Search Results (30)

Zinc is an essential trace element with a critical role in regulating immune functions. Patients with autoimmune diseases or chronic lymphatic leukemia often exhibit lower serum zinc levels. As T cells are key mediators of adaptive immunity, disturbances in zinc homeostasis can strongly affect their function. Effective T cell activity depends on directed migration to inflamed tissues, requiring coordinated cytoskeletal reorganization. This process involves the formation of a leading edge and a trailing edge (uropod) and is regulated by the ezrin–radixin–moesin (ERM) complex and its interaction with focal adhesion kinase (FAK). We investigated how zinc availability influences the expression and phosphorylation of FAK and ERM, as well as other migration-related molecules, including LFA-1 and the CD49d/CD44 complex, using Western blot, qRT-PCR, and flow cytometry in the HUT78 T cell line. Cells were cultured in media with different zinc concentrations. Zinc deficiency reduced FAK and ERM expression and decreased LFA-1 while increasing CD49d expression. Overall, these findings indicate that zinc deficiency compromises cytoskeletal remodeling and may impair T cell motility. Maintaining zinc homeostasis could thus enhance T cell migration and strengthen immune responsiveness, highlighting the potential therapeutic relevance of zinc in immune modulation. Full article

(1) Background: Ventricular arrhythmias (VAs) are a leading cause of morbidity and mortality in ischemic and non-ischemic heart disease. While automated implantable cardioverter–defibrillators (AICDs) are standard treatment for high-risk patients, predicting future VA post-implantation remains limited. This study evaluated echocardiographic and strain parameters for predicting VA risk in AICD recipients. (2) Methods: This retrospective cohort study included patients who underwent AICD implantation at Westmead Hospital, New South Wales, Australia (January 2014–May 2024). Pre-implant transthoracic echocardiograms (TTEs) were analysed for structural and functional parameters, including left-ventricular (LV) ejection fraction (LVEF), LV global longitudinal strain (GLS), mechanical dispersion (MD), and delta contraction duration (DCD). VA events, defined as appropriate AICD shock or anti-tachycardia pacing, were identified from electronic medical records and device checks. Univariate and multivariate Cox regression analyses were performed. (3) Results: Among 242 patients, 98 experienced VA events. Increased LV end-diastolic diameter, indexed LV mass, and right-ventricular basal diameter were associated with VA events (p < 0.05), whilst LVEF and GLS were not. LV dyssynchrony was greater in affected patients (MD 69.2 ms vs. 63 ms, p = 0.036; DCD 288.8 ms vs. 246.4 ms, p = 0.010). DCD was an independent predictor of VA events (HR 1.003; 95% CI: 1.000–1.006; p = 0.022). (4) Conclusions: DCD may improve risk stratification in AICD patients. Full article

Liver transplantation is commonly used for end-stage liver disease, but the demand for organs exceeds the supply, leading to the use of expanded criteria donors (ECDs). Organs from ECDs, especially from donors after circulatory death (DCD), encounter challenges like increased ischemia damage. Biomarkers, especially oxidative stress markers, may provide valuable insights for understanding and monitoring post-transplant events. Here, we highlight the unique value of organ preservation solution (OPS) as a non-invasive and early source of redox biomarkers, directly reflecting graft status during critical cold storage. This study investigated oxidative stress in 74 donated livers using OPS samples collected after cold storage, and also liver biopsies obtained before and after storage. We measured lipid peroxidation, protein carbonylation, DNA oxidation, and total antioxidant capacity from OPS, and performed gene expression analysis of liver biopsies. Oxidative stress markers differed based on donation type, with higher lipid peroxidation in DCD samples compared with donation after brain death (18.51 ± 2.77 vs. 11.03 ± 1.31 nmoles malondialdehyde (MDA)/mg protein; p = 0.049). Likewise, oxidative damage markers were associated with clinical outcomes: lipid peroxidation was increased in patients who developed biliary complications (21.86 ± 5.91 vs. 11.97 ± 1.12 nmol MDA/mg protein; p = 0.05), and protein carbonylation was elevated in those experiencing acute rejection (199.6 ± 22.02 vs. 141.6 ± 15.94 nmol carbonyl/mg protein; p = 0.005). Moreover, higher protein carbonylation levels showed a trend toward reduced survival (p = 0.091). Transcriptomic analysis revealed overexpression of genes associated with reactive oxygen species production in DCD livers. A predictive model for acute rejection integrating OPS biomarkers with clinical variables achieved 83% accuracy. Hence, this study underscores the importance of assessing oxidative stress status in preservation fluid as a biomarker for evaluating liver transplant outcomes and highlights the need for validation in larger, independent cohorts. Full article

Background: Primary sclerosing cholangitis (PSC) accounts for 10–15% of liver transplants but is the leading cause of retransplant. This study evaluates whether PSC patients have different survival and graft outcomes when receiving grafts from donors after brain death (DBD) versus circulatory (DCD) death. Methods: Using the SRTR database (2004–2024), we compared PSC patients receiving DCD vs. DBD grafts. Demographics and outcomes including graft loss, mortality, and retransplant were analyzed using multivariable logistic and Cox regression, along with propensity-matched analysis. Results: Among 5762 PSC patients, 391 (6.8%) received DCD grafts. Patients receiving DCD grafts were older but had lower MELD scores (19 vs. 22; p < 0.001) and were less often functionally dependent (11.3% vs. 24.4%; p < 0.001). Multivariable Cox regression demonstrated that receipt of a DCD graft was independently associated with time to graft loss (HR 1.59; CI 1.10–2.31; p = 0.013. Similarly, DCD graft receipt significantly increased the likelihood of requiring retransplant (HR 3.25; CI: 1.93–5.46; p < 0.001) but did not increase the likelihood of mortality. Propensity matched analysis further supported these finding with significantly higher graft loss with DCD grafts at one and two years and higher retransplant rates at all time points including 5-years (+7.9%, CI 4.4 to 11.4%; p < 0.001). Conclusions: DCD grafts in PSC patients are linked to worse graft survival and higher retransplant rates. They may be best suited for older, lower-MELD patients, but further studies on perfusion strategies are needed. Full article

Background/Objectives: Donation after circulatory death (DCD) has emerged to expand the heart-donor pool, but many DCD donors have risk factors such as cocaine or methamphetamine use. Stimulant use can cause coronary vasospasm and premature coronary artery disease, leading to routine donor coronary angiography (left heart catheterization, LHC) for coronary screening. However, performing LHC in DCD donors is challenging. We examined whether omitting LHC in stimulant-exposed DCD donors affects outcomes. Methods: A retrospective analysis was performed using the United Network for Organ Sharing (UNOS) database (2019–2024) to identify adult heart transplant recipients from DCD donors with documented cocaine or amphetamine use. Donors were stratified by whether antemortem LHC was performed. The primary outcome was 1-year recipient survival; secondary outcomes included graft failure and acute rejection. Kaplan–Meier survival curves and Cox regression analyses were performed. Results: A total of 485 DCD heart transplant recipients were identified; 135 (28%) donors underwent LHC and 350 (72%) did not. Recipient characteristics were similar between groups. No significant differences in 30-day (6% vs. 3%; p = 0.11), 90-day (6% vs. 3%; p = 0.21), or 1-year survival (7% vs. 6%; p = 0.48) were observed between the LHC and non-LHC cohorts. Graft failure and complication rates were also similar. However, among stimulant-exposed DCD donors with diabetes, an absence of LHC was associated with higher recipient mortality (HR 5.86, 95% CI: 1.57–21.87; p = 0.008). Conclusions: Routine donor coronary angiography may be unnecessary for stimulant-exposed DCD donors without additional risk factors. Omitting LHC did not compromise transplant outcomes. A selective LHC approach for high-risk DCD donors (e.g., diabetic donors) could safely expand the donor pool. Full article

Accurate three-dimensional change detection is essential for monitoring dynamic environments such as urban areas, infrastructure, and natural landscapes. Point-based methods are sensitive to noise and lack spatial coherence, while object-based approaches rely on clustering, which can miss fine-scale changes. To address these limitations, we introduce an object-based change detection framework integrating semantic segmentation and geometric change indicators. The proposed method first classifies bi-temporal point clouds into ground, vegetation, buildings, and moving objects. A cut-pursuit clustering algorithm then segments the data into spatially coherent objects, which are matched across epochs using a nearest-neighbor search based on centroid distance. Changes are characterized by a combination of geometric features—including verticality, sphericity, omnivariance, and surface variation—and semantic information. These features are processed by a random forest classifier to assign change labels. The model is evaluated on the Urb3DCD-v2 dataset, with feature importance analysis to identify important features. Results show an 81.83% mean intersection over union. An additional ablation study without clustering reached 83.43% but was more noise-sensitive, leading to fragmented detections. The proposed method improves the efficiency, interpretability, and spatial coherence of change classification, making it well suited for large-scale monitoring applications. Full article

Background: Children with motor delays often experience challenges in health-related fitness, but the impact on running skills remains unclear. Previous research has shown that children with motor coordination problems have lower cardiorespiratory fitness, muscle strength, endurance, and higher body weight compared to peers. Few studies have examined anaerobic capacity, muscular power, endurance, running performance, and fatigue in children with developmental coordination disorder (DCD). This study aims to compare repetitive running and running-induced fatigue in typically developing children and those with varying degrees of motor coordination problems. Methods: Groups were classified using the Movement Assessment Battery for Children, second edition (MABC-2), as probably having DCD (p-DCD, ≤5th percentile, age 9.7 (SD 1.6), n = 141), at risk for DCD (r-DCD, 6th–16th percentile, age 9.9 (SD1.6), n = 160), and typically developing (TD, >16th percentile, age 9.6 (SD 1.6), n = 191). Anaerobic fitness and fatigue were assessed using the Children’s Repetitive and Intermittent Sprinting Performance test (CRISP), while lower and upper body muscular strength, running, and agility were measured with the performance and fitness (PERF-FIT) test battery Power and Agility subscale. Age groups (6–9 and 10–12 years) were analyzed to determine when performance deficits emerged. Results: The p-DCD group was significantly slower, had less power, and fatigued more than the r-DCD and TD children (p < 0.01). This was already clearly the case in the 6–9-year-olds, who slowed down already after the first runs, while the older poorly coordinated children started slower than their peers and showed a more gradual decrease in performance over the runs. Conclusions: Moderate coordination differences between r-DCD and TD children did not significantly impact fatigue, but p-DCD children exhibited greater fatigue due to overestimating their start speed, higher body weight, lower power, and reduced agility, especially in younger age groups. (Too) High starting speed, especially in the younger less coordinated children (p-DCD), is likely to lead to more fatigue. Full article

Liver transplantation is the preferred treatment for end-stage liver disease. Emerging evidence suggests a potential role for liver transplantation in treating liver tumors such as colorectal liver metastases and cholangiocarcinoma. However, due to a limited donor pool, the use of marginal grafts from donation after circulatory death (DCD) donors is increasing to meet demand. Machine perfusion is crucial in this context for improving graft acceptance rates and reducing ischemia–reperfusion injury. Few studies have evaluated the role of machine perfusion in the context of transplant oncology. Perfusion machines can be utilized in situ (normothermic regional perfusion—NRP) or ex situ (hypothermic and normothermic machine perfusion), either in combination or as a complement to conventional in situ cold flush and static cold storage. The objective of this analysis is to provide an up-to-date overview of perfusion machines and their function in donation after circulatory death with particular attention to their current and likely potential effects on transplant oncology. A literature review comparing standard cold storage to machine perfusion methods showed that, so far, there is no evidence that these devices can reduce the tumor recurrence rate. However, some evidence suggests that these innovative perfusion techniques can improve graft function, reduce ischemia–reperfusion injury, and, based on this mechanism, may lead to future improvements in cancer recurrence. Full article

Both melatonin and hydrogen sulfide (H₂S) mitigate chromium (Cr) toxicity in plants, but the specific interaction between melatonin and H₂S in Cr detoxification remains unclear. In this study, the interaction between melatonin and H₂S in Cr detoxification was elucidated by measuring cell wall polysaccharide metabolism and antioxidant enzyme activity in maize. The findings revealed that exposure to Cr stress (100 μM K₂Cr₂O₇) resulted in the upregulation of L-/D-cysteine desulfhydrase (LCD/DCD) gene expression, leading to a 77.8% and 27.3% increase in endogenous H₂S levels in maize leaves and roots, respectively. Similarly, the endogenous melatonin system is activated in response to Cr stress. We found that melatonin had a significant impact on the relative expression of LCD/DCD, leading to a 103.3% and 116.7% increase in endogenous H₂S levels in maize leaves and roots, respectively. In contrast, NaHS had minimal effects on the relative mRNA expression of serotonin-Nacetyltransferase (SNAT) and endogenous melatonin levels. The production of H₂S induced by melatonin is accompanied by an increase in Cr tolerance, as evidenced by elevated gene expression, elevated cell wall polysaccharide content, increased pectin methylesterase activity, and improved antioxidant enzyme activity. The scavenging of H₂S decreases the melatonin-induced Cr tolerance, while the inhibitor of melatonin synthesis, p-chlorophenylalanine (p-CPA), has minimal impact on H₂S-induced Cr tolerance. In conclusion, our findings suggest that H₂S serves as a downstream signaling molecule involved in melatonin-induced Cr tolerance in maize. Full article

Controlled-release urea (CRU) fertilizers are widely used in agricultural production to reduce conventional nitrogen (N) fertilization-induced agricultural greenhouse gas emissions (GHGs) and improve N use efficiency (NUE). However, the long-term effects of different CRU fertilizers on GHGs and crop yields in vegetable fields remain relatively unexplored. This study investigated the variations in GHG emissions at four growth stages of lettuce in the spring and autumn seasons based on a five-year field experiment in the North China Plain. Four treatments were setup: CK (without N application), U (conventional urea—N application), ON (20% reduction in urea—N application), CRU (20% reduction in polyurethane-coated urea without topdressing), and DCRU (20% reduction in polyurethane-coated urea containing dicyandiamide [DCD] without topdressing). The results show that N application treatments significantly increased the GHG emissions and the lettuce yield and net yield, and DCRU exhibited the lowest N₂O and CO₂ emissions, the highest lettuce yield and net yield, and the highest lettuce N content of the N application treatments. When compared to U, the N₂O emission peak under CRU and DCRU treatments was notably decreased and delayed, and their average N₂O emission fluxes were significantly reduced by 10.20–20.72% and 17.51–29.35%, respectively, leading to a significant reduction in mean cumulative N₂O emissions during the 2017–2021 period. When compared to U, the CO₂ fluxes of DCRU significantly decreased by 8.0–16.54% in the seedling period, and mean cumulative CO₂ emission decreased by 9.28%. Moreover, compared to U, the global warming potential (GWP) and greenhouse gas intensity (GHGI) of the DCRU treatment was significantly alleviated by 9.02–17.13% and 16.68–20.36%, respectively. Compared to U, the N content of lettuce under DCRU was significantly increased by 6.48–17.25%, and the lettuce net yield was also significantly increased by 5.41–7.71%. These observations indicated that the simple and efficient N management strategy to strike a balance between enhancing lettuce yields and reduce GHG emissions in open-field lettuce fields could be obtained by applying controlled-release urea containing DCD without topdressing. Full article

Leaf senescence is the terminal stage of leaf development, and its initiation and progression are closely controlled by the integration of a myriad of endogenous signals and environmental stimuli. It has been documented that WRKY transcription factors (TFs) play essential roles in regulating leaf senescence, yet the molecular mechanism of WRKY-mediated leaf senescence still lacks detailed elucidation in crop plants. In this study, we cloned and identified a tobacco WRKY TF gene, designated NtWRKY70b, acting as a positive regulator of natural leaf senescence. The expression profile analysis showed that NtWRKY70b transcript levels were induced by aging and hydrogen peroxide (H₂O₂) and downregulated upon hydrogen sulfide (H₂S) treatment. The physiological and biochemical assays revealed that overexpression of NtWRKY70b (OE) clearly promoted leaf senescence, triggering increased levels of reactive oxygen species (ROS) and decreased H₂S content, while disruption of NtWRKY70b by chimeric repressor silencing technology (SRDX) significantly delayed the onset of leaf senescence, leading to a decreased accumulation of ROS and elevated concentration of H₂S. The quantitative real-time PCR analysis showed that the expression levels of various senescence-associated genes and ROS biosynthesis-related genes (NtRbohD and NtRbohE) were upregulated in OE lines, while the expression of H₂S biosynthesis-related genes (NtDCD and NtCYSC1) were inhibited in OE lines. Furthermore, the Yeast one-hybrid analysis (Y1H) and dual luciferase assays showed that NtWRKY70b could directly upregulate the expression of an ROS biosynthesis-related gene (NtRbohD) and a chlorophyll degradation-related gene (NtPPH) by binding to their promoter sequences. Accordingly, these results indicated that NtWYKY70b directly activated the transcript levels of NtRbohD and NtPPH and repressed the expression of NtDCD and NtCYCS1, thereby promoting ROS accumulation and impairing the endogenous H₂S production, and subsequently accelerating leaf aging. These observations improve our knowledge of the regulatory mechanisms of WRKY TFs controlling leaf senescence and provide a novel method for ensuring high agricultural crop productivity via genetic manipulation of leaf senescence in crops. Full article

Uncontrolled donation after circulatory death (uDCD) represents a potential source of lungs, and since Steen’s 2001 landmark case in Sweden, lungs have been recovered from uDCD donors and transplanted to patients in other European countries (France, the Netherlands, Spain and Italy) with promising results. Disparities still exist among European countries and among regions in Italy due to logistical and organizational factors. The present manuscript focuses on the clinical experiences pertaining to uDCD lungs in North America and European countries and on different lung maintenance methods. Existing experiences (and protocols) are not uniform, especially with respect to the type of lung maintenance, the definition of warm ischemic time (WIT) and, finally, the use of ex vivo perfusion (available in the last several years in most centers). In situ lung cooling may be superior to protective ventilation, but this process may be difficult to perform in the uDCD setting and is also time-consuming. On the other hand, the “protective ventilation technique” is simpler and feasible in every hospital. It may lead to a broader use of uDCD lung donors. To date, the results of lung transplants performed after protective ventilation as a preservation technique are scarce but promising. All the protocols comprise, among the inclusion criteria, a witnessed cardiac arrest. The detectable differences included preservation time (240 vs. 180 min) and donor age (<55 years in Spanish protocols and <65 years in Toronto protocols). Overall, independently of the differences in protocols, lungs from uDCD donors show promising results, and the possibility of optimizing ex vivo lung perfusion may broaden the use of these organs. Full article

Triple–negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer with a poor response rate to conventional systemic treatment and high relapse rates. Members of the natural killer group 2D ligand (NKG2DL) family are expressed on cancer cells but are typically absent from healthy tissues; thus, they are promising tumor antigens for novel immunotherapeutic approaches. We developed bispecific fusion proteins (BFPs) consisting of the NKG2D receptor domain targeting multiple NKG2DLs, fused to either anti–CD3 (NKG2D–CD3) or anti–CD16 (NKG2D–CD16) Fab fragments. First, we characterized the expression of the NKG2DLs (MICA, MICB, ULBP1–4) on TNBC cell lines and observed the highest surface expression for MICA and ULBP2. Targeting TNBC cells with NKG2D–CD3/CD16 efficiently activated both NK and T cells, leading to their degranulation and cytokine release and lysis of TNBC cells. Furthermore, PBMCs from TNBC patients currently undergoing chemotherapy showed significantly higher NK and T cell activation and tumor cell lysis when stimulated with NKG2D–CD3/CD16. In conclusions, BFPs activate and direct the NK and T cells of healthy and TNBC patients against TNBC cells, leading to efficient eradication of tumor cells. Therefore, NKG2D–based NK and T cell engagers could be a valuable addition to the treatment options for TNBC patients. Full article

An essential means of collecting more abdominal donor organs is controlled donation after circulatory death (cDCD). The organs are typically preserved during cDCD using the abdominal normothermic regional perfusion (A-NRP) technique to recirculate oxygenated blood flow following cardiac arrest and the withdrawal of life support. One of the challenges of A-NRP is ensuring the correct vascular devices’ positionings, specifically extracorporeal membrane oxygenation cannulae and aortic balloons, typically achieved through fluoroscopy with or without contrast agents. Here, we present a case report in which transesophageal echocardiography (TEE) helped the transplant team to effectively procure viable abdominal organs from a cDCD donor in the shortest time frame, as minimizing time is one of the most crucial factors in maintaining organ viability. TEE use leads to a more effective and efficient A-NRP procedure with limited complications. In addition, it allows us to observe the circulation of both the thoracic and part of the abdominal organs using one fast exam. This case is the first report describing TEE as a primary guide and useful tool for DCD donors. However, prospective studies are needed to confirm that TEE could be used as standard practice during all DCD organ retrieval procedures. Full article

Effective nitrogen management practices by using two cultivation techniques can improve corn productivity and soil carbon components such as soil carbon storage, microbial biomass carbon (MBC), carbon management index (CMI), and water-soluble carbon (WSC). It is essential to ensure the long-term protection of dry-land agricultural systems. However, excessive application of nitrogen fertilizer reduces the efficiency of nitrogen use and also leads to increased greenhouse gas emissions from farming soil and several other ecological problems. Therefore, we conducted field trials under two planting methods during 2019–2020: P: plastic mulching ridges; F: traditional flat planting with nitrogen management practices, i.e., 0: no nitrogen fertilizer; FN: a common nitrogen fertilizer rate for farmers of 290 kg ha⁻¹; ON: optimal nitrogen application rate of 230 kg ha⁻¹; _ON75%+DCD: 25% reduction in optimal nitrogen fertilizer rate + dicyandiamide; _ON75%+NC: 25% reduction in optimal nitrogen rate + nano-carbon. The results showed that compared to other treatments, the _PON75%+DCD treatment significantly increased soil water storage, water use efficiency (WUE), and nitrogen use efficiency (NUE) because total evapotranspiration (ET) and GHG were reduced. Under the P_ON75%+DCD or P_ON75%+NC, the soil carbon storage significantly (50% or 47%) increased. The P_ON75%+DCD treatment is more effective in improving MBC, CMI, and WSC, although it increases gaseous carbon emissions more than all other treatments. Compared with FFN, under the P_ON75%+DCD treatment, the overall CH₄, N₂O, and CO₂ emissions are all reduced. Under the P_ON75%+DCD treatment, the area scale GWP (52.7%), yield scale GWP (90.3%), biomass yield (22.7%), WUE (42.6%), NUE (80.0%), and grain yield (32.1%) significantly increased compared with F_FN, which might offset the negative ecological impacts connected with climate change. The P_ON75%+DCD treatment can have obvious benefits in terms of increasing yield and reducing emissions. It can be recommended to ensure future food security and optimal planting and nitrogen management practices in response to climate change. Full article