages of circulating segmented neutrophils were significantly decreased along with an increase of immature neutrophils in both groups. ART-naïve patients with moderate to severe neutropenia exhibited decreased proportion and accelerated apoptosis of relative mature segmented neutrophils. In contrast, ART-experienced patients with neutropenia displayed decreased proportion of granulocyte macrophage progenitors, indicating a defect at a stage of lineage determination. Meanwhile, ART-experienced patients with neutropenia also the expression of CXCR4 segmented neutrophils, suggesting an increased retention of segmented neutrophils inn the bone marrow. ART-naïve patients with neutropenia is caused by increased apoptosis of relatively differentiated neutrophils at committed granulopoiesis, whereas impaired lineage determination and enhanced retention of segmented neutrophils contribute to in ART-experienced patients.

Degradation of propranolol by UV-activated persulfate oxidation: Reaction kinetics, mechanisms, reactive sites, transformation pathways and Gaussian calculation.

Contamination with ß-blockers such as propranolol (PRO) poses a potential threat to human health and ecological system. The present study investigated the kinetics and mechanisms of PRO degradation by UV-activated persulfate (UV/PS) oxidation. Here, the experimental results showed that the degradation of PRO followed pseudo-first-order reaction kinetics, the degradation rate constant (kobs) was increased dramatically with increasing PS dosage or decreasing initial PRO concentration. And increasing the initial solution pH could also enhance the degradation efficiency of PRO. Radical scavenging experiments demonstrated that the main radical species was sulfate radicals (SO4•-), with hydroxyl radicals (HO·) playing a less important role. Meanwhile, the second-order rate constants of PRO degradation with SO4•- and HO· were determined to be 1.94 × 1010 M-1 s-1 and 6.77 × 109 M-1 s-1, respectively. In addition, the presence of natural organic matter (NOM) and nitrate anion (NO3-) showed inhibitory effect on PRO degradation, whereas bicarbonate anion (HCO3-) and chlorine anion (Cl-) greatly enhanced the degradation of PRO. Moreover, the transformation products of PRO were identified by applying ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) technique. Molecular orbital calculations were used to estimate the reaction site of PRO with radicals, simultaneously. Hence, the transformation pathways including hydroxylation, dehydration, naphthalene ring opening, and the cleavage of aldehyde groups were proposed. This work enriches the mechanism of PRO degradation under UV/PS system on the basis of results obtained by experimental characterization and Gaussian theoretical calculation.

Study on heterogeneous photocatalytic ozonation degradation of ciprofloxacin by TiO2/carbon dots: Kinetic, mechanism and pathway investigation.

In this study, the objective was mainly focusing on the mechanism investigation of ciprofloxacin (CIP) degradation by photocatalytic ozonation process which carried out by ozone and TiO2 with a low content of carbon-dots (CDs) under simulated sunlight irradiation. The physicochemical properties of the prepared photocatalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscope (SEM) X-ray photoelectron spectroscopy (XPS) and zeta potential. Comprehensive investigation has proven the process to be efficient in the removal of CIP with high yield of reactive species (OH, O2-, h+, etc.). Kinetic model on pH investigation found out a repulsive force between the photocatalysts and CIP intensified with the increasing pH, so did the production rate of hydroxyl radicals (OH), while eventually reached a balance and achieved a maximum degradation rate. The results indicated that the enhancement mechanism was triggered by the photoexcited electron accumulated on CDs and transferred by ozone, resulting in the continuous generation of h+, O3- and O2-. Possible photocatalytic ozonation degradation pathways of CIP were proposed according to the identifications of intermediates using high-resolution accurate-mass spectrometry (HRAM) LC-MS/MS.

A Clinical scoring model to predict mortality in HIV/TB co-infected patients at end stage of AIDS in China: An observational cohort study.

We construct and validate a non-invasive clinical scoring model to predict mortality in HIV/TB patients at end stage of AIDS in China. There were 1,007 HIV/TB patients admitted to Beijing Ditan Hospital from August 2009 to January 2018 included in this study, who were randomly assigned to form derivation cohort and validation cohort. A clinical scoring model was developed based on predictors associated with mortality identified with Cox proportional hazard models. The discrimination and accuracy of model were further validated using the area under the ROC curves. The derivation and validation cohort consisted of 807 and 200 patients in 8:2 ratio, respectively. In derivation cohort, anemia (HGB < 90g/L), tuberculous meningitis, severe pneumonia, hypoalbuminemia, unexplained infections or space-occupying lesions, and malignancies remained independent risk factors of mortality in HIV/TB co-infected patients, and included in this clinical scoring model. The model indicated good discrimination, including AUC = 0.858 (95% CI: 0.782-0.943) in the derivation cohort, and AUC = 0.867 (95% CI: 0.832-0.902) in validation cohort, respectively. The predicted scores were categorized into two groups to predict the mortality: low-risk (0-2 points with mortality with 3.6-9.1%) and high-risk (4-16 points with mortality with 26.42-74.62%), in which 54.55% and 74.62% of patients with score of 5 to 11 and 12-16 were died among high-risk group. Kaplan-Meier curve indicated a significant difference in the cumulative mortality in the two groups by log-rank test (p < 0.001). A clinical scoring model to assess the prognosis in HIV/TB patients at end stage of AIDS was constructed based on simple laboratory and clinical features available at admission, which may be an easy-to-use tool for physicians to evaluate the prognosis and treatment outcome in HIV/TB co-infected patients. The model was also applicable for predicting the death of end-stage HIV/TB patients within a 12 months period after discharge.

Ozonation of ketoprofen with nitrate in aquatic environments: kinetics, pathways, and toxicity.

In this study, nitrate ion (NO3 -) was found to collaborate with ozone thereby accelerating the degradation of ketoprofen. NO3 - was discovered to induce the generation of hydroxyl radicals (·OH), which was crucial to the decomposition of PPCPs in wastewater treatment plants. Kinetic studies on the decomposition of ketoprofen were investigated under different concentrations of NO3 -. The impact mechanisms and degradation by-products were experimentally determined. The results revealed that all reactions fitted the pseudo-first-order kinetic model well. The presence of NO3 - had the capacity to accelerate the ozonation of ketoprofen. The reaction by-products were evaluated by UPLC-Q-TOF-MS, and a total of five intermediates generated via the ozonation of ketoprofen were assessed. The transformation pathways were concluded to be hydroxylation, nitration, and debenzophenone and ketonized reactions. Additionally, the toxicity of the by-products was evaluated by employing Chlorella and Daphnia magna.