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1.
Bioresour Technol ; 413: 131460, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39255947

RESUMEN

To enhance circularity in heterotrophic microalgal bioprocesses, this study completely substituted glucose and Bold's basal medium (BBM) with brewer's spent grain (BSG) and soy whey (SW) hydrolysates. Mild acid hydrolysis conditions of BSG (0.2 M H2SO4, 130 °C, 36 min) and SW (0.1 M HCl, 95 °C, 30 min) were optimised for glucose release, and their hydrolysates were optimally mixed (15 % SW-85 % BSG) to obtain a medium that best supported Auxenochlorella protothecoides growth. Maximum biomass production (Xmax) and productivity (PXmax) obtained in the hydrolysate medium containing 50.75 g/L endogenous glucose (Xmax: 22.17 g/L; PXmax: 7.06 g/L/day) were comparable to that in BBM containing 50.44 g/L exogenous glucose (Xmax: 20.02 g/L; PXmax: 6.34 g/L/day). Moreover, estimated hydrolysate medium production costs were within an order of magnitude to BBM. Overall, the integrated approach of tailored hydrolytic treatments and complementary side-streams presents a promising technical and economic feasibility, with applications extending beyond A. protothecoides.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39316129

RESUMEN

OBJECTIVES: To stratify the severity of cricoarytenoid joint fixation (CAJF) by surgery and understand the role of it played in the bilateral vocal fold immobility (BVFI). The second objective emphasizes on the significance of the preoperative differential diagnosis from neurogenic immobility with medical history and endoscopic findings. METHODS: A retrospective review was conducted of 74 patients between 2005 and 2022. Careful medical history inquiry, and videolaryngoscopy are conducted to recruit the appropriate surgical candidates. All patients underwent arytenoid remobilization (AR) followed by vocal fold medialization with arytenoid adduction (AA) or lateralization with suture lateralization (SL). The severity of CAJF is graded during the operation or inferred based on the period from operation to recurrence. RESULT: A total of 18 patients, aged between 18 and 76 years, were analyzed. Among them, 14 cases were classified as the adducted type with ventilation problems, with three presenting with dyspnea, and 11 requiring artificial airways. Additionally, four patients presented with the abducted type, characterized by aphonia. Meanwhile, two additional cases were considered for comparison but were not included in this cohort of 18 subjects due to incorrect diagnosis and inappropriate management. Using AR procedure, the AA procedure offered three aphonia subjects a voiced sound without airway impairment and the SL procedure decannulated 100% (11/11) of the artificial airways and improved the airway patency in 100% (3/3) of the non-tracheostomized subjects despite the severity of CAJF. The severity of joint ankylosis was distributed as follows: In the aphonia group, there were three subjects with grade I, one subject with grade II, and 0 subjects with grade III. In the ventilation group, there was one subject with grade I, seven subjects with grade II, and six subjects with grade III. In contrast, the two cases used for comparison experienced recurrent dyspnea and failed decannulation because the AR procedure was not performed. The follow-up period was averaged in 58 and 14 months at least. CONCLUSION: From this experience, it is the accurate preoperative diagnosis instead of the severity of CAJF that determines the successful rate in airway patency and voiced phonation if the AR procedure is utilized. Careful medical history inquiry and videolaryngoscopic examination can correctly differentiate the mechanical from neurogenic origin without the help of EMG. Evidence of level: 4.

3.
Chin J Nat Med ; 22(9): 854-863, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39326979

RESUMEN

Four novel macrocyclic trichothecenes, termed mytoxins D-G (1-4), along with four known analogs (5-8), were isolated from the ethyl acetate extract of fermented rice inoculated with the fungus Myrothecium verrucaria PA57. Each compound features a tricyclic 12,13-epoxytrichothec-9-ene (EPT) core. Notably, mytoxin G (4) represents the first instance of a macrocyclic trichothecene incorporating a glucosyl unit within the trichothecene structure. The structures of the newly identified compounds were elucidated through comprehensive spectroscopic analysis combined with quantum chemical calculations. All isolated compounds demonstrated cytotoxic activity against the CAL27 and HCT116 cell lines, which are models for human oral squamous cell carcinoma and colorectal cancer, respectively. Specifically, mytoxin D (1) and mytoxin F (3) exhibited pronounced cytotoxic effects against both cancer cell lines, with IC50 values ranging from 3 to 6 nmol·L-1. Moreover, compounds 1 and 3 were found to induce apoptosis in HCT116 cells by activating caspase-3.


Asunto(s)
Apoptosis , Hypocreales , Tricotecenos , Tricotecenos/química , Tricotecenos/farmacología , Tricotecenos/aislamiento & purificación , Tricotecenos/toxicidad , Humanos , Hypocreales/química , Estructura Molecular , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Células HCT116 , Oryza/química , Caspasa 3/metabolismo
4.
Food Res Int ; 195: 114992, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39277251

RESUMEN

Roasted carob pulp (Ceratonia siliqua) is a cocoa substitute known for its faint cocoa-like resemblance. However, the cocoa-carob flavour gap remains poorly uncharacterised. This study aimed to elucidate the sensory and molecular aspects of this flavour gap in a 70 % dark chocolate formulation via a two-pronged instrumental-sensorial approach. Descriptive Sensory Analysis (DSA) revealed carob-based chocolate was significantly sweeter, less sour and astringent than conventional dark chocolate due to the high total sugar content (45-50 % DM; HPLC/RID), low titratable acidity and tannin content, respectively. As for aroma, a distinct, albeit weak, cocoa-like aroma was present in carob-based chocolate. HS-SPME-GC-MS/FID revealed this was attributed to branched-chain Strecker aldehyde generation during roasting (2-methylbutanal, 1.17 µg/g; 3-methylbutanal, 2.89 µg/g). Notably, there was a distinct lack of alkylpyrazines. Additionally, a distinct woody, tree bark-like odour was uniquely associated with carob-based chocolates. This was due to furfural generation during roasting (2.33 µg/g). In conclusion, the aroma and taste gap between cocoa and carob was successfully characterised in this study. These findings substantiate the potential of carob application in chocolate manufacturing, thus empowering confectioners to make evidence-based decisions when evaluating cocoa substitutes.


Asunto(s)
Cacao , Chocolate , Fabaceae , Gomas de Plantas , Percepción del Gusto , Cacao/química , Gomas de Plantas/química , Fabaceae/química , Chocolate/análisis , Compuestos Orgánicos Volátiles/análisis , Humanos , Olfato , Reacción de Maillard , Odorantes
5.
Angew Chem Int Ed Engl ; : e202415726, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39240581

RESUMEN

The electrochemical CO2 reduction reaction (ECR) is a promising pathway to producing valuable chemicals and fuels. Despite extensive studies reported, improving CO2 adsorption for local CO2 enrichment or water dissociation to generate sufficient H* is still not enough to achieve industrial-relevant current densities. Herein, we report a "two-in-one" catalyst, defective Bi nanosheets modified by CrOx (Bi-CrOx), to simultaneously promote CO2 adsorption and water dissociation, thereby enhancing the activity and selectivity of ECR to formate. The Bi-CrOx exhibits an excellent Faradic efficiency (≈ 100 %) in a wide potential range from ‒0.4 to ‒0.9 V. In addition, it achieves a remarkable formate partial current density of 687 mA cm‒2 at a moderate potential of ‒0.9 V without iR compensation, the highest value at ‒0.9 V reported so far. Control experiments and theoretical simulations revealed that the defective Bi facilitates CO2 adsorption/activation while the CrOx accounts for enhancing the protonation process via accelerating H2O dissociation. This work presents a pathway to boosting formate production through tuning CO2 and H2O species at the same time.

6.
Bioorg Med Chem ; 113: 117895, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39259985

RESUMEN

Rhein, as a plant antibiotic, demonstrates a broad spectrum of pharmacological effects. Nevertheless, its limited water solubility, low bioavailability, and potential hepatotoxicity and nephrotoxicity making it difficult to directly become a medicine, thereby imposing significant constraints on its clinical application. In recent decades, extensive researches have been proceeded on the multifaceted structural modifications of rhein, resulting in notable improvements on pharmacological activities and druggabilities. This review offers a comprehensive overview and advanced update on the biological potential and structural-activity relationships (SARs) of various rhein derivatives, delineating the sites of structural modification and corresponding activity trends of rhein derivatives for future.

7.
World J Gastrointest Surg ; 16(8): 2724-2734, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39220064

RESUMEN

BACKGROUND: Neuroendocrine tumors (NETs) arise from the body's diffuse endocrine system. Coexisting primary adenocarcinoma of the colon and NETs of the duodenum (D-NETs) is a rare occurrence in clinical practice. The classification and treatment criteria for D-NETs combined with a second primary cancer have not yet been determined. CASE SUMMARY: We report the details of a case involving female patient with coexisting primary adenocarcinoma of the colon and a D-NET diagnosed by imaging and surgical specimens. The tumors were treated by surgery and four courses of chemotherapy. The patient achieved a favorable clinical prognosis. CONCLUSION: Coexisting primary adenocarcinoma of the colon and D-NET were diagnosed by imaging, laboratory indicators, and surgical specimens. Surgical resection combined with chemotherapy was a safe, clinically effective, and cost-effective treatment.

8.
Artículo en Inglés | MEDLINE | ID: mdl-39230610

RESUMEN

BACKGROUND: Diagnosing and treating tonsillitis pose no significant challenge for otolaryngologists; however, it can increase the infection risk for healthcare professionals amidst the coronavirus pandemic. In recent years, with the advancement of artificial intelligence (AI), its application in medical imaging has also thrived. This research is to identify the optimal convolutional neural network (CNN) algorithm for accurate diagnosis of tonsillitis and early precision treatment. METHODS: Semi-supervised learning with pseudo-labels used for self-training was adopted to train our CNN, with the algorithm including UNet, PSPNet, and FPN. A total of 485 pharyngoscopic images from 485 participants were included, comprising healthy individuals (133 cases), patients with the common cold (295 cases), and patients with tonsillitis (57 cases). Both color and texture features from 485 images are extracted for analysis. RESULTS: UNet outperformed PSPNet and FPN in accurately segmenting oropharyngeal anatomy automatically, with average Dice coefficient of 97.74% and a pixel accuracy of 98.12%, making it suitable for enhancing the diagnosis of tonsillitis. The normal tonsils generally have more uniform and smooth textures and have pinkish color, similar to the surrounding mucosal tissues, while tonsillitis, particularly the antibiotic-required type, shows white or yellowish pus-filled spots or patches, and shows more granular or lumpy texture in contrast, indicating inflammation and changes in tissue structure. After training with 485 cases, our algorithm with UNet achieved accuracy rates of 93.75%, 97.1%, and 91.67% in differentiating the three tonsil groups, demonstrating excellent results. CONCLUSION: Our research highlights the potential of using UNet for fully automated semantic segmentation of oropharyngeal structures, which aids in subsequent feature extraction, machine learning, and enables accurate AI diagnosis of tonsillitis. This innovation shows promise for enhancing both the accuracy and speed of tonsillitis assessments.

9.
J Med Econ ; : 1-15, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39267577

RESUMEN

BACKGROUNDS: Biologics and JAK inhibitors were the most effective innovative systemic treatments for moderate-to-severe atopic dermatitis (AD). However, their cost-effectiveness in China remains unclear. This study aims to compare both the short- and long-term cost-effectiveness of abrocitinib and dupilumab in adults with moderate-to-severe AD from the perspective of the Chinese healthcare system. METHODS: A hybrid decision tree and Markov model were developed to simulate the costs and health outcomes of interventions on both short-term and long-term horizons. Short- and long-term horizons were employed to reflect the 26-week induction treatment and model the extended 10-year maintenance treatment period, respectively. The cost-effectiveness of strategies was measured by incremental cost-effectiveness ratios (ICERs), which were then compared with the willingness-to-pay threshold (WTP) that was equivalent to the gross domestic product (GDP) per capita of China in 2023 ($12,681 [€11679.26]). One-way and probabilistic sensitivity analyses were conducted to validate the robustness of the model. RESULTS: Over the short-term horizon, the QALYs (quality-adjusted life years) gained were 0.43 for the abrocitinib group and 0.42 for the dupilumab group, with the costs being $2,716.01 (€2501.46) and $3,940.33 (€3629.06), respectively. Over the long-time horizon, abrocitinib therapy yields higher QALYs (6.60 versus 6.53) and incurs a lower cost ($22,765.15 [€20966.81] versus $30,683.38 [€28259.54]) compared to dupilumab. The probability of abrocitinib being cost-effective was nearly 100% under the current WTP. Both short- and long-term results showed that abrocitinib was more effective and less costly than dupilumab, making abrocitinib the dominant option. CONCLUSIONS: Abrocitinib was dominant compared to dupilumab both over the short- and long-term horizon for moderate-to-severe AD in China. Future research incorporating real-world evidence and long-term efficacy outcomes could further refine these economic evaluations.

10.
Mycoscience ; 65(3): 151-155, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39233760

RESUMEN

The present study introduces a novel fungus, Cystoderma yongpingense, which was identified in the southwestern region of China. The new species is characterized by a pileus that ranges in color from light orange-red to orange-red; the pileus has a wrinkled surface and is accompanied by a persistent annulus that is membranous and floccose-scaly. Above the annulus, the color transitions from white to yellowish brown. This proposal is substantiated through analyses encompassing both morphological characteristics and phylogenetic relationships. The phylogenetic position of the newly discovered species has been further corroborated through comprehensive maximum likelihood and Bayesian sequence analyses of the ITS + nrLSU DNA regions. Additionally, the technical description of C. yongpingense is enhanced by detailed illustrations and comparative studies with species that are closely related.

11.
Photochem Photobiol Sci ; 23(9): 1697-1707, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39214922

RESUMEN

This study investigates the promotion of sodium chlorate (NaClO3) crystallization through optical trapping, enhanced by the addition of gold nanoparticles (AuNPs) and silicon nanoparticles (SiNPs). Using a focused laser beam at the air-solution interface of a saturated NaClO3 solution with AuNPs or SiNPs, the aggregates of these particles were formed at the laser focus, the nucleation and growth of metastable NaClO3 (m-NaClO3) crystals were induced. Continued laser irradiation caused these m-NaClO3 crystals to undergo repeated cycles of growth and dissolution, eventually transitioning to a stable crystal form. Our comparative analysis showed that AuNPs, due to their significant heating due to higher photon absorption efficiency, caused more pronounced size fluctuations in m-NaClO3 crystals compared to the stable behavior observed with SiNPs. Interestingly, the maximum diameter of the m-NaClO3 crystals that appeared during the size fluctuation step was consistent, regardless of nanoparticle type, concentration, or size. The crystallization process was also promoted by using polystyrene nanoparticles, which have minimal heating and electric field enhancement, suggesting that the reduction in activation energy for nucleation at the particle surface is a key factor. These findings provide critical insights into the mechanisms of laser-induced crystallization, emphasizing the roles of plasmonic heating, particle surfaces, and optical forces.

12.
RSC Adv ; 14(33): 24165-24174, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39101063

RESUMEN

Hyperuricemia, characterized by elevated uric acid levels and subsequent crystal deposition, contributing to conditions such as gout, cardiovascular events, and kidney injury, poses a significant health threat, particularly in developed countries. Current drug options for treatment are limited, with safety concerns, leading to suboptimal therapeutic outcomes in symptomatic hyperuricemia patients and a lack of pharmaceutical interventions for asymptomatic cases. Distinguishing from the previous drug design strategies, we directly target uric acid, the pathological molecule of hyperuricemia, resulting in a pyrimidine derivative capable of increasing the solubility and excretion of uric acid by forming a complex with it. Its prodrug showed an anti-hyperuricemia activity comparable to benzbromarone and a favorable safety profile in vivo. Our finding provides a strategy purely based on organic chemistry to address the largely unmet therapeutic needs on novel anti-hyperuricemia drugs.

13.
Front Neurol ; 15: 1431723, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39175761

RESUMEN

Introduction: Sclerotherapy is a commonly utilized treatment approach for venous malformations. Absolute ethanol is renowned for its remarkable efficacy as a potent sclerosants, but it is potentially associated with severe complications. Foam sclerotherapy is considered superior to liquid sclerotherapy owing to its heightened efficacy and diminished incidence of complications. Thus, our objective was to devise an ethanol foam sclerosant that delivers exceptional efficacy while mitigating complications. Methods: In the first set of experiments, we identified the suitable range of ethanol concentrations for sclerotherapy through human umbilical vein endothelial cell proliferation assays and blood clotting experiments. Next, the surfactants polysorbate 80, egg yolk lecithin, and hyaluronic acid were added to create stable ethanol foam, with their ratios meticulously optimized. Results: The optimal concentration range of ethanol was determined to be 30-60%. Eventually, a 48% ethanol foam was successfully produced with excellent stability. Other than ethanol, the formulation included 5 × 10-3 g/mL polysorbate 80, 10-2 g/mL egg yolk lecithin, and 0.04 mL/mL hyaluronic acid. Discussion: The novel ethanol foam produced here could be a promising candidate for the treatment of venous malformations.

14.
Nucleic Acids Res ; 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39180399

RESUMEN

Drug interactions pose significant challenges in clinical practice, potentially leading to adverse drug reactions, reduced efficacy, and even life-threatening consequences. As polypharmacy becomes increasingly common, the risk of harmful drug interactions rises, underscoring the need for comprehensive and user-friendly drug interaction resources to ensure patient safety. To address these concerns and support healthcare professionals in optimizing drug therapy, we present DDInter 2.0, a significantly expanded and enhanced update to our drug interaction database. This new version incorporates additional interaction types, including drug-food interactions (DFIs), drug-disease interactions (DDSIs), and therapeutic duplications, providing a more complete resource for clinical decision-making. The updated database covers 2310 drugs, with 302 516 drug-drug interaction (DDI) records accompanied by 8398 distinct, high-quality mechanism descriptions and management recommendations. DDInter 2.0 also includes 857 DFIs, 8359 DDSIs and 6033 therapeutic duplication records, each supplemented with detailed information and guidance. Furthermore, the enhanced user interface and advanced filtering options in this second release facilitate easy access to and analysis of the comprehensive drug interaction data. By providing healthcare professionals and researchers with a more complete and user-friendly resource, DDInter 2.0 aims to support clinical decision-making and ultimately improve patient outcomes. DDInter 2.0 is freely accessible at https://ddinter2.scbdd.com.

15.
Lancet Reg Health West Pac ; 50: 101157, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39156118

RESUMEN

Background: Annual Chinese National negotiations for including innovative drugs in the National Reimbursement Drug List (NRDL) reveal an increasing number of new drugs with overlapping action mechanisms of action and similar indications. Yet, it is unclear if competition affects reimbursement decisions. Thus, we explored the impact of competition on reimbursement decisions for cancer drugs in China. Methods: We identified the cancer drugs involved in NRDL negotiations from 2017 to 2022 and focused on the initial reimbursement decision for eligible newly negotiated drugs. Drugs were classified as within-class competitors based on their equivalent biological mechanisms of action and approved indications, including identified and potential competitors. Other variables included drug type, clinical benefit and safety, monthly drug cost, and disease incidence rate. We employed traditional univariate and multivariate Firth's penalized logistic regression to assess the association between reimbursement decisions and variables at the indication and drug levels. Findings: Between 2017 and 2022, 102 cancer drugs corresponding to 141 indications were studied, and 66 drugs (64.7%) covering 95 indications (67.4%) were added to the NRDL. The proportion of reimbursements for indications with identified competition was significantly higher than that for indications without identified competition (84.6% vs 52.6%, p < 0.0001). However, the difference in reimbursement proportions between groups with and without potential competition was not statistically significant (66.7% vs 68.3%, p = 0.84). Firth's penalized logistic regression showed that identified competition was positively correlated with successful NRDL inclusion, whereas potential competition had no significant effect on negotiation outcomes. Improved overall survival or progression-free survival were positively associated with NRDL inclusion, whereas disease incidence negatively impacted reimbursement decisions. Interpretation: Improved clinical benefit and identified competition were positively correlated with NRDL inclusion. In China's value-based negotiation model, clinical benefits served as a crucial foundation of price negotiation for cancer drugs, and market competition helped these drugs enter the NRDL at more reasonable prices. This has important implications for reimbursement decisions and accessibility and affordability improvement for innovative drugs worldwide. Funding: National Natural Science Foundation of China (No. 72104151).

16.
Orthop Clin North Am ; 55(4): 435-443, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39216948

RESUMEN

Minimally invasive interventional radiology procedures play an adjunctive role in treating the symptoms of osteoarthritis (OA) with the hopes of delaying total knee arthroplasty (TKA). However, currently available intra-articular injections offer only short-term benefits. This has led to evolution of new techniques such as genicular artery embolization and genicular nerve ablation, which show benefit in pain control and quality of life, especially for mild-to-moderate OA, positioning these techniques as potential alternatives to intra-articular injections to help delay TKA.


Asunto(s)
Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/terapia , Osteoartritis de la Rodilla/cirugía , Radiología Intervencionista/métodos , Embolización Terapéutica/métodos , Inyecciones Intraarticulares , Artroplastia de Reemplazo de Rodilla/métodos
17.
Langmuir ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39141493

RESUMEN

The adsorbed nanobubbles inside the nanochannels can cause fluid transport blockages, which will obviously degrade the nanodevice performance and reduce the lifetime. However, due to small-scale effects, the removal of nanobubbles is a huge challenge at the nanoscale. Herein, molecular dynamics simulations are carried out to study the effect of the electrostatic field on underwater nitrogen nanobubbles confined in nanochannels. It is found that the nanobubbles will collapse under an appropriate electrostatic field, thereby unblocking the transport of water in the nanochannels. The formation of ordered water structures induced by electrostatic fields plays an important role in the removal of nanobubbles from the nanochannels. Our findings provide a convenient, controllable, and remote way to address the blockage problem of nanobubbles in nanochannels, which may have potential applications in improving the performance of fuel cells.

18.
Bioact Mater ; 41: 485-498, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39210965

RESUMEN

The commercially available drug-eluting stent with limus (rapamycin, everolimus, etc.) or paclitaxel inhibits smooth muscle cell (SMC), reducing the in-stent restenosis, whereas damages endothelial cell (EC) and delays stent reendothelialization, increasing the risk of stent thrombosis (ST) and sudden cardiac death. Here we present a new strategy for promoting stent reendothelialization and preventing ST by exploring the application of precise molecular targets with EC specificity. Proteomics was used to investigate the molecular mechanism of EC injury caused by rapamycin. Endothelial protein C receptor (EPCR) was screened out as a crucial EC-specific effector. Limus and paclitaxel repressed the EPCR expression, while overexpression of EPCR protected EC from coating (eluting) drug-induced injury. Furthermore, the ligand activated protein C (APC), polypeptide TR47, and compound parmodulin 2, which activated the target EPCR, promoted EC functions and inhibited platelet or neutrophil adhesion, and enhanced rapamycin stent reendothelialization in the simulated stent environment and in vitro. In vivo, the APC/rapamycin-coating promoted reendothelialization rapidly and prevented ST more effectively than rapamycin-coating alone, in both traditional metal stents and biodegradable stents. Additionally, overexpression or activation of the target EPCR did not affect the cellular behavior of SMC or the inhibitory effect of rapamycin on SMC. In conclusion, EPCR is a promising therapeutical agonistic target for pro-reendothelialization and anti-thrombosis of eluting stent. Activation of EPCR protects against coating drugs-induced EC injury, inflammatory cell, or platelet adhesion onto the stent. The novel application formula for APC/rapamycin-combined eluting promotes stent reendothelialization and prevents ST.

19.
Nat Commun ; 15(1): 7569, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39217153

RESUMEN

In van der Waals heterostructures (vdWHs), the manipulation of interlayer stacking/coupling allows for the construction of customizable quantum systems exhibiting exotic physics. An illustrative example is the diverse range of states of matter achieved through varying the proximity coupling between two-dimensional (2D) quantum spin liquid (QSL) and superconductors within the TaS2 family. This study presents a demonstration of the intertwined physics of spontaneous rotational symmetry breaking, hidden magnetism, and Ising superconductivity (SC) in the three-fold rotationally symmetric, non-magnetic natural vdWHs 6R-TaS2. A distinctive phase emerges in 6R-TaS2 below a characteristic temperature (T*) of approximately 30 K, which is characterized by a remarkable set of features, including a giant extrinsic anomalous Hall effect (AHE), Kondo screening, magnetic field-tunable thermal hysteresis, and nematic magneto-resistance. At lower temperatures, a coexistence of nematicity and Kondo screening with Ising superconductivity is observed, providing compelling evidence of hidden magnetism within a superconductor. This research not only sheds light on unexpected emergent physics resulting from the coupling of itinerant electrons and localized/correlated electrons in natural vdWHs but also emphasizes the potential for tailoring exotic quantum states through the manipulation of interlayer interactions.

20.
Pharmaceuticals (Basel) ; 17(8)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39204158

RESUMEN

Kokusaginine is a bioactive ingredient extracted from Ruta graveolens L., which has a range of biological activities. Its pharmacokinetic (PK) properties are particularly important for clinical applications; however, they have not been fully elucidated. In addition, the effect of sex differences on drug metabolism is increasingly being recognized, but most studies have ignored this important factor. This study aims to fill this knowledge gap by taking an in-depth look at the PK properties of kokusaginine and how gender affects its metabolism and distribution in the body. It also lays the foundation for clinical drug development. In this study, a sensitive ultra-high-performance liquid chromatography (UPLC) method was developed and validated for quantifying kokusaginine in Sprague Dawley (SD) rat plasma and tissue homogenates. Metabolic stability was evaluated in vitro using gender-specific liver microsomes. Innovatively, we incorporated sex as a variable into both in vitro and in vivo PK studies in SD rats, analyzing key parameters with Phoenix 8.3.5 software. The developed UPLC method demonstrated high sensitivity and precision, essential for PK analysis. Notably, in vitro studies revealed a pronounced sex-dependent metabolic variability (p < 0.05). In vivo, gender significantly affected the Area Under the Moment Curve (AUMC)(0-∞) of the plasma PK parameter (p < 0.05) and the AUMC(0-t) of brain tissue (p < 0.0001), underscoring the necessity of sex-specific PK assessments. The calculated absolute bioavailability of 71.13 ± 12.75% confirmed the favorable oral absorption of kokusaginine. Additionally, our innovative tissue-plasma partition coefficient (Kp) analysis highlighted a rapid and uniform tissue distribution pattern. This study presents a sex-inclusive PK evaluation of kokusaginine, offering novel insights into its metabolic profile and distribution. These findings are instrumental for informing clinical medication practices, dosage optimization, and a nuanced understanding of drug efficacy and safety in a sex-specific context.

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