The glycolytic enzyme PFKFB3 drives kidney fibrosis through promoting histone lactylation-mediated NF-κB family activation.

Persistently elevated glycolysis in kidney has been demonstrated to promote chronic kidney disease (CKD). However, the underlying mechanism remains largely unclear. Here, we observed that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key glycolytic enzyme, was remarkably induced in kidney proximal tubular cells (PTCs) following ischemia-reperfusion injury (IRI) in mice, as well as in multiple etiologies of patients with CKD. PFKFB3 expression was positively correlated with the severity of kidney fibrosis. Moreover, patients with CKD and mice exhibited increased urinary lactate/creatine levels and kidney lactate, respectively. PTC-specific deletion of PFKFB3 significantly reduced kidney lactate levels, mitigated inflammation and fibrosis, and preserved kidney function in the IRI mouse model. Similar protective effects were observed in mice with heterozygous deficiency of PFKFB3 or those treated with a PFKFB3 inhibitor. Mechanistically, lactate derived from PFKFB3-mediated tubular glycolytic reprogramming markedly enhanced histone lactylation, particularly H4K12la, which was enriched at the promoter of NF-κB signaling genes like Ikbkb, Rela, and Relb, activating their transcription and facilitating the inflammatory response. Further, PTC-specific deletion of PFKFB3 inhibited the activation of IKKß, I κ B α, and p65 in the IRI kidneys. Moreover, increased H4K12la levels were positively correlated with kidney inflammation and fibrosis in patients with CKD. These findings suggest that tubular PFKFB3 may play a dual role in enhancing NF-κB signaling by promoting both H4K12la-mediated gene transcription and its activation. Thus, targeting the PFKFB3-mediated NF-κB signaling pathway in kidney tubular cells could be a novel strategy for CKD therapy.

Immunophenotypic clustering in paediatric acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a highly heterogeneous disease, exhibiting diverse subtypes according to the characteristics of tumour cells. The immunophenotype is one of the aspects acquired routinely through flow cytometry in the diagnosis of AML. Here, we characterized the antigen expression in paediatric AML cases across both morphological and molecular genetic subgroups. We discovered a subgroup of patients with unfavourable prognosis that can be immunologically characterized, irrespective of morphological FAB results or genetic aberrations. Cox regression analysis unveiled key antigens influencing the prognosis of AML patients. In terms of underlying genotypes, we observed that the antigenic profiles and outcomes of one specific group, primarily composed of CBFA2T3::GLIS2 and FUS::ERG, were analogous to the reported RAM phenotype. Overall, our data highlight the significance of immunophenotype to tailor treatment for paediatric AML.

High-dose methotrexate pharmacokinetics and its impact on prognosis of paediatric acute lymphoblastic leukaemia patients: A population pharmacokinetic study.

This study delivers a comprehensive evaluation of the efficacy and pharmacokinetics of high-dose methotrexate (HDMTX) in a large cohort of Chinese paediatric acute lymphoblastic leukaemia patients. A total of 533 patients were included in the prognostic analysis. An association was observed between lower steady-state MTX concentrations (<56 µmol/L) and poorer outcomes in intermediate-/high-risk (IR/HR) patients. Subgroup analysis further revealed that this relationship between concentrations and prognosis was even more pronounced in patients with MLL rearrangements. In contrast, such an association did not emerge within the low-risk patient group. Additionally, utilizing population pharmacokinetic modelling (6051 concentrations from 815 patients), we identified the significant impact of physiological maturation, estimated glomerular filtration rate, sex and concurrent dasatinib administration on MTX pharmacokinetics. Simulation-based recommendations include a reduced dosage regimen for those with renal insufficiency and a specific 200 mg/kg dosage for infants under 1 year. The findings underscore the critical role of HDMTX in treating IR/HR populations and call for a reassessment of its application in lower-risk groups. An individualized pharmacokinetic dosage regimen could achieve the most optimal results, ensuring the largest proportion of steady-state concentrations within the optimal range.

A noise robust sparse time-frequency representation method for measuring underwater gas leakage rate.

Passive acoustic monitors analyze sound signals emitted by seafloor gas bubbles to measure leakage rates. In scenarios with low-flux gas leaks, individual bubble sounds are typically non-overlapping. Measurement methods for these bubble streams aim to estimate the frequency peak of each bubble sound, which correlates with the bubble's size. However, the presence of ocean ambient noise poses challenges to accurately estimating these frequency peaks, thereby affecting the measurement of gas leakage rates in shallow sea environments using passive acoustic monitors. To address this issue, we propose a robust measurement method that includes a noise-robust sparse time-frequency representation algorithm and an adaptive thresholding approach for detecting bubble frequencies. We demonstrate the effectiveness of our proposed method using experimental data augmented with ocean ambient noise and ship-transit noise recorded from a bay area.

Recent Advances in Imaging Agents Anchored with pH (Low) Insertion Peptides for Cancer Theranostics.

The acidic extracellular microenvironment has become an effective target for diagnosing and treating tumors. A pH (low) insertion peptide (pHLIP) is a kind of peptide that can spontaneously fold into a transmembrane helix in an acidic microenvironment, and then insert into and cross the cell membrane for material transfer. The characteristics of the acidic tumor microenvironment provide a new method for pH-targeted molecular imaging and tumor-targeted therapy. As research has increased, the role of pHLIP as an imaging agent carrier in the field of tumor theranostics has become increasingly prominent. In this paper, we describe the current applications of pHLIP-anchored imaging agents for tumor diagnosis and treatment in terms of different molecular imaging methods, including magnetic resonance T1 imaging, magnetic resonance T2 imaging, SPECT/PET, fluorescence imaging, and photoacoustic imaging. Additionally, we discuss relevant challenges and future development prospects.

New method of internal fixation in laparoscopic Tenckhoff catheter placement.

BACKGROUND: Despite obvious advantages of peritoneal dialysis (PD), mechanical complications are responsible for the failure of PD at early stage. Suture fixation in laparoscopic PD catheter method could reduce mechanical complications. In our study, a simple method to fix PD catheter was developed. METHODS: Tenckhoff catheter placement was performed in 49 consecutive patients. In the technique, only two trocars were used. With the help of syringe needle and forceps, a loop of silk was prepared at the abdominal wall. The PD catheter was thread through the loop. The silk ligature was tied subcutaneously keeping the catheter suspended from the abdominal wall. Primary outcomes were catheter-related complications. Secondary outcomes were 6-month catheter survival rates and death within 30 days. Data were analyzed retrospectively. RESULTS: The average operation time was 49.7 ± 15.8 min. Minimum follow-up time was 6 months. No catheter displacement or hernia was detected. One patient had omental wrapping after silk suture rupture, 2 patients had outflow obstruction, and 3 patients had leakage. No one died within 30 days postoperatively. Catheter survival was 95.8% at 6 months. CONCLUSIONS: The method we described greatly reduced the risk of catheter displacement and omental wrap. Also, the required instrument and laparoscopic skill were simple.

Association between serum chloride levels with mortality in incident peritoneal dialysis patients.

BACKGROUND AND AIMS: Lower serum chloride (Cl) levels have been associated with excess mortality in pre-dialysis chronic kidney disease patients. However, the relationship between serum Cl levels and clinical outcomes in continuous ambulatory peritoneal dialysis (CAPD) patients is unclear. METHODS AND RESULTS: In this retrospective cohort study, we enrolled 1656 eligible incident patients undergoing CAPD from 2006 to 2013, and followed until December 2018. Cox regression analyses were used to examine the association between baseline and time-varying serum Cl levels and mortality. During a median follow-up of 46 months, 503 patients (30.4%) died. In analyses of baseline serum Cl, the adjusted hazard ratios (HR) for tertile 1 (<100.0 mmol/L), tertile 2 (100.0-103.0 mmol/L) versus tertile 3 (>103.0 mmol/L) were 2.34 [95% confidence interval (CI) 1.43-3.82] and 1.73 (95% CI 1.24-2.42) for all-cause mortality, 2.86 (95% CI 1.47-5.56) and 1.90 (95% CI 1.19-3.02) for cardiovascular disease (CVD) mortality, respectively. And a linear relationship was observed between serum Cl and mortality. Further, the inverse association between serum Cl and CVD mortality was particularly accentuated in the patients who were ≥50 years or with a history of diabetes. Similarly, lower time-varying serum Cl levels were also associated with a significant increased risk of all-cause and CVD death. CONCLUSION: Lower serum Cl levels predicted higher risk of all-cause and CVD mortality in CAPD patients.

Baicalein protects renal tubular epithelial cells againsthypoxia-reoxygenation injury.

BACKGROUND: To investigate the protective effects and mechanism of baicalein (BAI), a naturally occurring flavonoid, against hypoxia-reoxygenation (HR) injury in renal tubular epithelial cells (HK-2). METHODS: Cultured human renal proximal tubular cell line HK-2 was exposed to 24 h of hypoxia (5% CO2, 1% O2, and 94% N2), followed by 12 h of reoxygenation (5% CO2, 21% O2, and 74% N2). HK-2 cells were divided into three groups: control, HR, and HR-BAI (0.3 µg/ml). Reactive oxygen species (ROS) were measured and cell apoptosis was analyzed by flow cytometry and morphology. ELISAs were performed to determine the levels of IL-1, intercellular adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1). IL-1ß, ICAM-1, and MCP-1 mRNA levels were determined by real-time quantitative PCR. RESULTS: HK-2 cells that underwent HR exhibited increases in IL-1ß expression by 0.94%, ROS by 0.59%, ICAM-1 expression by 0.8%, and MCP-1 expression by 1.2%. Moreover, HK-2 cell apoptosis was increased after HR (p < .05). Compared with the HR group, BAI treatment reduced the elevation of oxidative stress (ROS) by 0.76%, as well as HR-mediated induction of IL-1ß and apoptosis of HK2 cells. Protein and mRNA levels of ICAM-1 and MCP-1 were also reduced. CONCLUSIONS: BAI protects renal tubular epithelial cells from HR injury by reducing inflammatory cytokine expression and oxidative stress.

Efficacy comparison of atorvastatin versus rosuvastatin on blood lipid and microinflammatory state in maintenance hemodialysis patients.

INTRODUCTION: To investigate the effect of Atorvastatin (ATO) and Rosuvastatin (ROS) on blood lipid, high sensitivity CRP (hs-CRP), interleukin-6 (IL-6), albumin (ALB), prealbumin (PA), and transferring (TF) in maintenance hemodialysis (MHD) patients. METHODS: Eighty MHD patients were enrolled and divided into two groups: ROS and ATO. Patients in Group ROS (n = 38) received ROS (10 mg/day), and those in group ATO (n = 42) received ATO (20 mg/day) for 12 weeks, respectively. FINDINGS: Administration of ROS and ATO both significantly reduced the concentrations of TC, LDL-C, TG, hs-CRP, and IL-6, but increased high-density lipoproteincholesterol (HDL-C), ALB, PA, and TF levels. Furthermore, the level of LDL-C decreased more significantly with inhibited microinflammation and improved nutrition situation in ROS group compared with ATO group. ATO and ROS not only decreased blood lipid levels but also inhibited the microinflammatory state and improved nutrition situation in MHD patients. DISCUSSION: The results have shown that ROS is better than ATO in the treatment of MHD patients.

Protective effect of baicalein on renal ischemia/reperfusion injury in the rat.

OBJECTIVE: To investigate the protective effect and the mechanism of baicalein (Bai) in rats with renal ischemia-reperfusion injury (RIRI). METHODS: Twenty-four male Sprague-Dawley rats were divided into three groups: sham, IR, and IR+Bai. Bai was administered by tail vein injection (30 mg/kg) 30 min before reperfusion in the IR+Bai group. The IR group and sham group received saline vehicle via the intravenous route. RESULTS: Rats that underwent RIRI exhibited renal functional impairment, histological changes, significantly increased advanced oxidation protein product (AOPP) and malondialdehyde (MDA) levels (p<0.01), and ICAM-1 and MCP-1 protein and mRNA expression were significantly upregulated (p<0.01). Administration of Bai reduced AOPP and MDA levels, significantly inhibited expression of inflammatory factors (p<0.05), and markedly improved renal function. CONCLUSION: Bai promotes the recovery of renal function in established acute RIRI, and alleviates kidney injury in a rat model.

Atorvastatin treatment attenuates renal injury in an experimental model of ischemia-reperfusion in rats.

BACKGROUND: Recent studies in animal models have shown that statins can protect against renal failure independent of their lipid-lowering actions, and there is also an association between statin use and improved renal function after suprarenal aortic clamping. We investigated the hypothesis that post-ischemic acute renal failure could be ameliorated with atorvastatin (ATO) treatment and the possible molecular mechanisms in a model of ischemia-reperfusion (IR) in rats. METHODS: Twenty-four male Sprague-Dawley rats were divided into three groups: sham, IR, and IR + ATO. ATO was given by a single intraperitoneal injection (10 mg/kg) 30 min before reperfusion in the IR + ATO group. The IR group and sham group received saline vehicle via the intraperitoneal route. RESULTS: After 24 h of IR, serum creatinine levels were increased in the IR group compared with the sham group (p < 0.001). ATO treatment reduced the elevation of serum creatinine level by 18% (p < 0.05) and significantly increased the creatinine clearance rate (p < 0.001). Concentrations of advanced oxidation protein products and malondialdehyde were reduced in the ATO group, approaching levels observed in sham-group rats. ATO treatment alleviated pathological changes in renal tubular cells. Protein and mRNA levels of intercellular adhesion molecule-1 and monocyte chemotactic protein-1 were reduced significantly. CONCLUSIONS: These data suggest that direct protection of injured kidneys by ATO was possible even though the drug was injected 30 min before reperfusion, and that ATO may reduce IR injury by anti-inflammatory effects and by reducing oxidation stress.

Application of biological agents in the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been traditionally treated using glucocorticoids and immunosuppressants. However, these treatment modes are associated with high recurrence AAV rates and adverse reactions. Therefore, treatment strategies for AAV need to be urgently optimized. The efficacy and safety of biological agents in the treatment of vasculitis have been clinically validated. This review comprehensively summarizes the evidence-based support for the clinical use of existing biological agents in AAV. The findings reveal that multiple biological agents not only effectively reduce the adverse reactions associated with glucocorticoids and immunosuppressants but also demonstrate significant therapeutic efficacy. Notably, rituximab, an anti-CD20 antibody, has emerged as a first-line treatment option for AAV. Mepolizumab has shown promising results in relapsed and refractory eosinophilic granulomatosis with polyangiitis. Other biological agents targeting cytokines, complement, and other pathways have also demonstrated clinical benefits in recent studies. The widespread application of biological agents provides new insights into the treatment of AAV and is expected to drive further clinical research. These advancements not only improve patient outcomes but also offer more possibilities and hope in the field of AAV treatment.

Effects of cell-free DNA on kidney disease and intervention strategies.

Kidney disease has become a global public health problem. Patients with end-stage kidney disease must rely on dialysis or undergo renal transplantation, placing heavy burdens on their families and society. Therefore, it is important to develop new therapeutic targets and intervention strategies during early stages of chronic kidney disease. The widespread application of liquid biopsy has led to an increasing number of studies concerning the roles of cell-free DNA (cfDNA) in kidney disease. In this review, we summarize relevant studies concerning the roles of cfDNA in kidney disease and describe various strategies for targeted removal of cfDNA, with the goal of establishing novel therapeutic approaches for kidney disease.

The Spermine Oxidase/Spermine Axis Coordinates ATG5-Mediated Autophagy to Orchestrate Renal Senescence and Fibrosis.

Decreased plasma spermine levels are associated with kidney dysfunction. However, the role of spermine in kidney disease remains largely unknown. Herein, it is demonstrated that spermine oxidase (SMOX), a key enzyme governing polyamine metabolism, is predominantly induced in tubular epithelium of human and mouse fibrotic kidneys, alongside a reduction in renal spermine content in mice. Moreover, renal SMOX expression is positively correlated with kidney fibrosis and function decline in patients with chronic kidney disease. Importantly, supplementation with exogenous spermine or genetically deficient SMOX markedly improves autophagy, reduces senescence, and attenuates fibrosis in mouse kidneys. Further, downregulation of ATG5, a critical component of autophagy, in tubular epithelial cells enhances SMOX expression and reduces spermine in TGF-ß1-induced fibrogenesis in vitro and kidney fibrosis in vivo. Mechanically, ATG5 readily interacts with SMOX under physiological conditions and in TGF-ß1-induced fibrogenic responses to preserve cellular spermine levels. Collectively, the findings suggest SMOX/spermine axis is a potential novel therapy to antagonize renal fibrosis, possibly by coordinating autophagy and suppressing senescence.

circRNAs as prognostic markers in pediatric acute myeloid leukemia.

Circular RNAs (circRNAs) arise from precursor mRNA processing through back-splicing and have been increasingly recognized for their functions in various cancers including acute myeloid leukemia (AML). However, the prognostic implications of circRNA in AML remain unclear. We conducted a comprehensive genome-wide analysis of circRNAs using RNA-seq data in pediatric AML. We revealed a group of circRNAs associated with inferior outcomes, exerting effects on cancer-related pathways. Several of these circRNAs were transcribed directly from genes with established functions in AML, such as circRUNX1, circWHSC1, and circFLT3. Further investigations indicated the increased number of circRNAs and linear RNAs splicing were significantly correlated with inferior clinical outcomes, highlighting the pivotal role of splicing dysregulation. Subsequent analysis identified a group of upregulated RNA binding proteins in AMLs associated with high number of circRNAs, with TROVE2 being a prominent candidate, suggesting their involvement in circRNA associated prognosis. Through the integration of drug sensitivity data, we pinpointed 25 drugs that could target high-risk AMLs characterized by aberrant circRNA transcription. These findings underscore prognostic significance of circRNAs in pediatric AML and offer an alternative perspective for treating high-risk cases in this malignancy.

Gas-Mediated Intestinal Microbiome Regulation Prompts the Methanol Extract of Schizonepetae Spica to Relieve Colitis.

Intestinal dysbiosis plays an important role in the pathogenesis of colitis (UC). Schizonepetae Herba can achieve anti-inflammatory effects as a medicine and food homologous vegetable. Luteolin, eriodictyol, fisetin, and kaempferol are the main anti-inflammatory active compounds obtained through mass spectrometry from the methanol extract of Schizonepetae Spica (JJSM). JJSM intervention resulted in attenuated weight loss, high disease-activity-index score, colon length shortening and colonic pathological damage in DSS-induced colitis mice. Interestingly, hydrogen sulfide (H2S) was inhibited remarkably, which is helpful to elucidate the relationship between active substance and intestinal flora. Furthermore, JJSM administration improved intestinal flora with down-regulating the abundance of harmful bacteria such as Clostridiales and Desulfovibrio and up-regulating the abundance of beneficial bacteria such as Muribaculaceae and Ligolactobacillus and enhanced the production of SCFAs. It is worth noticing that Desulfovibrio is related to the production of intestinal gas H2S. The elevated levels of Desulfovibrio and H2S will hasten the onset of colitis, which is a crucial risk factor for colitis. The results displayed that JJSM could considerably ameliorate colitis by rebuilding H2S-related intestinal flora, which provides a new therapeutic strategy for Schizonepetae Spica to be utilized as a functional food and considered as an emerging candidate for intestinal inflammation.

Prediction and potential risk factors for electronic cigarette use behaviors among adolescents: a pilot study in Chiayi, Taiwan.

Introduction: Electronic cigarette (e-cigarette) use among adolescents has become increasingly common; therefore, effectively reducing adolescent e-cigarette use is an urgent issue. We aimed to predict and identify potential factors related to adolescent e-cigarette use behaviors. Methods: This cross-sectional study was conducted using anonymous questionnaires given to Taiwanese high school students in 2020. Approximately 1,289 adolescent students completed questions on e-cigarette use, personal characteristics, family environment, and substances used. We performed multivariate logistic regression analyses to assess the model's predictive performance in terms of the area under the receiver operating characteristic curve. Results: We found that 9.3% of adolescent students used e-cigarettes. Tobacco smoking, close friends' reactions to e-cigarette use, and the use of other substances were independent risk factors for adolescent e-cigarette use. Furthermore, relative to tobacco nonuse, tobacco use and tobacco smoking dependence had odds ratios of 76.49 and 113.81, respectively. The predictive accuracy of adolescent e-cigarette use from personal characteristics, family environment, and substance use status was 73.13, 75.91, and 93.80%, respectively. Conclusion: The present study highlights the need for early prevention of e-cigarette use among adolescents, particularly those with a history of using tobacco and other substances and those who have close friends with positive attitudes towards e-cigarette use.

Therapeutic mechanism of baicalein in peritoneal dialysis-associated peritoneal fibrosis based on network pharmacology and experimental validation.

Baicalein (5,6,7-trihydroxyflavone) is a traditional Chinese medicine with multiple pharmacological and biological activities including anti-inflammatory and anti-fibrotic effects. However, whether baicalein has a therapeutic impact on peritoneal fibrosis has not been reported yet. In the present study, network pharmacology and molecular docking approaches were performed to evaluate the role and the potential mechanisms of baicalein in attenuating peritoneal dialysis-associated peritoneal fibrosis. The results were validated in both animal models and the cultured human mesothelial cell line. Nine intersection genes among baicalein targets and the human peritoneum RNA-seq dataset including four encapsulating peritoneal sclerosis samples and four controls were predicted by network analysis. Among them, MMP2, BAX, ADORA3, HIF1A, PIM1, CA12, and ALOX5 exhibited higher expression in the peritoneum with encapsulating peritoneal sclerosis compared with those in the control, which might be crucial targets of baicalein against peritoneal fibrosis. Furthermore, KEGG and GO enrichment analyses suggested that baicalein played an anti-peritoneal fibrosis role through the regulating cell proliferation, inflammatory response, and AGE-RAGE signaling pathway. Moreover, molecular docking analysis revealed a strong potential binding between baicalein and MMP2, which was consistent with the predictive results. Importantly, using a mouse model of peritoneal fibrosis by intraperitoneally injecting 4.25% glucose dialysate, we found that baicalein treatment significantly attenuated peritoneal fibrosis, as evident by decreased collagen deposition, protein expression of α-SMA and fibronectin, and peritoneal thickness, at least, by reducing the expression of MMP2, suggesting that baicalein may have therapeutic potential in suppressing peritoneal dialysis-related fibrosis.

Systemic Immune-Inflammation Index Was Significantly Associated with All-Cause and Cardiovascular-Specific Mortalities in Patients Receiving Peritoneal Dialysis.

Purpose: The prognosis of patients receiving peritoneal dialysis (PD) is associated with inflammation. Systemic immune-inflammation index (SII) is one of inflammatory markers, and the role in predicting clinical outcomes in PD patients is unclear. We aimed to investigate the relationship between the SII and all-cause and cardiovascular-specific mortalities in patients undergoing PD. Patients and Methods: A total of 1419 PD patients from the First Affiliated Hospital of Sun Yat-sen University between January 1, 2007 and December 31, 2019 were retrospectively included at baseline, and the patients were followed up until November 31, 2021. SII was calculated as platelet count×neutrophil count/lymphocyte count. Kaplan-Meier curves and Cox proportional hazards regression models were used to determine the relationship between SII levels and all-cause and cardiovascular-specific mortalities. Results: During follow-up (median period was 42 months), 321 patients died (171 died of cardiovascular disease). With adjustment for the potential confounding factors, each 1-SD increase in the SII was associated with 20.2% increase in all-cause mortality (hazard ratio [HR]: 1.202, 95% confidence interval [CI]: 1.088-1.327, P<0.001) and 28.0% increase in cardiovascular-specific mortality (HR: 1.280, 95% CI: 1.126-1.456, P<0.001). High SII (vs low SII) was significantly associated with increased risks of all-cause mortality (HR: 1.391, 95% CI: 1.066-1.815, P-value: 0.015) and cardiovascular-specific mortality (HR: 1.637, 95% CI: 1.185-2.261, P-value: 0.003). Subgroups analyses showed similar results for those younger than 65-year-old only. Conclusion: Elevated SII level was independently associated with increased risks of all-cause and cardiovascular-specific mortalities in PD patients, especially for those younger than 65-year-old.

Polyglycerol-Amine Covered Nanosheets Target Cell-Free DNA to Attenuate Acute Kidney Injury.

Increased levels of circulating cell-free DNA (cfDNA) are associated with poor clinical outcomes in patients with acute kidney injury (AKI). Scavenging cfDNA by nanomaterials is regarded as a promising remedy for cfDNA-associated diseases, but a nanomaterial-based cfDNA scavenging strategy has not yet been reported for AKI treatment. Herein, polyglycerol-amine (PGA)-covered MoS2 nanosheets with suitable size are synthesized to bind negatively charged cfDNA in vitro, in vivo and ex vivo models. The nanosheets exhibit higher cfDNA binding capacity than polymer PGA and PGA-based nanospheres owing to the flexibility and crimpability of their 2D backbone. Moreover, with low cytotoxicity and mild protein adsorption, the nanosheets effectively reduced serum cfDNA levels and predominantly accumulated in the kidneys to inhibit the formation of neutrophil extracellular traps and renal inflammation, thereby alleviating both lipopolysaccharide and ischemia-reperfusion induced AKI in mice. Further, they decreased the serum cfDNA levels in samples from AKI patients. Thus, PGA-covered MoS2 nanosheets can serve as a potent cfDNA scavenger for treating AKI and other cfDNA-associated diseases. In addition, this work demonstrates the pivotal feature of a 2D sheet-like structure in the development of the cfDNA scavenger, which can provide a new insight into the future design of nanoplatforms for modulating inflammation.