Ammonia detoxification promotes CD8+ T cell memory development by urea and citrulline cycles.

Amino acid metabolism is essential for cell survival, while the byproduct ammonia is toxic and can injure cellular longevity. Here we show that CD8+ memory T (TM) cells mobilize the carbamoyl phosphate (CP) metabolic pathway to clear ammonia, thus promoting memory development. CD8+ TM cells use ß-hydroxybutyrylation to upregulate CP synthetase 1 and trigger the CP metabolic cascade to form arginine in the cytosol. This cytosolic arginine is then translocated into the mitochondria where it is split by arginase 2 to urea and ornithine. Cytosolic arginine is also converted to nitric oxide and citrulline by nitric oxide synthases. Thus, both the urea and citrulline cycles are employed by CD8+ T cells to clear ammonia and enable memory development. This ammonia clearance machinery might be targeted to improve T cell-based cancer immunotherapies.

TCR activation directly stimulates PYGB-dependent glycogenolysis to fuel the early recall response in CD8+ memory T cells.

Glycolysis facilitates the rapid recall response of CD8+ memory T (Tm) cells. However, it remains unclear whether Tm cells uptake exogenous glucose or mobilize endogenous sugar to fuel glycolysis. Here, we show that intracellular glycogen rather than extracellular glucose acts as the major carbon source for the early recall response. Following antigenic stimulation, Tm cells exhibit high glycogen phosphorylase (brain form, PYGB) activity, leading to glycogenolysis and release of glucose-6-phosphate (G6P). Elevated G6P mainly flows to glycolysis but is also partially channeled to the pentose phosphate pathway, which maintains the antioxidant capacity necessary for later recall stages. Mechanistically, TCR signaling directly induces phosphorylation of PYGB by LCK-ZAP70. Functionally, the glycogenolysis-fueled early recall response of CD8+ Tm cells accelerates the clearance of OVA-Listeria monocytogenes in an infected mouse model. Thus, we uncover a specific dependency on glycogen for the initial activation of memory T cells, which may have therapeutic implications for adaptive immunity.

Sustained AhR activity programs memory fate of early effector CD8+ T cells.

Identification of mechanisms that program early effector T cells to either terminal effector T (Teff) or memory T (Tm) cells has important implications for protective immunity against infections and cancers. Here, we show that the cytosolic transcription factor aryl hydrocarbon receptor (AhR) is used by early Teff cells to program memory fate. Upon antigen engagement, AhR is rapidly up-regulated via reactive oxygen species signaling in early CD8+ Teff cells, which does not affect the effector response, but is required for memory formation. Mechanistically, activated CD8+ T cells up-regulate HIF-1α to compete with AhR for HIF-1ß, leading to the loss of AhR activity in HIF-1αhigh short-lived effector cells, but sustained in HIF-1αlow memory precursor effector cells (MPECs) with the help of autocrine IL-2. AhR then licenses CD8+ MPECs in a quiescent state for memory formation. These findings partially resolve the long-standing issue of how Teff cells are regulated to differentiate into memory cells.

Modulation of anti-cardiac fibrosis immune responses by changing M2 macrophages into M1 macrophages.

BACKGROUND: Macrophages play a crucial role in the development of cardiac fibrosis (CF). Although our previous studies have shown that glycogen metabolism plays an important role in macrophage inflammatory phenotype, the role and mechanism of modifying macrophage phenotype by regulating glycogen metabolism and thereby improving CF have not been reported. METHODS: Here, we took glycogen synthetase kinase 3ß (GSK3ß) as the target and used its inhibitor NaW to enhance macrophage glycogen metabolism, transform M2 phenotype into anti-fibrotic M1 phenotype, inhibit fibroblast activation into myofibroblasts, and ultimately achieve the purpose of CF treatment. RESULTS: NaW increases the pH of macrophage lysosome through transmembrane protein 175 (TMEM175) and caused the release of Ca2+ through the lysosomal Ca2+ channel mucolipin-2 (Mcoln2). At the same time, the released Ca2+ activates TFEB, which promotes glucose uptake by M2 and further enhances glycogen metabolism. NaW transforms the M2 phenotype into the anti-fibrotic M1 phenotype, inhibits fibroblasts from activating myofibroblasts, and ultimately achieves the purpose of treating CF. CONCLUSION: Our data indicate the possibility of modifying macrophage phenotype by regulating macrophage glycogen metabolism, suggesting a potential macrophage-based immunotherapy against CF.

Enhanced Alkaline Hydrogen Evolution Reaction through Lanthanide-Modified Rhodium Intermetallic Catalysts.

Design of highly efficient electrocatalysts for alkaline hydrogen evolution reaction (HER) is of paramount importance for water electrolysis, but still a considerable challenge because of the slow HER kinetics in alkaline environments. Alloying is recognized as an effective strategy to enhance the catalytic properties. Lanthanides (Ln) are recognized as an electronic and structural regulator, attributed to their unique 4f electron behavior and the phenomenon known as lanthanide contraction. Here, a new class of Rh3Ln intermetallics (IMs) are synthesized using the sodium vapor reduction method. The alloying process induced an upshift of the d-band center and electron transfer from Ln to Rh, resulting in optimized adsorption and dissociation energies for H2O molecules. Consequently, Rh3Tb IMs exhibited outstanding HER activity in both alkaline environments and seawater, displaying an overpotential of only 19 mV at 10 mA cm-2 and a Tafel slope of 22.2 mV dec-1. Remarkably, the current density of Rh3Tb IMs at 100 mV overpotential is 8.6 and 5.7 times higher than that of Rh/C and commercial Pt/C, respectively. This work introduces a novel approach to the rational design of HER electrocatalysis and sheds light on the role of lanthanides in electrocatalyst systems.

Enhanced Alkaline Hydrogen Evolution Reaction via Electronic Structure Regulation: Activating PtRh with Rare Earth Tm Alloying.

Developing high-performance electrocatalysts for alkaline hydrogen evolution reaction (HER) is crucial for producing green hydrogen, yet it remains challenging due to the sluggish kinetics in alkaline environments. Pt is located near the peak of HER volcano plot, owing to its exceptional performance in hydrogen adsorption and desorption, and Rh plays an important role in H2O dissociation. Lanthanides (Ln) are commonly used to modulate the electronic structure of materials and further influence the adsorption/desorption of reactants, intermediates, and products, and noble metal-Ln alloys are recognized as effective platforms where Ln elements regulate the catalytic properties of noble metals. Here Pt1.5Rh1.5Tm alloy is synthesized using the sodium vapor reduction method. This alloy demonstrates superior catalytic activity, being 4.4 and 6.6 times more effective than Pt/C and Rh/C, respectively. Density Functional Theory (DFT) calculations reveal that the upshift of d-band center and the charge transfer induced by alloying promote adsorption and dissociation of H2O, making Pt1.5Rh1.5Tm alloy more favorable for the alkaline HER reaction, both kinetically and thermodynamically.

Correlation between Metabolic Parameters and Warfarin Dose in Patients with Heart Valve Replacement of Different Genotypes.

Background: Warfarin has become the first choice for anticoagulation in patients who need lifelong anticoagulation due to its clinical efficacy and low price. However, the anticoagulant effect of warfarin is affected by many drugs, foods, etc. accompanied by a high risk of bleeding and embolism. The Vitamin K epoxide reductase complex 1 (VKORC1) and Cytochrome P450 2C9 (CYP2C9) genotypic variation can influence the therapeutic dose of warfarin. However, it is not clear whether there is a correlation between warfarin dose and liver function, kidney function and metabolic markers such as uric acid (UA) in patients with different genotypes. We performed a single-center retrospective cohort study to evaluate the factors affecting warfarin dose and to establish a dose conversion model for warfarin patients undergoing heart valve replacement. Methods: We studied 343 patients with a mechanical heart valve replacement, compared the doses of warfarin in patients with different warfarin-related genotypes (CYP2C9 and VKORC1), and analyzed the correlation between liver function, kidney function, UA and other metabolic markers and warfarin dose in patients with different genotypes following heart valve replacement. Results: Genotype analysis showed that 72.01% of patients had CYP2C9*1/*1 and VKORC1 mutant AA genotypes. Univariate regression analysis revealed that the warfarin maintenance dose was significantly correlated with gender, age, body surface area (BSA), UA and genotype. There was no correlation with liver or kidney function. Multiple linear regression analysis showed that BSA, genotype and UA were the independent factors influencing warfarin dose. Conclusions: There is a significant correlation between UA content and warfarin dose in patients with heart valve replacement genotypes CYP2C9*1/*1/VKORC1(GA+GG), CYP2C9*1/*1/VKORC1AA and CYP2C9*1/*1/VKORC1AA.

Ni-P-PTFE cathode with low surface energy for enhancing electrochemical water softening performance.

Efficient cathode regeneration is a significant challenge in the electrochemical water softening process. This work explores the use of an electroless plating Ni-P-PTFE electrode with low surface energy for this purpose. The Ni-P-PTFE electrode demonstrates improved self-cleaning performance at high current densities. By combining the low surface energy of the electrode with fluid flushing shear force, the precipitation rate on the Ni-P-PTFE electrode remains stable at approximately 18 g/m2·h over extended periods of operation. Additionally, the cleaning efficiency of the Ni-P-PTFE electrode surpasses that of stainless steel by 66.34%. The Ni-P-PTFE electrode can maintain a larger active area and a longer operational lifespan is attributed to its self-cleaning performance derived from low surface energy. Furthermore, the loose scale layers on the electrode surface are easily removed during electrochemical water softening processes, presenting a novel approach to cathode surface design.

Facet-dependent diversity of Pt-O coordination for Pt 1 /CeO 2 catalysts achieved by oriented atomic deposition.

The surface chemistry of CeO2 is dictated by the well-defined facets, which exert great influence on the supported metal species and the catalytic performance. Here we report Pt1/CeO2 catalysts exhibiting specific structures of Pt-O coordination on different facets by using adequate preparation methods. The simple impregnation method results in Pt-O3 coordination on the predominantly exposed {111} facets, while the photo-deposition method achieves oriented atomic deposition for Pt-O4 coordination into the "nano-pocket" structure of {100} facets at the top. Compared to the impregnated Pt1/CeO2 catalyst showing normal redox properties and low-temperature activity for CO oxidation, the photo-deposited Pt1/CeO2 exhibits uncustomary strong metal-support interaction and extraordinary high-temperature stability. The preparation methods dictate the facet-dependent diversity of Pt-O coordination, resulting in the further activity-selectivity trade-off. By applying specific preparation routes, our work provides an example of disentangling the effects of support facets and coordination environments for nano-catalysts.

Electrochemical Potential-Driven Shift of Frontier Orbitals in M-N-C Single-Atom Catalysts Leading to Inverted Adsorption Energies.

Electronic structure is essential to understanding the catalytic mechanism of metal single-atom catalysts (SACs), especially under electrochemical conditions. This study delves into the nuanced modulation of "frontier orbitals" in SACs on nitrogen-doped graphene (N-C) substrates by electrochemical potentials. We observe shifts in Fermi level and changes of d-orbital occupation with alterations in electrochemical potentials, emphasizing a synergy between the discretized atomic orbitals of metals and the continuous bands of the N-C based environment. Using O2 and CO2 as model adsorbates, we highlight the direct consequences of these shifts on adsorption energies, unveiling an intriguing inversion of adsorption energies on Co/N-C SAC under negative electrochemical potentials. Such insights are attributed to the role of the dxz and dz2 orbitals, pivotal for stabilizing the π* orbitals of O2. Through this exploration, our work offers insights on the interplay between electronic structures and adsorption behaviors in SACs, paving the way for enhanced catalyst design strategies in electrochemical processes.

Controllable Conversion of Platinum Nanoparticles to Single Atoms in Pt/CeO2 by Laser Ablation for Efficient CO Oxidation.

Downsizing metal nanoparticles to single atoms (monoatomization of nanoparticles) has been actively pursued to maximize the metal utilization of noble-metal-based catalysts and regenerate the activity of agglomerated metal catalysts. However, precise control of monoatomization to optimize the catalytic performance remains a great challenge. Herein, we developed a laser ablation strategy to achieve the accurate regulation of Pt nanoparticles (PtNP) to Pt single atoms (Pt1) conversion on CeO2. Owing to the excellent tunability of input laser energy, the proportion of Pt1 versus total Pt on CeO2 can be precisely controlled from 0 to 100% by setting different laser powers and irradiation times. The obtained Pt1PtNP/CeO2 catalyst with approximately 19% Pt1 and 81% PtNP exhibited much-enhanced CO oxidation activity than Pt1/CeO2, PtNP/CeO2, and other Pt1PtNP/CeO2 catalysts. Density functional theory (DFT) calculations showed that PtNP was the major active center for CO oxidation, while Pt1 changed the chemical potential of lattice oxygen on CeO2, which decreased the energy barrier required for CO oxidation by lattice oxygen and resulted in an overall performance improvement. This work provides a reliable strategy to redisperse metal nanoparticles for designing catalysts with various single-atom/nanoparticle ratios from a top-down path and valuable insights into understanding the synergistic effect of nano-single-atom catalysts.

Microfluidic Investigation of the Ion-Specific Effect on Bubble Coalescence in Salt Solutions.

A microfluidic method was developed to study the ion-specific effect on bubble coalescence in salt solutions. Compared with other reported methods, microfluidics provides a more direct and accurate means of measuring bubble coalescence in salt solutions. We analyzed the coalescence time and approach velocity between bubbles and used simulation to investigate the pressure evolution during the coalescence process. The coalescence time of the three salt solutions decreased initially and then increased as the concentration of the salt solution was increased. The concentration with the shortest coalescence time is considered as the transition concentration (TC) and exhibits ion-specific. At the TC, the change in coalescence time indicates a shift in the effect of salt on bubble coalescence from facilitation to initial inhibition. Meanwhile, it can be seen that the sodium halide solutions significantly inhibit the bubble coalescence and the inhibition capability follows the order NaCl > NaBr > NaI. The results of the approach velocity show that the coalescence time decreases with increasing approach velocity, as well as the approach velocity was strongly influenced by concentration. The approach velocity undergoes a significant change at the TC. Furthermore, simulations of bubble coalescence in the microchannel indicate that the vertical pressure gradient at the center point of the bubble pairs increases as bubbles approach, driving liquid film drainage until bubble coalescence. The pressure at the center of the bubble pair reaches the maximum when the bubbles have first coalesced. It was further revealed that the concentration of the salt solution has a significant impact on the maximum pressure, as evidenced by the observed trend of decreasing pressure values with increasing concentrations.

Effect of direct endovascular treatment versus standard bridging therapy in large artery anterior circulation stroke (DEVT): 18-month follow-up of a randomized controlled trial.

BACKGROUND: Two trials in Chinese population showed that endovascular treatment (EVT) alone was noninferior to alteplase follow by EVT at 90 days. However, results of long-term clinical outcomes remain unknown. We reported the results of prespecified 18-month analysis of the DEVT trail. MATERIALS AND METHODS: We assessed clinical outcomes 18 months after patients were randomly assigned to receive EVT alone or bridging therapy for acute ischemic stroke (AIS). The primary outcome was the proportion of functional independence [modified Rankin scale (mRS), 0-2] at 18 months. Secondary outcomes included all-cause mortality and the quality of life at 18 months as measured by means of a health utility index according to the European Quality of Life 5-Dimension 5-level scale (EQ-5D-5L). Kaplan-Meier event curves were used to investigate the risk of mortality in participants with EVT alone or bridging therapy. RESULTS: Among 234 patients (EVT alone, n = 116; bridging therapy, n = 118) in the DEVT trial, only 231 (98.7%) patients were extended follow-up to 18 months. A total of 60 (51.7%) patients in the EVT alone achieved functional independence vs 56 (47.5%) patients in the bridging therapy (difference, 4.3%; 1-sided 97.5% CI, - 8.4% to ∞, P for noninferiority =0.014). No significant between-group difference was detected in EQ-5D-5L score (0.81 vs 0.73; difference, 0; 95% CI, 0 to 0.005). The cumulative mortality was 27.6% in the EVT alone and 28.8% in the bridging therapy. CONCLUSION: At 18 months follow-up, EVT alone was noninferior to bridging therapy regarding favorable functional outcome in patients with AIS. TRIAL REGISTRATION: Trial was registered on Chinese Clinical Trial Registry (ChiCTR-IOR-17013568) on 27/11/2017.

Exposure of zebrafish (Danio rerio) to graphene oxide for 6 months suppressed NOD-like receptor-regulated anti-virus signaling pathways.

Environmental exposure to graphene oxide (GO) is likely to happen due to the use and disposal of these materials. Although GO-induced ecological toxicity has been evaluated before by using aquatic models such as zebrafish, previous studies typically focused on the short-term toxicity, whereas this study aimed to investigate the long-term toxicity. To this end, we exposed zebrafish to GO for 6 months, and used RNA-sequencing to reveal the changes of signaling pathways. While GO exposure showed no significant effects on locomotor activities, it induced histological changes in livers. RNA-sequencing data showed that GO altered gene expression profiles, resulting in 82 up-regulated and 275 down-regulated genes, respectively. Through the analysis of gene ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we found that GO suppressed the signaling pathways related with immune systems. We further verified that GO exposure suppressed the expression of genes involved in anti-virus responses possibly through the inhibition of genes involved in NOD-like receptor signaling pathway. Furthermore, NOD-like receptor-regulated lipid genes were also inhibited, which may consequently lead to decreased lipid staining in fish muscles. We concluded that 6 month-exposure to GO suppressed NOD-like receptor-regulated anti-virus signaling pathways in zebrafish.

GPR30 Alleviates Pressure Overload-Induced Myocardial Hypertrophy in Ovariectomized Mice by Regulating Autophagy.

The incidence of heart failure mainly resulting from cardiac hypertrophy and fibrosis increases sharply in post-menopausal women compared with men at the same age, which indicates a cardioprotective role of estrogen. Previous studies in our group have shown that the novel estrogen receptor G Protein Coupled Receptor 30 (GPR30) could attenuate myocardial fibrosis caused by ischemic heart disease. However, the role of GPR30 in myocardial hypertrophy in ovariectomized mice has not been investigated yet. In this study, female mice with bilateral ovariectomy or sham surgery underwent transverse aortic constriction (TAC) surgery. After 8 weeks, mice in the OVX + TAC group exhibited more severe myocardial hypertrophy and fibrosis than mice in the TAC group. G1, the specific agonist of GPR30, could attenuate myocardial hypertrophy and fibrosis of mice in the OVX + TAC group. Furthermore, the expression of LC3II was significantly higher in the OVX + TAC group than in the OVX + TAC + G1 group, which indicates that autophagy might play an important role in this process. An in vitro study showed that G1 alleviated AngiotensionII (AngII)-induced hypertrophy and reduced the autophagy level of H9c2 cells, as revealed by LC3II expression and tandem mRFP-GFP-LC3 fluorescence analysis. Additionally, Western blot results showed that the AKT/mTOR pathway was inhibited in the AngII group, whereas it was restored in the AngII + G1 group. To further verify the mechanism, PI3K inhibitor LY294002 or autophagy activator rapamycin was added in the AngII + G1 group, and the antihypertrophy effect of G1 on H9c2 cells was blocked by LY294002 or rapamycin. In summary, our results demonstrate that G1 can attenuate cardiac hypertrophy and fibrosis and improve the cardiac function of mice in the OVX + TAC group through AKT/mTOR mediated inhibition of autophagy. Thus, this study demonstrates a potential option for the drug treatment of pressure overload-induced cardiac hypertrophy in postmenopausal women.

Metal Affinity of Support Dictates Sintering of Gold Catalysts.

Sintering during heterogeneous catalytic reactions is one of the most notorious deactivation channels in catalysts of supported metal nanoparticles. It is therefore critical to understand the effect of support on the sintering behavior. Here, by using in situ aberration-corrected transmission electron microscopy and computational modeling, the atomic-scale dynamic interactions are revealed between Au nanoparticles and various supports. It is found that Au nanoparticles on ceria have a smaller contact angle and are apparently less mobile, especially at surface steps when compared with those on the amorphous silica. Analogous to hydrophilicity, we attribute the origin of mobility of small nanoparticles to metal affinity, which determines the interaction between metal and support material. Ab initio molecular dynamics (AIMD) and machine learning-based deep potential molecular dynamics (DPMD) simulations directly capture a coalescence process on the silica surface and the strong pinning of gold on ceria. The joint experimental and theoretical results on the atomic scale demonstrate the metal affinity of active and inert supports as the key descriptor pertinent to sintering and deactivation of heterogeneous catalysts.

Atomic Replacement of PtNi Nanoalloys within Zn-ZIF-8 for the Fabrication of a Multisite CO2 Reduction Electrocatalyst.

Exploring the transformation/interconversion pathways of catalytic active metal species (single atoms, clusters, nanoparticles) on a support is crucial for the fabrication of high-efficiency catalysts, the investigation of how catalysts are deactivated, and the regeneration of spent catalysts. Sintering and redispersion represent the two main transformation modes for metal active components in heterogeneous catalysts. Herein, we established a novel solid-state atomic replacement transformation for metal catalysts, through which metal atoms exchanged between single atoms and nanoalloys to form a new set of nanoalloys and single atoms. Specifically, we found that the Ni of the PtNi nanoalloy and the Zn of the ZIF-8-derived Zn1 on nitrogen-doped carbon (Zn1-CN) experienced metal interchange to produce PtZn nanocrystals and Ni single atoms (Ni1-CN) at high temperature. The elemental migration and chemical bond evolution during the atomic replacement displayed a Ni and Zn mutual migration feature. Density functional theory calculations revealed that the atomic replacement was realized by endothermically stretching Zn from the CN support into the nanoalloy and exothermically trapping Ni with defects on the CN support. Owing to the synergistic effect of the PtZn nanocrystal and Ni1-CN, the obtained (PtZn)n/Ni1-CN multisite catalyst showed a lower energy barrier of CO2 protonation and CO desorption than that of the reference catalysts in the CO2 reduction reaction (CO2RR), resulting in a much enhanced CO2RR catalytic performance. This unique atomic replacement transformation was also applicable to other metal alloys such as PtPd.

Few-Atom Pt Ensembles Enable Efficient Catalytic Cyclohexane Dehydrogenation for Hydrogen Production.

Identification of catalytic active sites is pivotal in the design of highly effective heterogeneous metal catalysts, especially for structure-sensitive reactions. Downsizing the dimension of the metal species on the catalyst increases the dispersion, which is maximized when the metal exists as single atoms, namely, single-atom catalysts (SACs). SACs have been reported to be efficient for various catalytic reactions. We show here that the Pt SACs, although with the highest metal atom utilization efficiency, are totally inactive in the cyclohexane (C6H12) dehydrogenation reaction, an important reaction that could enable efficient hydrogen transportation. Instead, catalysts enriched with fully exposed few-atom Pt ensembles, with a Pt-Pt coordination number of around 2, achieve the optimal catalytic performance. The superior performance of a fully exposed few-atom ensemble catalyst is attributed to its high d-band center, multiple neighboring metal sites, and weak binding of the product.

Deep learning-based prediction of coronary artery stenosis resistance.

Coronary artery stenosis resistance (SR) is a key factor for noninvasive calculations of fractional flow reserve derived from coronary CT angiography (FFRCT). Existing computational fluid dynamics (CFD) methods, including three-dimensional (3-D) computational and zero-dimensional (0-D) analytical models, are usually limited by high calculation cost or low precision. In this study, we have developed a multi-input back-propagation neural network (BPNN) that can rapidly and accurately predict coronary SR. A training data set including 3,028 idealized anatomic coronary artery stenosis models was constructed for 3-D CFD calculation of SR with specific blood flow boundaries. Based on 3-D calculation results, we established a BPNN whose input is geometric parameters and blood flow, whereas output is SR. Then, a test set (324 cases) was constructed to evaluate the performance of the BPNN model. To verify the validity and practicability of the network, BPNN prediction results were compared with 3-D CFD and 0-D analytical model results from patient-specific models. For test set, the mean square error (MSE) between CFD and prediction results was 2.97%, linear regression analysis indicating a good correlation between the two (P < 0.001). For 30 patient-specific models, the MSE of BPNN and the 0-D model were 3.26 and 9.7%, respectively. The calculation time for BPNN and the 3-D CFD model for 30 cases was about 2.15 s and 2 h, respectively. The present results demonstrate the practicability of using deep learning methods for fast and accurate predictions of coronary artery SR. Our study represents an advance in noninvasive calculations of FFRCT.NEW & NOTEWORTHY This study developed a multi-input back-propagation neural network (BPNN) that can be used to predict coronary artery stenosis resistance by inputting vascular geometric parameters and blood flow. Compared with previous studies, the network developed in this study can accurately and rapidly predict coronary artery stenosis resistance, which can not only meet clinical requirements but also reduce the cost of calculation duration. This study contributes to the noninvasive methods for the numerical calculation of fractional flow reserve derived from coronary CT angiography (FFRCT) and indicates that this technique can potentially be used for evaluating myocardial ischemia.

Warfarin-Induced Calcification: Potential Prevention and Treatment Strategies.

Warfarin is clinically used as the first choice for long-term anticoagulant therapy, and for the prevention of thromboembolic events. However, when used at low doses in the long term or high doses in the short term, warfarin treatment may result in tissue calcifications-such as calcifications in the coronary arteries, peripheral vascular system, blood vessels of patients with atrial fibrillation and chronic kidney disease, and vascular valves-and atherosclerotic plaque calcification. These warfarin-induced calcifications may affect cardiovascular function and exacerbate diseases such as diabetes and hypertension. Studies have shown that quercetin, osteoprotegerin, sclerosin, and sodium thiosulfate may alleviate these effects by interfering in the Wnt/ ß -catenin, TG2/ ß -catenin, Bone Morphogenetic Protein 2 (BMP2), and Eicosapentaenoic Acid/Matrix Metallopeptidase-9 (EPA/MMP-9) pathways, respectively. Nevertheless, the mechanism underlying warfarin-induced calcification remains unknown. Therefore, the question as to how to effectively attenuate the calcification induced by warfarin and ensure its anticoagulant effect remains an urgent clinical problem that needs to be resolved. To utilize warfarin rationally and to effectively attenuate the calcifications, we focused on the clinical phenomena, molecular mechanisms, and potential strategies to prevent calcification. Highlighting these aspects could provide new insights into the effective utilization of warfarin and the reduction of its associated calcification effects.