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Achillea alpina L. (Alpine yarrow) is a noteworthy herb in the genus Achillea with many uses in vegetables and traditionally used to treat stomach disorders. In our continuous research on the chemical constituents and biological activities of medicinal plants, ten previously undescribed terpenoids including eight eudesmane-type sesquiterpenes (1-8), one nor-eudesmane-type sesquiterpene (9), one cyclo-geraniol derivative (10), and twenty-one known compounds were isolated and structurally elucidated from the aerial parts of A. alpina. Structures and absolute configurations of the undescribed terpenoids were identified using comprehensive spectroscopic analysis (NMR, HRESI-MS, and CD data) and computational methods (ECD and NMR calculation). Enzyme inhibitory assays showed that the isolated sesquiterpene (19), triterpene (22), and sterol (26) were protein tyrosine phosphatase 1B (PTP1B) inhibitors with IC 50 values ranging from 14.87 to 23.09 μM in comparison with positive control - ursolic acid, showing IC 50 value of 5.93 ± 0.16 μM. Further enzyme kinetics and molecular docking studies were performed to provide valuable insights into their mechanism of action., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The utilization of agricultural by-products for the synthesis of hybrid nanomaterials represents an environmentally sustainable approach. This research aims to comprehensively investigate high-performance silver and copper nanoparticles hybrid materials based on carboxymethyl-modified cellulose / lignin derived from rice husks (CMC / CML-AgNPs and CMC / CML-CuONPs) and apply them for antimicrobial activities. CMC / CML was used to reduce Ag / Cu cations to the atomic level and then efficiently stabilize Ag / CuO nanoparticles, an eco-friendly method and sustainable development. The hybrid nanomaterials were successfully synthesized with spherical shapes and particle sizes ranging from 4 to 16 nm. The diffraction peaks at 38.46°, 46.57°, 64.93°, and 77.55° were ascribed to the face-centered cubic crystal lattice (111), (200), (220), and (311) of silver nanoparticles in the CMC / CML-AgNPs. The peaks were 32.26°, 46.06°, 52.16°, 61.71°, 63.80°, and 71.23° associating with the (110,20-2), (112), (11-3), (310), and (221) plane orientations of CuO nanoparticles. The proposed materials demonstrated highly efficient antimicrobial performances. Particularly, CMC-AgNPs and CML-CuONPs exhibited an inhibitory capability of up to 100 % against E. coli and S. aureus within 72 h. Simultaneously, the antifungal results showed that hybrid nanomaterials have a better ability to inhibit the A. niger than A. flavus fungus. When experimenting on peanut seeds, hybrid nanomaterials showed an inhibitory capability of up to 99.0 % against A. niger. IC 50 values of the hybrid nanomaterials range from 0.872 mg/mL to 1.188 mg/mL, confirming that these materials are non-cytotoxic. These materials exhibit significant stability and enduring antimicrobial efficacy, making them ideal for sustainable development of various antibacterial and antifungal blocks for the near future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Historically, Astragalus membranaceus Bunge has been used as a beneficial medicinal plant, particularly in the Asian traditional medical systems, for the treatment of various human diseases such as stomach ulcers, diarrhea, and respiratory issues associated with phlegm. In this study, a phytochemical characterization of the aerial parts of A. membranaceusled to the isolation of 29 oleanane-type triterpenoid saponins, including 11 new compounds named astraoleanosides E-P (6-9, 13, 14, 18-22), as well as 18 known ones. The structures of these compounds were elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. Among them, astraoleanoside H (9) and cloversaponin III (15) demonstrated the most potent β-glucuronidase inhibitory activities, with IC 50 values of 21.20 ± 0.75 and 9.05 ± 0.47 µM, respectively, compared to the positive control d-saccharic acid 1,4-lactone (IC 50  = 20.62 ± 1.61 µM). Enzyme kinetics studies were then conducted to investigate the type of inhibition exhibited by these active compounds. In addition, the binding mechanism, key interactions, binding stability, and dynamic behavior of protein-ligand complexes were investigated through in silico approaches, such as molecular docking and molecular dynamics simulations. These findings highlight the promising potential of triterpenoid saponins from A. membranaceus as lead compounds for β-glucuronidase inhibitors, offering new possibilities for the development of therapeutic agents targeting various diseases where β-glucuronidase plays a crucial role., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Heart transplant programs and regulatory entities require highly accurate performance metrics to support internal quality improvement activities and national oversight of transplant programs, respectively. We assessed the accuracy of publicly reported performance measures., Methods: We used the United Network for Organ Sharing registry to study patients who underwent heart transplantation between January 1, 2016 and June 30, 2018. We used tests of calibration to compare the observed rate of 1-year graft failure to the expected risk of 1-year graft failure, which was calculated for each recipient using the July 2019 method published by the Scientific Registry of Transplant Recipients (SRTR). The primary study outcome was the joint test of calibration, which accounts for both the total number of events predicted (calibration-in-the-large) and dispersion of risk predictions (calibration slope)., Results: 6,528 heart transplants were analyzed. The primary test of calibration failed (p <0.0001), indicating poor accuracy of the SRTR model. The calibration-in-the-large statistic (0.63, 95% confidence interval [CI] 0.58-0.68, p < 0.0001) demonstrated overestimation of event rates while the calibration slope statistic (0.56, 95% CI 0.49-0.62, p <0.0001) indicated over-dispersion of event rates. Pre-specified subgroup analyses demonstrated poor calibration for all subgroups (each p <0.01). After recalibration, program-level observed/expected ratios increased by a median of 0.14 (p <0.0001)., Conclusions: Risk models employed for publicly-reported graft survival at U.S. heart transplant centers lack accuracy in general and in all subgroups tested. The use of disease-specific models may improve the accuracy of program performance metrics., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Adult Congenital Heart Disease (ACHD) heart transplant recipients may have lower post-transplant survival resulting from higher peri-operative mortality than non-ACHD patients. However, the late risk of mortality appears lower in ACHD recipients. This study seeks to establish whether long-term heart transplant survival is reduced among ACHD recipients relative to non-ACHD recipients., Methods: Adult patients who received a heart transplant between January, 2000 and December, 2019 in the United Network for Organ Sharing database were stratified by the presence of ACHD. Propensity-matched cohorts (1:4) were created to adjust for differences between groups. Graft survival at time points from 1 to 18 years was compared between groups using restricted mean survival time (RMST) analysis., Results: The matched cohort included 1,139 ACHD and 4,293 non-ACHD patients. Median age was 35 years and 61% were male. Average survival time at 1 year was 0.85 years for ACHD patients and 0.93 years for non-ACHD patients (average difference: -0.08 years, 95% Confidence Interval [CI] -0.10 to -0.06, p < 0.001), reflecting higher immediate post-transplant mortality. Average survival time at 18 years was not clinically or statistically different: 11.14 years for ACHD patients and 11.40 years for non-ACHD patients (average difference: -0.26 years, 95% CI: -0.85 to + 0.32 years, p = 0.38)., Conclusions: Despite increased medium-term mortality among ACHD patients after heart transplant, differences in long-term survival are minimal. Allocation of hearts to ACHD patients results in acceptable utility of donor hearts., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

As the population of adult congenital heart disease patients ages and grows, so too does the burden of heart failure in this population. Despite the advances in medical and surgical therapies over the last decades, heart failure in adult congenital heart disease remains a formidable complication with high morbidity and mortality. This review focuses on the challenges in determining the true burden and management of heart failure in adult congenital heart disease. There is a particular focus on the need for developing a common language for classifying and reporting heart failure in adult congenital heart disease, the clinical presentation and prognostication of heart failure in adult congenital heart disease, the application of hemodynamic evaluation, and advanced heart failure treatment. A common case study of heart failure in adult congenital heart disease is utilized to illustrate these key concepts., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Many mangrove forests have suffered from the contaminated environments near industrial areas. This study addresses the question how these environments influence the renewal of mangrove forests. To this end ecophysiological responses of the young mangrove species Rhizophora apiculata (Blume) grown under combinations of the factors heavy metals (here chromium), nutrition and soil/water environment were analyzed. We tested the hypothesis that soil/water conditions and nutrient status of the soil strongly influence the toxic effect of chromium. Seedlings of R. apiculata were grown in three different soil/water environments (natural saline soil with brackish water, salt-leached soil with fresh water and salt-leached-sterilized soil with fresh water) treated with different levels of chromium and NPK fertilizer. The system was inundated twice a day as similar to natural tidal condition in the mangrove wetland in the south of Vietnam. The experiments were carried out for 6months. Growth data of root, leaf and stem, root cell number and stomata number were recorded and analyzed. Results showed that growth of R. apiculata is slower in natural saline soil/water condition. The effect of chromium and of nutrients respectively depends on the soil/water condition. Under high concentrations of chromium, NPK fertilizer amplifies the toxic effect of chromium. Stomata density increases under chromium stress and is largest under the combination of chromium and salty soil/water condition. From the data a nonlinear multivariate regression model was derived capturing the toxicity threshold of R. apiculata under different treatment combinations., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Heterogeneity of risk within heart transplant urgency designations is undesirable. Regional competition for donor hearts may contribute to this variation in risk. In this study we assessed whether an association exists between center competition and variation in event rates within status designations on the waiting list., Methods: Our study sample included 20,237 adult transplant registrants initially listed between July 1, 2006 and July 1, 2013. Market competition was quantified using the Herfindahl-Hirshman Index (HHI) and number of centers within a donor service area (DSA) per 1 million people. A Cox model was used to assess for variation in waiting list outcomes within status designation by both HHI and DSA density. The primary outcome was death or delisting as too ill., Results: Outcome rates within status designations differed significantly between centers: Status 1A, center p < 0.0001; Status 1B, center p < 0.0001; and Status 2, center p < 0.0001. Market competition (decreasing HHI) was associated with differential outcome rates within higher urgency status designation [Status 1A hazard ratio (HR) 0.94, p = 0.012; Status 1B HR 0.95, p = 0.010; and Status 2 HR 1.02, p = 0.360]. Center density within the DSA was not associated with outcome rates within each status designation (Status 1A HR 0.99, p = 0.961; Status 1B HR 1.03, p = 0.901; and Status 2 HR 1.20, p = 0.399)., Conclusions: The rate of death or delisting as too ill within urgency designations varies between transplant centers and is partially explained by competition between transplant programs. Further methods of normalizing risk within status designations are necessary., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Adult T-cell leukemia (ATL), a heterogeneous disease, can be divided into smoldering, chronic, lymphoma, and acute types clinically. In addition to different clinical manifestations, different stages of ATL have different molecular signatures. Here, we demonstrated that smoldering/chronic ATL peripheral blood mononuclear cells spontaneously proliferated ex vivo in a cytokine (interleukin-12 [IL-12]/IL-9/IL-15)-dependent manner, while acute-type ATL peripheral blood mononuclear cells did not proliferate or proliferated independent of cytokines. Smoldering/chronic ATL cells produced IL-2 and IL-9 in 6-day ex vivo cultures. Interestingly, the addition of an anti-IL-2R-α monoclonal antibody profoundly inhibited IL-9 expression, suggesting optimal expression of IL-9 was dependent on IL-2 signaling in these patients. To determine whether there would be autonomous proliferation of ATL leukemic cells, we purified leukemic cells from patients with smoldering/chronic ATL. Purified leukemic cells cultured alone produced IL-2/IL-9, and the downstream Janus kinase/signal transducer and activator of transcription pathway was activated. However, the leukemic cells did not proliferate independently, but required coculture with autologous monocytes to induce proliferation. Moreover, interaction between leukemic cells and monocytes was contact dependent, and major histocompatibility complex class II expression may have contributed to this interaction. In conclusion, our data provide evidence that there is autocrine/paracrine cytokine stimulation of leukemic cell proliferation in patients with smoldering/chronic ATL that could be targeted for treatment.

Background: Bioprosthetic valve replacement in young patients remains a controversial issue due to a high rate of early calcification. Previous studies in our laboratory have shown that high-temperature fixation of glutaraldehyde preserved bioprosthesis (HTF) mitigates calcification. The first clinical application of this technique was started in 1991., Methods: From January 1991 to September 1998, 50 patients in whom anticoagulants were contraindicated underwent single aortic valve replacement (n = 33) or mitral valve replacement (n = 17) using HTF bioprostheses. The age of the patients ranged from 7 months to 35 years (mean 22.7+/-6.8 years). The mean New York Heart Association status was 2.4. Mean follow-up 4 years +/- 1.8 for a total follow-up of 196 patient-years., Results: There were no operative deaths and but there were two late deaths, one valve related. Structural failure occured in 4 patients (2%/patient-year) requiring a reoperation in 3 patients (1.5%/patient-year). No endocarditis or thromboembolic episodes were observed. At late examination (June 2000), 46 patients (92%) were in New York Heart Association class I or II, with a well functioning valve., Conclusions: Replacement with HTF bioprostheses in young patients has demonstrated encouraging midterm results with a low incidence of structural failure