Efficacy of Raw Corn Starch in Insulinoma-Related Hypoglycemia: A Promising Supportive Therapy.

Objective To investigate the efficacy of raw corn starch (RCS) in clinical management of insulinoma-induced hypoglycemia.Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively, and analyzed the therapeutic effects of the RCS intervention on blood glucose control, weight change, and its adverse events.Results The study population consisted of 24 case of insulinoma patients, 7 males and 17 females, aged 46.08 ± 14.15 years. Before RCS-supplemented diet, all patients had frequent hypoglycemic episodes (2.51 ± 3.88 times/week), concurrent with neuroglycopenia (in 83.3% of patients) and autonomic manifestations (in 75.0% of patients), with the median fasting blood glucose (FBG) of 2.70 [interquartile range (IQR): 2.50-2.90] mmol/L. The patients' weight increased by 0.38 (IQR: 0.05-0.65) kg per month, with 8 (33.3%) cases developing overweight and 7 (29.2%) cases developing obesity. All patients maintained the RCS-supplemented diet until they underwent tumor resection (23 cases) and transarterial chemoembolization for liver metastases (1 case). For 19 patients receiving RCS throughout the day, the median FBG within one week of nutritional management was 4.30 (IQR: 3.30-5.70) mmol/L, which was a significant increase compared to pre-nutritional level [2.25 (IQR: 1.60-2.90) mmol/L; P = 0.000]. Of them, 10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment [3.20 (IQR: 2.60-3.95) mmol/L vs. 2.15 (IQR: 1.83-2.33) mmol/L; P = 0.000). Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management [3.50 (IQR: 2.50-3.65) mmol/L vs. 2.20 (IQR:1.80-2.60) mmol/L; P = 0.000], but only one patient who continued to receive RCS for over 4 weeks did not have a significant improvement in FBG. No improvement in weight gain was observed upon RCS supplementation. Mild diarrhea (2 cases) and flatulence (1 case) occurred, and were relieved by reduction of RCS dose.Conclusion The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

A homogeneous electrochemiluminescence immunoassay platform based on carbon quantum dots and magnetic beads enrichment for detection of thyroglobulin in serum.

Considering the high probability of recurrence or metastasis after thyroidectomy, it is meaningful to develop a rapid, sensitive and specific method for monitoring thyrophyma-related biomarkers. In this study, a homogeneous electrochemiluminescence immunoassay (HO-ECLIA) coupled with magnetic beads (MBs)-based enrichment tactic was established for the determination of thyrophyma-related thyroglobulin (Tg). Importantly, owing to the abundant surface groups and good biocompatibility of carbon quantum dots (CQDs), the incorporation of CQDs onto the Tg antigen surface was achieved, resulting in the formation of Tg-encapsulated CQDs (CQDs-Tg), which served not only as an ECL probe but as a biorecognition element. Under optimal experimental conditions, the proposed platform demonstrated a wide linear range from 0.01 to 100 ng·mL-1 with a detection limit of 6.9 pg·mL-1 (S/N = 3), and performed well in real serum sample analysis against interference. Collectively, the proposed platform exhibited the rapid response, satisfactory sensitivity and specificity toward Tg in complex serum milieu, and held a considerable potential for clinical prognosis monitoring of thyrophyma.

Prenylated indole diketopiperazine alkaloids as phosphatase inhibitors from the marine-derived fungus Talaromyces purpureogenus.

Six previously undescribed prenylated indole diketopiperazine alkaloids, talaromyines A-F (1-6), were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data including NMR, HR-ESI-MS, and electronic circular dichroism calculations, together with chemical analysis of hydrolysates. Compounds 1-5 represent the first example of spirocyclic indole diketopiperazines biosynthesized from the condensation of L-tryptophan and L-alanine. Compounds 2 and 4-5 showed selective inhibitory activities against phosphatases TCPTP and MEG2 with IC50 value of 17.9-29.7 µM, respectively. Compounds 4-5 exhibited mild cytotoxic activities against two human cancer cell lines H1975 and HepG-2.

The discovery of a novel pyrrolo[2,3-b]pyridine as a selective CDK8 inhibitor offers a new approach against psoriasis.

Currently, the drugs used in clinical to treat psoriasis mainly broadly suppress cellular immunity. However, these drugs can only provide temporary and partial symptom relief, they do not cure the condition and may lead to recurrence or even serious toxic side effects. In this study, we describe the discovery of a novel potent CDK8 inhibitor as a treatment for psoriasis. Through structure-based design, compound 46 was identified as the most promising candidate, exhibiting a strong inhibitory effect on CDK8 (IC50 value of 57 nM) along with favourable inhibition against NF-κB. Additionally, it demonstrated a positive effect in an in vitro psoriasis model induced by TNF-α. Furthermore, this compound enhanced the thermal stability of CDK8 and exerted evident effects on the biological function of CDK8, and it had favourable selectivity across the CDK family and tyrosine kinase. This compound showed no obvious inhibitory effect on CYP450 enzyme. Further studies confirmed that compound 46 exhibited therapeutic effect on IMQ-induced psoriasis, alleviated the inflammatory response in mice, and enhanced the expression of Foxp3 and IL-10 in the dorsal skin in vivo. This discovery provides a new strategy for developing selective CDK8 inhibitors with anti-inflammatory activity for the treatment of psoriasis.

Drymariamides A-J, Antiadipogenic Cyclopeptides Incorporating Noncanonical Amino Acids from Drymaria cordata.

Herein, we report an extensive phytochemical study on the whole plant of Drymaria cordata, which led to the isolation of ten new orbitides, named drymariamides A-J (1-10). Compounds 2, 3, and 5 incorporate rare residues of noncanonical amino acids of kynurenine (Kyn) or 3a-hydroxypyrroloindoline (HPI). Their structures with absolute configurations were elucidated by a combination of spectroscopic analysis, advanced Marfey's method, X-ray diffraction, and electronic circular dichroism analysis. Compounds 1-10 exhibited antiadipogenic effects in 3T3-L1 adipocytes, and the most potent compound 7 showed an EC50 value of 1.17 ± 0.19 µM.

New progress in roles of TGF-ß signaling crosstalks in cellular functions, immunity and diseases.

The family of secreted dimeric proteins known as the Transforming Growth Factor-ß (TGF-ß) family plays a critical role in facilitating intercellular communication within multicellular animals. A recent symposium on TGF-ß Biology - Signaling, Development, and Diseases, held on December 19-21, 2023, in Hangzhou, China, showcased some latest advances in our understanding TGF-ß biology and also served as an important forum for scientific collaboration and exchange of ideas. More than twenty presentations and discussions at the symposium delved into the intricate mechanisms of TGF-ß superfamily signaling pathways, their roles in normal development and immunity, and the pathological conditions associated with pathway dysregulation.

Risk prediction algorithms for prolonged postoperative ileus: A systematic review.

AIM: Prolonged postoperative ileus (PPOI) is common and is associated with a significant healthcare burden. Previous studies have attempted to predict PPOI clinically using risk prediction algorithms. The aim of this work was to systematically review and compare risk prediction algorithms for PPOI following colorectal surgery. METHOD: A systematic literature search was conducted using MEDLINE, Embase, Web of Science and CINAHL Plus. Studies that developed and/or validated a risk prediction algorithm for PPOI in adults following colorectal surgery were included. Data were collected on study design, population and operative characteristics, the definition of PPOI used and risk prediction algorithm design and performance. Quality appraisal was assessed using the PROBAST tool. RESULTS: Eleven studies with 87 549 participants were included in our review. Most were retrospective, single-centre analyses (6/11, 55%) and rates of PPOI varied from 10% to 28%. The most commonly used variables were sex (8/11, 73%), age (6/11, 55%) and surgical approach (5/11, 45%). Area under the curve ranged from 0.68-0.78, and only three models were validated. However, there was significant variation in the definition of PPOI used. No study reported sensitivity, specificity or positive/negative predictive values. CONCLUSION: Currently available risk prediction algorithms for PPOI appear to discriminate moderately well, although there is a lack of validation data. Future studies should aim to use a standardized definition of PPOI, comprehensively report model performance and validate their findings using internal and external methodologies.

Nanoparticles targeting OPN loaded with BY1 inhibits vascular restenosis by inducing FTH1-dependent ferroptosis in vascular smooth muscle cells.

Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.

Identification of ACAA1 and HADHB as potential prognostic biomarkers based on a novel fatty acid oxidation-related gene model in head and neck squamous cell carcinoma: A retrospective study.

OBJECTIVES: To investigate the importance of fatty acid oxidation (FAO)-related genes in predicting the progression and prognosis of head and neck squamous cell carcinoma (HNSCC). METHODS: The FAO-related gene prognostic model was established employing Cox regression analyses, during which accuracy and sensitivity of the gene model were evaluated in The Cancer Genome Atlas (TCGA) internal testing and Gene Expression Omnibus (GEO) external validation cohorts. Ultimately, hub genes were identified among 13 model genes using STRING and Cytoscape, with preliminary validation carried out through immunohistochemistry. RESULTS: The model, which comprised 13 genes (ABCD2, ACAA1, ACACB, AKT1, CNR1, CPT1C, CROT, ECHDC2, ETFA, HADHB, IRS2, LONP2, and SLC25A17), was established. On the basis of the median risk score, the two cohorts were grouped into low-and high-risk groups in the subsequent test and validation, and the former exhibited significantly higher survival rates than the latter. Nomograms were established based on prognostic factors, including stage and risk score, and individualized for the prediction of HNSCC patients. Ultimately, immunohistochemical staining showed that ACAA1 and HADHB were significantly under-expressed in HNSCC, with a favorable prognosis associated with low HADHB and high ACAA1. CONCLUSIONS: The gene prognostic model has illustrated promising capability in predicting the prognosis, and ACAA1 and HADHB might serve as potential therapeutic biomarkers for HNSCC patients.

Dietary fiber intake and its association with diabetic kidney disease in American adults with diabetes: A cross-sectional study.

BACKGROUND: Dietary fiber (DF) intake may have a protective effect against type 2 diabetes (T2D); however, its relationship with diabetic kidney disease (DKD) remains unclear. AIM: To investigate the potential association between DF intake and the prevalence of DKD in individuals diagnosed with T2D. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey collected between 2005 and 2018. DF intake was assessed through 24-h dietary recall interviews, and DKD diagnosis in individuals with T2D was based on predefined criteria, including albuminuria, impaired glomerular filtration rate, or a combination of both. Logistic regression analysis was used to assess the association between DF intake and DKD, and comprehensive subgroup and sensitivity analyses were performed. RESULTS: Among the 6032 participants, 38.4% had DKD. With lower DF intake-T1 (≤ 6.4 g/1000 kcal/day)-as a reference, the adjusted odds ratio for DF and DKD for levels T2 (6.5-10.0 g/1000 kcal/day) and T3 (≥ 10.1 g/1000 kcal/day) were 0.97 (95%CI: 0.84-1.12, P = 0.674) and 0.79 (95%CI: 0.68-0.92, P = 0.002), respectively. The subgroup analysis yielded consistent results across various demographic and health-related subgroups, with no statistically significant interactions (all P > 0.05). CONCLUSION: In United States adults with T2D, increased DF intake may be related to reduced DKD incidence. Further research is required to confirm these findings.

Assessing recent recurrence after hepatectomy for hepatitis B-related hepatocellular carcinoma by a predictive model based on sarcopenia.

BACKGROUND: Sarcopenia may be associated with hepatocellular carcinoma (HCC) following hepatectomy. But traditional single clinical variables are still insufficient to predict recurrence. We still lack effective prediction models for recent recurrence (time to recurrence < 2 years) after hepatectomy for HCC. AIM: To establish an interventable prediction model to estimate recurrence-free survival (RFS) after hepatectomy for HCC based on sarcopenia. METHODS: We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time, and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography. 94 of these patients were enrolled for external validation. Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort. A nomogram model was developed to predict the RFS of HCC patients, and its predictive performance was validated. The predictive efficacy of this model was evaluated using the receiver operating characteristic curve. RESULTS: Multivariate analysis showed that sarcopenia [Hazard ratio(HR) = 1.767, 95%CI: 1.166-2.678, P < 0.05], alpha-fetoprotein ≥ 40 ng/mL (HR = 1.984, 95%CI: 1.307-3.011, P < 0.05), the maximum diameter of tumor > 5 cm (HR = 2.222, 95%CI: 1.285-3.842, P < 0.05), and hepatitis B virus DNA level ≥ 2000 IU/mL (HR = 2.1, 95%CI: 1.407-3.135, P < 0.05) were independent risk factors associated with postoperative recurrence of HCC. Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease (SAMD) was established combined with other the above risk factors. The area under the curve of the SAMD model was 0.782 (95%CI: 0.705-0.858) in the training cohort (sensitivity 81%, specificity 63%) and 0.773 (95%CI: 0.707-0.838) in the validation cohort. Besides, a SAMD score ≥ 110 was better to distinguish the high-risk group of postoperative recurrence of HCC. CONCLUSION: Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC. A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC, which is superior to other models and contributes to prognosis prediction.

Ni-Catalyzed Csp2 and Csp3 Coupling for Divergent Bisboronic Ester Synthesis.

Bisboronic esters are critical compounds in various research fields, including drug discovery, chemical biology, and material sciences. Currently, the bisboronic esters with reactive functional groups are difficult to synthesize; this is partially due to the lack of a robust method to produce these products with diverse structures and various functional groups at specific locations. To overcome this issue, this study introduced a Ni-catalysis approach to produce bisboronic esters efficiently via cross-coupling and homocoupling using readily available halogenated boronic esters as the starting material under mild reaction conditions. This newly developed strategy enables Csp2-Csp2, Csp3-Csp3, and Csp2-Csp3 couplings, demonstrating a broad substrate scope and excellent compatibility with various functional groups.

Prognostic value of neutrophil-to-lymphocyte ratio in end-stage liver disease: A meta-analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is commonly utilized as a prognostic indicator in end-stage liver disease (ESLD), encompassing conditions like liver failure and decompensated cirrhosis. Nevertheless, some studies have contested the prognostic value of NLR in ESLD. AIM: To investigate the ability of NLR to predict ESLD. METHODS: Databases, such as Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Weipu, and Wanfang, were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD. Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1. RESULTS: A total of thirty studies involving patients with end-stage liver disease (ESLD) were included in the evaluation. Among the pooled results of eight studies, it was observed that the Neutrophil-to-Lymphocyte Ratio (NLR) was significantly higher in non-survivors compared to survivors (random-effects model: standardized mean difference = 1.02, 95% confidence interval = 0.67-1.37). Additionally, twenty-seven studies examined the associations between NLR and mortality in ESLD patients, reporting either hazard ratios (HR) or odds ratios (OR). The combined findings indicated a link between NLR and ESLD mortality (random-effects model; univariate HR = 1.07, 95%CI = 1.05-1.09; multivariate HR = 1.07, 95%CI = 1.07-1.09; univariate OR = 1.29, 95%CI = 1.18-1.39; multivariate OR = 1.29, 95%CI = 1.09-1.49). Furthermore, subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality, with Asian studies demonstrating a more pronounced effect. CONCLUSION: Increased NLR in patients with ESLD is associated with a higher risk of mortality, particularly in Asian patients. NLR is a useful prognostic biomarker in patients with ESLD.

Calcium signaling facilitates chilling- and GA- induced dormancy release in tree peony.

Calcium plays a crucial role in plant growth and development, yet little is known about its function in endodormancy regulation. Tree peony (Paeonia suffruticosa), characterized by compound buds and large flowers, is well-known for its ornamental and medicinal value. To break bud dormancy release is a prerequisite of flowering and forcing culture, particularly during the Spring Festival. In this study, the Ca2+ chelator EGTA and Ca2+ channel blocker LaCl3 were applied, resulting in a significant delay in budburst during both chilling- and gibberellin (GA)- induced dormancy release in a dosage-dependent manner. As expected, the retardation of bud break was recovered by the supplementation of 30 mM CaCl2, indicating a facilitating role of calcium in dormancy release. Accordingly, several calcium-sensor-encoding genes including Calmodulin (CaM) and Ca2+-dependent protein kinases (CDPKs) were significantly up-regulated by prolonged chilling and exogenous GAs. Ultrastructure observations revealed a decline in starch grains and the reopening of transport corridors following prolonged chilling. Calcium deposits were abundant in the cell walls and intercellular spaces at the early dormant stage but were enriched in the cytosol and nucleus before dormancy release. Additionally, several genes associated with dormancy release, including EBB1, EBB3, SVP, GA20ox, RGL1, BG6, and BG9, were differentially expressed after calcium blocking and recovery treatments, indicating that calcium might partially modulate dormancy release through GA and ABA pathways. Our findings provide novel insights into the mechanism of dormancy release and offer potential benefits for improving and perfecting forcing culture technology in tree peonies.

New anti-inflammatory limonoids from the fruits of Melia azedarach.

The phytochemical study of the fruits of Melia azedarach (Meliaceae) led to the isolation and characterisation of two novel natural limonoids1-deoxy- 3, 20-dicinnamoyl-11-methoxy-meliacarpinin (1) and 12ß- O- methyl nimbolinin A (2), along with twelve known limonoids. Its structure was identified by 1D- and 2D-NMR, HR-ESI-MS and comparison with published data. The anti-inflammatory effect of the compounds was measured in vitro in RAW 264.7 cells by evaluating the production of NO stimulated by LPS. Compounds 1, 8 and 14 indicated significant anti-inflammatory effect with inhibition rate of 11.76, 8.45 and 6.59 µM, respectively. Limonoid 1 significantly inhibited the production of NO, TNF-α and IL-1ß in RAW 264.7 cells. Therefore, limonoid derivative may be a promising source of bioactive metabolite for inflammatory diseases.

Integrated Analysis Construct a Tumor-Associated Macrophage Novel Signature with Promising Implications in Predicting the Prognosis and Immunotherapeutic Response of Gastric Cancer Patients.

BACKGROUND: Gastric cancer (GC) remains one of the most prevalent malignant tumors worldwide. At present, tumor-associated macrophages (TAMs) are essential in the progression, metastasis, and drug resistance of tumors. Therefore, TAMs can be a crucial target for tumor treatment. AIMS: We intended to investigate the TAM characteristics in GC and develop a risk signature based on TAM to predict the prognosis of GC patients. METHODS: The single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data were acquired from a publicly available database. We utilized the Seurat pipeline to process the scRNA-seq data and determine TAM cell types using marker genes. Univariate Cox regression analysis was utilized to examine TAM-related prognostic genes, and then we employed Lasso-Cox regression analysis, and Multivariate Cox regression analysis established a novel risk profile to forecast the clinical value of the model with a new nomogram combining risk profiles and clinicopathological characteristics. RESULTS: The current study employed scRNA-seq data to identify five TAM clusters in GC, among which four were significantly associated with GC prognosis. Accordingly, we further developed a TAM-related risk signature utilizing nine genes. After evaluation, our model accurately predicted the prognosis of gastric cancer. Generally, GC patients with low TAMS scores exhibited a more favorable prognosis, greater benefits from immunotherapy, and higher levels of immune cell infiltration. CONCLUSIONS: The prognosis of GC can be effectively predicted by TAM-based risk signatures, and the signature may provide a new perspective for comprehensively guiding clinical diagnosis, prediction, and immunotherapy for gastric cancer.

Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis.

BACKGROUND: Acute liver failure (ALF) has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis. The silent information regulator sirtuin 1 (SIRT1)-mediated deacetylation affects multiple biological processes, including cellular senescence, apoptosis, sugar and lipid metabolism, oxidative stress, and inflammation. AIM: To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms. METHODS: This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) testing. C57BL/6 mice were also intraperitoneally pretreated with SIRT1, p53, or glutathione peroxidase 4 (GPX4) inducers and inhibitors and injected with lipopolysaccharide (LPS)/D-galactosamine (D-GalN) to induce ALF. Gasdermin D (GSDMD)-/- mice were used as an experimental group. Histological changes in liver tissue were monitored by hematoxylin and eosin staining. ALT, AST, glutathione, reactive oxygen species, and iron levels were measured using commercial kits. Ferroptosis- and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction. SIRT1, p53, and GSDMD were assessed by immunofluorescence analysis. RESULTS: Serum AST and ALT levels were elevated in patients with ALF. SIRT1, solute carrier family 7a member 11 (SLC7A11), and GPX4 protein expression was decreased and acetylated p5, p53, GSDMD, and acyl-CoA synthetase long-chain family member 4 (ACSL4) protein levels were elevated in human ALF liver tissue. In the p53 and ferroptosis inhibitor-treated and GSDMD-/- groups, serum interleukin (IL)-1ß, tumour necrosis factor alpha, IL-6, IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated. In mice with GSDMD knockout, p53 was reduced, GPX4 was increased, and ferroptotic events (depletion of SLC7A11, elevation of ACSL4, and iron accumulation) were detected. In vitro, knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels, the cytostatic rate, and GSDMD expression, restoring SLC7A11 depletion. Moreover, SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group, accompanied by reduced p53, GSDMD, and ACSL4, and increased SLC7A11 and GPX4. Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalN-induced in vitro and in vivo models. CONCLUSION: SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.