RESUMEN
Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of haematological malignancies such as acute lymphoblastic leukaemia, B cell lymphoma and multiple myeloma1-4, but the efficacy of CAR T cell therapy in solid tumours has been limited5. This is owing to a number of factors, including the immunosuppressive tumour microenvironment that gives rise to poorly persisting and metabolically dysfunctional T cells. Analysis of anti-CD19 CAR T cells used clinically has shown that positive treatment outcomes are associated with a more 'stem-like' phenotype and increased mitochondrial mass6-8. We therefore sought to identify transcription factors that could enhance CAR T cell fitness and efficacy against solid tumours. Here we show that overexpression of FOXO1 promotes a stem-like phenotype in CAR T cells derived from either healthy human donors or patients, which correlates with improved mitochondrial fitness, persistence and therapeutic efficacy in vivo. This work thus reveals an engineering approach to genetically enforce a favourable metabolic phenotype that has high translational potential to improve the efficacy of CAR T cells against solid tumours.
Asunto(s)
Proteína Forkhead Box O1 , Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , Células Madre , Linfocitos T , Humanos , Ratones , Línea Celular Tumoral , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Mitocondrias/metabolismo , Fenotipo , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/citología , Microambiente Tumoral/inmunología , Células Madre/citología , Células Madre/inmunología , Células Madre/metabolismo , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/terapiaRESUMEN
Plants possess remarkable capability to regenerate upon tissue damage or optimal environmental stimuli. This ability not only serves as a crucial strategy for immobile plants to survive through harsh environments, but also made numerous modern plant improvements techniques possible. At the cellular level, this biological process involves dynamic changes in gene expression that redirect cell fate transitions. It is increasingly recognized that chromatin epigenetic modifications, both activating and repressive, intricately interact to regulate this process. Moreover, the outcomes of epigenetic regulation on regeneration are influenced by factors such as the differences in regenerative plant species and donor tissue types, as well as the concentration and timing of hormone treatments. In this review, we focus on several well-characterized epigenetic modifications and their regulatory roles in the expression of widely studied morphogenic regulators, aiming to enhance our understanding of the mechanisms by which epigenetic modifications govern plant regeneration.
Asunto(s)
Epigénesis Genética , Plantas , Plantas/genética , Plantas/metabolismo , Cromatina/metabolismo , Diferenciación Celular , Regeneración/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
The emerging two-photon polymerization (TPP) technique enables high-resolution printing of complex 3D structures, revolutionizing micro/nano additive manufacturing. Various fast scanning and parallel processing strategies have been proposed to promote its efficiency. However, obtaining large numbers of uniform focal spots for parallel high-speed scanning remains challenging, which hampers the realization of higher throughput. We report a TPP printing platform that combines galvanometric mirrors and liquid crystal on silicon spatial light modulator (LCoS-SLM). By setting the target light field at LCoS-SLM's diffraction center, sufficient energy is acquired to support simultaneous polymerization of over 400 foci. With fast scanning, the maximum printing speed achieves 1.49 × 108 voxels s-1, surpassing the existing scanning-based TPP methods while maintaining high printing resolution and flexibility. To demonstrate the processing capability, functional 3D microstructure arrays are rapidly fabricated and applied in micro-optics and micro-object manipulation. Our method may expand the prospects of TPP in large-scale micro/nanomanufacturing.
RESUMEN
Inspired by the reverse thrust generated by fuel injection, micromachines that are self-propelled by bubble ejection are developed, such as microrods, microtubes, and microspheres. However, controlling bubble ejection sites to build micromachines with programmable actuation and further enabling mechanical transmission remain challenging. Here, bubble-propelled mechanical microsystems are constructed by proposing a multimaterial femtosecond laser processing method, consisting of direct laser writing and selective laser metal reduction. The polymer frame of the microsystems is first printed, followed by the deposition of catalytic platinum into the desired local site of the microsystems by laser reduction. With this method, a variety of designable microrotors with selective bubble ejection sites are realized, which enable excellent mechanical transmission systems composed of single and multiple mechanical components, including a coupler, a crank slider, and a crank rocker system. We believe the presented bubble-propelled mechanical microsystems could be extended to applications in microrobotics, microfluidics, and microsensors.
RESUMEN
Numerous studies have demonstrated that regulatory T (Treg) cells play an important role in the tumour microenvironment (TME). The aim of this study was to investigate whether VEGFR2 affects the expression of miR-3200-3p in exosomes secreted by tumour cells, thereby influencing Treg senescence in the TME. The results showed that VEGFR2 expression level was the highest in Calu-1 cells, and after transfection with si-VEGFR2, the exosomes secreted from Calu-1 cells were extracted and characterised with no significant difference from the exosomes of the untransfected group, but the expression of miR-3200-3p in the exosomes of the transfected si-VEGFR2 group was elevated. The Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM) results suggested that exosomes highly expressing miR-3200-3p could inhibit Treg cell viability and promote apoptosis levels when treated with Treg cells. Detection of the senescence-associated proteins p16 INK4A and MMP3 by western blot (WB) revealed that exosomes highly expressing miR-3200-3p were able to elevate their protein expression levels. Tumour xenograft experiments demonstrated that exosomes with high miR-3200-3p expression promoted Treg cell senescence and inhibited subcutaneous tumour growth in nude mice. Dual-luciferase reporter assays and RNA pull-down assays showed that miR-3200-3p could be linked with DDB1. Overexpression of DDB1 reverses changes in DCAF1/GSTP1/ROS protein expression caused by exosomes with high miR-3200-3p expression. In conclusion, inhibition of VEGFR2 expression in tumour cells promotes the expression of miR-3200-3p in exosomes secreted by tumour cells. miR-3200-3p enters the TME through exosomes and acts on DDB1 in Treg cells to promote senescence of Treg cells to inhibit tumour progression.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Exosomas , Neoplasias Pulmonares , MicroARNs , Animales , Ratones , Humanos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patología , Neoplasias Pulmonares/patología , Exosomas/genética , Exosomas/metabolismo , Ratones Desnudos , Senescencia de Células T , Proliferación Celular/genética , Microambiente TumoralRESUMEN
To address the issue of bacterial growth on fresh-cut fruits, this paper reports the synthesis of nanosized γ-cyclodextrin metal-organic frameworks (CD-MOFs) using an ultrasound-assisted method and their application as carriers of limonene for antibacterial active packaging. The effects of the processing parameters on the morphology and crystallinity of the CD-MOFs are investigated, and the results prove that the addition of methanol is the key to producing nanosized CD-MOFs. The limonene loading content of the nanosized CD-MOFs can reach approximately 170 mg g-1. The sustained-release behaviors of limonene in the CD-MOFs are evaluated. Molecular docking simulations reveal the distribution and binding sites of limonene in the CD-MOFs. CD-MOFs are deposited on the surfaces of polycaprolactone (PCL) nanofibers via an immersion method, and limonene-loaded CD-MOF@PCL nanofibers are prepared. The morphology, crystallinity, thermal stability, mechanical properties, and antibacterial activity of the nanofibers are also studied. The nanofiber film effectively inhibits bacterial growth and prolongs the shelf life of fresh-cut apples. This study provides a novel strategy for developing antibacterial active packaging materials based on CD-MOFs and PCL nanofibers.
Asunto(s)
Frutas , Limoneno , Estructuras Metalorgánicas , Nanofibras , Poliésteres , gamma-Ciclodextrinas , Limoneno/química , Limoneno/farmacología , Nanofibras/química , Poliésteres/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , gamma-Ciclodextrinas/química , Frutas/química , Terpenos/química , Terpenos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Simulación del Acoplamiento MolecularRESUMEN
Exposing different facets on metal-organic frameworks (MOFs) is highly desirable to enhance the performance for various applications, however, exploiting a concise and effective approach to achieve facet-controlled synthesis of MOFs remains challenging. Here, by modulating the ratio of metal precursors to ligands, the facet-engineered iron-based MOFs (Fe-MOFs) exhibits enhanced catalytic activity for Fenton reaction are explored, and the mechanism of facet-dependent performance is revealed in detail. Fully exposed (101) and (100) facets on spindle-shaped Fe-MOFs enable rapid oxidation of colorless o-phenylenediamine (OPD) to colored products, thereby establishing a dual-mode platform for the detection of hydrogen peroxide (H2O2) and triacetone triperoxide (TATP). Thus, a detection limit as low as 2.06 nm is achieved, and robust selectivity against a wide range of common substances (>16 types) is obtained, which is further improved by incorporating a deep learning architecture with an SE-VGG16 network model, enabling precise differentiation of oxidizing agents from captured images. The present strategy is expected will shine light on both the rational synthesis of nanomaterials with modulated morphologies and the exploitation of high-performance trace chemical sensors.
RESUMEN
MAIN CONCLUSION: In flowers multiple secretory systems cooperate to deliver specialized metabolites to support specific roles in defence and pollination. The collective roles of cell types, enzymes, and transporters are discussed. The interplay between reproductive strategies and defense mechanisms in flowering plants has long been recognized, with trade-offs between investment in defense and reproduction predicted. Glandular trichomes and secretory cavities or ducts, which are epidermal and internal structures, play a pivotal role in the secretion, accumulation, and transport of specialized secondary metabolites, and contribute significantly to defense and pollination. Recent investigations have revealed an intricate connection between these two structures, whereby specialized volatile and non-volatile metabolites are exchanged, collectively shaping their respective ecological functions. However, a comprehensive understanding of this profound integration remains largely elusive. In this review, we explore the secretory systems and associated secondary metabolism primarily in Asteraceous species to propose potential shared mechanisms facilitating the directional translocation of these metabolites to diverse destinations. We summarize recent advances in our understanding of the cooperativity between epidermal and internal secretory structures in the biosynthesis, secretion, accumulation, and emission of terpenes, providing specific well-documented examples from pyrethrum (Tanacetum cinerariifolium). Pyrethrum is renowned for its natural pyrethrin insecticides, which accumulate in the flower head, and more recently, for emitting an aphid alarm pheromone. These examples highlight the diverse specializations of secondary metabolism in pyrethrum and raise intriguing questions regarding the regulation of production and translocation of these compounds within and between its various epidermal and internal secretory systems, spanning multiple tissues, to serve distinct ecological purposes. By discussing the cooperative nature of secretory structures in flowering plants, this review sheds light on the intricate mechanisms underlying the ecological roles of terpenes in defense and pollination.
Asunto(s)
Magnoliopsida , Polinización , Transporte Biológico , Reproducción , TerpenosRESUMEN
AIMS: The astaxanthin-producing yeast Xanthophyllomyces dendrorhous is widely used in aquaculture. Due to the production of carotenoid, this yeast shows visible color; however, high-throughput approaches for identification of astaxanthin-overproducing strains remain rare. METHODS AND RESULTS: This study verified an effective approach to identify astaxanthin-overproducing mutants of X. dendrorhous by flow cytometry (FCM) and cell sorting. First, the mutant libraries were generated by atmospheric and room-temperature plasma (ARTP) mutagenesis. Second, a highly direct correlation between the concentrations of intracellular astaxanthin and the levels of emitting fluorescence was constructed by testing a variety of astaxanthin-contained populations via FCM and cell sorting. Third, iterative cell sorting efficiently improves the identification of astaxanthin-overproducing strains. Finally, two mutants producing 4.96 mg astaxanthin g-1 DCW (dry cell weight) and 5.30 mg astaxanthin g-1 DCW were obtained, which were 25.3% and 33.8% higher than that of the original strain, respectively. CONCLUSIONS: This study demonstrated that iterative ARTP mutagenesis along with cell sorting by FCM is effective for identifying astaxanthin-overproduction strains.
Asunto(s)
Basidiomycota , Citometría de Flujo/métodos , Mutagénesis , XantófilasRESUMEN
Percutaneous coronary intervention (PCI) patients combined with thrombocytopenia (TP) are usually considered to be at low ischemic risk, receiving less proper antiplatelet therapy. However, recent studies reported a paradoxical phenomenon that PCI patients with TP were prone to experience thrombotic events, while the mechanisms and future treatment remain unclear. We aim to investigate whether inflammation modifies platelet reactivity among these patients. Consecutive 10 724 patients undergoing PCI in Fuwai Hospital were enrolled throughout 2013. High-sensitivity C-reactive protein (hsCRP) ≥2 mg/L was considered inflammatory status. TP was defined as platelet count <150×109/L. High on-treatment platelet reactivity (HTPR) was defined as adenosine diphosphate-induced platelet maximum amplitude of thromboelastogram >47mm. Among 6617 patients finally included, 879 (13.3%) presented with TP. Multivariate logistic regression demonstrated that patients with TP were associated with a lower risk of HTPR (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.53-0.76) than those without TP in the overall cohort. In further analysis, among hsCRP <2 mg/L group, patients with TP exhibited a decreased risk of HTPR (OR 0.53, 95% CI 0.41-0.68); however, in hsCRP ≥2mg/L group, TP patients had a similar risk of HTPR as those without TP (OR 0.83, 95% CI 0.63-1.08). Additionally, these results remain consistent across subgroups, including patients presenting with acute coronary syndrome and chronic coronary syndrome. Inflammation modified the platelet reactivity of PCI patients with TP, providing new insights into the mechanisms of the increased thrombotic risk. Future management for this special population should pay more attention to inflammation status and timely adjustment of antiplatelet therapy in TP patients with inflammation.
What is the context? Recent studies reported a paradoxical phenomenon that percutaneous coronary intervention (PCI) patients with thrombocytopenia (TP) were prone to experience thrombotic events. The potential mechanisms underlying the increased thrombotic risk and how to manage antiplatelet therapy in PCI patients with TP remain unclear.Growing attention has been paid to immunothrombosis. Inflammation is closely associated with high-on treatment platelet reactivity (HTPR) and thrombotic risk.HTPR is an independent risk factor of thrombosis and can provide information for guiding antiplatelet therapy.What is new? This prospective cohort study enrolled 10 724 patients undergoing PCI in Fuwai Hospital (National Center for Cardiovascular Diseases, Beijing, China), with HTPR risk being the study endpoint of interest.We first reported that inflammation significantly modified the platelet reactivity of PCI patients with TP.When hsCRP level <2 mg/L, PCI patients with TP had a decreased risk of HTPR. However, when hsCRP ≥2 mg/L, TP patients had similar HTPR risk as those without TP.HsCRP levels could modify the relationship between TP and HTPR risks both in patients with acute coronary syndrome and chronic coronary syndrome.What is the impact? These results provide insights into potential mechanisms of the increased thrombotic risk in PCI patients with TP. Specifically, inflammation might be involved in the thrombotic risk of PCI patients with TP by modifying the platelet reactivity.As for future management, personalized antiplatelet therapy should be administrated to TP patients with inflammation status.
Asunto(s)
Intervención Coronaria Percutánea , Trombocitopenia , Anciano , Femenino , Masculino , Persona de Mediana Edad , Plaquetas , Proteína C-Reactiva/metabolismo , China/epidemiología , Estudios de Cohortes , Inflamación , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/estadística & datos numéricos , Estudios Prospectivos , Trombocitopenia/epidemiología , Trombocitopenia/metabolismo , HumanosRESUMEN
Pterostilbene (PTE, trans-3,5-dimethoxy-4'-hydroxystilbene), a natural plant polyphenol, possesses numerous pharmacological effects, including antioxidant, antidiabetic, antiatherosclerotic, and neuroprotective aspects. This study aims to investigate whether PTE plays a protective role against oxidative stress injury by GAS6/Axl signaling pathway in cardiomyocytes. Hydrogen peroxide (H2 O2 )-induced oxidative stress HL-1 cells were used as models. The mechanism by which PTE protected oxidative stress is investigated by combining cell viability, cell ROS levels, apoptosis assay, molecular docking, quantitative real-time PCR, and western blot analysis. GAS6 shRNA was performed to investigate the involvement of GAS6/Axl pathways in PTE's protective role. The results showed that PTE treatment improved the cell morphology and viability, and inhibited the apoptosis rate and ROS levels in H2 O2 -injured HL-1 cells. Particularly, PTE treatment upregulated the levels of GAS6, Axl, and markers related to oxidative stress, apoptosis, and mitochondrial function related. Molecular docking showed that PTE and GAS6 have good binding ability. Taken together, PTE plays a protective role against oxidative stress injury through inhibiting oxidative stress and apoptosis and improving mitochondrial function. Particularly, GAS6/Axl axis is the surprisingly prominent in the PTE-mediated pleiotropic effects.
Asunto(s)
Tirosina Quinasa del Receptor Axl , Estrés Oxidativo , Proteínas Tirosina Quinasas Receptoras , Estilbenos , Apoptosis , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Simulación del Acoplamiento Molecular , Proteínas Proto-Oncogénicas/metabolismo , Especies Reactivas de Oxígeno , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Transducción de Señal , Animales , Ratones , Estilbenos/farmacología , Línea CelularRESUMEN
BACKGROUND: The aim of this study was to report the clinical profile of new-onset and relapse of uveitis following rapid spreading of coronavirus disease 2019 (COVID-19) infection due to change of anti-COVID-19 policies in China and investigate potential risk factors for inflammation relapse. METHODS: In this retrospective case-control study, patients with new-onset or a history of uveitis between December 23, 2022, and February 28, 2023, were included to assess the influence of COVID-19 infection on uveitis. Detailed information on demographic data, clinical characteristics, treatment measures, treatment response, and ocular inflammatory status before and after COVID-19 infection was collected. RESULTS: This study included 349 patients with a history of uveitis. The uveitis relapse rate was higher (28.8%, n = 288) in those with COVID-19 infection than in patients without COVID-19 infection (14.8%, n = 61) (P = 0.024). Among the relapse cases, 50.8% experienced a relapse of anterior uveitis, while 49.2% had a relapse of uveitis involving the posterior segment. Multivariable regression analysis indicated a positive correlation between disease duration and uveitis relapse, while the last relapse exceeding one year before COVID-19 infection and the use of methotrexate during COVID-19 infection were negatively correlated with relapse of uveitis. Thirteen patients who developed new-onset uveitis following COVID-19 infection were included; among them, three (23.1%) had anterior uveitis and 10 (76.9%) had uveitis affecting the posterior segment. Regarding cases involving the posterior segment, four patients (30.8%) were diagnosed with Vogt-Koyanagi-Harada disease. CONCLUSIONS: COVID-19 infection increases the rate of uveitis relapse. Long disease duration is a risk factor, while time since the last relapse more than 1 year and methotrexate use are protective factors against uveitis relapse.
Asunto(s)
COVID-19 , Recurrencia , SARS-CoV-2 , Uveítis , Humanos , COVID-19/epidemiología , COVID-19/complicaciones , Masculino , Femenino , Estudios Retrospectivos , China/epidemiología , Factores de Riesgo , Uveítis/diagnóstico , Uveítis/epidemiología , Uveítis/etiología , Uveítis/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Estudios de Casos y Controles , AncianoRESUMEN
D-glucuronic acid is a kind of glucose derivative, which has excellent properties such as anti-oxidation, treatment of liver disease and hyperlipidemia, and has been widely used in medicine, cosmetics, food and other fields. The traditional production methods of D-glucuronic acid mainly include natural extraction and chemical synthesis, which can no longer meet the growing market demand. The production of D-glucuronic acid by biocatalysis has become a promising alternative method because of its high efficiency and environmental friendliness. This review describes different production methods of D-glucuronic acid, including single enzyme catalysis, multi-enzyme cascade, whole cell catalysis and co-culture, as well as the intervention of some special catalysts. In addition, some feasible enzyme engineering strategies are provided, including the application of enzyme immobilized scaffold, enzyme mutation and high-throughput screening, which provide good ideas for the research of D-glucuronic acid biocatalysis.
Asunto(s)
Ingeniería , Biocatálisis , Catálisis , Técnicas de Cocultivo , Ácido GlucurónicoRESUMEN
Partial discharge (PD) fault diagnosis is of great importance for ensuring the safe and stable operation of power transformers. To address the issues of low accuracy in traditional PD fault diagnostic methods, this paper proposes a novel method for the power transformer PD fault diagnosis. It incorporates the approximate entropy (ApEn) of symplectic geometry mode decomposition (SGMD) into the optimized bidirectional long short-term memory (BILSTM) neural network. This method extracts dominant PD features employing SGMD and ApEn. Meanwhile, it improves the diagnostic accuracy with the optimized BILSTM by introducing the golden jackal optimization (GJO). Simulation studies evaluate the performance of FFT, EMD, VMD, and SGMD. The results show that SGMD-ApEn outperforms other methods in extracting dominant PD features. Experimental results verify the effectiveness and superiority of the proposed method by comparing different traditional methods. The proposed method improves PD fault recognition accuracy and provides a diagnostic rate of 98.6%, with lower noise sensitivity.
RESUMEN
Studying the physicochemical properties and biological activities of Lycium barbarum polysaccharides(LBPs) is of great significance. The previous study had extracted LBPs(LBP-1, LBP-2, LBP-3, LBP-4, and LBP-5) by five different methods(cold water extraction, boiling water reflux extraction of the residue after cold water extraction, ultrasonic extraction with 50% ethanol, ultrasonic extraction with 25% ethanol of the residue after 50% ethanol extraction, and hot water extraction). In this study, the structures of the obtained five LBPs were characterized by UV spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Furthermore, the antioxidant, blood lipid-lowering, nitrosation-inhibting, acetylcholinesterase-inhibiting, and tyrosinase-inhibiting activities of the five LBPs were measured in vitro. The results showed that high-temperature extraction destroyed the polysaccharide structure, while ultrasound-assisted extraction ensured the structural integrity. The thermal stability and degradation behaviors differed among the five LBPs. However, the UV spectroscopic results of the five LBPs did not show significant differences, and all of the five LBPs showed the characteristic absorption peaks of proteins. LBP-3 and LBP-4 exhibited strong antioxidant activity, while LBP-3 had the strongest blood lipid-lowering activity. In addition, LBP-3 outperformed other LBPs in inhibiting nitrosation and acetylcholineste-rase, and LBP-2 showed the strongest inhibitory effect on tyrosinase. This study explored the effects of different extraction methods on the physicochemical properties and biological activities of LBPs, with a view to providing a basis for the selection of suitable extraction methods to obtain LBPs with ideal biological activities.
Asunto(s)
Medicamentos Herbarios Chinos , Lycium , Lycium/química , Monofenol Monooxigenasa , Acetilcolinesterasa , Antioxidantes/farmacología , Antioxidantes/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Polisacáridos/farmacología , Polisacáridos/química , Lípidos , Etanol , AguaRESUMEN
Background: Bivalirudin reduces ischemic and hemorrhagic events in patients undergoing primary percutaneous coronary intervention (PCI), but the safety and efficacy for such individuals are unclear. Our aim was to evaluate the long-term safety and efficacy of bivalirudin in patients undergoing elective PCI. Methods: We examined 957 patients with bivalirudin anticoagulation and 1713 patients with unfractionated heparin (UFH) anticoagulation with and without glycoprotein IIb/IIIa inhibitors (GPI). The primary endpoint was net adverse clinical events (NACE), a composite of death, myocardial infarction, revascularization, stent thrombosis, stroke, and bleeding. The secondary endpoints were bleeding and major adverse cardiovascular and cerebrovascular events (MACCE). Results: In one year of follow-up, 307 (11.5%) NACEs, 72 (2.7%) bleedings, and 249 (9.3%) MACCEs occurred. Statistically, patients with bivalirudin anticoagulation had less NACE [hazard ratio (HR): 0.75, 95% confidence interval (CI): 0.58-0.96, p = 0.021] and bleeding (HR: 0.58, 95% CI: 0.34-0.99, p = 0.045) but not less MACCE, than did those with UFH anticoagulation. Furthermore, the risk of bleeding in the bivalirudin group was lower than in the UFH with GPI group (p = 0.001) but not lower than in the group of UFH without GPI (p = 0.197). Conclusions: In patients who undergo elective PCI, the use of bivalirudin significantly decreased the risk of NACE and bleeding without increasing the risk of MACCE; the reduction of bleeding risk with bivalirudin was mainly attributed to the presence of GPIs in the UFH group.
RESUMEN
Dry eye disease (DED) is a prevalent ophthalmic ailment with intricate pathogenesis and that occurs primarily due to various factors which affect the ocular surface. DED is characterized by the disruption of tear film homeostasis, inflammatory reaction, and neuroparesthesia. Transient receptor potential vanilloid 1 (TRPV1) is a versatile receptor that can be stimulated by heat, acid, capsaicin (CAP), hyperosmolarity, and numerous inflammatory agents. There is accumulating evidence that implicates TRPV1 in the initiation and progression of DED through its detection of hypertonic conditions and modulation of inflammatory pathways. In this article, we present a comprehensive review of the expression and function of the TRPV1 channel in tissues and cells associated with DED. In addition, we outline the potential mechanisms that implicate TRPV1 in the pathophysiology of DED. The aim of this review is to establish a theoretical basis for TRPV1 as a possible therapeutic target in DED, thereby encouraging further investigations into its role in DED.
Asunto(s)
Síndromes de Ojo Seco , Canales Catiónicos TRPV , Canales Catiónicos TRPV/metabolismo , Humanos , Síndromes de Ojo Seco/metabolismo , Síndromes de Ojo Seco/fisiopatología , AnimalesRESUMEN
Considering the long-term memory and volatility clustering of the European Union (EU) Carbon Emission Allowances (EUA) futures returns, based on the economy-energy-environment system perspective and the assumption of investors' heterogeneity, this study proposes a joint modeling approach combining the fractionally integrated generalized autoregressive conditional heteroscedasticity model (FIGARCH) and the stochastic cusp catastrophe model (SCC) to examine the equilibrium bifurcations and extreme risks in the EU carbon futures market. The relevant results are threefold. (1) The SCC model has good fitting effect and interpretability, and is an effective method for investigating catastrophe reactions under time-varying volatility conditions. (2) In the EUA futures market, chartists are mainly affected by short-term price and trading volume changes, which leads to the emergence of equilibrium bifurcations, while fundamentalists make investment decisions based on the economy, the energy market, and market supply-demand, which affects the asymmetry of equilibrium bifurcations. (3) Using the catastrophe criterion (i.e., Cardan's discriminant of the equilibrium surface equation), we identify148 equilibrium bifurcation time points in the EUA futures market from December 3, 2009 to September 16, 2020, most of which are concentrated in two upward periods with an average scale of extreme risks is about 32.51 %. Our analysis provides theoretical support for regulatory authorities to stabilize the carbon futures market and build a collaborative extreme risk management framework covering energy and macroeconomics, also proposing suggestions for traders to effectively prevent extreme risks.
RESUMEN
In this study, electrospun zein/alginate dialdehyde (AD) nanofibers were prepared by green crosslinking. The degree of crosslinking could reach 50.72 %, and the diameter of electrospun fibers ranged from 446.2 to 541.8 nm. The generation of AD and the bonding of crosslinking were further confirmed by the changes on characteristic peaks and conformational ratios in the infrared spectroscopy and secondary structure analysis. High concentrations of AD led to improved thermal stabilities, mechanical properties, and hydrophobicity. And the highly crosslinked nanofibers (Z-8) owned the highest elastic modulus (24.92 MPa), tensile strength (0.28 MPa), and elongation at break (8.14 %) among five samples. Moreover, Z-8 possessed a high swelling ratio of 5.45 g/g, and a low weight loss of 6.09 %. The samples could encapsulate curcumin efficiently and show controllable release behaviors based on different AD addition. And the oxidation resistance of nanofibers gradually improved, consistent with the release performances. This study indicated AD crosslinking favored the preparation and application of zein nanofibers, and the oxidized polysaccharide acted as the green crosslinking agent, which provided reference value for the application of polysaccharides in food-related electrospun materials.
Asunto(s)
Curcumina , Nanofibras , Zeína , Zeína/química , Alginatos , Nanofibras/química , Resistencia a la TracciónRESUMEN
Single-fiber-based sensing and imaging probes enable the co-located and simultaneous observation and measurement (i.e., 'sense' and 'see') of intricate biological processes within deep anatomical structures. This innovation opens new opportunities for investigating complex physiological phenomena and potentially allows more accurate diagnosis and monitoring of disease. This prospective review starts with presenting recent studies of single-fiber-based probes for concurrent and co-located fluorescence-based sensing and imaging. Notwithstanding the successful initial demonstration of integrated sensing and imaging within single-fiber-based miniaturized devices, the realization of these devices with enhanced sensing sensitivity and imaging resolution poses notable challenges. These challenges, in turn, present opportunities for future research, including the design and fabrication of complex lens systems and fiber architectures, the integration of novel materials and other sensing and imaging techniques.