Exosomes derived from bone marrow mesenchymal stem cells alleviate biliary ischemia reperfusion injury in fatty liver transplantation by inhibiting ferroptosis.

Fatty liver grafts are susceptible to ischemia reperfusion injury (IRI), increasing the risk of biliary complications after liver transplantation (LT). Ferroptosis, a newly recognized programmed cell death, is expected to be a novel therapeutic target for IRI. We investigated whether exosomes derived from heme oxygenase 1-modified bone marrow mesenchymal stem cells (HExos) relieve ferroptosis and protect biliary tracts from IRI in a rat fatty liver transplantation model. Rats were fed with a methionine choline deficient (MCD) diet for 2 weeks to induce severe hepatic steatosis. Steatotic grafts were implanted and HExos were administered after liver transplantation. A series of functional assays and pathological analysis were performed to assess ferroptosis and biliary IRI. The HExos attenuated IRI following liver transplantation, as demonstrated by less ferroptosis, improved liver function, less Kupffer and T cell activation, and less long-term biliary fibrosis. MicroRNA (miR)-204-5p delivered by HExos negatively regulated ferroptosis by targeting a key pro-ferroptosis enzyme, ACSL4. Ferroptosis contributes to biliary IRI in fatty liver transplantation. HExos protect steatotic grafts by inhibiting ferroptosis, and may become a promising strategy to prevent biliary IRI and expand the donor pool.

Impact of different ischemia times on biliary stricture after living donor liver transplantation with biliary atresia.

Biliary atresia (BA) is the most common indication for pediatric liver transplantation, and biliary stricture (BS) remains an Achilles' heel for pediatric living donor liver transplantation (LDLT). We investigated the impact of different ischemia times on BS after LDLT in patients with BA. We retrospectively analyzed patients (<18 y) with BA who underwent LDLT between January 2016 and December 2020. Cases with hepatic artery thrombosis, bile leakage, early BS (<2 wk), and early death (<3 mo) were excluded. In all, 572 cases were included. A total of 26 cases (4.55%, 26/572) developed BS: 25 patients with anastomotic stricture and 1 patient with anastomotic stricture combined with left hepatic duct stricture. In addition, the time to diagnosis of BS ranged from 1.8 to 53.0 months (mean, 13.0 mo and median, 8.2 mo) after transplantation. A multivariate logistic regression analysis showed that arterial ischemia time (AIT), per 10 minutes (OR=1.222, 95% CI: 1.007-1.438, p =0.04) was the only independent risk factor for the development of BS after LDLT in patients with BA. What is more, the 5-year cumulative risk of BS between the AIT ≥40 minutes and AIT <40 minutes groups was 2.79% versus 10.57%. AIT was the only independent risk factor for the development of BS after LDLT with BA, and AIT ≥40 minutes would increase the 5-year cumulative risk of BS in our study. A shorter AIT, especially AIT <40 minutes, should be kept to decrease BS.

Outcome of split-liver transplantation from pediatric donors weighing 25 kg or less.

The lower limit of body weight for "splitable" liver grafts remains unknown. To examine the outcome of split-liver transplantation (SLT) from pediatric donors ≤25 kg relative to conventional graft-type liver transplantation from deceased donors under corresponding conditions, a total of 158 patients who received primary liver transplantation, including 22 SLTs from donors ≤25 kg, 46 SLTs from donors >25 kg, 76 whole-liver transplantations, and 14 reduced-liver transplantations in donors ≤25 kg between January 2018 and December 2019, were included in the study. There was no significant difference in the complications, patient survival, and graft survival between each of the latter three groups and the SLT ≤25 kg group. Pediatric End-Stage Liver Disease (PELD) score was the independent predictor of graft loss (death or retransplantation). Graft weight was the independent predictor of hepatic artery thrombosis. SLT using well-selected pediatric donors ≤25 kg is an effective strategy to increase organ availability, especially for low-body-weight recipients, compared with conventional graft type from deceased donors under the condition of corresponding donor weight without increasing morbidity and mortality.

Incidence and risk factors of subclinical rejection after pediatric liver transplantation, and impact on allograft fibrosis.

INTRODUCTION: Subclinical rejection (SCR) is a common injury in protocol biopsy after pediatric liver transplantation (pLT), but its effect on the recipient is not clearly understood. We herein investigated the incidence and risk factors involved in SCR and analyzed the relationship between SCR and allograft fibrosis (AF). METHODS: We retrospectively reviewed the biopsy results from 507 children between May 2013 and May 2019, and 352 patients underwent protocol biopsy 2 years after pLT, 203 underwent protocol biopsy 5 years after pLT, and 48 underwent protocol biopsy both 2 and 5 years after pLT. RESULTS: The incidence of SCR in the 5-year group was higher than that in the 2-year group (20.2% vs.13.4%, respectively, p = .033). The number of patients with mild and moderate SCR in the 5-year group was also higher than that in the 2-year group (p = .039). Logistic regression analysis showed that acute rejection before liver biopsy and deceased donor liver transplantation (DDLT) were independent risk factors for SCR in the two groups, and that the incidence and severity of AF in protocol biopsies at both periods in the SCR group were higher than those in the non-SCR group (p < .05). CONCLUSIONS: The incidence and severity of SCR increased with the prolongation of protocol biopsy time. We postulate that acute rejection and DDLT are independent risk factors for SCR after transplantation. As the occurrence of SCR also augmented the incidence and severity of AF.

Tandem Synthesis of 2-Azaspiro[4.5]deca-1,6,9-trien-8-ones Based on Tf2O-Promoted Activation of N-(2-Propyn-1-yl) Amides.

Structurally novel 2-azaspiro[4.5]deca-1,6,9-trien-8-ones were synthesized from N-(2-propyn-1-yl) amides and 1,3,5-trimethoxybenzenes by a tandem method consisting of a Tf2O-promoted amide activation and a TfOH-promoted Friedel-Crafts ipso-cyclization. The method offered the first example of using N-(2-propyn-1-yl) amides as substrates in both Tf2O-promoted secondary amide activation and the synthesis of azaspiro[4.5]deca-6,9-diene-8-ones.

The value of 18 F-FDG PET/CT quantitative indexes in the diagnosis of nondestructive posttransplant lymphoproliferative disorders after pediatric liver transplantation.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication after pediatric liver transplantation (pLT), which may lead to death. 18 F-FDG PET/CT is rarely considered in PTLD after pLT and lacks clear diagnostic guidelines, especially in the differential diagnosis of nondestructive PTLD. The aim of this study was to find a quantifiable 18 F-FDG PET/CT index to identify nondestructive PTLD after pLT. METHODS: This retrospective study collected the data of patients who underwent pLT, postoperative lymph node biopsy, and 18 F-FDG PET/CT at Tianjin First Central Hospital from January 2014 to December 2021. Quantitative indexes were established using lymph node morphology and the maximum standardized uptake value (SUVmax). RESULTS: A total of 83 patients met the inclusion criteria and were included in this retrospective study. To distinguish between PTLD-negative cases and nondestructive PTLD cases, according to the receiver operating characteristic curve, (the shortest diameter of the lymph node at the biopsy site [SDL]/the longest diameter of the lymph node at the biopsy site [LDL])*(SUVmax at the biopsy site [SUVmaxBio]/SUVmax of the tonsils [SUVmaxTon]) had the maximum area under the curve (0.923; 95% confidence interval: 0.834-1.000), and the cutoff value was 0.264 according to the maximum value of Youden's index. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93.6%, 94.7%, 97.8%, 85.7%, and 93.9%, respectively. CONCLUSIONS: (SDL/LDL)*(SUVmaxBio/SUVmaxTon) has good sensitivity, specificity, positive predictive and negative predictive values, and accuracy, and can be used as a good quantitative index for the diagnosis of nondestructive PTLD.

Heme Oxygenase-1-Modified BMMSCs Activate AMPK-Nrf2-FTH1 to Reduce Severe Steatotic Liver Ischemia-Reperfusion Injury.

BACKGROUND: Ischemia-reperfusion injury (IRI) is an important cause of graft dysfunction post-liver transplantation, where donor liver with severe steatosis is more sensitive to IRI. Liver IRI involves ferroptosis and can be alleviated by heme oxygenase-1-modified bone marrow mesenchymal stem cells (HO-1/BMMSCs). AIMS: To explore the role and mechanism of HO-1/BMMSCs in severe steatotic liver IRI. METHODS: A severe steatotic liver IRI rat model and a hypoxia/reoxygenation (H/R) of severe steatosis hepatocyte model were established. Liver and hepatocyte damage was evaluated via liver histopathology and cell activity. Ferroptosis was evaluated through ferroptosis indexes. Nuclear factor erythroid 2-related factor 2 (Nrf2) was knocked down in severe steatotic hepatocytes. The role of Nrf2 and AMPK in HO-1/BMMSC inhibition of ferroptosis was examined using the AMP-activated protein kinase (AMPK) pathway inhibitor Compound C. RESULTS: The HO-1/BMMSCs alleviated severe steatotic liver IRI and ferroptosis. HO-1/BMMSCs promoted ferritin heavy chain 1(FTH1), Nrf2, and phosphorylated (p)-AMPK expression in the H/R severe steatotic hepatocytes. Nrf2 knockdown decreased FTH1 expression levels but did not significantly affect p-AMPK expression levels. The protective effect of HO-1/BMMSCs against H/R injury in severe steatotic hepatocytes and the inhibitory effect on ferroptosis were reduced. Compound C decreased p-AMPK, Nrf2, and FTH1 expression levels, weakened the HO-1/BMMSC protective effect against severe steatotic liver IRI and H/R-injured severe steatotic hepatocytes, and reduced the inhibition of ferroptosis. CONCLUSIONS: Ferroptosis was involved in HO-1/BMMSC reduction of severe steatotic liver IRI. HO-1/BMMSCs protected against severe steatotic liver IRI by inhibiting ferroptosis through the AMPK-Nrf2-FTH1 pathway. HO-1/BMMSCs activate AMPK, which activates Nrf2, promotes its nuclear transcription, then promotes the expression of its downstream protein FTH1, thereby inhibiting ferroptosis and attenuating severe steatotic liver IRI in rats. Glu: glutamic acid; Cys: cystine; GSH: glutathione; GPX4: glutathione peroxidase 4; HO-1/BMMSCs: HO-1-modified BMMSCs; Fer-1: ferrostatin-1; DFO: deferoxamine; FTH1: ferritin heavy chain1; p-AMPK: phosphorylated AMP-activated protein kinase; Nrf2: nuclear factor erythroid 2-related factor 2; IRI: ischemia-reperfusion injury; MCD: methionine-choline deficiency.

HBsAg seroconversion in de novo hepatitis B virus-infected paediatric liver transplant recipients with anti-viral therapy.

We investigated the clinical characteristics and therapeutic strategies for paediatric liver transplant (PLT) recipients who experienced de novo hepatitis B virus infection and the features of HBsAg seroconversion. A total of 821 PLT were performed in HBV-free recipients between January 2013 and January 2019 in Paediatric Organ Transplant Center, Tianjin First Central Hospital. Twenty-one recipients developed de novo HBV infection, the clinical data were analysed. The overall incidence of de novo HBV infection was 2.5%. Only one recipient received an HBcAb-negative graft, 20 recipients received HBcAb-positive grafts. The incidence of de novo HBV infection in HBcAb-negative and HBcAb-positive graft recipients were 0.2% and 6.3%, respectively. Fifteen de novo HBV-infected recipients showed HBsAg seroconversion, the incidence of HBsAg seroconversion was 71.4%. The median time from the diagnosis of de novo HBV infection to HBsAg seroconversion was 15 (1, 73) months. Recipients with hepatitis B surface antigen (HBsAg) titre <1000 IU/L and negative hepatitis B e antigen (HBeAg) at the time of de novo HBV infection diagnosis were more likely to achieve HBsAg seroconversion. Nucleotide analogues were effective in treating recipients with de novo HBV infection. De novo HBV infection does not impact liver graft function as well as recipient and graft survival rate. De novo HBV infection does not impact PLT recipient outcomes under close monitoring and appropriate treatment. High incidence of HBsAg seroconversion can be achieved after anti-viral therapy.

Impact of allograft types on outcomes after pediatric liver transplantation due to biliary atresia.

BACKGROUND: Several surgical strategies, including split donor transplantation and living donor transplantation, have been used to increase the donor liver pool. This report focuses on the effects of whole, split, and LDLT on recipient outcomes. METHODS: We retrospectively analyzed the records of all patients with biliary atresia at Tianjin First Central Hospital between April 2013 and December 2019. RESULTS: A total of 882 patients were included and divided into three groups by graft type, with 198 in the whole-liver-transplantation group, 78 in the split liver transplantation group, and 606 in the LDLT group. The median follow-up time was 39 months, patient survival rates of three groups were 94.4%, 88.5%, and 95.0%, respectively, and graft survival rates were 90.2%, 83.3%, and 94.7%, respectively. We divided the split liver transplantation group into two subgroups according to the donor's age, and patient survival rates exhibited a significant difference only in the group whose donor age was over 45 years. The postoperative complication rates were significantly higher with respect to hepatic artery thrombosis, portal stenosis, and AR; and lower in hepatic venous stenosis, PTLDs, CMV virus, and EBV infection in the WLT group. Our multivariate model showed that donor age ≥45 years, RBC transfusion, pneumonia, and HAT were the independent predictors of allograft loss. CONCLUSIONS: The survival of split liver transplantation group was slightly lower. The types of complications are different from different graft types. Therefore, postoperative monitoring and treatment need to be adjusted according to the different graft types used.

The diagnosis and management of intestinal obstruction after pediatric liver transplantation.

BACKGROUND: The aim of this study was to analyze the risk factors, causes, and management of intestinal obstruction after pediatric liver transplantation. METHODS: Retrospective analysis was performed on pediatric liver transplantation recipients from January 1st 2013 to December 31st 2019 at Organ Transplant Center, Tianjin First Central Hospital. The cases of intestinal obstruction were analyzed. RESULTS: A total of 1034 pediatric liver transplantations were performed during the study period, 66 intestinal obstructions were diagnosed in 61 recipients. Three recipients suffered intestinal obstructions twice, and one recipient suffered three times. Forty of the 66 cases were treated with non-surgical treatment, including fasting, gastrointestinal decompression, purgation, enema, and parenteral nutrition. Surgical intervention was performed in 26 cases. Diaphragmatic hernia, intestinal inflammatory stenosis, PTLD, and intestine perforation are essential causes of intestinal obstruction in pediatric liver transplant recipients. Diaphragmatic hernia was independent risk factors for intestinal obstruction. The 1-, 2- and 3-year survival rate of the recipients with or without intestinal obstruction were 98.4%, 96.5%, 96.5% and 95.3%, 94.4%, 94.0%, respectively, without significant difference. CONCLUSIONS: Most cases of intestinal obstruction after liver transplantation in children can be remitted by non-surgical treatment, but there are still some cases need to be treated by surgery. Both measures are related to ideal outcomes, intestinal obstruction does not increase the mortality rate in pediatric liver transplantation.

Diagnostic Value of the Iliac Vein Stenosis Percentage Combined With Indicators of Venous Reflux for Iliac Vein Compression Syndrome With Computed Tomography Venography.

OBJECTIVES: To identify a cutoff value of iliac vein stenosis in computed tomography venography (CTV) for assisting in the diagnosis of iliac vein compression syndrome (IVCS). Meanwhile, determining whether the inclusion of venous return and collateral imaging findings could further enhance the diagnostic performance. METHODS: We conducted a retrospective study on 264 patients suspected of IVCS who underwent both CTV and digital subtraction venography (DSV) from January 2016 to December 2020; they were assigned to either a control group (n = 101) or an IVCS group (n = 163) based on the DSV results. The narrowest anteroposterior diameter of the common iliac vein and the anteroposterior diameter of the distal end were measured to calculate the percentage of iliac vein stenosis. Receiver operating characteristic curve analysis was performed to determine the predictive accuracy of the percentage of iliac vein stenosis for IVCS and whether the inclusion of venous reflux indicators can further improve the diagnostic accuracy. RESULTS: With respect to the DSV results, the area under the curve was 0.797 ( P < 0.001). The best cutoff value was 46.67%, corresponding to a sensitivity of 83.44% and a specificity of 69.31% for predicting IVCS. Moreover, the combination diagnostic method had higher sensitivity and accuracy (94.48% vs 83.44% [ P = 0.01] and 84.85% vs 78.03% [ P = 0.04], respectively). CONCLUSIONS: The best cutoff percentage of iliac vein stenosis to diagnose IVCS was 46.67% with CTV. The sensitivity and accuracy of the combined diagnostic method were higher than those of the iliac vein stenosis ratio diagnostic method.

miR-124-3p delivered by exosomes from heme oxygenase-1 modified bone marrow mesenchymal stem cells inhibits ferroptosis to attenuate ischemia-reperfusion injury in steatotic grafts.

BACKGROUND: Steatotic livers tolerate ischemia-reperfusion injury (IRI) poorly, increasing the risk of organ dysfunction. Ferroptosis is considered the initiating factor of organ IRI. Heme oxygenase oxygen-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) (HO-1/BMMSCs) can reduce hepatic IRI; however, the role of ferroptosis in IRI of steatotic grafts and the effect of HO-1/BMMSCs-derived exosomes (HM-exos) on ferroptosis remain unknown. METHODS: A model of rat liver transplantation (LT) with a severe steatotic donor liver and a model of hypoxia and reoxygenation (H/R) of steatotic hepatocytes were established. Exosomes were obtained by differential centrifugation, and the differentially expressed genes (DEGs) in liver after HM-exo treatment were detected using RNA sequencing. The expression of ferroptosis markers was analyzed. microRNA (miRNA) sequencing was used to analyze the miRNA profiles in HM-exos. RESULTS: We verified the effect of a candidate miRNA on ferroptosis of H/R treated hepatocytes, and observed the effect of exosomes knockout of the candidate miRNA on hepatocytes ferroptosis. In vitro, HM-exo treatment reduced the IRI in steatotic grafts, and enrichment analysis of DEGs suggested that HM-exos were involved in the regulation of the ferroptosis pathway. In vitro, inhibition of ferroptosis by HM-exos reduced hepatocyte injury. HM-exos contained more abundant miR-124-3p, which reduced ferroptosis of H/R-treated cells by inhibiting prostate six transmembrane epithelial antigen 3 (STEAP3), while overexpression of Steap3 reversed the effect of mir-124-3p. In addition, HM-exos from cell knocked out for miR-124-3p showed a weakened inhibitory effect on ferroptosis. Similarly, HM-exo treatment increased the content of miR-124-3p in grafts, while decreasing the level of STEAP3 and reducing the degree of hepatic ferroptosis. CONCLUSION: Ferroptosis is involved in the IRI during LT with a severe steatotic donor liver. miR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft IRI, which might be a promising strategy to treat IRI in steatotic grafts.

Prophylactic Strategy Against De Novo Hepatitis B Virus Infection for Pediatric Recipients Who Receive Hepatitis B Core Antibody-Positive Liver Grafts.

The goal of this study was to evaluate the efficacy of a perioperative prophylactic strategy against de novo hepatitis B virus (HBV) infection in pediatric liver transplantation (LT) recipients with hepatitis B core antibody (HBcAb)-positive grafts. A total of 482 pediatric recipients transplanted between 2013 and 2017 were enrolled, and 170 recipients received HBcAb-positive liver grafts. The overall graft and recipient survival rates in HBcAb-positive and HBcAb-negative graft recipients were 91.8% versus 91.3% and 95.3% versus 94.2% at the end of follow-up. Preoperative hepatitis B surface antibody (HBsAb) titer ≥ 1000 IU/L and postoperative HBsAb titer ≥200 IU/L were our prophylactic targets for recipients receiving HBcAb-positive grafts. While 11 recipients developed de novo HBV infection, 10 received HBcAb-positive grafts. Both the preoperative and postoperative HBsAb targets were achieved in 78 recipients, the infection rate of de novo HBV was 1.3%; 24 recipients met the preoperative target, the infection rate was 4.2%; 52 recipients met the postoperative target, the infection rate was 1.9%; and 16 recipients met neither the preoperative nor postoperative HBsAb target, 43.8% of the recipients were infected with de novo HBV, which was significantly higher than the recipients who met both or either of the preoperative and postoperative targets. Split-liver grafts positive for HBcAb showed higher risk of de novo HBV infection. Postoperative application of lamivudine to recipients whose preoperative HBsAb titer < 1000 IU/L did not show preventive effect. Out of 11 infected recipients, 3 showed seroconversion under entecavir treatment. In conclusion, the graft and recipient survival rates were similar in pediatric LT recipients receiving HBcAb-positive or HBcAb-negative grafts. Our prophylactic strategy was effective for preventing de novo HBV infection in HBcAb-positive liver graft recipients.

Aptamer-based biosensors for the diagnosis of sepsis.

Sepsis, the syndrome of infection complicated by acute organ dysfunction, is a serious and growing global problem, which not only leads to enormous economic losses but also becomes one of the leading causes of mortality in the intensive care unit. The detection of sepsis-related pathogens and biomarkers in the early stage plays a critical role in selecting appropriate antibiotics or other drugs, thereby preventing the emergence of dangerous phases and saving human lives. There are numerous demerits in conventional detection strategies, such as high cost, low efficiency, as well as lacking of sensitivity and selectivity. Recently, the aptamer-based biosensor is an emerging strategy for reasonable sepsis diagnosis because of its accessibility, rapidity, and stability. In this review, we first introduce the screening of suitable aptamer. Further, recent advances of aptamer-based biosensors in the detection of bacteria and biomarkers for the diagnosis of sepsis are summarized. Finally, the review proposes a brief forecast of challenges and future directions with highly promising aptamer-based biosensors.

Nutritional status and risk of contrast-associated acute kidney injury in elderly patients undergoing percutaneous coronary intervention.

BACKGROUND: This study aimed to investigate the connection between malnutrition evaluated by the Controlling Nutritional Status (CONUT) score and the risk of contrast-associated acute kidney injury (CA-AKI) in elderly patients who underwent percutaneous coronary intervention (PCI). METHODS: A total of 1308 patients aged over 75 years undergoing PCI was included. Based on the CONUT score, patients were assigned to normal (0-1), mild malnutrition (2-4), moderate-severe malnutrition group (≥ 5). The primary outcome was CA-AKI (an absolute increase in ≥ 0.3 mg/dL or ≥ 50% relative serum creatinine increase 48 h after contrast medium exposure). RESULTS: Overall, the incidence of CA-AKI in normal, mild, moderate-severe malnutrition group was 10.8%, 11.0%, and 27.2%, respectively (p < 0.01). Compared with moderate-severe malnutrition group, the normal group and the mild malnutrition group showed significant lower risk of CA-AKI in models adjusting for risk factors for CA-AKI and variables in univariate analysis (odds ratio [OR] = 0.48, 95% confidence interval [CI]: 0.26-0.89, p = 0.02; OR = 0.46, 95%CI: 0.26-0.82, p = 0.009, respectively). Furthermore, the relationship were consistent across the subgroups classified by risk factors for CA-AKI except anemia. The risk of CA-AKI related with CONUT score was stronger in patients with anemia. (overall interaction p by CONUT score = 0.012). CONCLUSION: Moderate-severe malnutrition is associated with higher risk of CA-AKI in elderly patients undergoing PCI.

Protective Effects of Bone Marrow Mesenchymal Stem Cells (BMMSCS) Combined with Normothermic Machine Perfusion on Liver Grafts Donated After Circulatory Death via Reducing the Ferroptosis of Hepatocytes.

BACKGROUND To improve the quality of liver grafts from extended-criteria donors donated after circulatory death (DCD), this study explored whether bone marrow mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP) have protective effects on DCD donor livers and the effects of ferroptosis in this procedure. MATERIAL AND METHODS Twenty-four male rat DCD donor livers were randomly and averagely divided into normal, static cold storage (SCS), NMP, and NMP combined with BMMSCs groups. Liver function, bile secretion, and pathological features of DCD donor livers were detected to evaluate the protective effects of NMP and BMMSCs on DCD donor livers. Hydrogen peroxide was used to induce an oxidative stress model of hepatocyte IAR-20 cells to evaluate the protective effects of BMMSCs in vitro. RESULTS Livers treated with NMP combined with BMMSCs showed better liver function, relieved histopathological damage, reduced oxidative stress injury and ferroptosis, and the mechanism of reduction was associated with downregulation of intracellular reactive oxygen species (ROS) and free Fe²âº levels. BMMSCs showed significant protective effects on the ultrastructure of DCD donor livers and ROS-induced injury to IAR-20 cells under electron microscopy. BMMSCs also significantly improved the expression level of microtubule-associated protein 1 light chain 3 (LC3)-II in both DCD donor livers and ROS-induced injured IAR-20 cells, including upregulating the expression of ferritin. CONCLUSIONS BMMSCs combined with NMP could reduce the level of ROS and free Fe²âº in oxidative stress damaged rat DCD donor livers, potentially reduce the ferroptosis in hepatocytes, and repair both morphology and function of DCD donor livers.

Clustering by Errors: A Self-Organized Multitask Learning Method for Acoustic Scene Classification.

Acoustic scene classification (ASC) tries to inference information about the environment using audio segments. The inter-class similarity is a significant issue in ASC as acoustic scenes with different labels may sound quite similar. In this paper, the similarity relations amongst scenes are correlated with the classification error. A class hierarchy construction method by using classification error is then proposed and integrated into a multitask learning framework. The experiments have shown that the proposed multitask learning method improves the performance of ASC. On the TUT Acoustic Scene 2017 dataset, we obtain the ensemble fine-grained accuracy of 81.4%, which is better than the state-of-the-art. By using multitask learning, the basic Convolutional Neural Network (CNN) model can be improved by about 2.0 to 3.5 percent according to different spectrograms. The coarse category accuracies (for two to six super-classes) range from 77.0% to 96.2% by single models. On the revised version of the LITIS Rouen dataset, we achieve the ensemble fine-grained accuracy of 83.9%. The multitask learning models obtain an improvement of 1.6% to 1.8% compared to their basic models. The coarse category accuracies range from 94.9% to 97.9% for two to six super-classes with single models.

Application of pediatric donors in split liver transplantation: Is there an age limit?

The experience of using pediatric donors in split liver transplant is exceedingly rare. We aim to investigate the outcomes of recipients receiving split pediatric grafts. Sixteen pediatric recipients receiving split liver grafts from 8 pediatric donors < 7 years were enrolled. The donor and recipient characteristics, perioperative course, postoperative complications, and graft and recipient survival rates were evaluated. The mean follow-up time was 8.0 ± 2.3 months. The graft and recipient survival rates were 100%. The liver function remained in the normal range at the end of the follow-up time in all recipients. No life-threatening complications were seen in these recipients, and the only surgery-related complication was portal vein stenosis in 1 recipient. Cytomegalovirus infection was the most common complication (62.5%). The transaminase level was significant higher in extended right lobe recipients in the early postoperative days, but the difference vanished at the end of first week; postoperative complications and graft and recipient survival rates did not differ between left and right graft recipients. Notably, the youngest split donor graft (2.7 years old) was associated with ideal recipient outcomes. Split liver transplant using well-selected pediatric donors is a promising strategy to expand pediatric donor source in well-matched recipients.

Acyl Cyanides as Bifunctional Reagent: Application in Copper-Catalyzed Cyanoamidation and Cyanoesterification Reaction.

Cu-catalyzed domino decyanation and cyanation reaction of acyl cyanides with amines or alcohols have been developed. The cyano sources were generated in situ via C-CN cleavage yielding the corresponding cyano substituted amides or esters in moderate to excellent yields. This approach features a cheap copper catalyst, domino decyanation and cyanation reaction, readily available starting materials, broad substrate scope, operational simplicity, and the potential for further transformation of the cyano group.

miR-544a Stimulates endometrial carcinoma growth via targeted inhibition of reversion-inducing cysteine-rich protein with Kazal motifs.

Endometrial carcinoma (EC) is a female-specific malignant tumor. Although current treatments can achieve good outcomes and improve patient survival, there remains a high incidence of treatment-induced infertility, a serious side effect that is unacceptable to those of childbearing age. Studies have demonstrated that micro ribonucleic acids (microRNAs or miRNAs) such as miR-544a regulate tumor-related gene expression. However, whether miR-544a is involved in the progression of EC is unknown. This study aimed to investigate the biological functions and underlying mechanisms of miR-544a in EC in vivo and in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed miR-544a overexpression in EC tissue and cell lines, which was associated with a decreased in overall survival as revealed by Kaplan-Meier analysis. Functionally, the miR-544a inhibitor restricted the proliferation [detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay], invasion, and migration (detected by transwell assay) of human endometrial adenocarcinoma cells (HEC-1B and Ishikawa) and facilitated cell apoptosis (detected by flow cytometry assay). Western blotting analysis revealed that the miR-544a inhibitor decreased the expressions of matrix metalloproteinase (MMP)-2 and MMP-9 and elevated the levels of cleaved caspase3 and cleaved poly (ADP-ribose) polymerase. Furthermore, animal experiments indicated that the miR-544a antagonist (antagomir-544a) suppressed tumor growth significantly in a mouse xenograft model. The mechanistic, qRT-PCR, and immunohistochemical indications were that a reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and miR-544a had inverse expression changes in EC. Bioinformatics analysis revealed RECK as a potential target for miR-544a, and this was verified by the dual-luciferase reporter assay. Subsequently, in vitro experiments, including transwell assay, MTT assay, flow cytometry assay, and Western blotting analysis, demonstrated that RECK exerted antitumor effects on EC, which were negatively regulated by miR-544a. Taken together, our study findings suggested miR-544a as a valuable target in EC therapy.