Background Hypothermic oxygenated perfusion (HOPE) is a promising technology to improve donated after cardiac death (DCD) liver graft. It was found that protein phosphatase 2A (PP2A) could regulate autophagy and apoptosis, which play a pivotal role in hepatic ischemia reperfusion injury (IRI). In this study, we aim to explore whether PP2A take part in the mechanism that reduces organ damage after HOPE. Method Adult male Sprague Dawley rats were divided into four groups at random. DCD livers of HOPE group were preserved in a HOPE system after 23 hours of cold storage (CS). All groups’ livers were reperfused in an isolated perfused rat liver (IPRL) system for 1 hour at 37°C. After reperfusion, markers related to IRI and protein expression of PP2A related pathway were examined. BRL-3A cells were cultured and incubated with different concentrations H2O2 (0, 50 μM and100 μM). The cellular production of Reactive Oxygen Species (ROS) was detected via the fluorescent intensity of 2,7-Dichlorodihydrofluorescein diacetate (DCFH-DA), and PP2A related pathway protein expression was measured. Results HOPE group suffered the lighter IRI when compared with CS group, evidenced by the lower hepatocytes injury degree, apoptosis rate, and oxidative stress. Further, compared with CS group, the PP2A and ERK1/2 related autography pathway activation of HOPE group was higher, while the JNK and p38 related apoptosis pathway was down-regulated. Cellular experiment showed that mild oxidative stress (50 μM H2O2) could activate the expression of PP2A and autography pathway protein. Severe oxidative stress (100 μM H2O2) shown the opposite regulation effect. Conclusion Through reducing oxidative stress, HOPE attenuates IRI to rat DCD livers via activating PP2A related autography pathway and inhibiting apoptosis pathway.

BACKGROUND:Primary liver cancer (PLC) is a global health concern. The plasma dual-target methylation (PDTM) test, which interrogates the methylation status of GNB4 and Riplet, exhibits a commendable ability to discriminate hepatocellular carcinoma (HCC) from controls. Nevertheless, its performance in detecting PLC in larger populations remains to be validated. RESULTS:A multicenter, double-blind, cross-sectional study was conducted. Blood samples were collected from all participants for the PDTM test, which is based on a triplex quantitative methylation-specific polymerase chain reaction (qMSP) platform. Additionally, Sanger sequencing was performed to confirm the accuracy of methylation detection by the PDTM test. The study enrolled 430 PLC patients and 752 controls. The PDTM test demonstrated an overall sensitivity of 92.3% (95% confidence interval [CI], 89.4-94.7) for PLC patients and an overall specificity of 93.4% (95% CI, 91.3-95.0) for controls with benign liver disease (BLD) or non-liver primary malignancies (NLPM). Specifically, the sensitivities of the PDTM test for patients with HCC, intrahepatic cholangiocarcinoma (ICC) or early-stage (TNM stages I and II) PLC were 91.9% (95% CI, 87.6-95.0), 93.3% (95% CI, 85.9-97.5) and 88.7% (95% CI, 83.9-92.5), respectively. Furthermore, the kappa values for both GNB4 and Riplet between the PDTM test and Sanger sequencing exceeded 0.99, indicating a high level of consistency. CONCLUSIONS:The PDTM test demonstrates excellent diagnostic performance for PLC, particularly in cases of early-stage PLC. It is a promising early screening or surveillance tool for PLC, and further prospective research is required to ascertain its full utility.

Zn-In2S3 has attracted much attention in electrochemiluminescence (ECL) due to its electronic properties, but severe carrier recombination and low content of sulfur vacancy (Sv) limit its electrocatalytic activity in the ECL process. In this study, the catalytic performance of Zn-In2S3 for ECL process was enhanced by synthesizing Ag@Zn-In2S3-(3-MPA). The composite of Ag increased sulfur vacancies via electronic metal-support interaction (EMSI), which in turn enhanced the electrocatalytic activity of Zn-In2S3. Meanwhile the grafting of 3-mercaptopropionic acid (3-MPA) was to further enhance the electrocatalytic activity through bonding interaction and amorphization effect. All these improvements enhance the carrier separation efficiency and reduce their recombination, while facilitating the electron transfer during the generation of reactive oxygen species (ROS, e.g., *OH). This process further accelerates the electron transfer between luminol•- and ROS, which significantly enhances the ECL signal of luminol. A sensor for the detection of carcinoembryonic antigen (CEA) was successfully constructed using Ag@Zn-In2S3-(3-MPA)/luminol as a secondary antibody marker with a wide detection range and high sensitivity. The study solves the problem of low catalytic activity of Zn-In2S3 and provides new ideas for the application of Zn-In2S3 in the fields of electrocatalysis, photocatalysis and electrochemiluminescence.

Elucidating the electron transfer mechanism and its regulatory strategy in the electrochemiluminescence (ECL) phenomenon is undoubtedly a challenging task. In this paper, when characterized using cyclic voltammetry, we found that modifying the catalyst significantly affected the electron transfer efficiency of reactive oxygen species (ROS, e.g. O2(center dot)-) generation, and consequently the electron transfer of luminol. The effect is more significant than the addition of reactant H2O2. Thus modifying the catalyst becomes a more effective way to influence the ECL. In addition, thanks to the fact that Au/SiO2:0.6% Mn@MnO possesses the composite effect of Au in the core-shell structure, the material was able to be used as an efficient negative catalyst, which ultimately led to the preparation of a more effective ECL quencher than SiO2:0.6% Mn. The material can achieve ECL quenching of luminol by reducing the electron transfer required for ROS generation during electrocatalysis, which in turn improves the detection performance and stability of the sensors. Based on these findings, we constructed a dual-strategy ECL quenching system for the highly sensitive detection of carcinoembryonic antigen (CEA). This not only opens up a new research direction for ECL technology in weakly alkaline media, but also further extends the application of ECL technology in biological applications.

>To the Editor:Perihilar cholangiocarcinoma （PHCCA） is the most well-known biliary malignancy, representing around 60%of all bile duct cancers [1] . As of now, radical resection is the only possible means to cure PHCCA patients. The median survival time of patients undergoing radical resection can exceed 40 months, and the overall survival rate at 5 years after surgery is 25% to 67%, while the median survival time of patients who cannot be resected is only 10 to 12 month [2] .

Conventional luminol co-reactant electrochemiluminescence (ECL) systems suffer from low stability and accuracy due to factors such as the ease of decomposition of hydrogen peroxide and inefficient generation of reactive oxygen species (ROS) from dissolved oxygen. Inspired by the luminol ECL mechanism mediated by oxygen evolution reaction (OER), the nickel-cobalt layered double hydroxide (NiCo-LDH) hollow nanocages with hollow structure and defect state are used as co-reaction promoters to enhance the ECL emission from the luminol-H2 O system. Thanks to the hollow structure and defect state, NiCo-LDH hollow nanocages show excellent OER catalytic activity, which can stabilize and efficiently produce ROS and enhance the ECL emission. Additionally, mechanistic exploration suggests that the ROS involved in the co-reaction of the luminol-H2 O system are derived from the OER reaction process, and there is a positive correlation between ECL intensity and the OER catalytic activity of the co-reaction promoter. The selection of catalysts with excellent OER catalytic activity is a key factor in improving ECL emission. Finally, a dual-mode immunosensor is constructed for the detection and analysis of alpha-fetoprotein (AFP) based on the promoting effect of NiCo-LDH hollow nanocages on the luminol-H2 O ECL system.

Carcinoembryonic antigen (CEA) is often employed as a crucial tumor marker for both colon and rectal cancer. The assessment of CEA levels holds significant therapeutic importance in the diagnosis of these malignancies. In this study, an electrochemiluminescence immunosensor with a signal off was ingeniously designed with Ru@TiO2-MXene as the base material of the energy donor, and Pd@UiO-66-NH2 as the marker of the energy acceptor. This immunosensor was constructed based on the strong interaction between the two components of ECL-RET. Remarkably, TiO2-MXene exhibits favorable film -forming properties and electrical conductivity while effectively immobilizing Ru(bpy)3+. On the other hand, Pd@UiO-66-NH2 has excellent biocompatibility and light absorption, making it an ideal choice for use as a secondary antibody marker. The electrochemiluminescence immunosensor constructed exhibits an extensive detection range of 1 x 10-5 ng center dot ml-1 to 80 ng center dot ml-1 and a narrow detection limit of 2.65 fg center dot ml-1. The novel electrochemiluminescence immunosensor, as presented in this investigation, introduces a distinct methodology for CEA detection, carrying immense clinical significance in the field of colon and rectal cancer diagnosis.

At present, tumor markers are becoming an increasingly important factor in the diagnosis and treatment of cancer. In this study, an attractive sandwich-type electrochemiluminescence sensor was established for the monitoring of embryonic antigen (CEA),on account of the Ru(bpy)(3)(2+)/PEI luminescence system and the faclitation of PEI by MIL-53 (Fe) metal-organic frameworks. In order to achieve the effect of reducing the leakage of ruthenium bipyridyl (Ru(bpy)(3)(2+)) and stabilizing the luminescence in the system, a new type of ceria material (mCeO(2)) with large specific surface area and suitable pore size mesoporous structure was used to load Ru(bpy)(3)(2+). Interestingly, the face-centered depressed octahedral MIL-53(Fe) was synthesized in this experiment and used to support Polyethyleneimine (PEI), which also promoted the formation of PEI center dot. More importantly, MIL-53(Fe) can be used as a new co-reaction promoter for PEI to effectively improve the ratio of Ru(bpy)(3)(2+)/PEI ,due to the large number of Fe-O clusters and the fast recombination of electron and hole pairs. As a result, the sensitive ECL immunosensor for detecting CEA prepared by sandwich immunoreaction can not only reduce the cumbersome operation of adding co-reaction reagents to the bottom solution, but also greatly improve the convenience of operation and the accuracy of detection. The as-prepared ECL biosensor demonstrated in this paper illustrates extremely selective and sensitive determination of CEA from 10(-5) ng/mL to 10 ng/mL and the detection limit of 4.04 fg/mL, which is a great contribution to the prevention and treatment of cancer.

With a shortage of organs for transplant, the use of marginal donors can be an effective measure to meet the shortfall. Myelodysplastic syndromes (MDS) are considered an absolute contraindication for organ donation because of the high invasive potential. Currently, organ transplantation from donors with a past history of MDS has not been reported. In this paper, we report the successful clinical experience of one liver transplantation and two kidney transplantations, with organs donated by a 39-year-old patient diagnosed with a past history of MDS following intracranial hemorrhage. Four and a half years after transplantation, the three recipients are all doing well. However, it is still not clear to what extent organs donated by patients with a past history of MDS can be safely transplanted. This report provides support for the careful use of marginal donors. With effective treatment and full peer assessment, livers and kidneys from donors with a past history of MDS may be safely transplanted.

Hypothermic machine perfusion (HMP) has been demonstrated to be more effective in mitigating ischemia–reperfusion injury (IRI) of donation after circulatory death (DCD) organs than cold storage (CS), yet the underlying mechanism remains obscure. We aimed to propose a novel therapeutic approach to ameliorate IRI in DCD liver transplantation. Twelve clinical liver samples were randomly assigned to HMP or CS treatment and subsequent transcriptomics analysis was performed. By combining in vivo HMP models, we discovered that HMP attenuated inflammation, oxidative stress, and apoptosis in DCD liver through a SEPRINA3-mediated PI3Kδ/AKT signaling cascade. Moreover, in the hypoxia/reoxygenation (H/R) model of BRL-3A, overexpression of SERPINA3 mitigated H/R-induced apoptosis, while SERPINA3 knockdown exacerbated cell injury. Idelalisib (IDE) treatment also reversed the protective effect of SERPINA3 overexpression. Overall, our research provided new insights into therapeutic strategies and identified potential novel molecular targets for therapeutic intervention against DCD liver.

By combining two different materials, metal-organic frameworks (MOF) and beta-cyclodextrins (beta-CD), a signal amplification electrochemical luminescence (ECL) immunosensor was constructed to realize the sensitive detection of AFP. The indium-based metal-organic framework (In-MOF) was used as the carrier of Ru(bpy)(3)(2+), and Ru(bpy)(3)(2+) was immobilized by In-MOF through suitable pore size and electrostatic interaction. At the same time, using host-guest recognition, beta-CD enriched TPA into the hydrophobic cavity for accelerating the electronic excitation of TPA, then, achieving the purpose of signal amplification. The signal amplification immunosensor structure is constructed among the primary antibody Ab(1) connected to the Ru(bpy)(3)(2+)@In-MOF modified electrode, AFP, BSA and the secondary antibody (Ab(2)) loaded with TPA-beta-CD. The immunosensor has a good linearity in the range of 10(-5) ng/mL-50 ng/mL, and the low limit of detection (LOD) is 1.1 x 10(-6) ng/mL. In addition, the electrochemiluminescence immunosensor that we designed has strong stability, good selectivity and repeatability, which provides a choice for the analysis of AFP.

BackgroundThe current rate of organ donation in China falls significantly below the global average and the actual demand. Nursing students play a crucial role in supporting and promoting social and public welfare activities. This study primary aims to analyze the levels of knowledge, attitudes, willingness toward organ donation, and attitudes toward death among nursing students, and investigate the mediating role of attitude in the relationship between knowledge and willingness. The secondary aims to identify factors that may influence the willingness.MethodsA convenience sample of nursing students completed online-administered questionnaires measuring the level of knowledge, attitudes, and willingness toward organ donation before and after clinical internship. Spearman correlation and mediation analyses were used for data analyses.ResultsBefore the clinical internship, there were 435 nursing students who had not yet obtained their degrees and were completing their clinical internships. After the internship, this number decreased to 323. The mean score for knowledge before and after the clinical internship (7.17 before and 7.22 after, with no significant difference), the attitude (4.58 before and 4.36 after, with significant difference), the willingness (12.41% before and 8.67% after, with significant difference), the Death Attitude Profile-Revised (DAP-R) score (94.41 before and 92.56 after, with significant difference). The knowledge indirectly affected nursing students’ willingness to organ donation through attitude. Knowledge had a direct and positive impact on attitudes (β = 1.564). Additionally, nursing students’ attitudes positively affected their willingness (β = 0.023). Attitudes played a mediating role in the relationship between knowledge and willingness (β = 0.035). Additionally, attitude toward death, fear of death, and acceptance of the concept of escape were found to be correlated with their willingness.ConclusionOrgan donation willingness was found to be low among nursing students. Positive attitudes were identified as a mediating factor between knowledge and willingness. Additionally, DAP-R was a related factor. Therefore, it is recommended to focus on improving knowledge and attitude, as well as providing death education to help nursing students establish a positive attitude toward death. These efforts can contribute to the promotion of organ donation.

Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.

In this paper, we report a novel quasi-solid electrochemiluminescence (ECL) immunosensor platform for the detection of tumor marker carcinoembryonic antigen (CEA). Referring to the conventional three-electrode system of electrochemistry, a gel alternative solution was introduced, and a quasi-solid solvent-free scheme was designed. The use of gels brings several advantages. Firstly, the introduction of gels also provides a new platform for the specific recognition of antigens and antibodies. Secondly, gels can be mass-manufactured like ELISA plate, which reduces the cost of testing and thus provides a reference scheme for large-scale sensor applications. Thirdly, a new device was designed to accommodate the improved sensors. In addition, a simple one-step hydrothermal method was used to synthesize AuNPs/MnO2/TiO2 materials. Utilizing its excellent catalytic activity for CO-reaction reagents H₂C₂O₄, it promotes the production of CO2–• and thus enhances the ECL of Ru(bpy)32+. Thus, this biosensor provides a novel and efficient strategy for CEA detection. The gel system sensor also provides a general model for the detection of other biomarkers and provides new applications for biochemical analysis and clinical diagnosis.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths in the world. However, there are currently few clinical diagnosis and treatment options available, and there is an urgent need for novel effective approaches. More research is being undertaken on immune-associated cells in the microenvironment because they play a critical role in the initiation and development of HCC. Macrophages are specialized phagocytes and antigen-presenting cells (APCs) that not only directly phagocytose and eliminate tumor cells, but also present tumor-specific antigens to T cells and initiate anticancer adaptive immunity. However, the more abundant M2-phenotype tumor-associated macrophages (TAMs) at tumor sites promote tumor evasion of immune surveillance, accelerate tumor progression, and suppress tumor-specific T-cell immune responses. Despite the great success in modulating macrophages, there are still many challenges and obstacles. Biomaterials not only target macrophages, but also modulate macrophages to enhance tumor treatment. This review systematically summarizes the regulation of tumor-associated macrophages by biomaterials, which has implications for the immunotherapy of HCC.

Liver and kidney failure can lead to extensive accumulation of toxic metabolites in the blood and tissues, such as bilirubin, blood ammonia, endotoxins, cytokines, creatinine, uric acid, and urea, which aggravate the progression of the disease. Hemoperfusion can effectively adsorb and remove toxins from the blood and treat liver and kidney failure. However, the adsorption efficiency and safety of traditional hemoperfusion adsorbents are not ideal. Thus, it is urgent to develop new toxin adsorbents with good blood compatibility, as well as high adsorption and strong selective capacities, to fulfill the growing clinical needs. In recent years, new hemoperfusion adsorption materials that can improve the adsorption performance of blood toxins while maintaining good blood compatibility have been developed, with promising potential for clinical applications. This review classifies and summarizes the recent research progress in hemoperfusion adsorbents for common blood toxins (bilirubin, blood ammonia, endotoxins, cytokines, creatinine, uric acid, and urea) produced by liver and kidney failure. The composition and structure of various toxin adsorbents, toxin adsorption performance, biocompatibility, blood safety, and the mechanisms of toxin adsorption are discussed. Based on a summary of recent studies, feasible strategies have been explored for designing and preparing hemoperfusion adsorbents to fulfill future development requirements. The trends and clinical application prospects of various toxin adsorbents are also discussed. This article is protected by copyright. All rights reserved.

本文介绍了美国临床肾移植专家工作组于2021年发表在American Journal of Kidney Diseases杂志的评论文章[1].由国家肾脏基金会-肾脏疾病质量倡议(National Kidney Foundation-Kidney Disease Outcomes Quality Initiative,NKF-KDOQI)召集美国移植肾病专家组制定了这篇评论的关键主题,旨在提出更广泛的讨论.本文对 2020 年改善全球肾脏病预后组织(Kidney Disease :Improving Global Outcomes,KDIGO)临床实践指南的关键建议进行了总结,并对相应的临床效用和实践进行简要评论,可作为移植专业人员的有效参考指南.