Search Results (432)

Background/Objectives. Ebstein’s anomaly (EA), which accounts for fewer than 1% of congenital heart diseases, and atrioventricular canal defect (AVCD), present in approximately 4–5% of cases, exceptionally coexist, with this combination observed in fewer than 0.5% of patients with AVCD. We aim to report the oldest documented case of a 45-year-old female with the exceptionally rare combination of complete AVCD, EA, and right ventricular hypoplasia and to provide a concise review of these anomalies. Case presentation. Diagnosed in early childhood with a complete AVCD, pulmonary stenosis, and right ventricular (RV) hypoplasia, the patient underwent palliative surgical intervention with a modified Blalock–Taussig shunt at the age of 10 but did not receive subsequent regular follow-up. Over the ensuing 35 years, she remained largely untreated until presentation at 45 years of age with progressive exertional dyspnea, central cyanosis, and palpitations, corresponding to NYHA class III. Comprehensive multimodal imaging, including transthoracic echocardiography and cardiac magnetic resonance, revealed a complete AVCD with moderate-to-severe mitral regurgitation secondary to an anterior mitral leaflet cleft, severe tricuspid regurgitation, RV hypoplasia, and hallmark features of EA. Given the complex cardiac anatomy and the elevated surgical risk, the patient was considered inoperable, and a strategy of conservative management with multidisciplinary follow-up was implemented. Conclusions. This case highlights the exceptional longevity of a patient with the rare coexistence of complete AVCD, EA, and RV hypoplasia, surviving 45 years from diagnosis despite limited early intervention. It underscores the importance of lifelong follow-up in complex congenital heart disease and illustrates the role of multimodal imaging in assessing anatomy and guiding management when surgical options are high-risk or not feasible. Full article

Background: Epidural analgesia (EA) is widely used in pancreatic surgery but is associated with hypotension and delayed recovery. The shift towards minimally invasive surgery has led to the exploration of alternative multimodal analgesia strategies. Methadone, with its unique pharmacological properties, may further optimize recovery. Methods: This retrospective cohort study included 213 patients undergoing pancreatic resection, receiving EA (n = 63), multimodal analgesia without methadone (MA; n = 92), or with methadone (MM; n = 58). MA and MM included intravenous ketamine, lidocaine and continuous wound infiltration. Primary outcome was maximum daily postoperative pain scores. Secondary outcomes included opioid consumption, vasopressor use, mobilization, bowel recovery, urinary catheter duration, and ICU/hospital stay. Results: Compared with EA, pain scores were slightly higher in MM (mean difference 2.22; 95% CI 1.22–3.90; p = 0.01) and in MA (mean difference 2.06; 95% CI 0.99–4.30; p = 0.06). Opioid use was comparable between MM and EA (OR 0.99, 95% CI [0.98, 1.00], p = 0.20), and significantly lower in MA (OR 0.97, 95% CI [0.96, 0.98], p < 0.001). Both MA and MM demonstrated reduced vasopressor requirements (both 0 vs. 2.0 median days) and shorter urinary catheterization durations (MA 1.2 MM 1.9 vs. EA 4.0 median days). MA improved mobilization (0 vs. 1 median days; OR 0.52, p = 0.03) and bowel recovery (OR 0.76, p = 0.02). ICU stay was longer in EA due to routine ICU admission for open surgery. Conclusions: Multimodal analgesia, with or without methadone, offers alternative strategies in pancreatic surgery. While EA provides superior pain control, multimodal regimens are associated with improved functional recovery. Full article

High-performance low dropout regulator (LDO) chips are core components that provide clean power for high-precision sensors, radio frequency (RF) circuits, low noise amplifiers and other noise-sensitive circuits. In the reported literature, the designed LDO chip has advantages in certain parameters, but it cannot meet all the requirements of a high power supply rejection ratio (PSRR), low output noise and low standby current at the same time, which makes the high-end applications of LDOs greatly limited. In this paper, an LDO chip with high PSRR, low output noise and low standby current has been designed and fabricated. By increasing the loop gain, introducing an improved feedforward path, and adopting isolated power supply, the PSRR of the LDO at different frequency bands is greatly improved. By optimizing the design of the error amplifier (EA) and adding a low-pass filter to filter out the reference noise, the output voltage noise of the LDO is reduced. Within the depletion process and an optimized reference structure, the standby power consumption of the LDO is reduced without damaging the output voltage accuracy. The chip is taped out with SMIC’s 0.18 μm/5 V/BCD process. The measured PSRR of the chip is as high as 95dB at a frequency of 1 kHz, and the high-frequency (1 MHz) PSRR is above 45 dB. The amplitude of integrated output noise is below 5.4 μVrms within the frequency range of 10 Hz to 100 KHz. When the load current is zero, the measured standby current is less than 400 nA. The test results indicate that the chip has excellent performance in terms of PSRR, output noise and standby power consumption. Full article

Background/Objectives: Chimeric antigen receptor (CAR) T cells are a powerful cancer therapy, but their function depends heavily on internal signaling domains and metabolic adaptability. Most studies evaluate CAR behavior upon antigen exposure, yet intrinsic signaling properties may pre-program CAR T cell states even in the absence of stimulation. This study investigates how CAR design and metabolic support shape baseline transcriptional programs, focusing on tonic signaling and NF-κB-related pathways. Methods: We engineered CAR T cells targeting HER2 or GPC3 antigens, incorporating either 4-1BB or CD28 co-stimulatory domains, respectively. A subset of cells was further modified with adenosine deaminase 1 (ADA1) and CD26 to degrade extracellular adenosine and supply inosine, a metabolic strategy termed metabolic refueling (MR). Bulk RNA-seq was performed on resting T cells without antigen stimulation. We analyzed differential gene expression, gene set enrichment (GO, KEGG, Hallmarks), and transcription factor activity (DoRothEA) to assess the impact of CAR design and MR on T cell programming. Results: All CAR T cells exhibited activation of NF-κB–centered inflammatory programs at baseline, indicating tonic signaling. GPC3 CAR T cells showed stronger baseline activation than HER2 CAR T cells. Metabolic refueling amplified these programs without altering their directionality, enhancing inflammatory, survival, and effector modules. Transcription factor activity scores mirrored these trends, highlighting RELA, FOS, and STATs as key regulatory nodes. Conclusions: CAR-intrinsic features, notably co-stimulatory domain choice, define the tonic NF-κB activation tone in resting CAR T cells. Metabolic refueling boosts these baseline states without overstimulation, suggesting it may be especially valuable for weaker CAR constructs. These findings provide a framework for tuning CAR T cell function through combinatorial design strategies targeting signaling and metabolism. Full article

Dragon’s Blood, from the Dracaena cochinchinensis plant, is known for enhancing blood circulation. Its main components are Dragon’s Blood phenolic extracts (DBE). To pinpoint the active DBE constituents that are effective against thrombosis and understand their mechanism of action, the PT-stroke model was employed to assess DBE’s antithrombotic effects on cerebral blood flow and platelet aggregation. This investigation demonstrates that DBE enhances cerebral blood flow and inhibits ADP-induced platelet aggregation in photothrombotic (PT) stroke models. An FeCl₃-induced carotid artery thrombosis model was developed to test the antithrombotic activity of four DBE fractions. Through screening with this model, the ethyl acetate (EA) and methanol fractions were identified as the principal active components that effectively reduced thrombus weight and improved hemodynamics. Furthermore, the EA fraction was found to preserve the integrity of the blood–brain barrier. Phytochemical isolation allowed for the identification of compounds in the EA fractions, and UHPLC-MS was performed to characterize DBE and its active components in the bloodstream. In vitro ADP-induced platelet aggregation assays highlighted the active compounds. Through phytochemical analysis, Loureirin D (compound 17) was identified as a predominant constituent present in plasma. In vitro assays revealed that compounds 1 and 17 possess strong antiplatelet activity, with Loureirin D being confirmed as a selective P2Y12 receptor antagonist via molecular docking and cellular thermal shift assays. These findings substantiate Loureirin D as a pivotal antithrombotic component in DBE and its potential as a P2Y12-targeting therapeutic agent for thrombosis treatment. Full article

Background: Right-ventricular (RV) involvement is starting to gain recognition in pediatric dilated cardiomyopathy (DCM), but its deformation characteristics and its relationship to functional status remain insufficiently defined. Methods: Twenty-nine children with primary DCM were compared with age- and sex-matched healthy controls. Conventional echocardiography and two-dimensional speckle-tracking echocardiography (2D-STE) were performed. Segmental deformation (basal, mid-ventricular and apical levels) was analyzed using a linear mixed-effects model. Associations between strain indices and advanced functional limitation (NYHA/Ross Class III-IV) were evaluated using exploratory logistic regression and ROC analysis. Results: Children with DCM showed significant impairment in both ventricles. Conventional parameters (TAPSE, tricuspid E/A ratio, RV E′ velocity, and LV ejection fraction) were reduced. Right ventricular strain was significantly lower in DCM compared with controls (p < 0.05). Segmental analysis demonstrated a basal-predominant reduction in RV strain. Right-ventricular free-wall longitudinal strain correlated with RV S′ (r = −0.49), RV E′ (r = −0.46), LVGLS (r = 0.79) and LV ejection fraction (r = −0.63, all p < 0.05). In univariable analysis, RVFWSL predicted advanced functional class (OR 1.13 per 1% decrease, p = 0.026), while LVGLS remained the independent predictor in the multivariable model. A combined model incorporating RVFWSL and LVGLS demonstrated excellent discriminative accuracy (AUC 0.95). Conclusions: Pediatric DCM is characterized by RV involvement with a distinct basal-dominant deformation pattern. Biventricular strain assessment improves the identification of children with advanced functional class and may enhance functional stratification beyond conventional indices. Full article

Background: Acute coronary syndromes (ACSs) remain a leading cause of death and disability. Since the publication of the 2023 ESC ACS guidelines, multiple studies and an ESC/EAS dyslipidaemia update have refined how clinicians diagnose, revascularize, and treat ACS across the care continuum. Content: This state-of-the-art review synthesizes advances from 2023 to 2025 across five domains. Diagnosis: High-sensitivity troponin-based accelerated pathways remain foundational; GRACE 3.0 improves calibration for early vs. delayed angiography, while selective use of CCTA and routine use of intracoronary imaging/physiology help define the mechanism and optimize PCI. Revascularization: complete revascularization continues to underpin care in multivessel disease, with recent data favouring culprit-only PCI acutely and staged non-culprit treatment during the index stay in most STEMI presentations, particularly with heart-failure physiology. Antithrombotic therapy: Aspirin remains critical early after ACS-PCI; emerging evidence supports shorter DAPT and aspirin withdrawal after 1 month in carefully selected, low-ischaemic-risk patients, whereas day-0 aspirin-free strategies in unselected ACS are not non-inferior. Secondary prevention: A “strike early and strong” approach to LDL-cholesterol—often with combination therapy in hospital—is emphasized, alongside nuanced roles for SGLT2 inhibitors and GLP-1 receptor agonists. Special populations and implementation: Sex- and age-aware tailoring (including MINOCA/SCAD evaluation), pragmatic bleeding-risk mitigation, digitally enabled cardiac rehabilitation, and registry-driven quality improvement translate evidence into practice. Summary: Contemporary ACS care is moving from uniform protocols toward risk-stratified, mechanism-informed pathways. We offer practical algorithms and checklists to align interventional timing, antithrombotic intensity/duration, and secondary prevention with individual patient risk—bridging new evidence to bedside decisions. Full article

Background: Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with limited treatment efficacy. Alternating current electroacupuncture (AC-EA) represents a novel neuromodulatory approach, though its mechanisms—particularly its influence on the gut–brain axis—remain underexplored. Methods: We investigated the neurobehavioral and microbiological effects of AC-EA in a rat model of PTSD induced by single prolonged stress. Animals received AC-EA at Baihui (GV20) and Mingmen (GV4) acupoints with varying parameters (0.5 mA/20 Hz, 1 mA/20 Hz, and 1 mA/2 Hz). Behavioral tests (open field test, elevated plus maze), histopathological assessments, immunofluorescence for TLR4, and 16S rRNA sequencing of gut microbiota were performed. Results: AC-EA at 1 mA/2 Hz significantly improved exploratory behavior and reduced anxiety-like responses (p < 0.05). This regimen also restored neuronal integrity in the hippocampus and cortex and reversed PTSD-induced gut dysbiosis, enriching beneficial genera such as Ligilactobacillus. Furthermore, AC-EA downregulated hepatic TLR4 expression, indicating suppression of neuroinflammatory signaling. Conclusions: Our findings demonstrate that AC-EA exerts neuromodulatory and microbiota-rebalancing effects via the gut–brain axis, highlighting its potential as a non-invasive therapeutic strategy for PTSD and related brain health disorders. Full article

Background: Chronic heart failure (HF) is a significant public health issue. The principal risk factors for left ventricular diastolic dysfunction (LVDD) include older age, female sex, obesity, hypertension, smoking, and diabetes, among others, all of which can reduce physical activity. Additionally, peripheral factors such as skeletal muscle mass (SMM) abnormalities decrease maximal oxygen consumption. In elderly HF patients, the prevalence of sarcopenia is higher than in those without HF; however, the relationship between sarcopenia and HF remains insufficiently explained, particularly in right HF (RHF). Our objective was to describe the echocardiographic alterations between sarcopenic and non-sarcopenic subjects with RHF. Methods: A cross-sectional study was conducted. Outpatients aged 18 years or older with a confirmed diagnosis of RHF were included. Sarcopenia was defined according to EWGSOP2. Results: A total of 183 patients were included; 24.5% had sarcopenia. The mean age was 64.34 ± 13.97 years. Echocardiographic characteristics revealed evidence of LVDD in sarcopenic subjects, as indicated by lower E wave velocity, E/A ratio, and e’ lateral and medial values, as well as lower right ventricular (RV) wall thickness compared with non-sarcopenic subjects. The multivariate model showed that sarcopenia subjects had lower RV wall thickness (B: −1.36 mm, 95% CI: −2.30 to −0.42), e’ medial (B: −1 cm/s, 95% CI: −1.99 to −0.02), and e’ lateral (B: −1.78 cm/s, 95% CI: −2.97 to −0.60). Conclusions: The prevalence of sarcopenia in RHF patients was 24.6%, which was associated with LVDD and lower RV wall thickness, suggesting a loss of cardiac muscle mass. Full article

Severe equine asthma (sEA) is characterized by increased lower airway neutrophils that contribute to dysregulated inflammation through the release of cytokines, reactive oxygen species and neutrophil extracellular traps (NETs). NETs are composed of cell-free DNA (cfDNA) intercalated with enzymatic proteins and are known to be increased in the lower airway of asthmatic horses. The objectives of this study were two-fold: 1. Determine if cfDNA can be accurately measured in equine bronchoalveolar lavage fluid (BALF) and tracheal wash (TW) with a Qubit 4 fluorometer. 2. Determine whether Qubit-measured cfDNA in BALF or TW is significantly different in horses with sEA, mild/moderate neutrophilic equine asthma, mastocytic equine asthma and healthy horses. A total of sixty-three horses received a physical examination and clinical score followed by a BAL +/− TW. Cell-free DNA was measured using three methods in unfiltered BAL and TW as well as BAL and TW supernatant. Cell-free DNA concentrations were highly correlated between the Qubit 4 fluorometer and NanoDrop spectrophotometer as well as between the Qubit 4 fluorometer and SYTOX green plate-based assay. Cell-free DNA concentrations were highly correlated between unfiltered TW and TW supernatant as well as between unfiltered BALF and BAL supernatant. Cell-free DNA concentrations in BAL and TW supernatant were significantly higher in horses with sEA compared to healthy horses or horses with mild/moderate equine asthma. Cell-free DNA is a biomarker of sEA that can be easily measured in the field with the small portable Qubit 4 fluorometer in BAL and TW fluid. These findings support further investigation of NETs as a biomarker and potential therapeutic target for severe equine asthma. Full article

The Kherlen River Basin is a typical basin in the eastern Mongolian Plateau and is dominated by grassland. This study estimated the grassland yield in the Kherlen River Basin using the Carnegie–Ames–Stanford approach (CASA) model, combined with Theil–Sen median trend analysis and the Geodetector, to explore its spatiotemporal changes and driving factors. This integrated framework links temporal trend detection with spatial interaction analysis to better reveal ecological responses to climatic and anthropogenic influences. The results showed the following: (1) The root mean square error (RMSE) between the estimated grassland yield and the laboratory measurements was 37.88 g/m², with an estimation accuracy (EA) of 73.52%. (2) From 2000 to 2024, the grassland yield increased significantly at a rate of 1.98 g/(m²·a) (p < 0.05), with the fastest growth in the middle reaches. (3) Spatially, 79.78% of the basin exhibited significant increases, mainly in the central and western regions. The proportion of significant increase was highest in the upper reaches (40.36%), followed by the middle (32.89%) and lower reaches (6.53%). (4) Due to limited temporal resolution of socioeconomic data, the driving factor analysis covered the period 2000–2020, during which the overall grassland yield was primarily influenced by the interaction between precipitation and elevation (q = 0.6371). Specifically, the upper, middle, and lower reaches were mainly influenced by the interactions between temperature and precipitation (q = 0.6772), precipitation and elevation (q = 0.6377), and temperature and elevation (q = 0.4255), respectively. The study indicates that grassland yield in the Kherlen River Basin exhibited an overall increasing trend during 2000–2024, with climatic factors (precipitation and temperature) and the geographic factor (elevation) identified as the dominant drivers. The influence of human activities was not significant, although this result may be affected by uncertainties associated with data resolution limitations. Future work should incorporate higher-resolution remote sensing and socioeconomic datasets to better assess the impacts of human activities. Full article

Prolonged application and low recycling rates of agricultural plastic films have resulted in significant accumulation of microplastics (MPs) in soils, posing a threat to soil health. However, the impacts of MPs on microbial communities and enzyme activities in Mollisols remain poorly understood. To address the key question of whether soil pH drives the responses of catalase (CAT) activity and bacterial communities to MPs—a core focus of this Mollisol-based case study—we investigated the effects of different MP concentrations (1%, 5%, and 10%) on bacterial community structure and CAT activity across three Mollisol farmlands with distinct pH levels. CAT activity was stimulated at low MP concentrations but inhibited at high levels, whereas dynamic and thermodynamic parameters displayed irregular responses. Temperature sensitivity (Q₁₀) of CAT remained stable, whereas Q₁₀ of kinetic parameters varied among soils. Correlation analysis indicated that E_a and Q₁₀ in acidic soil and V_max/K_m in neutral soil and alkaline soil governed CAT activity. MPs altered α-diversity in acidic and neutral soils, changed β-diversity only in acidic soil, and promoted deterministic assembly processes. PICRUSt functional prediction suggested that functional gene shifts were most evident in acidic and neutral soils, with soil organic matter and V_max/K_m as key drivers in acidic soils and CAT in neutral soils. In contrast, responses in alkaline soil were negligible. These findings highlight soil type-specific microbial responses to MPs and their ecological risks in agricultural soils. Full article

Amidst the backdrop of energy transition, scheduling problems in offshore manufacturing have emerged as critical challenges in marine engineering. However, the inherently coupled constraints of sequence-dependent setup times (SDST) and limited buffers (LB) have been largely overlooked. Therefore, this paper establishes the first multi-objective scheduling model, DHFSP-SDST&LB, specifically tailored for large components like turbine blades. A hybrid optimization algorithm, DDQN-MOCE, integrating an evolutionary algorithm (EA) and a double deep Q-network (DDQN), is proposed to overcome the inherent limitations of traditional MOEAs. In the EA component, a three-phase crossover and mutation policy is employed to generate offspring. In the DDQN component, the dimension-reduced feature vectors serve as the state input, and three makespan-oriented and two energy-oriented heuristic search actions are defined based on the knowledge. Finally, the optimal parameter combination is determined via Taguchi experimental design, and the effectiveness of DDQN-MOCE is evaluated on 36 instances and 1 industrial case. Experimental results demonstrate that DDQN-MOCE’s HV surpasses the second-best result by over 50% in 34 instances. It achieves the best GD, near-absolute dominance, and saves over 22% in total energy, with its high volume of solutions compensating for a minor weakness in spacing. Full article

This study mapped a wide range of naturally derived odors, including those derived from wood, on the two-dimensional axes of tense arousal (TA) and energetic arousal (EA), and examined whether quadrant differences influenced recovery following stress. In the context of Attention Restoration Theory and biophilic design, the study provided preliminary evidence that olfactory stimuli can be treated as a designable element in a functional and reproducible manner. In Experiment 1, wood flours, wood essential oils, and non-wood oils were mapped based on subjective ratings conducted under identical conditions, and differences in their TA–EA positions were revealed. Ratings of “naturalness” were associated with lower EA, suggesting that quadrant mapping can capture meaningful dimensions of odor perception. In Experiment 2, Hinoki and camphor were selected as contrasting stimuli. Hinoki facilitated initial recovery of autonomic nervous system activity, as shown by lower heart rate compared with no odor, whereas camphor showed no effect. These findings demonstrate that TA–EA quadrant mapping provides a practical framework for olfactory design in indoor environments. Full article