TMEM2 inhibits the development of Graves' orbitopathy through the JAK-STAT signaling pathway.

A mouse model was used to investigate the role of the hyaluronidase, transmembrane protein 2 (TMEM2), on the progression of Graves' orbital (GO) disease. We established a GO mouse model through immunization with a plasmid expressing the thyroid stimulating hormone receptor. Orbital fibroblasts (OFs) were subsequently isolated from both GO and non-GO mice for comprehensive in vitro analyses. The expression of TMEM2 was assessed using qRT-PCR, Western blot and immunohistochemistry in vivo. Disease pathology was evaluated by H&E staining and Masson's trichrome staining in GO mouse tissues. Our investigation revealed a notable reduction in TMEM2 expression in GO mouse orbital tissues. Through overexpression and knockdown assays, we demonstrated that TMEM2 suppresses inflammatory cytokines and reactive oxygen species production. TMEM2 also inhibits the formation of lipid droplets in OFs and the expression of adipogenic factors. Further incorporating Gene Set Enrichment Analysis of relevant GEO datasets and subsequent in vitro cell experiments, robustly confirmed that TMEM2 overexpression was associated with a pronounced upregulation of the JAK/STAT signaling pathway. In vivo, TMEM2 overexpression reduced inflammatory cell infiltration, adipogenesis, and fibrosis in orbital tissues. These findings highlight the varied regulatory role of TMEM2 in GO pathogenesis. Our study reveals that TMEM2 plays a crucial role in mitigating inflammation, suppressing adipogenesis, and reducing fibrosis in GO. TMEM2 has potential as a therapeutic target and biomarker for treating or alleviating GO. These findings advance our understanding of GO pathophysiology and provide opportunities for targeted interventions to modulate TMEM2 for therapeutic purposes.

The effects of diet quality, eating behavior, and sleep on the academic performance among elementary school students.

The academic success of children contributes to their income, social status, and public health. This study was conducted with 217 elementary school students from western China. Scores on the Chinese Children Dietary Index (CCDI), Dietary Approaches to Stop Hypertension (DASH), adjusted DASH, and KIDMED index were calculated to evaluate diet quality. Eating behavior and sleep quality were assessed using the Children's Eating Behavior Questionnaire (CEBQ) and Children's Sleep Habits Questionnaire (CHSQ), respectively. Academic achievement was measured using school-provided average grades. Higher CCDI scores, longer sleep time, lower total CHSQ scores, and lower subscores on "satiety responsiveness," "slowness in eating," "emotional undereating," and "food fussiness" dimensions of the CEBQ were associated with high academic achievement. In conclusion, good diet quality, sleep quality, healthy eating behaviors, and adequate sleep duration were associated with better academic performance. Interventions are recommended to be developed in education system to improve healthy diets and lifestyles, enhancing academic achievement.

Systemic Inflammatory Biomarkers Predict Survival of Patients Treated With Tyrosine Kinase Inhibitors for Metastatic Renal Cell Carcinoma.

OBJECTIVE: We aimed to retrospectively investigate whether the neutrophil to lymphocyte ratio (NLR) and the monocyte to lymphocyte ratio (MLR) can predict the prognosis of patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib or sorafenib. METHODS: We retrospectively identified 210 patients with mRCC treated with sunitinib or sorafenib from 2007 to 2017 at Fudan University- and Hexi University-affiliated hospitals. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. Multivariate regression analysis was used to evaluate predictors of PFS and OS. RESULTS: Low NLR (<2.85) and MLR (<.30) were strongly associated with increased PFS and OS. Multivariable analyses verified that the NLR and MLR were both independent prognostic factors. Additionally, the NLR was negatively correlated with CD8+ and CD4+ T-cell infiltration in tumors. CONCLUSION: In patients with mRCC treated with sunitinib and sorafenib, an NLR <2.85 and MLR <.30 was associated with superior PFS and OS, which may be related to the reduced lymphocytic infiltration of tumors.

The rapid start-up of CANON process through adding partial nitration sludge to ANAMMOX system.

This study aimed to start up the completely autotrophic nitrogen removal over nitrite (CANON) process after adding partial nitration (PN) sludge to the ANAMMOX reactor, so as to help the rapid start-up and stable operation of the CANON process in practical engineering applications. There were three steps in the research: cultivating the PN sludge, building a reliable ANAMMMOX system, and finally starting and running the CANON process. The PN sludge was successfully cultivated in less than 45 days with around 90% nitrite accumulation rate. The ANAMMOX reactor enriched a significant quantity of red granular sludge within 70 days, achieving the maximum nitrogen removal rate of 1.74 kg/(m3·d). Eventually, the CANON reactor was started up successfully, which achieved 95.08% of average ammonium removal efficiency and 84.51% of average total nitrogen removal efficiency in 60 days. The residual recalcitrant nitrite-oxidizing bacteria in the CANON process was successfully inhibited by intermittent aeration and 12 mg/L free ammonia in UASB reactor. Besides, Candidatus Kuenenia, Candidatus Brocadia and Nitrosomonas were the main functional microorganisms involved in the CANON process.

SPE-UPLC-MS/MS for Determination of 36 Monomers of Alkylphenol Ethoxylates in Tea.

Alkylphenol ethoxylates (APEOs) represent a non-ionic surfactant widely used as adjuvants in pesticide formulation, which is considered to cause an endocrine-disrupting effect. In the current study, we established a detection method for the APEOs residue in tea based on solid-phase extraction (SPE) for the simultaneous analysis of nonylphenol ethoxylates (NPEOs) and octylphenol ethoxylates (OPEOs) by UPLC-MS/MS. In the spiked concentrations from 0.024 to 125.38 µg/kg for 36 monomers of APEOs (nEO = 3-20), the recoveries of APEOs range from 70.3-110.7% with RSD ≤ 16.9%, except for OPEO20 (61.8%) and NPEO20 (62.9%). The LOQs of OPEOs and NPEOs are 0.024-6.27 and 0.16-5.01 µg/kg, respectively. OPEOs and NPEOs are detected in 50 marketed tea samples with a total concentration of 0.057-12.94 and 0.30-215.89 µg/kg, respectively. The detection rate and the range of the monomers of NPEOs are generally higher than those of OPEOs. The current study provides a theoretical basis for the rational use of APEOs as adjuvants in commercial pesticide production.

Method validation for detection of afidopyropen and M440I007 in tea.

BACKGROUND: Afidopyropen is a novel biorational insecticide for controlling piercing pests with great potential for application in tea gardens that can form the metabolite M440I007 when utilized for crops. However, because of a lack of analytical method for afidopyropen and M440I007 in tea, there is no means of monitoring the residues. Therefore, method development, validation and simultaneous determination of afidopyropen and M440I007 in fresh tea leaves, dried tea and tea infusion is of prime significance. RESULTS: A TPT cartridge-based method was developed for the solid phase extraction of afidopyropen and M440I007 from tea matrices. Extraction and clean-up conditions, including the composition, volume and temperature of elutions, were optimized to achieve the best results. Both targets were extracted using water and acetonitrile, with a water:acetonitrile (v/v) ratio of 4:10 for fresh leaves and 8:10 for dried tea, which were then cleaned and analyzed using ultraperformance liquid chromatography-tandem mass spectrometry. Both analytes demonstrated excellent linearity with a correlation coefficient above 0.998. The optimized analytical method offered limits of quantifications of 0.005, 0.005 and 0.002 mg kg-1 (converted to dried tea) in fresh tea shoots, dried tea and tea infusion for both targets, respectively. Average recoveries of afidopyropen and M440I007 ranged from 79.0% to 101.5%, with relative standard deviations ≤ 14.7%. CONCLUSION: The results showed that the method of determination for these insecticides in tea matrices was practical and efficient. © 2023 Society of Chemical Industry.

Expression of Shh, Gli1, and Cyr61 in Gastric Cancer Predicts Overall Survival of Patients: A Retrospective Study.

OBJECTIVE: This study aimed to evaluate the expression levels of Shh, Gli1, and Cyr61 proteins in gastric cancer tissues and analyze the relationship between these three proteins and the clinicopathological factors and prognosis of patients. METHODS: This was a retrospective study. Four hundred gastric cancer tissue specimens from patients who underwent radical gastrectomy in Zhangye People's Hospital affiliated to Hexi University between February 2013 and February 2021 underwent immunohistochemical analysis. RESULTS: The positive expression rates of Shh, Gli1, and Cyr61 in gastric cancer tissues were 55.5%, 56.5%, and 64.5%, respectively. The expressions of Shh, Gli1, and Cyr61 in gastric cancer tissues were significantly correlated with tumor size, depth of invasion, and degree of differentiation (P < .05). The expression of Shh protein was positively correlated with the expression of Gli1 protein (P < .01), and the expression of Gli1 protein was positively correlated with the expression of Cyr61 protein (P < .01). Univariate and multivariate analyses showed that the expression of Shh, Gli1, and Cyr61 could predict the prognosis of patients (P < .05). Receiver operating characteristic curve analysis combined with TNM staging could better predict the three-year overall survival of patients (P < .05). CONCLUSION: Shh, Gli1, and Cyr61 proteins are significantly expressed in gastric cancer tissues and are risk factors for the prognosis of patients with gastric cancer.

A new abyssomicin polyketide with anti-influenza A virus activity from a marine-derived Verrucosispora sp. MS100137.

Marine microorganisms live in dramatically different environments and have attracted much attention for their structurally unique natural products with potential strong biological activity. Based on the one strain-many compounds (OSMAC) strategy and liquid chromatography mass spectrometry (LC-MS) methods, our continuing efforts on the investigation of novel active compounds from marine Verrucosispora sp. MS100137 has led to the identification of a new polycyclic metabolite, abyssomicin Y (1), together with six known abyssomicin and proximicin analogs (2-7). Abyssomicin Y is a type I abyssomicin with an epoxide group at C-8 and C-9. Compounds 1-3 showed potent inhibitory effects against the influenza A virus; their observed inhibition rates were 97.9%, 98.3%, and 95.9%, respectively, at a concentration of 10 µM, and they displayed lower cytotoxicity than 4. The structures were determined by different NMR techniques and HRMS experiments. This investigation revealed that OSMAC could serve as a useful method for enabling the activation of the silent genes in the microorganism and for the formation of previously unreported active secondary metabolites.

Low concentrations of FA exhibits the Hormesis effect by affecting cell division and the Warburg effect.

Formaldehyde (FA), a ubiquitous indoor environmental pollutant, has been classified as a carcinogen. There are many studies showed that low levels of FA could promote cell proliferation, however, little is known about the signal pathways. To determine the potential molecular mechanisms, human chronic myeloid leukemia cells (K562 cells) and human bronchial epithelial cells (16HBE cells) were exposed to different concentrations of FA. The data showed that FA at 0-125 µM or 0-60 µM promoted the proliferation of K562 cells or 16HBE cells respectively, indicating that FA did have the Hormesis effect. FA at 75 µM (K562 cells) and 40 µM (16HBE cells) significantly promoted cell proliferation, increased intracellular reactive oxygen species (ROS) levels, and decreased glutathione (GSH) content. At the same time, FA treatment induced a marked increase in the key molecules of cell division like CyclinD-cdk4 and E2F1. In addition, pyruvate kinase isozyme M2 (PKM2), glucose, glucose transporter 1 (GLUT1), lactic acid and lactate dehydrogenase A (LDHA) content in the Warburg effect were increased. Administering Vitamin E (VE), significantly disrupted cell division and disturbed the Warburg effect, effectively indicating the decrease of cell activity. Conclusively, these findings suggested that low concentrations of FA could promote cell proliferation by accelerating cell division process or enhancing the Warburg effect to embody the Hormesis effect.

MicroRNA-33a disturbs influenza A virus replication by targeting ARCN1 and inhibiting viral ribonucleoprotein activity.

In order to explore the roles of microRNA(s) [miRNA(s)] in the influenza A virus life cycle, we compared the miRNA profiles of 293T and HeLa cell lines, as influenza A virus can replicate efficiently in 293T cells but only poorly in HeLa cells. We analysed differentially expressed miRNAs and identified five, including miR-33a, that could disturb influenza A virus replication significantly. Using TargetScan analysis, we found that ARCN1 could be a potential target of miR-33a. To confirm whether miR-33a could truly target ARCN1, we generated a luciferase reporter for the ARCN1 3' untranslated region (UTR) and performed a luciferase assay. The data indicated that miR-33a could suppress the luciferase activity of the reporter for the ARCN1 3' UTR but not a reporter in which the predicted miR-33a targeting sites on ARCN1 3' UTR were mutated. We performed immunoblotting to confirm that miR-33a could downregulate the protein level of ARCN1. Consistently, the level of ARCN1 protein in HeLa cells was significantly lower than that in 293T cells. We also demonstrated that ectopic expression of ARCN1 could partially rescue the inhibitory effect of miR-33a on virus replication. Furthermore, we demonstrated that miR-33a could impede virus replication at the stage of virus internalization, which was similar to the pattern for knockdown of ARCN1, indicating that miR-33a inhibits influenza virus infection by suppressing ARCN1 expression. In addition, we found that miR-33a could also weaken the viral ribonucleoprotein activity in an ARCN1-independent manner. In conclusion, we found that miR-33a is a novel inhibitory factor for influenza A virus replication.

Inhibition effect of Cu(II) on nitrogen removal in anammox-denitrification couple system.

Due to the wide application in industries, copper can be detected in some nitrogen-rich wastewater. In this research, short-term and long-term experiments were conducted to explore the effects of Cu(II) on the anammox-denitrification couple system. It concluded that the half inhibition concentration (IC50) of Cu(II) was 35.54 mg/L. The system in reactor could tolerate low concentrations of Cu(II) (≤5 mg/L), while the total nitrogen removal efficiency decreased from 93 % to 33 % under 10 mg/L of Cu(II). After 45 days exposure to Cu(II) (1-10 mg/L), 14.54 mg/g SS copper accumulated in the sludge, which largely inhibited the microbial activity. More extracellular polymeric substances (EPS) were secreted to defend against copper toxicity. Proteobacteria (19.18 %-44.04 %) was the dominant phylum and showed excellent tolerance and adaptability to Cu(II). The dominant anammox bacteria, Candidatus_Brocadia, was slightly enhanced under low concentrations of Cu(II), but was highly inhibited under 10 mg/L of Cu(II). PICRUSt2 results showed that some metabolic activities were suppressed under the exposure of copper while defensive responses were also induced. Metabolic disorders eventually led to the death of some microbes, resulting in unrecoverable deterioration in microbial activity. Overall, this study explores the effect of Cu(II) on the anammox-denitrification process and provides a possible inhibition mechanism.

Nitrite accumulation performance and microbial community of Algal-Bacterial symbiotic system constructed by Chlorella sp. And Navicula sp.

Chlorella sp. and Navicula sp. were separately used to construct an algal-bacterial symbiotic system in two identical sequencing batch reactors (R1 and R2) to explore the influence of algal species differences on nitrite accumulation. The Navicula-bacterial symbiotic system showed a higher nitrite accumulation efficiency of 85% and a stronger resistance to ammonia load. It secreted twice as many extracellular polymeric substances than the Chlorella-bacterial symbiotic system. Nitrospira and SM1A02 were the dominant functional genera of nitrite-oxidizing bacteria in R1. The dominant functional genus of ammonium-oxidizing bacteria and the dominant functional genus of denitrifying bacteria were Ellin6067 and unclassified_Saprospiraceae in R2, respectively. In general, this research provided some reference for the construction of an algal-bacterial symbiotic system and achieving nitrite accumulation through an algal-bacterial symbiotic system.

Case report: Recombinant human type II tumour necrosis factor receptor-antibody fusion protein induced occult hepatitis B virus reactivation leading to liver failure.

Recombinant human type II tumour necrosis factor receptor-antibody fusion protein (rh TNFR:Fc) is an immunosuppressant approved for treating rheumatoid arthritis (RA). This case report describes a case of hepatitis B reactivation in a patient with drug-induced acute-on-chronic liver failure. A 58-year-old woman with a history of RA was treated with rh TNFR:Fc; and then subsequently received 25 mg rh TNFR:Fc, twice a week, as maintenance therapy. No anti-hepatitis B virus (HBV) preventive treatment was administered. Six months later, she was hospitalized with acute jaundice. HBV reactivation was observed, leading to acute-on-chronic liver failure. After active treatment, the patient's condition improved and she recovered well. Following careful diagnosis and treatment protocols are essential when treating RA with rh TNFR:Fc, especially in anti-hepatitis B core antigen antibody-positive patients, even when the HBV surface antigen and the HBV DNA are negative. In the case of HBV reactivation, liver function parameters, HBV surface antigen and HBV DNA should be closely monitored during treatment, and antiviral drugs should be used prophylactically when necessary, as fatal hepatitis B reactivation may occur in rare cases. A comprehensive evaluation and medication should be administered in a timely manner after evaluating the patient's physical condition and closely monitoring the patient.

Investigation of denitrification to Anammox phase transformation performance of Up-Flow anaerobic sludge blanket reactor.

For investigating the microbial community and nitrogen removal performance during the transformation from heterotrophic denitrification (HtDn), mixotrophic denitrification (MtDn), and autotrophic denitrification (AtDn) to anaerobic ammonia oxidation (Anammox), an up-flow anaerobic sludge blanket reactor was constructed by changing the influent substrates and their ratios. The reactor got a total nitrogen removal efficiency (TNRE) of 98.0 % at the molar ratio of carbon, nitrogen, and sulfur sources was 5:8:4 in the MtDn process. In the last phase, the conversion of AtDn to Anammox was successful in 33 days, and a stable TNRE was 87.7 %. The dominant functional bacteria of the microbial communities were Thauera and unclassified_Comamonadaceae in the HtDn process; Thiobacillus, Thauera, Denitratisoma, and Pseudoxanthomonas in the MtDn process; Thiobacillus and Sulfurimonas in the AtDn process; and unclassified_Gemmatimonadaceae, unclassified_SBR1031, and Candidatus_Brocadia in the Anammox process.

Treatment of rectal anastomotic atresia with transurethral prostate resection instrumentation: A report of three cases.

Dixon surgery for rectal cancer can lead to severe intestinal narrowing and blockage that is difficult to treat with open surgery or colonoscopy. The aim of the present study was to develop a minimally invasive approach for treating rectal anastomotic atresia based on three cases that were managed with transurethral prostate resection instrumentation. Preoperative imaging determined the distance from the anastomotic closure to the anal margin, the length of the anastomotic closure and the degree of proximal intestinal dilation for all cases. During the procedure, the anastomotic site was visualized, and a circular electrode was used to excavate and open the blockage. Membrane-like closures were directly incised to achieve satisfactory results, with an anastomotic diameter >20 mm. Those cases with tubular atresia required an initial incision using the prostate resectoscope to relieve the obstruction, followed by radial incisions until achieving an anastomotic diameter >20 mm. At 3-6 months post-dilation, two of the patients with anastomotic atresia >20 mm had satisfactory bowel movements, whereas the remaining patient experienced tumor recurrence at the anastomotic site and discontinued treatment. This case series demonstrates the potential of transurethral prostate resection instrumentation as a safe and effective minimally invasive approach for rectal anastomotic atresia. Given that prostate resection instrumentation is readily available in hospitals in China, this approach is widely accessible to most patients. Furthermore, the technique leverages existing surgical technology and practices, requiring only a shift in the surgical site.

The coupling of anammox with microalgae-bacteria symbiosis: Nitrogen removal performance and microbial community.

The partial nitrification-anammox process for ammonia nitrogen wastewater treatment requires mechanical aeration to provide oxygen, which is not conducive to energy saving. The microalgae-bacteria symbiotic system (MaBS) has the advantages of low carbon and energy saving in wastewater biological nitrogen removal. Therefore, this study combined the MaBS with an anammox process to provide oxygen, through the photosynthesis of microalgae instead of mechanical aeration. We investigated the nitrogen removal efficiency and long-term operation of a co-culture system comprising microalgae, nitrifying bacteria (NB), denitrifying bacteria (DnB), and anaerobic ammonium-oxidation bacteria (AnAOB) in a sequencing batch reactor without mechanical aeration. The experiment was divided into three steps: firstly, cultivating NB; then, adding three kinds of microalgae which were Chlorella sp., Anabaena sp., and Navicula sp. to the bioreactor to construct a microalgae-bacteria symbiotic system; finally, adding anammox sludge to construct the anammox and microalgae-bacteria symbiosis (Anammox-MaBS) system. The results demonstrated that nitrification, denitrification, and anammox processes were coupled successfully, and the maximum TN removal efficiency of the stable Anammox-MaBS system was 99.51 % when the concentration of the influent NH4+-N was 100 mg/L. The addition of microalgae in ammonia wastewater promoted the enrichment of DnB and AnAOB, which were Denitratisoma, Haliangium, unclassified_Rhodocyclaceae, and Candidatus_Brocadia. Furthermore, the unique biofilm structure could effectively alleviate the photoinhibition of light-sensitive bacteria, which may be the reason for the long-term adaptation of Candidatus_Brocadia to light conditions. This research can provide a low-cost solution to bacterial photoinhibition in the coexistence system of microalgae and bacteria without mechanical aeration, offering theoretical support for low-carbon and energy-efficient treatment of wastewater.

Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases: A case report.

BACKGROUND: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are two common clinical autoimmune liver diseases, and some patients have both diseases; this feature is called AIH-PBC overlap syndrome. Autoimmune thyroid disease (AITD) is the most frequently overlapping extrahepatic autoimmune disease. Immunoglobulin (IgG) 4-related disease is an autoimmune disease recognized in recent years, characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues. CASE SUMMARY: A 68-year-old female patient was admitted with a history of right upper quadrant pain, anorexia, and jaundice on physical examination. Laboratory examination revealed elevated liver enzymes, multiple positive autoantibodies associated with liver and thyroid disease, and imaging and biopsy suggestive of pancreatitis, hepatitis, and PBC. A diagnosis was made of a rare and complex overlap syndrome of AIH, PBC, AITD, and IgG4-related disease. Laboratory features improved on treatment with ursodeoxycholic acid, methylprednisolone, and azathioprine. CONCLUSION: This case highlights the importance of screening patients with autoimmune diseases for related conditions.

The combination of uridine and nitrogen-deprivation promotes the efficient formation of astaxanthin-rich motile cells in Haematococcus pluvialis.

Astaxanthin accumulation in Haematococcus pluvialis typically occurs alongside the formation of secondary cell wall (SCW), hindering astaxanthin extraction and bio-accessibility. A potential solution lies in cultivating astaxanthin-rich motile cells lacking SCW. This study explored the influence and underlying mechanism of nitrogen-deprivation (ND) on SCW formation and established a connection between pyrimidine metabolism and SCW development. Then, various pyrimidine and ND combinations were examined to cultivate astaxanthin-rich motile cells. The results indicated that, compared to the nitrogen-replete group, the combination of uridine and ND increased the proportion of motile cells by 25-33 times, achieving 95 %, and enhanced astaxanthin yield by 26.52 %. Moreover, the efficiency of astaxanthin extraction from intact, wet motile cells was 91 % - 95 %, which was 5.6-9.0 times that from non-motile cells. This study not only presents a promising method for producing astaxanthin-rich motile cells in H. pluvialis but also provides insights into the relationship between pyrimidine metabolism and SCW development.

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.

ABCB4 gene mutation-associated cirrhosis with systemic amyloidosis: A case report.

BACKGROUND: Gene mutations in ATP-binding cassette, subfamily B (ABCB4) lead to autosomal recessive disorders. Primary light amyloidosis is a rare and incurable disease. Here, we report a rare case of liver cirrhosis caused by ABCB4 gene mutation combined with primary light amyloidosis. CASE SUMMARY: We report a case of a 25-year-old female who was hospitalized due to recurrent abdominal pain caused by calculous cholecystitis and underwent cholecystectomy. Pathological examination of the liver tissue suggested liver cirrhosis with bile duct injury. Exon analyses of the whole genome from the patient's peripheral blood revealed the presence of a heterozygous mutation in the ABCB4 gene. Bone marrow biopsy tissues, renal puncture examination, and liver mass spectrometry confirmed the diagnosis of a rare progressive familial intrahepatic cholestasis type 3 with systemic light chain type κ amyloidosis, which resulted in cirrhosis. Ursodeoxycholic acid and the cluster of differentiation 38 monoclonal antibody daretozumab were administered for treatment. Following treatment, the patient demonstrated significant improvement. Urinary protein became negative, peripheral blood-free light chain and urine-free light chain levels returned to normal, and the electrocardiogram showed no abnormalities. Additionally, the patient's lower limb numbness resolved, and her condition remained stable. CONCLUSION: This report presents the diagnosis and treatment of liver cirrhosis, a rare disease that is easily misdiagnosed or missed.