Near-infrared fluorescent probe for the imaging of viscosity in fatty liver mice and valuation of drug efficacy.

Fatty liver disease affects at least 25 percent of the population worldwide and is a severe metabolic syndrome. Viscosity is closely related to fatty liver disease, so it is urgent to develop an effective tool for monitoring viscosity. Herein, a NIR fluorescent probe called MBC-V is developed for imaging viscosity, consisting of dimethylaniline and malonitrile-benzopyran. MBC-V is non-fluorescent in low viscosity solutions due to intramolecular rotation. In high viscosity solution, the intramolecular rotation of MBC-V is suppressed and the fluorescence is triggered. MBC-V has long emission wavelength at 720 nm and large Stokes shift about 160 nm. Moreover, MBC-V can detect changes in cell viscosity in fatty liver cells, and can image the therapeutic effects of drug in fatty liver cells. By taking advantage of NIR emission, MBC-V can be used as an imaging tool for fatty liver disease and a way to evaluate the therapeutic effect of drug for fatty liver disease.

Prevalence of metabolic syndrome among patients with hepatocellular carcinoma of different etiologies: a retrospective study.

AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

Classification of congenital cataracts based on multidimensional phenotypes and its association with visual outcomes.

AIM: To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes. METHODS: Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited. Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients' medical records. A hierarchical cluster analysis was performed. The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts. RESULTS: A total of 164 children (299 eyes) were divided into two clusters based on their ocular features. Cluster 1 (96 eyes) had a shorter axial length (mean±SD, 19.44±1.68 mm), a low prevalence of macular abnormalities (1.04%), and no retinal abnormalities or posterior cataracts. Cluster 2 (203 eyes) had a greater axial length (mean±SD, 20.42±2.10 mm) and a higher prevalence of macular abnormalities (8.37%), retinal abnormalities (98.52%), and posterior cataracts (4.93%). Compared with the eyes in Cluster 2 (57.14%), those in Cluster 1 (71.88%) had a 2.2 times higher chance of good best-corrected visual acuity [<0.7 logMAR; OR (95%CI), 2.20 (1.25-3.81); P=0.006]. CONCLUSION: This retrospective study categorizes congenital cataracts into two distinct clusters, each associated with a different likelihood of visual outcomes. This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit, thereby making strides toward precision medicine in the field of congenital cataracts.

Gate-defined quantum point contacts in a germanium quantum well.

We report an experimental study of quantum point contacts defined in a high-quality strained germanium quantum well with layered electric gates. At a zero magnetic field, we observed quantized conductance plateaus in units of 2e2/h. Bias-spectroscopy measurements reveal that the energy spacing between successive one-dimensional subbands ranges from 1.5 to 5 meV as a consequence of the small effective mass of the holes and the narrow gate constrictions. At finite magnetic fields perpendicular to the device plane, the edges of the conductance plateaus get split due to the Zeeman effect and Landé g factors were estimated to be ∼6.6 for the holes in the germanium quantum well. We demonstrate that all quantum point contacts in the same device have comparable performances, indicating a reliable and reproducible device fabrication process. Thus, our work lays a foundation for investigating multiple forefronts of physics in germanium-based quantum devices that require quantum point contacts as building blocks.

The use of longitudinal CT-based radiomics and clinicopathological features predicts the pathological complete response of metastasized axillary lymph nodes in breast cancer.

BACKGROUND: Accurate assessment of axillary status after neoadjuvant therapy for breast cancer patients with axillary lymph node metastasis is important for the selection of appropriate subsequent axillary treatment decisions. Our objectives were to accurately predict whether the breast cancer patients with axillary lymph node metastases could achieve axillary pathological complete response (pCR). METHODS: We collected imaging data to extract longitudinal CT image features before and after neoadjuvant chemotherapy (NAC), analyzed the correlation between radiomics and clinicopathological features, and developed models to predict whether patients with axillary lymph node metastasis can achieve axillary pCR after NAC. The clinical utility of the models was determined via decision curve analysis (DCA). Subgroup analyses were also performed. Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and was validated using the calibration plots. RESULTS: A total of 549 breast cancer patients with metastasized axillary lymph nodes were enrolled in this study. 42 independent radiomics features were selected from LASSO regression to construct a logistic regression model with clinicopathological features (LR radiomics-clinical combined model). The AUC of the LR radiomics-clinical combined model prediction performance was 0.861 in the training set and 0.891 in the testing set. For the HR + /HER2 - , HER2 + , and Triple negative subtype, the LR radiomics-clinical combined model yields the best prediction AUCs of 0.756, 0.812, and 0.928 in training sets, and AUCs of 0.757, 0.777 and 0.838 in testing sets, respectively. CONCLUSIONS: The combination of radiomics features and clinicopathological characteristics can effectively predict axillary pCR status in NAC breast cancer patients.

Elevated Saliva Pepsin Concentration as a Risk Factor for Asthma in Children with Allergic Rhinitis: A Preliminary Study.

Objective: This study aimed to explore whether saliva pepsin concentration (SPC) could be regarded as a risk factor for the occurrence and unfavorable control of asthma in children with allergic rhinitis. Methods: A prospective study was conducted on a group of 20 consecutive children newly diagnosed with allergic rhinitis and asthma (referred to as the asthma group). All these children underwent fractional exhaled nitric oxide (FeNO) measurement, lung function tests, and assessment of asthma control using the 7-item Childhood Asthma Control Test (C-ACT) score. Simultaneously, a control group consisting of 20 children with simple allergic rhinitis, matched for baseline characteristics, was included. SPC measurement was performed in the two groups. Results: The SPC value was significantly higher in the asthma group than that in the control group (165.0 ± 82.8 ng/mL vs 68.4 ± 34.5 ng/mL) (P < 0.001). In the asthma group, SPC was independently associated with FeNO, the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), and forced expiratory flow at 50% and 75% of FVC (FEF50 and FEF75) (all P < 0.05). The severity of nasal symptoms evaluated by the visual analogue scale (N-VAS) was independently associated with FEF75, the maximal mid-expiratory flow (MMEF), and C-ACT score (P < 0.05). Conclusion: Direct pepsin exposure and uncontrolled nasal symptoms may play crucial roles in the pathogenesis and progression of childhood allergic asthma. The SPC value can be considered as a risk factor for asthma in children with allergic rhinitis.

Erector spinae plane block versus quadratus lumborum block for postoperative analgesia after laparoscopic nephrectomy: A randomized controlled trial.

STUDY OBJECTIVE: We compared the analgesic effects of erector spinae plane block versus quadratus lumborum block following laparoscopic nephrectomy. DESIGN: A randomized controlled trial. SETTING: A tertiary hospital in Beijing, China. PATIENTS: Patients scheduled for elective laparoscopic nephrectomy. INTERVENTIONS: A total of 110 patients were enrolled and randomized to receive either erector spinae plane block (n = 55) or quadratus lumborum block (n = 55) under ultrasound guidance. Patient-controlled sufentanil analgesia was provided after surgery. MEASUREMENTS: Our primary outcome was cumulative opioid consumption within 24 h after surgery. Secondary outcomes included postoperative pain intensity, subjective sleep quality, and quality of recovery. MAIN RESULTS: All 110 patients (mean 53 years, 57.3% female) were included in the intention-to-treat analysis. Cumulative sufentanil equivalent within 24 h was lower in patients given erector spinae plane block (median 13 µg, interquartile range 4 to 33) than in those given quadratus lumborum block (median 25 µg, interquartile range 13 to 39; median difference - 8 µg, 95% CI -15 to 0, P = 0.041). Pain intensity (0-10 range where 0 = no pain and 10 = the worst pain) at 2, 6, 12, and 24 h after surgery was lower with erector spinae plane block (at rest: median differences -1 point, all P ≤ 0.009; with movement: median differences -2 to -1 points, all P < 0.001). Subjective sleep quality on the night of surgery (the Richards-Campbell Sleep Questionnaire: 0-100 range, higher score better; median difference 12, 95% CI 2 to 23, P = 0.018) and quality of recovery at 24 h (the Quality of Recovery-15: 0-150 range, higher score better; median difference 8, 95% CI 2 to 15, P = 0.012) were better with erector spinae plane block. No procedure-related adverse events occurred. CONCLUSIONS: Compared with quadratus lumborum block, erector spinae plane block provided better analgesia as manifested by lower opioid consumption and pain intensity for up to 24 h after laparoscopic nephrectomy.

Deliberate self-harm among pediatric psychiatric inpatients in China: A single-center retrospective study.

BACKGROUND: For children and adolescents, deliberate self-harm (DSH) is becoming a mental health problem of concern. Despite several studies on the prevalence and factors of DSH in the world, there is little information on DSH among children and adolescents in China. This study explores the prevalence, types, associated risk factors and tendency of DSH in pediatric psychiatric inpatients in China. AIM: To understand the situation of DSH among hospitalized children and adolescents and its related factors. METHODS: In this study, we retrospectively studied 1414 hospitalized children and adolescents with mental illness at Xiamen Mental Health Center from 2014 to 2019, extracted the demographic and clinical data of all patients, and analyzed clinical risk factors of DSH. RESULTS: A total of 239 (16.90%) patients engaged in at least one type of DSH in our study. Cutting (n = 115, 48.12%) was the most common type of DSH. Females (n = 171, 71.55%) were more likely to engage in DSH than males (n = 68, 28.45%). DSH was positively associated with depressive disorders [OR = 3.845 (2.196-6.732); P < 0.01], female [OR = 2.536 (1.815-3.542); P < 0.01], parental marital status [OR = 5.387 (2.254-12.875); P < 0.01] and negative family history of psychiatric illness [OR = 7.767 (2.952-20.433); P < 0.01], but not with occupation, substance use and history of physical abuse. CONCLUSION: Our findings suggest that for patients with depression, females, an abnormal marriage of parents, and no history of mental illness, attention should be paid to the occurrence of DSH.

STING-dependent trained immunity contributes to host defense against Clostridium perfringens infection via mTOR signaling.

Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING­deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.

Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

Palladium-Catalyzed Asymmetric Decarboxylation of 5-Vinyloxazolidine-2,4-Diones Triggering the Dearomatization of Electron-Deficient Indoles for the Synthesis of Chiral Highly Functionalized Pyrroloindolines.

A catalyst system consisting of a chiral phosphoramidite ligand and Pd2(dba)3·CHCl3 causes the decarboxylation of 5-vinyloxazolidine-2,4-diones to generate amide-containing aza-π-allylpalladium 1,3-dipole intermediates, which are capable of triggering the dearomatization of 3-nitroindoles for diastereo- and enantioselective [3+2] cycloaddition, leading to the formation of a series of highly functionalized pyrroloindolines containing three contiguous stereogenic centers with excellent results (up to 99% yield, 88:12 dr, and 96% ee).

Recurrent myocardial injury in a de novo SON mutation ZTTK syndrome patient: a case report.

BACKGROUND: Zhu-Tokita-Takenouchi-Kim syndrome (ZTTK syndrome) is a severe multi-systemic developmental disorder, caused by variants in the SON gene. A patient diagnosed with ZTTK syndrome who carried a de novo SON mutation and exhibited recurrent myocardial injury was described in this case. CASE PRESENTATION: A 7-year-old girl was admitted to the Cardiology Department of Beijing Children's Hospital in November 2019 due to myocardial injury following respiratory infection. She displayed elevated myocardial enzymes and severe T-wave changes on electrocardiogram. Over the past three years, she had experienced myocardial injury on three occasions. Additionally, she exhibited intellectual disability, congenital amblyopia, and dysmorphic facial features. Genetic analysis revealed a de novo heterozygous mutation c.3852_3856delGGTAT in the SON gene, which was confirmed by Sanger sequencing of her parents. She received anti-infection treatment and was administered metoprolol orally. Her condition was stable at the time of discharge. Over a 42-month follow-up period at the outpatient clinic, she complained intermittent fatigue and palpitation. CONCLUSIONS: The identified SON mutation, which plays a crucial role in heart development and mitochondrial function, may be associated with an increased susceptibility to myocardial injury or cardiomyopathy. This case report contributes novel insights into this rare condition and suggests the expansion of the ZTTK syndrome phenotype.

The Efficacy & Molecular Mechanisms of a Terpenoid Compound Ganoderic Acid C1 on Corticosteroid-Resistant Neutrophilic Airway Inflammation: In vivo and in vitro Validation.

Introduction: Neutrophil predominant airway inflammation is associated with severe and steroid-resistant asthma clusters. Previously, we reported efficacy of ASHMI, a three-herb TCM asthma formula in a steroid-resistant neutrophil-dominant murine asthma model and further identified Ganoderic Acid C1 (GAC1) as a key ASHMI active compound in vitro. The objective of this study is to investigate GAC1 effect on neutrophil-dominant, steroid-resistant asthma in a murine model. Methods: In this study, Balb/c mice were systematically sensitized with ragweed (RW) and alum and intranasally challenged with ragweed. Unsensitized/PBS challenged mice served as normal controls. Post sensitization, mice were given 4 weeks of oral treatment with GAC1 or acute dexamethasone (Dex) treatment at 48 hours prior to challenge. Pulmonary cytokines were measured by ELISA, and lung sections were processed for histology by H&E staining. Furthermore, GAC1 effect on MUC5AC expression and on reactive oxygen species (ROS) production in human lung epithelial cell line (NCI-H292) was determined by qRT-PCR and ROS assay kit, respectively. Computational analysis was applied to select potential targets of GAC1 in steroid-resistant neutrophil-dominant asthma. Molecular docking was performed to predict binding modes between GAC1 and Dex with TNF-α. Results: The result of the study showed that chronic GAC1 treatment, significantly reduced pulmonary inflammation (P < 0.01-0.001 vs Sham) and airway neutrophilia (P < 0.01 vs Sham), inhibited TNF-α, IL-4 and IL-5 levels (P < 0.05-0.001 vs Sham). Acute Dex treatment reduced eosinophilic inflammation and IL-4, IL-5 levels, but had no effect on neutrophilia and TNF-α production. GAC1 treated H292 cells showed decreased MUC5AC gene expression and production of ROS (P < 0.001 vs stimulated/untreated cells). Molecular docking results showed binding energy of complex GAC1-TNF was -10.8 kcal/mol. Discussion: GAC1 may be a promising anti-asthma botanical drug for treatment of steroid-resistant asthma.

The awareness rate of knowledge of chronic diseases and influencing factors among 4790 adults in anhui province: An online survey using WeChat.

Objective: To investigate public awareness about core information regarding chronic diseases and identify factors influencing that awareness among Anhui Province residents, provide a scientific basis for policy-making, and formulate corresponding intervention measures. Methods: From March to April 2021, 12 provincial-level representative counties and districts of Anhui province in the China Adult Chronic Disease and Nutrition Surveillance were selected as survey sites, and 4790 residents were recruited for the survey using stratified multi-stage cluster random sampling. Basic details about the study participants were collected and their awareness of core information about major chronic diseases was measured through an online survey using WeChat. Results: In 2021, the awareness rate of core information about chronic diseases among residents of Anhui Province was 54.93%. Multivariate logistic regression analysis showed that a higher awareness rate was associated with the following factors: non-housework occupations (agriculture, forestry, animal husbandry, and fishery: OR = 1.309, commercial services and production and transportation: OR = 1.450, institutions, and professional and technical personnel: OR = 1.461), a high education level (high school/junior high school/technical school OR = 1.357, college and above OR = 2.133), and residence in the southern and northern Anhui areas (southern Anhui OR = 1.282, northern Anhui OR = 1.431); whereas in rural areas (by district and country) (OR = 0.863), the awareness rate was low (all P < 0.05). Conclusions: The awareness rate of core information about chronic diseases among residents of Anhui, China, is low. It is necessary to strengthen awareness about chronic disease prevention and management by targeting specific groups of people in this region.

Identification and biological characteristics of Enterococcus casseliflavus TN-47 isolated from Monochamus alternatus.

With the widespread use of antibiotics, the incidence of antibiotic resistance in microorganisms has increased. Monochamus alternatus is a trunk borer of pine trees. This study aimed to investigate the in vitro antimicrobial and biological characteristics of Enterococcus casseliflavus TN-47 (PP411196), isolated from the gastrointestinal tract of M. alternatus in Jilin Province, PR China. Among 13 isolates obtained from the insects, five were preliminarily screened for antimicrobial activity. E. casseliflavus TN-47, which exhibited the strongest antimicrobial activity, was identified. E. casseliflavus TN-47 possessed antimicrobial activity against Staphylococcus aureus USA300 and Salmonella enterica serovar Pullorum ATCC 19945. Furthermore, E. casseliflavus TN-47 was sensitive to tetracyclines, penicillins (ampicillin, carbenicillin, and piperacillin), quinolones and nitrofuran antibiotics, and resistant to certain beta-lactam antibiotics (oxacillin, cefradine and cephalexin), macrolide antibiotics, sulfonamides and aminoglycosides. E. casseliflavus TN-47 could tolerate low pH and pepsin-rich conditions in the stomach and grow in the presence of bile acids. E. casseliflavus TN-47 retained its strong auto-aggregating ability and hydrophobicity. This strain did not exhibit any haemolytic activity. These results indicate that E. casseliflavus TN-47 has potential as a probiotic. This study provides a theoretical foundation for the future applications of E. casseliflavus TN-47 and its secondary metabolites in animal nutrition and feed.

Neutrophil extracellular traps promote acetaminophen-induced acute liver injury in mice via AIM2.

Excessive acetaminophen (APAP) can induce neutrophil activation and hepatocyte death. Along with hepatocyte dysfunction and death, NETosis (a form of neutrophil-associated inflammation) plays a vital role in the progression of acute liver injury (ALI) induced by APAP overdose. It has been shown that activated neutrophils tend to migrate towards the site of injury and participate in inflammatory processes via formation of neutrophil extracellular traps (NETs). In this study we investigated whether NETs were involved in hepatocyte injury and contributed to APAP-induced ALI progression. ALI mouse model was established by injecting overdose (350 mg/kg) of APAP. After 24 h, blood and livers were harvested for analyses. We showed that excessive APAP induced multiple programmed cell deaths of hepatocytes including pyroptosis, apoptosis and necroptosis, accompanied by significantly increased NETs markers (MPO, citH3) in the liver tissue and serum. Preinjection of DNase1 (10 U, i.p.) for two consecutive days significantly inhibited NETs formation, reduced PANoptosis and consequently alleviated excessive APAP-induced ALI. In order to clarify the communication between hepatocytes and neutrophils, we induced NETs formation in isolated neutrophils, and treated HepaRG cells with NETs. We found that NETs treatment markedly increased the activation of GSDMD, caspase-3 and MLKL, while pre-treatment with DNase1 down-regulated the expression of these proteins. Knockdown of AIM2 (a cytosolic innate immune receptor) abolished NETs-induced PANoptosis in HepaRG cells. Furthermore, excessive APAP-associated ALI was significantly attenuated in AIM2KO mice, and PANoptosis occurred less frequently. Upon restoring AIM2 expression in AIM2KO mice using AAV9 virus, both hepatic injury and PANoptosis was aggravated. In addition, we demonstrated that excessive APAP stimulated mtROS production and mitochondrial DNA (mtDNA) leakage, and mtDNA activated the TLR9 pathway to promote NETs formation. Our results uncover a novel mechanism of NETs and PANoptosis in APAP-associated ALI, which might serve as a therapeutic target.