Fluorescent probe for imaging N2H4 in plants, food, and living cells and for quantitative detection of N2H4 in soil and water using a smartphone.

Hydrazine is volatile and highly toxic, causing severe harm to water, soil, air, and organisms. Therefore, real-time detection and long-term monitoring of hydrazine are crucial for environmental protection and human health. Herein, an "OFF-ON" fluorescent probe 5-((10-ethyl-2-methoxy-10 H-phenothiazin-3-yl)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione (MPD) for hydrazine detection through a nucleophilic addition reaction was developed. MPD could exclusively identify hydrazine through colorimetric and fluorescent dual-channel responses within 30 s, which also demonstrated high sensitivity (detection limit, 12 nM) and a wide pH range (6 -12). The sensing mechanism of MPD was confirmed using theoretical calculations, where fluorescence was emitted following the recognition of hydrazine because of the disappearance of the photoinduced electron transfer (PET) process. Using a smartphone, MPD enabled the quantitative detection of hydrazine in real water samples and sandy soil. Notably, in the process of detecting hydrazine in actual water samples, the establishment of analytical methods and the completion of rapid quantitative detection only required a smartphone and built-in apps. Additionally, we showed that MPD could recognize hydrazine in various environmental samples, including plants, food, hydrazine vapors, and cells. We believe that the fluorescent probe MPD developed in this study and the established smartphone visualization platform will provide a convenient and effective tool for detecting hydrazine in environmental monitoring, food safety assessment, biological system safety, and other fields.

Capecitabine mitigates cardiac allograft rejection via inhibition of TYMS-Mediated Th1 differentiation in mice.

OBJECTIVES: Previous studies elucidated that capecitabine (CAP) works as an anti-tumor agent with putative immunosuppressive effects. However, the intricate mechanisms underpinning these effects remain to be elucidated. In this study, we aimed to unravel the molecular pathways by which CAP exerts its immunosuppressive effects to reduce allograft rejection. METHODS: Hearts were transplanted from male BALB/c donors to male C57BL/6 recipients and treated with CAP for seven days. The rejection of these heart transplants was assessed using a range of techniques, including H&E staining, immunohistochemistry, RNA sequencing, LS-MS/MS, and flow cytometry. In vitro, naïve CD4+ T cells were isolated and cultured under Th1 condition medium with varying treatments, flow cytometry, LS-MS/MS were employed to delineate the role of thymidine synthase (TYMS) during Th1 differentiation. RESULTS: CAP treatment significantly mitigated acute allograft rejection and enhanced graft survival by reducing graft damage, T cell infiltration, and levels of circulating pro-inflammatory cytokines. Additionally, it curtailed CD4+ T cell proliferation and the presence of Th1 cells in the spleen. RNA-seq showed that TYMS, the target of CAP, was robustly increased post-transplantation in splenocytes. In vitro, TYMS and its metabolic product dTMP were differentially expressed in Th0 and Th1, and were required after activation of CD4+ T cell and Th1 differentiation. TYMS-specific inhibitor, raltitrexed, and the metabolite of capecitabine, 5-fluorouracil, could inhibit the proliferation and differentiation of Th1. Finally, the combined use of CAP and the commonly used immunosuppressant rapamycin can induce long-term survival of allograft. CONCLUSION: CAP undergoes metabolism conversion to interfere pyrimidine metabolism, which targets TYMS-mediated differentiation of Th1, thereby playing a significant role in mitigating acute cardiac allograft rejection in murine models.

Self-Assembly Enabled Printable Asymmetric Self-Insulated Stretchable Conductor for Human Interface.

Soft and stretchable conductors with high electrical conductivity and tissue-like mechanical properties are crucial for both on-skin and implantable electronic devices. Liquid metal-based conductors hold great promise due to their metallic conductivity and minimal stiffness. However, the surface oxidation of liquid metal particles in polymeric matrices poses a challenge in forming a continuous pathway for highly conductive elastic composites. Here, it is reported a printable composite material based on liquid metal and conducting polymer that undergoes a self-assembly process, achieving high conductivity (2089 S cm-1) in the bottom surface while maintaining an insulated top surface, high stretchability (>800%), and a modulus akin to human skin tissue. This material is further applied to fabricate skin-interfaced strain sensors and electromyogram sensors through 3D printing.

Metronomic capecitabine with rapamycin exerts an immunosuppressive effect by inducing ferroptosis of CD4+ T cells after liver transplantation in rat.

Liver transplantation is one of the most effective treatments for hepatocellular carcinoma (HCC). The balance between inhibiting immune rejection and preventing tumor recurrence after liver transplantation is the key to determining the long-term prognosis of patients with HCC after liver transplantation. In our previous study, we found that capecitabine (CAP), an effective drug for the treatment of HCC, could exert an immunosuppressive effect after liver transplantation by inducing T cell ferroptosis. Recent studies have shown that ferroptosis is highly associated with autophagy. In this study, we confirmed that the autophagy inducer rapamycin (RAPA) combined with metronomic capecitabine (mCAP) inhibits glutathione peroxidase 4 (GPX4) and promotes ferroptosis in CD4+ T cells to exert immunosuppressive effects after rat liver transplantation. Compared with RAPA or mCAP alone, the combination of RAPA and mCAP could adequately reduce liver injury in rats with acute rejection after transplantation. The CD4+ T cell counts in peripheral blood, spleen, and transplanted liver of recipient rats significantly decreased, and the oxidative stress level and ferrous ion concentration of CD4+ T cells significantly increased in the combination group. In vitro, the combination of drugs significantly promoted autophagy, decreased GPX4 protein expression, and induced ferroptosis in CD4+ T cells. In conclusion, the autophagy inducer RAPA improved the mCAP-induced ferroptosis in CD4+ T cells. Our results support the concept of ferroptosis as an autophagy-dependent cell death and suggest that the combination of ferroptosis inducers and autophagy inducers is a new research direction for improving immunosuppressive regimens after liver transplantation.

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients' T cell ferroptosis.

BACKGROUND: Capecitabine (CAP) is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation (LT) in clinical studies. Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice. Ferroptosis, a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation, is an important mechanism by which CAP induces cell death. Therefore, ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after trans-plantation. AIM: To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP. METHODS: A rat LT model of acute rejection was established, and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT. In vitro, primary CD3+ T cells were sorted from rat spleens and human peripheral blood, and co-cultured with or without 5-fluorouracil (5-FU) (active agent of CAP). The levels of ferroptosis-related proteins, ferrous ion concentration, and oxidative stress-related indicators were observed. The changes in mito-chondrial structure were observed using electron microscopy. RESULTS: With no significant myelotoxicity, metronomic CAP alleviated graft injury (Banff score 9 vs 7.333, P < 0.001), prolonged the survival time of the recipient rats (11.5 d vs 16 d, P < 0.01), and reduced the infiltration rate of CD3+ T cells in peripheral blood (6.859 vs 3.735, P < 0.001), liver graft (7.459 vs 3.432, P < 0.001), and spleen (26.92 vs 12.9, P < 0.001), thereby inhibiting acute rejection after LT. In vitro, 5-FU, an end product of CAP metabolism, induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4, which caused the accumulation of ferrous ions. It also inhibited nuclear erythroid 2 p45-related factor 2, heme oxygenase-1, and glutathione peroxidase 4, eventually leading to oxidative damage and ferroptosis of T cells. CONCLUSION: Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+ T cell ferroptosis, which makes it an effective immunosuppressive agent after LT.

The impact of portal vein reconstruction on portal vein complications after pediatric living-donor liver transplantation with left lobe graft.

BACKGROUND: This study aimed to determine whether the different methods of portal vein reconstruction have an impact on the occurrence of portal vein complications after pediatric living-donor liver transplantation with left lobe graft. METHODS: A total of 567 recipients were eligible for enrollment in this study and were divided into the following 2 groups according to the type of portal vein reconstruction: group 1 underwent anastomosis of the left and right bifurcations of the recipient portal vein to the donor portal vein (type 1), whereas group 2 underwent anastomosis of the bevel formed by the main trunk and right branch of the recipient portal vein to the donor portal vein (type 2). Postoperative portal vein complications and recipient and graft survival rates were compared between the 2 groups before and after propensity score matching. RESULTS: Portal vein complications occurred in 53 (9.3%) patients, including 46 recipients with portal vein stenosis and 7 with portal vein thrombosis. After propensity score matching, the incidence of portal vein stenosis in group 2 was lower than that in group 1 (P = .035). The first diagnosis time of portal vein stenosis in group 2 was later than that in group 1 (P = .033), and the incidence of early portal vein stenosis was lower than that in group 1 (P = .009). There were no statistically significant differences in the incidence of portal vein thrombosis and recipient and graft survival rates between the 2 groups. CONCLUSIONS: Type 2 portal vein reconstruction appears to be a viable technique in pediatric living-donor liver transplantation with left lobe graft that can effectively reduce the incidence of portal vein stenosis.

Nomogram based on spleen volume expansion rate predicts esophagogastric varices bleeding risk in patients with hepatitis B liver cirrhosis.

Background: We aimed to explore the risk factors for hemorrhage of esophagogastric varices (EGVs) in patients with hepatitis B cirrhosis and to construct a novel nomogram model based on the spleen volume expansion rate to predict the risk of esophagogastric varices bleeding. Methods: Univariate and multivariate logistic regression analysis was used to analyze the risk factors for EGVs bleeding. Nomograms were established based on the multivariate analysis results. The predictive accuracy of the nomograms was assessed using the area under the curve (AUC or C-index) of the receiver operating characteristic (ROC) and calibration curves. Decision curve analysis was used to determine the clinical benefit of the nomogram. We created a nomogram of the best predictive models. Results: A total of 142 patients' hepatitis B cirrhosis with esophagogastric varices were included in this study, of whom 85 (59.9%) had a history of EGVs bleeding and 57 (40.1%) had no EGVs bleeding. The spleen volume expansion rate, serum sodium levels (mmol/L), hemoglobin levels (g/L), and prothrombin time (s) were independent predictors for EGVs bleeding in patients with hepatitis B liver cirrhosis (P < 0.05). The above predictors were included in the nomogram prediction model. The area under the ROC curve (AUROC) of the nomogram was 0.781, the C-index obtained by internal validation was 0.757, and the calibration prediction curve fit well with the ideal curve. The AUROCs of the PLT-MELD and APRI were 0.648 and 0.548, respectively. Conclusion: In this study, a novel nomogram for predicting the risk of EGVs bleeding in patients with hepatitis B cirrhosis was successfully constructed by combining the spleen volume expansion rate, serum sodium levels, hemoglobin levels, and prothrombin time. The predictive model can provide clinicians with a reference to help them make clinical decisions.

Triplexed Tracking Labile Sulfur-Containing Species on a Single-Molecule "Nezha" Sensor.

Sulfur-containing species (SCS), especially sulfur dioxide-relevant species, play an essential role in ecological balance. Owing to the intrinsically labile and mobile characteristics of SCS, it is still considered to be an insurmountable challenge for multiplexed tracking dynamics of SCS with distinct molecular structure, valence state, and condensed state. To address this key problem, we proposed herein alternative versatile single-molecule sensors (VSMs) that intramolecularly integrate high affinity target-guided multiple recognition units into a single sensory molecule, clarified as molecular Nezha available in triplexed responses to gaseous sulfur dioxide, liquid sulfur trioxide, and aqueous bisulfite through ubiquitous charge transfer and nucleophilic addition. High-performance molecular Nezha remarkably facilitated promising applications in a quantitative visualization of SCS on lab-on-paper and tracking the dynamics transformation of SCS as well comprehensive evaluation of multiphase adsorption science of SCS on an advanced Zeolitic imidazolate framework-8 (ZIF-8).

A glucose-activatable trimodal glucometer self-assembled from glucose oxidase and MnO2 nanosheets for diabetes monitoring.

Daily monitoring of blood glucose is of great importance for the treatment of diabetes mellitus. Herein, we present an ensemble glucometer with a sandwich structure formed by the spontaneous entrapment of glucose oxidase (GOD) onto manganese dioxide nanosheets (MnO2 NSs) via the hydrophobic effect and hydrogen bond interaction. Within the hybrid glucometer, the ultrathin MnO2 NSs act as an enzyme nanosupport and target-activated signal transducer. Trimodal self-indication by fluorescence (FL) and UV-absorbance (UV) and magnetic resonance signal (MRS) activation with glucose-specificity provides multiple response signals to glucose. Taking account of its operational simplicity and convenience, even being observable by the naked eye, a detection limit as low as 0.1 µM was obtained by using the ensemble glucometer in a colorimetric assay, whilst the precision for 11 replicated detections of 10 µM glucose was 3.5% (relative standard deviation, RSD). Notably, the value of the Michaelis-Menton constant of GOD involved the presented glucometer is estimated to be 0.051 mM, showing an exceptional enhanced enzymatic activity of free GOD measured by far. The designed glucometer, with its high sensitivity and simplicity highlighted, was capable of routine blood glucose monitoring for type-I diabetes mellitus in rats. Furthermore, the fully integrated platform can be readily generalized in principle for a number of biomarkers for point of care diagnostics in the future.