A novel liposomal formulation of irinotecan comprising a combination of copper complexation and a transmembrane pH gradient to significantly improve irinotecan encapsulation and retention.

Population arterial input function measured from low dose breast ultrafast dynamic contrast enhanced MRI and fitted with a new mathematic model.

Sleep disruption is associated with increased risks of metabolic, cardiovascular, and neuropsychiatric disorders. Cannabidiol (CBD) and L-theanine have attracted attention as potential sleep-supporting agents due to their neuroactive properties. This study investigated the individual and combined effects of CBD and L-theanine in a caffeine-induced sleep disturbance mouse model using behavioral assessments and neurochemical analyses. Mice were orally administered CBD and L-theanine at ratios of 1:1, 2:1, or 1:2 prior to pentobarbital-induced sleep testing. Co-administration significantly reduced sleep onset latency and increase total sleep duration compared with single treatments under sleep-disturbed conditions. Combination index analysis indicated a synergistic interaction at lower doses, whereas such interaction was not observed at higher doses under normal conditions. To further characterize associated neurochemical changes, serum serotonin and melatonin levels, as well as cortical gamma-aminobutyric acid (GABA), were measured using enzyme-linked immunosorbent assay. CBD increased serotonin levels in a dose-dependent manner, while L-theanine elevated serotonin at lower doses. Combination treatment was associated with increased serotonin and melatonin levels which rose by more than 40% relative to the caffeine-treated group. Cortical GABA levels were also elevated following combination treatment. Collectively, these findings indicate that co-administration of CBD and L-theanine improves sleep-related outcomes and is associated with neurochemical changes, although the precise mechanisms remain to be determined. This study suggests the potential of CBD and L-theanine co-administration as an alternative approach for managing stimulant-induced sleep disturbances.

Regulatory role of MRTF-A in macrophage polarization and the therapeutic mechanism of Bushen Wenyang Huayu decoction in endometriosis.

Recurrent pericarditis represents the most challenging complication of acute pericarditis and has a significant impact on patients' quality of life. It is defined by the occurrence of a new episode after complete remission and should be distinguished from incessant pericarditis, in which symptoms persist without clinical remission. The causes are often idiopathic, likely post-viral or related to autoimmune/autoinflammatory mechanisms, but also include forms secondary to systemic diseases, interventional procedures, or, more rarely, malignancies. The diagnosis is based on the criteria for acute pericarditis applied to a recurrent episode, supported by biomarkers and multimodality imaging. First-line treatment consists of non-steroidal anti-inflammatory drugs or high-dose aspirin combined with colchicine and restriction of physical activity. Corticosteroids are reserved for selected cases and should be used at low doses with very gradual tapering. In refractory or corticosteroid-dependent patients, interleukin-1 inhibitors have revolutionized management, significantly reducing recurrences in forms with an inflammatory phenotype. Prognosis is generally favorable in idiopathic forms but requires structured follow-up and personalized therapeutic strategies. In this article, we address the most common clinical questions regarding recurrent pericarditis, aiming to translate current guideline recommendations into everyday clinical practice.

The main objective of this study was to investigate how ultra-fast CT scanning influences cardiac pulsation artefacts and image quality in low dose chest CT, clinically and in a non-moving 3D resolution phantom. 30 patients underwent two non-contrast chest CT examinations within 6months using one ultra-fast and one standard speed protocol. Three radiologists scored general image quality and motion artefacts (ascending aorta, superior aortic recess, left ventricle, lung tissue) using a 4-point Likert scale. Lung parenchyma, pulmonary fissures, segmental bronchi, pleuromediastinal border, carina and pulmonary vessels were compared between ultra-fast and standard speed scans. Volumetric resolution was measured with an image quality phantom containing a 3D resolution wave module to assess the non-motion resolution on both protocols. With ultra-fast scans 59-70% of the investigated areas in 30 patients were scored as having no artefacts versus 10-29% of the standard speed scans (p<0,001). General image quality was scored excellent or good in 94% of the cases with ultra-fast scans and in 59% of the cases with standard speed scans (p<0,001). Comparing anatomical structures, ultra-fast scans were considered equal or better than standard speed scans in 78%/90%/93%/92%/91%/74% of the examinations (lung parenchyma/pulmonary fissures/segmental bronchi/pleuromediastinal border/carina/pulmonary vessels). Phantom scans showed a slight reduction in volumetric resolution MTFxyz, and no change in in-plane resolution, MTFxy. In this study, ultra-fast scans reduce motion artefacts and increase image quality in low dose non-contrast chest CT when compared to standard speed scans, despite a possible slight degradation in resolution in non-moving objects.

Dexmedetomidine can attenuate delirium in patients who are critically ill, but evidence with regards to its preventive effect on postoperative delirium remains equivocal. We hypothesised that the risk of delirium after intra-operative dexmedetomidine administration varies depending on the dose administered and aimed to identify the optimum dose to mitigate delirium. We included 114,786 adults undergoing general anaesthesia for non-cardiac, non-transplant surgery. Primary exposure was intra-operative dexmedetomidine dose in cumulative μg.kg-1 body weight, dichotomised into high vs. low dose based on the cohort median (0.49 μg.kg-1). Primary outcome was delirium within 7 days, identified from discharge notes, Confusion Assessment Method assessments and diagnostic codes. A total of 4804 (4.2%) patients received dexmedetomidine, with a median (IQR [range]) cumulative dose of 0.49 (0.28-0.84 [0.01-2.50]) μg.kg-1. Postoperative delirium occurred in 3227 (2.8%) patients. Compared with no dexmedetomidine, the risk of delirium was lower in patients receiving low doses (≤ 0.49 μg.kg-1) of dexmedetomidine (adjusted odds ratio 0.61, 95%CI 0.44-0.85, p = 0.004), but not among those receiving high doses (> 0.49 μg.kg-1) (adjusted odds ratio 1.06, 95%CI 0.84-1.34, p = 0.62). Fractional polynomial regression analyses suggested that doses between 0.25 μg.kg-1 and 0.35 μg.kg-1 were associated with the lowest delirium risk. Threshold regression and restricted cubic splines confirmed these findings. Low, but not high, dose dexmedetomidine administration was associated with lower risks of delirium, with optimal doses ranging between 0.25 μg.kg-1 and 0.35 μg.kg-1.

Mitigating UV-B radiation effects on growth and grain yield of qingke via abscisic acid-induced pathways and transcript-driven metabolic reprogramming.

Pyrvinium pamoate inhibits the survival of intracellular Mycobacterium tuberculosis through suppression of macrophage ferroptosis.

Boronic acid group modified Mn-porphyrin nanoparticles evade macrophage uptake for lymph node metastasis diagnosis via MRI.

Pharmaceutical residues, particularly urinary analgesics and their metabolites, are emerging contaminants that pose potential environmental and health risks. This study reports the synthesis of a novel nanocomposite (GOHD) obtained by citric acid crosslinking of H. dulcis with PCT, and its application for adsorbing PhP and PCT from fresh synthetic and real human urine. The material was characterized using various characterization techniques, indicating the formation of a heterogeneous, mesoporous structure with the presence of different functional groups. Adsorption studies revealed that GOHD reached a maximum capacity of 204.82 mg g −1 at the lowest dosage (0.125 g L −1 ). PhP uptake was favored at pH 5.0, and the general-order model well described the kinetic data. Equilibrium analysis revealed that the Freundlich isotherm effectively described the data. At the same time, the M5 statistical physics model provided a deeper interpretation, indicating the presence of two to three adsorption layers with a parallel molecular arrangement ( n < 0.5). Thermodynamic parameters confirmed that the process was spontaneous, exothermic, and governed by weak interactions ( Δ G < 0, Δ H = −12.74 kJ mol −1 ). This is corroborated by the adsorption energy values, which confirm the occurrence of physisorption. In the binary system, GOHD showed high selectivity for PhP, increasing its removal to 80.98% ( q e = 100.73 mg g −1 ), while PCT removal decreased to 11.86% ( q e = 3.75 mg g −1 ), evidencing competitive adsorption. In human urine, PhP removal reached 14.29% ( q e = 29.39 mg g −1 ), whereas PCT adsorption was not observed. The adsorption energy obtained by DFT ( E ads = 49.3 kJ mol −1 ) corroborates the statistical physics energies for the first adsorption layer Δε₁ = 8.27–13.73 kJ mol −1 ), confirming stable, surface-confined adsorption dominated by strong physical interactions. DFT calculations revealed that PhP exhibits higher chemical softness (η = 1.64 eV), electrophilicity (ω = 4.36 eV), and a lower HOMO–LUMO gap (3.27 eV) than PCT, explaining its stronger affinity and preferential adsorption on GOHD. These findings demonstrate that GOHD is a promising, sustainable adsorbent for the adsorption of PhP. • Hovenia dulcis croslinked graphene oxide for drug adsorption in synthetic urine; • A maximum adsorption capacity of 204.82 mg g −1 for phenazopyridine (PhP); • The nanocomposite (GOHD) was selective for phenazopyridine.

X-ray imaging is extensively used in clinical practice due to its low cost, accessibility, and relatively low radiation dose. However, its intrinsic two-dimensional (2D) projection mechanism inevitably leads to severe structural overlap and lesion occlusion in single-view acquisitions, substantially limiting the completeness and reliability of anatomicalinterpretation. To overcome the loss of spatial information caused by limited viewing angles, this study proposes a diffusion-based novel view synthesis framework for X-ray imaging that directly generates target-view X-ray images from a small number of reference views, without relying on explicit three-dimensionalreconstruction. Built upon the Stable Diffusion framework, the proposed method introduces a lightweight and physically interpretable angular-difference conditioning mechanism to explicitly model cross-view geometric relationships. By embedding the relative angular offset between reference and target views into the attention-based feature interaction process, the model effectively captures view-dependent structural transformations and synthesizes anatomically consistent novel-view X-rayimages. Extensive experiments on a synthesized multi-view X-ray dataset demonstrate that the proposed approach achieves robust and stable performance under sparse-view input conditions, significantly outperforming existing methods in terms of view generalization and structural preservation. In particular, for target view offsets of , , and , the proposed method achieves PSNR values of dB, dB, and dB, respectively, together with consistently improved SSIM and LPIPSscores. These results indicate that the proposed framework provides an efficient and flexible solution for supplementing missing X-ray views in clinically constrained imagingscenarios.

VRON-0200 alone and in combination with investigational antivirals for participants with chronic hepatitis B virus infection receiving stable nucleos(t)ide therapy: a phase 1b, randomised, open-label, multicentre trial.

Pulmonary microcirculatory dysfunction is a hallmark of sepsis, contributing to hypoxemia, pulmonary edema, and multiple organ failure. Anisodamine hydrobromide (ADM), a natural alkaloid with anti-inflammatory and endothelial-protective properties, has been used clinically in China for septic shock. However, its effects on pulmonary microcirculatory dysfunction in septic shock remain unclear. A rat model of sepsis was established via cecal ligation and puncture (CLP). Rats were treated with low, medium, or high doses of ADM. Seven-day survival rates and arterial blood gas parameters were monitored. Pulmonary microvascular leakage was evaluated using Evans blue extravasation and FITC-dextran imaging. Histological analysis, immunofluorescence, and Western blotting were performed to assess leukocyte adhesion, inflammatory cell infiltration, endothelial junction proteins, basement membrane proteins, and matrix metalloproteinases. ADM treatment significantly improved 7-day survival and restored arterial partial pressure of oxygen (PaO2), oxygen saturation (SaO2), and pH in CLP rats. High-dose ADM markedly reduced Evans blue and FITC-dextran leakage, attenuated pulmonary edema, and preserved alveolar architecture. ADM inhibited leukocyte adhesion in pulmonary microvessels and decreased infiltration of MPO- and CD68-positive inflammatory cells. Mechanistically, ADM suppressed CLP-induced Caveolin-1 upregulation, restored the expression of VE-Cadherin, Occludin, and Claudin-5, and prevented degradation of Collagen IV and Laminin. Additionally, ADM significantly downregulated MMP-9 expression, while MMP-2 levels remained unchanged, suggesting a role in limiting junctional and basement membrane degradation. ADM protects against CLP-induced pulmonary microcirculation dysfunction in rats by attenuating inflammatory cell infiltration, preserving pulmonary endothelial junctions, and maintaining basement membrane integrity. These results provide mechanistic insight into ADM's therapeutic potential in sepsis-induced pulmonary microcirculation dysfunction and support its use for sepsis in clinic.

Dissection of crucial components of Chinese medicinal formula for COPD treatment by combining cell-based assays, animal studies, and lung organoid platforms.

Background: Atopic dermatitis (AD) is a chronic and burdensome condition that causes intense itching and painful skin lesions and affects around 10% of adults and adolescents across the US. Potent systemic treatments, such as tralokinumab, are needed to treat patients with moderate-to-severe disease who have experienced inadequate symptom control using topical therapies. Novel systemic treatments can not only provide effective relief for these patients but can also be cost saving. Aim: To evaluate the budgetary implications of tralokinumab as a treatment for moderate-to-severe AD in a hypothetical US commercial healthcare plan with 1 million (M) members. Materials & methods: A budget impact model was developed to estimate the difference in total systemic treatment costs between two scenarios: one in which dupilumab, lebrikizumab, nemolizumab, abrocitinib and upadacitinib are assumed to be the only treatments available, and one in which tralokinumab is assumed to be an additional option. The analysis took the perspective of a US commercial payer and estimated total treatment costs over a 3-year time horizon. Patients were distributed to treatments based on forecasted market share data and could switch from dupilumab to other systemic treatments in the model at any time. Switching rates were also informed using forecasting data. Adult patients receiving tralokinumab and adults or adolescents receiving lebrikizumab and nemolizumab could switch to a lower frequency administration schedule if they achieved clear or almost clear skin, reducing the number of doses received and consequently the treatment costs. Treatment costs were informed by 2025 wholesale acquisition costs. Results: Total costs when tralokinumab was not available were estimated to be $21.0M, $27.7M and $35.9M in years 1-3, respectively. When tralokinumab was available, estimates were $20.6M (Δ-0.5M) in year 1, $26.6M (Δ-1.1M) in year 2 and $34.1M (Δ-1.8M) in year 3. Therefore, availability of tralokinumab led to cumulative cost savings of $3.4M across all 3years ($2.3M in adults and $1.1M in adolescents). Cumulative treatment costs per plan member at year 3 also reduced from $84.68 to $81.26 (Δ-3.42) due to tralokinumab. Lastly, cumulative per patient treatment costs across the 653 patients estimated to receive systematic therapy over the 3years reduced from $129,794 to $124,556 when tralokinumab was available. Conclusion: Tralokinumab is a cost-saving therapy when used for the treatment of moderate-to-severe AD in both adult and adolescent populations, with cost savings driven by competitive skin clearance rates, low monthly treatment costs and flexible dosing options in adults (i.e., Q2W → Q4W).

Radiotherapy and immunotherapy for advanced cancers: A meta-analysis of dose, sequencing, and survival patterns.

Mutations in antithrombin (SERPINC1) lead to the hereditary antithrombin deficiency. Conventional therapies for hereditary antithrombin deficiency are prophylactic or on-demand oral anticoagulants, which have poor compliance and side effects. This study explored the therapeutic efficacy of adeno-associated virus serotype 8 (AAV8)-mediated human SERPINC1 gene (AAV8-hSERPINC1) in AT (antithrombin)-deficiency mice. AAV8-hSERPINC1 carrying luciferase was injected into AT+/- mice via tail vein injection at low, medium, and high doses. The biodistribution and expression of the carrier were visualized by in vivo bioimaging technology. Plasma AT levels were serially monitored by ELISA, and an inferior vena cava model was established to evaluate thrombotic propensity. Safety was evaluated by monitoring hepatic, renal, and cardiac function parameters and employing flow cytometry. A dose-dependent increase in AT expression was observed in AT+/- mice after AAV8-hSERPINC1 injection. Compared with the untreated mice, medium-dose treatment restored plasma AT activity and antigen in AT+/- mice to normal levels by week 8, with maintenance within the normal reference range for 40 weeks. In the venous thrombosis model, the rate of thrombosis in mice treated with medium-dose AAV8-hSERPINC1, rivaroxaban, low-molecular-weight-heparin, and wild-type mice were 60%, 60%, 70% and 60%, respectively. After AAV injection, transient elevations in hepatic transaminases and cytokines were observed in mice during a short-term period. Our study demonstrates that AAV8-hSERPINC1 gene delivery resulted in durable AT expression, sustained blood hypercoagulation state correction, thereby rescuing thrombophilia in AT-deficient male mice. These data support the long-term efficacy and safety of AAV gene therapy for hereditary antithrombin deficiency.

A poly(sodium 4-styrenesulfonate)-MXene composite as an ultrathin separator coating for high-performance lithium‑sulfur batteries.

To evaluate the necessity of breast implant-inclusion (BII) views in breast cancer screening for women with breast implants. This retrospective study was conducted on patients who underwent full-field digital mammography, including four BII and four implant-displacement (BID) views, at three institutions in South Korea between January 2009 and December 2020. The true positive rate and radiologic findings were assessed and compared between BII and BID views. Factors associated with the change in suspicion level of malignancy and radiation dose were analyzed. Of the total 1470 patients (45.6 ± 8.4 years) evaluated, 215 were diagnosed with breast cancer (15%), and the cancer was not demonstrable in 37 cases in both BII and BID views. Thetrue positive rates of theBII and BID views were 54% (116/215) and 83% (178/215), respectively (p < 0.01). The suspicion level of malignancy increased in 72% (129/178) and remained unchanged in 28% (49/178) in BID view compared to BII view. The implant location and tumor size differed between the increased suspicion and unchanged groups (p = 0.01 and < 0.01, respectively). The radiation dose per breast was 1.2 ± 0.5 mGy and 1.1 ± 0.4 mGy in BII and BID views (p < 0.01), respectively. BID view alone may be sufficient for breast cancer screening in women with breast implants while minimizing radiation exposure, particularly in those with subpectoral implants. Question Does the implant-inclusion view provide additional diagnostic value over the implant-displacement view in breast cancer screening for women with breast implants? Findings Implant-displacement view demonstrated a higher true positive rate and lower radiation dose than implant-inclusion view, with no cancers detected exclusively by implant-inclusion view. Clinical relevance Screening with implant-displacement view alone in women with breast implants is sufficient for cancer detection while reducing radiation exposure-particularly in those with subpectoral implants, supporting a protocol that benefits patient safety and clinical efficiency.