Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma: a multicenter cohort study in China.

OBJECTIVE: Sex-specific differences are observed in various liver diseases, but the influence of sex on the outcomes of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains to be determined. This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC. METHODS: Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed. The associations between donor, recipient, or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching (PSM). The survival associated with different sex-based donor-recipient transplant patterns was further studied. RESULTS: Among 3,769 patients enrolled in this study, the 1-, 3-, and 5-year overall survival (OS) rates of patients with HCC after LT were 96.1%, 86.4%, and 78.5%, respectively, in female recipients, and 95.8%, 79.0%, and 70.7%, respectively, in male recipients after PSM (P = 0.009). However, the OS was comparable between recipients with female donors and male donors. Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival (HR = 1.381, P = 0.046). Among the donor-recipient transplant patterns, the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival (P < 0.05). CONCLUSIONS: Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients, and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival. Livers from male donors may provide the most benefit to female recipients. Our results indicate that sex should be considered as a critical factor in organ allocation.

Impact of preoperative infection on the outcomes of liver transplant recipients: a national propensity score-matched retrospective cohort study in China.

BACKGROUND: Impact of preoperative infection on liver transplantation (LT) needs further investigation. MATERIALS AND METHODS: From 1 January 2015 to 31 December 2022, 24 122 eligible patients receiving LT were enrolled from the China Liver Transplant Registry database. The outcomes of LT were compared after using the propensity score-matched analysis. RESULTS: Compared to the noninfection group, patients in the infection group were more likely to have postoperative effusion, infection, abdominal bleeding, and biliary complications (all P <0.01), and they had shorter 30-day, 90-day survival, and overall survival (all P <0.01). Cox proportional hazards regression analysis revealed that MELD score and cold ischemia time were risk factors for the overall survival in the infection group (both P <0.05). Besides, compared to the nonpulmonary group, patients in the pulmonary group were more likely to have postoperative effusion and infection (both P <0.0001), and less likely to have postoperative abscess and early allograft dysfunction (both P <0.05). Patients in the nonabdominal group also had a higher proportion of postoperative infection than those in the abdominal group ( P <0.05). Furthermore, compared to the number=1 group, patients in the number ≥2 group were more prone to postoperative effusion and infection (both P <0.01), and they also had shorter 30-day and 90-day survival (both P <0.05). CONCLUSION: Preoperative infection can result in a higher incidence of early postoperative complications and shorter survival in liver transplant recipients. The types and number of infection sites will also influence the prognosis of liver transplant recipients.

ARHGAP6 Suppresses Breast Cancer Tumor Growth by Promoting Ferroptosis via RhoA-ROCK1-p38 MAPK Signaling.

BACKGROUND: Ferroptosis, a distinct iron-dependent form of regulated cell death, is induced by severe lipid peroxidation due to reactive oxygen species (ROS) generation. Breast cancer patient survival is correlated with the tumor-suppressing properties of Rho guanosine triphosphatase hydrolase enzyme (GTPase)-activating protein 6 (ARHGAP6). This study investigates the impact and mechanisms of ARHGAP6 on ferroptosis in breast cancer. METHODS: Using quantitative RT-PCR, Western blotting, and immunofluorescence staining, ARHGAP6 expression was detected in a gene expression dataset, cancer tissue samples, and cells. ARHGAP6 was overexpressed or silenced in breast cancer cell lines. Cell proliferation was measured using 5-ethynyl-2-deoxyuridine (EdU) assay, and cell death rate was determined using LDH cytotoxicity assay. As indicators of ferroptosis, Fe2+ ion content, lipid ROS, glutathione peroxidase 4 (GPX4), ChaC glutathione specific gamma-glutamylcyclotransferase 1 (CHAC1), prostaglandin-endoperoxide synthase 2 (PTGS2), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long chain family member 4 (ACSL4) levels were evaluated. RESULTS: ARHGAP6 was obviously downregulated in cancer tissues and cells. ARHGAP6 overexpression decreased cell proliferation, elevated cell death and lipid ROS, decreased GPX4 and SLC7A11, increased PTGS2, ACSL4, and CHAC1, and inhibited RhoA/ROCK1 and p38 MAPK signaling in cancer cells. ARHGAP6 knockdown exerted opposite effects to those of ARHGAP6 overexpression. p38 signaling suppression reversed the effect of ARHGAP6 knockdown on ferroptosis, while RhoA/ROCK1 signaling inhibition compromised the effect of ARHGAP6 on p38 MAPK signaling. In mice models, ARHGAP6 together with the ferroptosis inducer RSL3 cooperatively enhanced ferroptosis and inhibited tumor growth of cancer cells. ARHGAP6 mRNA level was positively correlated with that of ferroptosis indicators in tumor tissues. CONCLUSIONS: This study revealed that ARHGAP6 inhibited tumor growth of breast cancer by inducing ferroptosis via RhoA/ROCK1/p38 MAPK signaling. Integrating ARHGAP6 with ferroptosis-inducing agents may be a promising therapeutic strategy for breast cancer treatment.

Development of an ubiquitin-proteasome system signature for predicting prognosis and providing therapeutic guidance for patients with triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a pathological subtype with a high mortality, and the development of inhibitors in the ubiquitin-proteasome system (UPS) component could be a novel therapeutic tool. METHODS: Triple-negative breast cancer data were obtained from The Cancer Genome Atlas (TCGA), and subtype analysis was performed by consistent clustering analysis to identify molecular subtypes of TNBC according to UPS characteristics. Differential analysis, COX and least absolute shrinkage and selection operator (LASSO) COX regression analyses were performed to select genes associated with overall survival in TNBC. The final prognostic model (UPS score) was determined using the LASSO COX model. The model performance was assessed using receiver operating characteristic (ROC) curves and survival curves. In addition, the results of the UPS score on analyzing the abundance of immune cell infiltration and immunotherapy were explored. Finally, we developed a nomogram for TNBC survival prediction. RESULTS: Two UPS subtypes (UPSMS1 and UPSMS2) showing significant survival differences were classified. COX regression analysis on differentially expressed genes in UPSMS1 and UPSMS2 filtered five genes that affected overall survival. Based on the regression coefficients and expression data of the five genes, we built a prognostic assessment system (UPS score). The UPS score showed consistent prognostic and therapeutic guidance values. Finally, the ROC curve of the nomogram and UPS score showed the highest predictive efficacy compared with traditional clinical prognostic indicators. CONCLUSION: The UPS score represented a promising prognostic tool to predict overall survival and immune status and guide personalized treatment selection in TNBC patients, and this study may provide a more practical alternative for clinical monitoring and management of TNBC.

Incorporation of protein induced by vitamin K absence or antagonist-II into transplant criteria expands beneficiaries of liver transplantation for hepatocellular carcinoma: a multicenter retrospective cohort study in China.

INTRODUCTION: In order to maximize the utilization of precious donor liver, precisely determining potential hepatocellular carcinoma (HCC) candidates who will benefit from liver transplantation (LT) is essential. As a crucial diagnostic biomarker for HCC, protein induced by vitamin K absence or antagonist-II (PIVKA-II) has become one of the key indicators for assessing tumor recurrence risk after LT. This study aims to investigate the role of PIVKA-II in recipient selection and prognostic stratification. METHODS: The clinicopathologic data of HCC patients undergoing LT from 2015 to 2020 in six Chinese transplant centers were collected. Univariate and multivariate analyses were performed to determine risk factors for disease free survival (DFS). Based on these risk factors, survival analysis was made by Kaplan-Meier method and their value in prognostic stratification was assessed. RESULTS: A total of 522 eligible HCC patients with pre-LT PIVKA-II records were finally included in this study. Tumor burden>8 cm, α-fetoprotein>400 ng/ml, histopathologic grade III and PIVKA-II>240 mAU/ml were identified as independent risk factors for DFS. DFS of patients with PIVKA-II≤240 mAU/ml ( N =288) were significantly higher than those with PIVKA-II>240 mAU/ml ( N =234) (1-year, 3-year, and 5-year DFS: 83.2, 77.3, and 75.9% vs. 75.1, 58.5, and 50.5%; P <0.001). Compared with Hangzhou criteria ( N =305), incorporating PIVKA-II into Hangzhou criteria (including tumor burden, α-fetoprotein, and histopathologic grade) increased the number of patients with eligibility for LT by 21.6% but achieved comparable DFS and overall survival. CONCLUSIONS: Incorporating PIVKA-II into existing LT criteria could increase the number of eligible HCC patients without compromising post-LT outcomes.

Comparative Analysis of Donor Liver Allograft Outcomes in Hepatocellular Carcinoma Patients Who Underwent Liver Transplant.

OBJECTIVES: Liver transplant for patients with hepatocellular carcinoma involves 3 main types of donor allografts: donation after brain death, donation after cardiac death, and donation after brain and cardiac death. Data on this topic are limited, and controversies exist regarding liver transplant outcomes in hepatocellular carcinoma patients who have received these allografts. MATERIALS AND METHODS: Data from 490 hepatocellular carcinoma patients who received liver transplant from 2015 to 2021 at the Shulan (Hangzhou) Hospital were retrospectively analyzed. Participants were divided into 3 cohorts according to allograft type: donation after brain death, donation after cardiac death, and donation after brain and cardiac death. Kaplan-Meier and Cox regression methods were used to evaluate patient survival, graft survival, and recurrence-free survival rates after liver transplant. RESULTS: Kaplan-Meier analysis revealed that 3-year patient survival rates were 69.2% for donations after brain death, 69.2% for donations after cardiac death, and 46.6% for donations after brain and cardiac death (P = .42); the 3-year graft survival rates were 53.3% for donations after brain death, 56.4% for donations after cardiac death, and 46.6% for donations after brain and cardiac death (P = .44); and 3-year recurrence-free survival rates were 55% for donations after brain death, 56.6% for donations after cardiac death, and 39.5% for donations after brain and cardiac death (P = .46). Complications were also similar across the 3 cohorts (P = .36). Multivariable analysis showed that intraoperative red blood cell transfusion (hazard ratio: 1.820; P = .042) and early allograft dysfunction (hazard ratio: 3.240; P = .041) were independent risk factors for graft survival. CONCLUSIONS: Similar outcomes can be achieved for hepatocellular carcinoma patients who undergo liver transplant with donations after brain death, donations after cardiac death, or donations after brain and cardiac death allografts, especially when strict donor selection criteria are applied.

Stratified Analysis of Survival Benefit for ABO-incompatible Deceased-donor Liver Transplantation: Multicenter Propensity Score-matched Study.

Background and Aims: Liver transplantation (LT) using ABO-incompatible (ABOi) grafts can extend the donor pool to a certain extent and hence reduce the waiting time for transplantation. However, concerns of the impending prognosis associated with this option, especially for patients with liver failure and higher model for end-stage liver disease (MELD) scores, who tend to be more fragile during the waiting period before LT. Methods: Recipients undergoing LT for acute-on-chronic liver failure or acute liver failure were retrospectively enrolled at four institutions. Overall survival was compared and a Cox regression analysis was performed. Propensity score matching was performed for further comparison. Patients were stratified by MELD score and cold ischemia time (CIT) to determine the subgroups with survival benefits. Results: Two hundred ten recipients who underwent ABOi LT and 1,829 who underwent ABO compatible (ABOc) LT were enrolled. The 5-year overall survival rate was significantly inferior in the ABOi group compared with the ABOc group after matching (50.6% vs. 75.7%, p<0.05). For patients with MELD scores ≤30, using ABOi grafts achieved a comparable overall survival rate as using ABOc grafts (p>0.05). Comparison of the survival rates revealed no statistically significant difference for patients with MELD scores ≥40 (p>0.05). For patients with MELD scores of 31-39, the overall survival rate was significantly inferior in the ABOi group compared with the ABOc group (p<0.001); however, the rate was increased when the liver graft CIT was<8 h. Conclusions: For recipients with MELD scores ≤30, ABOi LT had a prognosis comparable to that of ABOc LT and can be regarded as a feasible option. For recipients with MELD scores ≥40, ABOi should be adopted with caution in emergency cases. For recipients with MELD scores of 31-39, the ABOi LT prognosis was worse. However, those patients benefited from receiving ABOi grafts with a CIT of <8 h.

Generalization of learned Fourier-based phase-diversity wavefront sensing.

Proper initialization of the nonlinear optimization is important to avoid local minima in phase diversity wavefront sensing (PDWS). An effective neural network based on low-frequency coefficients in the Fourier domain has proved effective to determine a better estimate of the unknown aberrations. However, the network relies significantly on the training settings, such as imaging object and optical system parameters, resulting in a weak generalization ability. Here we propose a generalized Fourier-based PDWS method by combining an object-independent network with a system-independent image processing procedure. We demonstrate that a network trained with a specific setting can be applied to any image regardless of the actual settings. Experimental results show that a network trained with one setting can be applied to images with four other settings. For 1000 aberrations with RMS wavefront errors bounded within [0.2 λ, 0.4 λ], the mean RMS residual errors are 0.032 λ, 0.039 λ, 0.035 λ, and 0.037 λ, respectively, and 98.9% of the RMS residual errors are less than 0.05 λ.

Older liver grafts from donation after circulatory death are associated with impaired survival and higher incidence of biliary non-anastomotic structure.

BACKGROUND: Grafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past. But it has seemed to remain controversial in the last decade, as a result of modified clinical protocols, selected recipients, and advanced technology of organ perfusion and preservation. The present study aimed to examine the impact of older donor age on complications and survival of liver transplant using grafts from donation after circulatory death (DCD). METHODS: A total of 944 patients who received DCD liver transplantation from 2015 to 2020 were included and divided into two groups: using graft from older donor (aged ≥ 65 years, n = 87) and younger donor (age < 65 years, n = 857). Propensity score matching (PSM) was applied to eliminate selection bias. RESULTS: A progressively increased proportion of liver transplants with grafts from older donors was observed from 1.68% to 15.44% during the study period. The well-balanced older donor (n = 79) and younger donor (n = 79) were 1:1 matched. There were significantly more episodes of biliary non-anastomotic stricture (NAS) in the older donor group than the younger donor group [15/79 (19.0%) vs. 6/79 (7.6%); P = 0.017]. The difference did not reach statistical significance regarding early allograft dysfunction (EAD) and primary non-function (PNF). Older livers had a trend toward inferior 1-, 2-, 3-year graft and overall survival compared with younger livers, but these differences were not statistically significant (63.1%, 57.6%, 57.6% vs. 76.9%, 70.2%, 67.7%, P = 0.112; 64.4%, 58.6%, 58.6% vs. 76.9%, 72.2%, 72.2%, P = 0.064). The only risk factor for poor survival was ABO incompatible transplant (P = 0.008) in the older donor group. In the subgroup of ABO incompatible cases, it demonstrated a significant difference in the rate of NAS between the older donor group and the younger donor group [6/8 (75.0%) vs. 3/14 (21.4%); P = 0.014]. CONCLUSIONS: Transplants with grafts from older donors (aged ≥ 65 years) after circulatory death are more frequently associated with inferior outcome compared to those from younger donors. Older grafts from DCD are more likely to develop NAS, especially in ABO incompatible cases.

Phosphotungstate-Based Anode Interfacial Material for Constructing High-Performance Polymer Solar Cells with a Fill Factor over 80.

In the field of organic solar cells (OSCs), the interfacial layer plays the role of enhancing carrier extraction/transportation, inhibiting their recombination, etc. In contrast to the wide variety of cathode interfacial materials with good modification ability, much less effort has been reported for anode interfacial materials. In this study, we report a polyoxometalate-based inorganic molecular cluster, zinc phosphotungstate (Zn3P2W24O80, denoted ZnPW), as an anode interfacial layer. Based on the PM6/EH-HD-4F/L8-BO-F ternary system, the device with ZnPW modification achieved a high power conversion efficiency (PCE) and a fill factor of up to 18.67 and 80.29%, respectively, which are higher than the counterpart device (PCE of 18.01%) with PEDOT/PSS as the anode interfacial layer. Detailed studies revealed that under the modification of ZnPW, the devices obtained promoted light absorption and suitable energy level matching between the active layer and the electrode, reduced contact resistance, and suppressed charge recombination. In addition, the ZnPW-modified devices had improved photostability and storage stability compared to PEDOT/PSS-modified devices. Our work shows that the polyoxometalate-based inorganic nanocluster ZnPW has great advantages in enhancing the device performance and stability of OSCs.

Phase-diversity wavefront sensing enhanced by a Fourier-based neural network.

Phase diversity wavefront sensing (PDWS) has been a successful approach to quantifying wavefront aberrations with only a few intensity measurements and nonlinear optimization. However, the inherent non-convexity of the inverse problem may lead to stagnation at a local minimum far from the true solution. Proper initialization of the nonlinear optimization is important to avoid local minima and improve wavefront retrieval accuracy. In this paper, we propose an effective neural network based on low-frequency coefficients in the Fourier domain to determine a better estimate of the unknown aberrations. By virtue of the proposed network, only a small amount of simulation data suffice for a robust training, two orders of magnitude less than those in existing work. Experimental results show that, when compared with some existing methods, our method achieves the highest accuracy while drastically reducing the training time to 1.4 min. The minimum, maximum, and mean values of the root mean square (RMS) residual errors for 800 aberrations are 0.017λ, 0.056λ, and 0.039λ, respectively, and 95% of the RMS residual errors are less than 0.05λ.

Dopant-Free Bithiophene-Imide-Based Polymeric Hole-Transporting Materials for Efficient and Stable Perovskite Solar Cells.

The development of hole-transport materials (HTMs) with high mobility, long-term stability, and comprehensive passivation is significant for simultaneously improving the efficiency and stability of perovskite solar cells (PVSCs). Herein, two donor-acceptor (D-A) conjugated polymers PBTI and PFBTI with alternating benzodithiophene (BDT) and bithiophene imide (BTI) units are successfully developed with desirable hole mobilities due to the good planarity and extended conjugation of molecular backbone. Both copolymers can be employed as HTMs with suitable energy levels and efficient defect passivation. Shortening the alkyl chain of the BTI unit and introducing fluorine atoms on the BDT moiety effectively enhances hole mobility and hydrophobicity of the HTMs, leading to improved efficiency and stability of PVSCs. As a result, the organic-inorganic hybrid PVSCs with PFBTI as the HTM deliver a power conversion efficiency (PCE) of 23.1% with enhanced long-term operational and ambient stability, which is one of the best efficiencies reported for PVSCs with dopant-free polymeric HTMs to date. Moreover, PFBTI can be applied in inorganic PVSCs and perovskite/organic tandem solar cells, achieving a high PCE of 17.4% and 22.2%, respectively. These results illustrate the great potential of PFBTI as an efficient and widely applicable HTM for cost-effective and stable PVSCs.

High-Performance Deep Red Colloidal Quantum Well Light-Emitting Diodes Enabled by the Understanding of Charge Dynamics.

Colloidal quantum wells (CQWs) have emerged as a promising family of two-dimensional (2D) optoelectronic materials with outstanding properties, including ultranarrow luminescence emission, nearly unity quantum yield, and large extinction coefficient. However, the performance of CQWs-based light-emitting diodes (CQW-LEDs) is far from satisfactory, particularly for deep red emissions (≥660 nm). Herein, high efficiency, ultra-low-efficiency roll-off, high luminance, and extremely saturated deep red CQW-LEDs are reported. A key feature for the high performance is the understanding of charge dynamics achieved by introducing an efficient electron transport layer, ZnMgO, which enables balanced charge injection, reduced nonradiative channels, and smooth films. The CQW-LEDs based on (CdSe/CdS)@(CdS/CdZnS) ((core/crown)@(colloidal atomic layer deposition shell/hot injection shell)) show an external quantum efficiency of 9.89%, which is a record value for 2D nanocrystal LEDs with deep red emissions. The device also exhibits an ultra-low-efficiency roll-off and a high luminance of 3853 cd m-2. Additionally, an exceptional color purity with the CIE coordinates of (0.719, 0.278) is obtained, indicating that the color gamut covers 102% of the International Telecommunication Union Recommendation BT 2020 (Rec. 2020) standard in the CIE 1931 color space, which is the best for CQW-LEDs. Furthermore, an active-matrix CQW-LED pixel circuit is demonstrated. The findings imply that the understanding of charge dynamics not only enables high-performance CQW-LEDs and can be further applied to other kinds of nanocrystal LEDs but also is beneficial to the development of CQW-LEDs-based display technology and related integrated optoelectronics.

A Novel YTHDF3-Based Model to Predict Prognosis and Therapeutic Response in Breast Cancer.

Background: Due to high tumor heterogeneity, breast cancer (BC) patients still suffer poor survival outcomes. YTHDF3 plays a critical role in the prognosis of BC patients. Hence, we aimed to construct a YTHDF3-based model for the prediction of the overall survival (OS) and the sensitivity of therapeutic agents in BC patients. Methods: Based on The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/) database, we obtained BC patients' data (n = 999) with YTHDF3 expression profiles. The association between YTHDF3 expression and 5-year OS was determined via Cox proportional hazards regression (CPHR) analysis. By integrating the variables, we established a prognostic nomogram. The model was estimated via discrimination, calibration ability, and decision curve analysis (DCA). The performance of the model was compared with the TNM stage system through receiver operating characteristic (ROC) curves and DCA. By means of the Genomics of Drug Sensitivity in Cancer (GDSC) database (https://www.cancerrxgene.org/), the therapeutic agents' response was estimated. Gene set enrichment analysis (GSEA) demonstrated possible biological mechanisms related to YTHDF3. TIMER and CIBERSORTx were employed to analyze the association between YTHDF3 and tumor-infiltrating immune cells. Results: The high YTHDF3 expression was significantly correlated with poor 5-year OS in BC patients. Through multivariate CPHR, four independent prognostic variables (age, TNM stage, YTHDF3 expression, and molecular subtype) were determined. On the basis of the four factors, a YTHDF3-based nomogram was built. The area under the curve (AUC) of the ROC curve for the model surpassed that of the TNM stage system (0.72 vs. 0.63, p = 0.00028). The model predictions showed close consistency with the actual observations via the calibration plot. Therapeutic response prediction was conducted in high- and low-risk groups and compared with each other. The BC patients with higher risk scores showed more therapeutic resistance than those with a lower risk score. Conclusion: YTHDF3 was verified as a prognostic biomarker of BC, and a novel YTHDF3-based model was constructed to predict the 5-year OS of BC patients. Our model could be applied to effectively predict the therapeutic response of commonly used agents for BC patients.

Development of a Novel Prognostic Nomogram for High Model for End-Stage Liver Disease Score Recipients Following Deceased Donor Liver Transplantation.

Background: A high model of end-stage liver disease (MELD) score (>30) adversely affects outcomes even if patients receive prompt liver transplantation (LT). Therefore, balanced allocation of donor grafts is indispensable to avoid random combinations of donor and recipient risk factors, which often lead to graft or recipient loss. Predictive models aimed at avoiding donor risk factors in high-MELD score recipients are urgently required to obtain satisfactory outcomes. Method: Data of patients with MELD score >30 who underwent LT at three transplantation institutes between 2015 and 2018 were retrospectively reviewed. Early allograft dysfunction (EAD), length of intensive care unit (ICU) stay, and graft loss were recorded. Corresponding independent risk factors were analyzed using stepwise multivariable regression analysis. A prediction model of graft loss was developed, and discrimination and calibration were measured. Results: After applying the exclusion criteria, 778 patients were enrolled. The incidence of EAD was 34.8% (271/778). Donor graft macrovesicular steatosis, graft-to-recipient weight ratio (GRWR), warm ischemia time (WIT), cold ischemia time (CIT), and ABO blood incompatibility, together with donor serum albumins, were independent predictors of EAD. The incidence of ICU stay over 10 days was 64.7% (503/778). Donor age, recipient's MELD score, Child score, and CIT were independent predictors of ICU stay. The 3-year graft survival rates (GSRs) in the training and validation cohorts were 64.2 and 59.3%, respectively. The independent predictors of graft loss were recipient's Child score, ABO blood type incompatibility, donor serum total bilirubin over 17.1 µmol/L, and cold CIT. A nomogram based on these variables was internally and externally validated and showed good performance (area under the receiver operating characteristic curve = 70.8 and 66.0%, respectively). For a recipient with a high MELD score, the avoidance of ABO blood type incompatibility and CIT ≥6 h would achieve a 3-year GSR of up to 78.4%, whereas the presence of the aforementioned risk factors would decrease the GSR to 35.4%. Conclusion: The long-term prognosis of recipients with MELD scores >30 could be greatly improved by avoiding ABO blood type incompatibility and CIT ≥6 h.

Multi-Spectroscopic and Molecular Simulation Approaches to Characterize the Intercalation Binding of 1-Naphthaleneacetic Acid With Calf Thymus DNA.

1-Naphthaleneacetic acid (NAA), having high-quality biological activity and great yield-increasing potential in agricultural production, is a broad-spectrum plant growth regulator. Although NAA is of low toxicity, it can affect the balance of the human metabolism and damage the body if it is used in high quantity for a long time. In this study, the interaction of NAA with calf thymus DNA (ctDNA) was investigated under simulated human physiological acidity (pH 7.4) using fluorescence, ultraviolet-visible absorption, and circular dichroism spectroscopy combined with viscosity measurements and molecular simulation techniques. The quenching of the endogenous fluorescence of NAA by ctDNA, observed in the fluorescence spectrum experiment, was a mixed quenching process that mainly resulted from the formation of the NAA-ctDNA complex. NAA mainly interacted with ctDNA through hydrophobic interaction, and the binding constant and quenching constant at room temperature (298 K) were 0.60 × 105 L mol-1 and 1.58 × 104 L mol-1, respectively. Moreover, the intercalation mode between NAA and ctDNA was verified in the analysis of melting point, KI measurements, and the viscosity of ctDNA. The results were confirmed by molecular simulation, and it showed that NAA was enriched near the C-G base of ctDNA. As shown in circular dichroism spectra, the positive peak intensity of ctDNA intensified along with a certain degree of redshift, while the negative peak intensity decreased after binding with NAA, suggesting that the binding of NAA induced the transformation of the secondary structure of ctDNA from B-form to A-form. These researches will help to understand the hazards of NAA to the human body more comprehensively and concretely, to better guide the use of NAA in industry and agriculture.

Groove binding between ferulic acid and calf thymus DNA: spectroscopic methodology combined with chemometrics and molecular docking studies.

Ferulic acid (FA), a dietary phenolic acid compound, is proved to possess numerous biological activities. Hence, this study was devoted to explore the interaction between FA and calf thymus DNA (ctDNA) by UV - vis absorption, fluorescence, circular dichroism (CD) spectroscopy combined with multivariate curve resolution-alternating least-squares (MCR - ALS) and molecular docking studies. The concentration curves and the pure spectra of compositions (FA, ctDNA and FA - ctDNA complex) were obtained by MCR - ALS approach to verify and monitor the interaction of FA with ctDNA. The groove binding mode between FA and ctDNA was confirmed by the results of melting analysis, viscosity measurements, single-stranded DNA experiments, and competitive studies. The binding constant of FA - ctDNA complex was 4.87 × 104 L mol-1 at 298 K. The values of enthalpy (ΔH°) and entropy (ΔS°) changes in the interaction were -16.24 kJ mol-1 and 35.02 J mol-1 K-1, respectively, indicating that the main binding forces were hydrogen bonds and hydrophobic interactions. The result of CD spectra suggested that a decrease in right-handed helicity of ctDNA was induced by FA and the DNA conformational transition from the B-form to the A-form. The results of docking indicated that FA binding with ctDNA in the minor groove. These findings may be conducive to understand the interaction mechanism of FA with ctDNA and the pharmacological effects of FA. Communicated by Ramaswamy H. Sarma[Formula: see text].

Exploring the binding interaction of Maillard reaction by-product 5-hydroxymethyl-2-furaldehyde with calf thymus DNA.

BACKGROUND: 5-Hydroxymethyl-2-furaldehyde (5-HMF), a by-product of the Maillard reaction, usually present in fried and baked food, may cause potential harm to the human body. Here, the interaction between 5-HMF and calf thymus DNA (ctDNA) under physiological buffer (pH 7.4) was studied using multi-spectroscopic methods combined with multivariate curve resolution-alternating least squares (MCR-ALS) chemometrics and molecular simulation techniques. RESULTS: The concentration profiles and pure spectra of the three components (5-HMF, ctDNA and 5-HMF-ctDNA complex) were extracted from highly overlapping spectra using MCR-ALS analysis, which verified the formation of 5-HMF-ctDNA complex. The binding constant being of the order of 103 L mol-1 at four temperatures (292, 298, 304 and 310 K) indicated a weak affinity in the binding of 5-HMF to ctDNA. The binding interaction was mainly driven by hydrogen bonds and van der Waals forces. Viscosity analysis, melting assay, ionic strength effect and competitive fluorescence studies ascertained that 5-HMF bound to ctDNA through groove binding, and it tended to bind to guanine-cytosine rich region of ctDNA which was characterized using Fourier transform infrared spectra and molecular docking. Circular dichroism spectral analysis and DNA cleavage assays indicated that the ctDNA conformation was altered from B to A form and 5-HMF caused DNA damage at higher concentration. CONCLUSIONS: The results suggested that 5-HMF bound to ctDNA through groove binding and caused DNA damage. This research may contribute to understand the binding mechanism of 5-HMF to ctDNA and to the assessment of the toxicological effect of 5-HMF in biological processes. © 2018 Society of Chemical Industry.