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Pooling of gastropod samples is frequently used in surveys of the neurotropic nematode Angiostrongylus cantonensis to reduce cost and processing time. Here we highlight a potential limitation of this technique using the snail Theba pisana as an example. Pooled samples tested negative using a high-sensitivity qPCR assay, whereas subsequent individual testing revealed positive cases. This pattern is consistent with a dilution effect, where low parasite DNA concentrations could lead to false-negative results. These findings suggest that pooling may reduce diagnostic sensitivity in regions where infection intensities are low and should be applied with caution.
Superhydrophobic material design has predominantly relied on direct structural replication of singular natural archetypes, such as the lotus leaf. While this biomimetic strategy has driven significant progress, it fundamentally fails to translate the dynamic droplet super-repellency into universally applicable predictive models. Here, we report a biomimetic laboratory toolkit designed to overcome the variability of natural leaves and establish a standardized paradigm for herbicide formulation screening. By integrating the high-ridge architecture of C3 grasses with the dense-groove networks of C4 grasses, we engineered a structural test strip that serves as a conservative worst-case benchmark. This engineered platform, combined with kinetic contact tension (KCT) analysis, enables the precise prediction of droplet deposition kinetics, facilitating high-throughput adjuvant screening prior to field trials.
The aquaculture industry is undergoing a critical transition from marine-based to plant-based and novel protein sources. However, the physiological impacts of these dietary shifts remain largely obscured when evaluated solely by traditional performance metrics such as Feed Conversion Ratio (FCR) and Specific Growth Rate (SGR). This 'Black Box' approach fails to detect sub-clinical metabolic disorders, gut dysbiosis, and molecular stress responses until phenotypic losses occur. This review provides a comprehensive synthesis of how omics technologies - nutrigenomics, proteomics, metabolomics, and metagenomics - are elucidating the molecular mechanisms underlying fish nutrition. We examine the capacity of transcriptomics to identify early markers of soybean meal-induced enteritis and the role of proteomics in assessing muscle quality beyond mere gene expression. Furthermore, we highlight the integration of these layers into a 'Systems Biology' approach, utilizing multi-omics and bioinformatics to unravel the complex diet-microbiota-host axis. Finally, the review discusses the transition towards 'Precision Aquafeed.' It identifies the current challenges in cost, data standardization, and bioinformatics that must be overcome to implement these high-throughput tools in commercial feed formulation.
The simulation of magnetic properties in strongly correlated systems remains a central challenge in electronic structure theory. The Difference-Dedicated Configuration Interaction (DDCI) method is widely regarded as a gold standard for computing magnetic exchange couplings, but its applicability is limited to small magnetic systems due to the steep growth of the configuration-interaction space with the number of correlated electrons and orbitals. Here, we introduce a stochastic formulation of DDCI based on Full Configuration Interaction Quantum Monte Carlo (FCIQMC) and the Generalized Active Space framework, which largely alleviates the computational bottleneck of conventional DDCI. The implementation is validated by comparison with conventional DDCI for the spin ladder of a trinuclear [Mn(IV)3O4]3+ cluster (Slocal = 3/2). Using a small CAS(9,9) reference, DDCI fails to reproduce the spin-state energy differences defined by a two-parameter (J = -76, J' = -11 cm-1) Heisenberg-Dirac-van Vleck Hamiltonian extracted from experimental measurements. In contrast, Stochastic-DDCI enables calculations with a much larger CAS(33,21) reference and reproduces the experimental spin ladder with remarkable accuracy, yielding deviations smaller than 33 cm-1 with respect to the spin ladder extracted from the experimental measurements. This development extends DDCI methodologies to substantially larger active spaces and opens the door to the study of more complex magnetic systems.
Nitrate reductase (NR) is a key enzyme in nitrate assimilation, yet its function within nodules remains poorly understood. In Medicago truncatula, three NR genes, MtNR1, MtNR2, and MtNR3, exhibit distinct evolutionary origins and regulatory features. Phylogenetic analyses indicate that NR3-type genes, originated from a duplication of NR1 within Inverted Repeat-Lacking Clade (IRLC) legumes, have lost the conserved phosphorylation sites critical for post-translational regulation. To assess the functional significance of these isoforms, we characterized single and double nr mutants obtained through Tnt1 transposon insertion under nitrate nutrition and during symbiosis. MtNR1 is the primary contributor to total NR activity: with nr1 and nr2 mutants retaining around 10% and 30% of wild-type levels, respectively. The nr1/nr2 double mutant shows an almost complete loss of NR activity and fails to survive under nitrate supply, demonstrating the essential and non-redundant roles of both isoforms. Under symbiotic conditions, single mutants displayed normal nodulation, whereas nodule development was nearly abolished in the double mutant despite continued MtNR3 expression. In addition to its role in nitrogen assimilation, single nr mutants showed increased sensitivity to hypoxic stress and impaired recovery of nitrogen fixation, revealing a role for NR in nodule energy metabolism through the phytoglobin-NO respiration pathway. We propose that the combined loss of NR1 and NR2 disrupts NO cycling linked to mitochondrial electron transport, thereby compromising the energy balance required for symbiosis under microoxic conditions. This work provides a framework to investigate NR diversification in legumes and opens perspectives for improving nitrogen fixation under environmental constraints.
With the expansion of high-speed road mileage and the aging of road networks, maintenance workloads have increased dramatically. Accurately forecasting preventive maintenance costs is a practical approach to rationally control maintenance expenditure, enhance capital utilization efficiency, and ensure the long-term stable operation of the road network. However, the current predictive model for preventive maintenance costs fails to adequately account for variations in types of preventive maintenance measures, limiting their ability to capture the actual cost variation patterns under different engineering conditions. Consequently, there remains scope for improvement in prediction accuracy. In this study, we developed three meta-heuristic-optimized hybrid models, each tailored to a specific asphalt pavement preventive maintenance measure: 1) the fruit fly optimization algorithm (FOA)-enhanced XGBoost model for crack filling; 2) the hiking optimization algorithm (HOA)-enhanced RF model for surface sealing; 3) the particle swarm optimization (PSO)-enhanced BPNN model for overlay. A case study demonstrates that FOA-XGBoost (R² = 0.8622, MAE = 0.0552) improved XGBoost's R² by 0.0526. In contrast, HOA-RF (MSE = 0.0032, RMSE = 0.0565) outperformed RF with lower error metrics. Furthermore, PSO-BPNN achieved the highest R² (0.9277) and the lowest MAE (0.0419) compared to BPNN. All models maintained MAPE below 5%. To further support the reliability of the results, the Wilcoxon signed-rank test was conducted to assess the statistical significance of model performance differences. In addition, nested cross-validation and sensitivity analysis were performed to evaluate the robustness and stability of the proposed models. These findings indicate that the optimized hybrid model has demonstrated improvements in both predictive accuracy and stability. Consequently, the developed models may provide useful support for maintenance cost estimation and resource allocation in expressway maintenance management.
Conventional imaging fails to quantify the true physical density and mass of organs. This study aims to develop a spectral CT-based physical modeling approach to quantify organ remodeling in type 2 diabetes mellitus (T2DM). A total of 97 subjects (46 T2DM patients and 51 non-diabetic controls) were evaluated. Organ regions (liver, pancreas, spleen) were automatically segmented using a V-Net neural network. A physical density model was constructed based on spectral parameters. We compared organ CT value, effective atomic number, mass, volume, and physical density between groups and analyzed their correlation with HbA1c levels. The physical density model showed high accuracy, with measured subcutaneous fat density aligning with standard physical references. In T2DM patients, pancreatic mass and physical density decreased significantly. Conversely, liver and spleen mass increased without significant changes in physical density. Pancreatic physical density showed a significant negative correlation with HbA1c, with rho = -0.411 and p < 0.001. The spectral physical density model provides a precise, non-invasive metric for assessing organ quality. The strong correlation between pancreatic density and glycemic supports its potential utility in evaluating functional reserve for artificial organ.
Social isolation (SI) is associated with a higher risk of cardiovascular disease (CVD). One mechanism linking SI and CVD is accelerated biological ageing, which can be assessed using artificial intelligence-enabled electrocardiography (AI-ECG). We investigated whether longitudinal changes in SI status are associated with changes in biological ageing patterns. A retrospective longitudinal cohort study including 17 663 individuals without significant CVD who completed ≥2 Berkman and Syme Social Network Index and had paired ECGs within 1 year of each questionnaire. Longitudinal SI status was defined by comparing baseline and follow-up SI status. Ageing trends were assessed using Δage-gap, defined as the change in the gap between AI-ECG-predicted age and chronological age from baseline to follow-up. Linear regression models predicting Δage-gap and survival analyses with Kaplan-Meier and multivariable Cox regression for all-cause mortality were performed. Persistently connected individuals were older [63.1 (52.1, 70.6) years] and had a higher prevalence of hyperlipidaemia and hypertension, yet demonstrated more favourable ageing trajectories. Similarly, those who became connected showed a non-significant attenuation of accelerated ageing. In multivariable linear regression, being persistently isolated [β = +0.412 years, P < 0.001] or becoming isolated [β = +0.438 years, P = 0.012] was associated with accelerated ageing compared to being persistently connected. In survival analyses, becoming isolated (aHR = 1.94, 95% CI = 1.53-2.46, P < 0.001) and being persistently isolated (aHR = 1.66, 95% CI = 1.40-1.96, P < 0.001) were associated with significantly higher all-cause mortality, independent of chronological age and comorbidities. Persistent social connection is associated with slower biological ageing and lower mortality. The effects of SI on ageing and survival appear to be potentially reversible, calling for a prospective study to evaluate interventions aimed at improving both the social and biological burden of SI. Social isolation (SI) is a well-recognized yet underestimated risk factor for cardiovascular morbidity and mortality, and accelerated biological ageing is a key mechanism linking SI to cardiovascular disease. However, most studies rely on a single assessment of SI and of ageing, which fails to capture the dynamic nature of both entities. Our study showed that:Repeated measurements of SI provide greater insight into individual ageing trajectories than a one-time assessment.Persistent social connections over time are associated with slower ageing, whereas becoming isolated or being persistently isolated is linked to accelerated biological ageing.
Aberrant phosphatidylinositol 3-kinase (PI3K) activation drives many cancers, but PI3K inhibitors like Pictilisib often induce cytostasis rather than cytotoxicity, limiting their therapeutic potential. Here we demonstrate that PI3K inhibition combined with nutrient stress triggers methuosis, a non-apoptotic form of programmed cell death characterized by dysregulated macropinosomes. This response occurs selectively in PI3K-aberrant cancer cells that maintain macropinocytic uptake despite PI3K inhibition. Methuosis-associated vacuoles originate from macropinosomes that retain endosomal markers but fail to undergo lysosomal fusion. Active macropinocytic uptake is essential for methuosis, as demonstrated by suppression with EIPA and Bafilomycin A1, whereas the AKT inhibitor MK2206 has no effect, establishing that direct PI3K inhibition, rather than AKT signaling, is required. Mechanistically, PI3K blockade prevents conversion of phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) to phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) causing PI(4,5)P2 to accumulate on internalizing macropinosomal membranes. This aberrant PI(4,5)P2 enrichment impairs ion channel function across multiple channel families, disrupting intracellular osmotic balance. Ion dysregulation triggers aquaporin-1-mediated water influx, driving catastrophic vacuolar expansion and cell death. Although Pictilisib activates pro-survival autophagy, this fails to prevent methuosis-mediated cytotoxicity. In xenograft models, dietary restriction synergizes with Pictilisib to suppress tumor growth, correlating with pronounced intratumoral vacuolization. These findings reveal that combining PI3K inhibition with nutrient restriction converts cytostatic responses into methuosis-driven cytotoxicity via PI(4,5)P2-dependent macropinocytic dysregulation, providing a rational pharmacologic-dietary strategy to enhance PI3K-targeted cancer efficacy.
This work introduces reverse EXAFS analysis (REA), a novel, ab initio framework that transforms extended X-ray absorption fine structure (EXAFS) spectroscopy from a complementary local probe into a primary tool for de novo crystal structure determination. By integrating iterative FEFF simulations with a reverse-fitting algorithm, REA directly extracts full crystallographic parameters, lattice constants, space group and atomic positions, from EXAFS oscillations, without requiring the user to supply an initial structural model from X-ray diffraction; instead, candidate models are retrieved from crystallographic databases and evaluated against EXAFS data. Validated on LiCrO2 and CuFeO2, REA uncovered unexpected phase complexities in CuFeO2, identifying secondary CuFe2O4 and CuFe5O8 phases undetected by conventional methods. This paradigm shift enables accurate structure solving in disordered, nanostructured and novel materials where diffraction fails, establishing EXAFS as a stand-alone crystallographic technique.
Patellar clunk syndrome is a complication of total knee arthroplasty. Surgical treatment with arthroscopic irrigation and debridement and lysis of adhesions is often required when conservative treatment fails. This study examines patient improvement following arthroscopic treatment of patellar clunk. This single-surgeon case series uses a posterior-stabilized implant design. We performed a retrospective review of all patients from September 2013 to November 2020 treated for patellar clunk syndrome with arthroscopic debridement. Patient variables analyzed included knee flexion/extension angle and symptoms, including pain and mechanical symptoms. Analysis used paired t-tests with an alpha level of 0.05. Fifty procedures were examined. Mean patient age was 61.4 years (standard deviation [SD] = 8.57 years), and 64% were female. Before arthroscopy, the mean maximum knee extension (KE) of the affected side was 0.85° (SD = 3°), and the mean maximum knee flexion (KF) was 120.5° (SD = 9.4°). At the last follow-up, the mean maximum KE was 0.36° (SD = 1.3°), and the mean maximum KF was 123.1° (SD = 9.4°). Paired t-tests comparing preoperative and postoperative KF and KE were P = .138 and P = .487, respectively. All patients reported less pain, and 90% (45/50) reported mechanical symptom improvement. Arthroscopic treatment of symptomatic patellar clunk syndrome is safe and effective: almost all included patients experienced symptom relief, with a slight improvement in KF. This was a retrospective cohort study with a level of evidence of III.
The United States continues to struggle with the opioid crisis, exacerbated by shifting political priorities and the aftermath of the COVID-19 pandemic. This critical review analyzes the One Big Beautiful Bill Act (OBBBA) and its implications for opioid use disorder (OUD) treatment through the lens of the Multiple Streams Framework. Drawing on Medicaid data, and evidence from state-level implementation, most notably Arkansas, this article evaluates how work requirements and administrative restructuring threaten access to medications for opioid use disorder (MOUD), harm reduction services, and continuity of care. Medicaid expansion has been influential in increasing treatment availability, reducing overdose deaths, and supporting rural health systems; however, OBBA's mandated community engagement requirements threaten the progress made in combatting this epidemic. These restrictions are projected to cause 11.8 million Americans to lose health insurance, disproportionately affecting individuals with OUD who already encounter significant barriers to care. Prior evidence demonstrates that similar policies failed to increase employment, generated widespread confusion, and produced significant losses in coverage. The losses in coverage lead to delayed care, medication interruptions, and worsened health outcomes. There are also substantial financial and operational burdens associated with national implementation, including an estimated $200 million in administrative costs, diversion of resources away from clinical services, and reduced capacity for evidence-based treatment. This analysis concludes that OBBBA is likely to undermine progress in reducing overdose mortality, amplify health disparities, and place added strain on healthcare systems, particularly in rural communities, which have experienced the most significant effects of the opioid epidemic.
A persistent sciatic artery is a rare congenital vascular anomaly resulting from the failed regression of the sciatic artery during fetal development. It is associated with complications such as thrombosis, aneurysm formation, and acute limb ischemia. A 49-year-old female presented with acute limb ischemia of the left lower limb. Computed tomography angiography confirmed bilateral persistent sciatic arteries with thrombosis affecting only the left limb. She underwent successful endovascular balloon angioplasty and percutaneous thrombectomy, resulting in symptom resolution. Acute limb ischemia is the second most common presentation of persistent sciatic artery, occurring in 33.3% of cases. While computed tomography angiography is the gold standard for diagnosis, magnetic resonance angiography has been used in select cases. Management includes conservative treatment, endovascular intervention, or surgical repair. A bilateral persistent sciatic artery with unilateral thrombosis is rare. Early diagnosis and appropriate intervention, such as endovascular therapy, are essential to prevent complications. Long-term vascular surveillance is crucial for optimal patient outcomes.
Increasing the cut-off voltages of lithium cobalt oxide (LiCoO2) is crucial for improving its energy density, but this exacerbates bulk structural degradation and interfacial side reactions under high-voltage conditions (≥4.5 V). Although various bulk doping and surface coating strategies have been developed to stabilize LiCoO2 at high voltages, most of these involve multi-step processes or are applied after material synthesis, often failing to achieve synergistic strengthening between the bulk and surface phases simultaneously within a single material. Here, we propose an innovative strategy for the precursor-doped modification of LiCoO2. Zirconium (Zr) is introduced during the CoCO3 preparation stage via a coprecipitation method, followed by the sequential synthesis of Zr-modified Co3O4 and LiCoO2, achieving the source-level regulation of LiCoO2. Additionally, during subsequent gradient sintering, Zr simultaneously enters the LiCoO2 lattice and segregates near the surface region, forming Zr-modified LiCoO2 (Zr-LCO) with an integrated structure featuring bulk doping and surface coating. Zr-LCO exhibits significantly enhanced cycle stability (retaining 85% of its reversible discharge capacity after 100 cycles at 0.5 C) and rate capability (89% capacity retention at 5 C compared to 0.1 C), while the corresponding 3 Ah pouch battery maintains a capacity retention rate of 92.7% after 520 cycles. This study achieved simultaneous control over the bulk and surface structures of LiCoO2 through a precursor modification strategy, providing a new approach with industrialization potential for the development of a high-voltage, long-life LiCoO2 cathode.
This study systematically reviewed randomized controlled trials (RCTs) of acupuncture for chronic atrophic gastritis (CAG) published over the past 25 years, aiming to analyze the current status of clinical research, with a focus on evaluating heterogeneity in outcome measures and methodological quality. A comprehensive search of major Chinese and English databases identified 55 RCTs involving 5,311 patients. Methodological quality was assessed using the Cochrane risk of bias tool. Outcome measures were categorized and analyzed by frequency. The results revealed notable methodological limitations in the current literature. Only 83.6% of the studies employed low-risk randomization methods, while very few implemented allocation concealment (3.6%) or blinding (1.8%). Furthermore, no study reported prospective registration, and 34.5% did not mention ethical approval. Regarding outcome measures, 57 different indicators were reported, with laboratory and imaging examinations accounting for the majority (55.4%). Notably, there was a severe lack of focus on patient-reported quality of life, health economic evaluation, and long-term disease prognosis. Considerable heterogeneity was observed in the naming, definition, and timing of outcome measurements, and most studies failed to clearly distinguish between primary and secondary outcomes. In conclusion, the absence of clear criteria hinders clinical translation and results in fragmented data in existing clinical studies on acupuncture treatment for CAG. Standardized clinical trial protocols and a core outcome set (COS) for this discipline are urgently needed. Building on this foundation, future research should conduct multicenter, large-sample, methodologically robust RCTs with long-term follow-up. Such efforts will scientifically advance the standardized development of acupuncture clinical practice and produce high-quality, generalizable, evidence-based conclusions.
The OECD's first Survey on Social and Emotional Skills (SSES) in 2019 assessed 10- and 15-year-olds across ten cities, employing a framework of 15 skills organized into five dimensions aligned with the Big Five personality traits. While this adult-derived model offers a parsimonious structure for measuring social-emotional skills, its applicability to children and early adolescents across diverse cultural contexts remains largely untested. This study examined the structural validity of the SSES framework employing exploratory graph analysis (EGA)-a network psychometrics technique using skill facets as nodes, regularized partial correlations as edge weights, and the walktrap algorithm for community detection. Drawing on self-report data from 60,440 participants aged 10 and 15 across ten international cities, our analysis revealed that contrary to expectation, the hypothesized five-factor structure did not emerge in any age group or city. Among 10-year-olds, skills remained largely undifferentiated or showed only preliminary clustering in most cities, suggesting developmental immaturity in functional organization. Among 15-year-olds, three to four distinct dimensions emerged, with significant cross-city variation in composition. Developmental trajectories also differed culturally: Houston, Sintra, and Istanbul exhibited early-but-stagnant differentiation, while Suzhou showed rapid progression from undifferentiated to four-dimensional structure. These findings identify key limitations in applying the SSES framework: (1) the pattern of conditional dependencies among skill facets violates the local independence assumption underlying the five-factor model; (2) the organization of skills is not equivalent across ages: 10-year-olds show largely undifferentiated structures while 15-year-olds exhibit clearer differentiation; and (3) dimensional configurations vary substantially across cities, challenging assumptions of cross-cultural universality. The results inform researchers and policymakers about the framework's limitations and highlight the need for age- and culture-sensitive approaches to social-emotional skills assessment.
Percutaneous femoral access serves as the cornerstone of endovascular therapy of lower extremity arterial disease. In complex cases, the arterial disease of lower extremity are involve in ipsilateral iliac artery pathology, which conventional treatment strategies typically require multiple punctures or staged procedures. This study aimed to explore the bilateral lower extremity endovascular intervention of patients with coexisting ipsilateral iliac artery stenosis using the long sheath-assisted access conversion technique (LS-ACT) via a single puncture. This is a retrospective cohort study of 18 patients with arteriosclerosis obliterans of the lower extremity who were treated between April 2023 and July 2025. The cohort included 13 males and 5 females, with a mean age of 70.4 ± 7.2 years. After retrograde femoral access, contralateral interventions were performed using the LS-ACT protocol. The LS-ACT was performed in all 18 patients, achieving successful transition from femoral retrograde to antegrade access. Seven of these patients underwent simultaneous bilateral lower extremity arterial interventions. In 11 patients, the LS-ACT was utilized following failed antegrade puncture due to obesity, scarred puncture sites, or a high bifurcation of the profunda femoris artery. Notably, 8 patients presented with hemodynamically significant improvement of ipsilateral iliac artery stenosis, including 2 who had undergone prior stenting. No LS-ACT relevant complications occurred. The LS-ACT demonstrates substantial clinical utility in real-world practice. It is particularly valuable for patients with ipsilateral iliac artery stenosis or those requiring single-session bilateral lower extremity interventions, and represents a reliable alternative in cases of failed antegrade puncture or when managing bilateral disease.
The sphericity deviation score (SDS) is a continuous parameter to describe femoral head shape in patients with Perthes disease. The aims of this study were to evaluate the reproducibility of SDS and its association with the 3-group Stulberg classification. Anteroposterior and frog-leg lateral radiographs of 41 healed Perthes hips were assessed. Six observers with varying levels of experience, independently performed SDS measurements on two occasions, 2 weeks apart. Associations between SDS and the modified 3-group Stulberg classification were tested using ANOVA or Kruskal-Wallis tests and Spearman's rank correlation coefficient (rho). Intra- and interobserver agreement was assessed with Bland-Altman 95% limits of agreement (LoA), and reliability was analyzed by intraclass correlation coefficients (ICC). The median SDS values in hips with a round femoral head were significantly higher when measured by inexperienced observers than those measured by experienced observers (30 vs 17; P < 0.001). The SDS values did not significantly correlate with the Stulberg classification among inexperienced observers. Among experienced observers, a strong correlation was found (Spearman's rho 0.670; P < 0.001); however, only 2 of 3 observers were able to distinguish between round and oval hips. Interobserver agreement for SDS was unacceptable (LoA >40) for inexperienced observers and marginal (LoA 20-40) for experienced observers. Interobserver reliability was poor for inexperienced observers (ICC 0.15; P = .02) and moderate for experienced observers (ICC 0.69; P < .001). SDS is a complex parameter that did not consistently differentiate between femoral head shapes when used by inexperienced observers. Even among experienced pediatric orthopaedic researchers, SDS showed marginal interobserver agreement. The method should be used only by experienced observers in scientific studies. (1)The Sphericity Deviation Score (SDS) correlates significantly with the Stulberg classification only when measured by experienced pediatric orthopaedic researchers.(2)SDS is a complex and time-consuming parameter that often failed to distinguish clearly between adjacent Stulberg categories (e.g., round vs. ovoid hips).(3)Among inexperienced observers, the limits of agreement (LoA) of SDS measurements were unacceptable and the reliability (ICC) was poor.(4)SDS should be used only by experienced observers in scientific studies. Even among experienced researchers, interobserver LoA was marginal, indicating that further methodological refinements are desirable. III, retrospective cohort study.
Spleen deficiency phlegm-turbidity syndrome (SD-PTS) is a common traditional Chinese medicine (TCM) pattern in unstable angina (UAP). Its core pathogenesis involves the spleen failing in its transportation and transformation functions, leading to the generation of phlegm-turbidity that obstructs the vessels. Jianpi Qutan Formula (JPQT) is a TCM compound formulated based on the therapeutic principles of "strengthening the spleen, resolving phlegm, and activating blood." It has been clinically used for the long-term treatment of patients with coronary heart disease, effectively alleviating angina symptoms and regulating lipid metabolism. However, the molecular mechanism by which JPQT stabilizes vulnerable plaques remains to be elucidated. of the Study: This study aimed to investigate the expression characteristics of the IGF-1/IGFBP3 axis in UAP patients with SD-PTS and explore the mechanism by which JPQT stabilizes vulnerable atherosclerotic plaques in mice by regulating this axis and endothelial-mesenchymal transition (EndMT). A quantitative proteomic analysis was conducted on plasma samples from UAP patients with SD-PTS, UAP patients with spleen deficiency phlegm-turbidity blood stasis syndrome (SD-PTBS), and healthy controls. Simultaneously, a high-fat diet was used to establish a mouse model of atherosclerotic vulnerable plaques with SD-PTS. The mice were randomly divided into six groups: normal control, model, atorvastatin, low-dose JPQT, medium-dose JPQT, and high-dose JPQT. After the intervention, plaque characteristics, serum levels of IGF-1/IGFBP3, and the expression of EndMT-related markers in aortic tissue were analyzed using histopathological staining, Western blotting, ELISA, and RT-qPCR. Proteomic analysis revealed that plasma IGFBP3 levels were significantly upregulated in UAP patients with SD-PTS compared to UAP patients with SD-PTBS, and it was identified as a core target associated with this syndrome. In the mouse model, compared to the normal control group, the model group exhibited significantly reduced IGF-1 levels, elevated IGFBP3 levels, abnormal activation of EndMT, and increased plaque vulnerability. Intervention with the JPQT significantly reversed these alterations, the plaque stability improved. The imbalance of the IGF-1/IGFBP3 axis and abnormal activation of EndMT are important pathological mechanisms in UAP with SD-PTS. JPQT can effectively stabilize atherosclerotic vulnerable plaques by regulating the balance of the IGF-1/IGFBP3 axis and inhibiting EndMT, providing a scientific basis for its clinical application.
Altered cardiac and systemic metabolism is a hallmark of heart failure (HF). In the failing heart, cardiomyocytes develop alterations in substrate preference, mitochondrial oxidative metabolism, and the shuttling of high-energy phosphates from mitochondria to the cytosol that compromise energetic efficiency and contribute to disease progression. At the systemic level, neurohormonal activation plays a dominant role in HF with reduced ejection fraction, whereas HF with preserved ejection fraction is shaped by the clustering of multiple comorbidities, such as diabetes, obesity and hypertension, which disrupt the physiological crosstalk between the heart and metabolically active organs. This review provides a perspective on cardiac metabolism in HF. We delineate the specific alterations in substrate metabolism that characterize HF with reduced ejection fraction versus HF with preserved ejection fraction, examine the impact of interorgan communication on myocardial function, and highlight how the benefits of emerging HF therapies, including sodium-glucose cotransporter 2 inhibitors and GLP-1 receptor agonists, may be mediated, at least in part, through the restoration of metabolic homeostasis.