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Decreased hippocampal tropomyosin receptor kinase B (TrkB) level is implicated in the pathophysiology of stress-induced mood disorder and cognitive decline. However, how TrkB is modified and mediates behavioral responses to chronic stress remains largely unknown. Here the effects and mechanisms of TrkB cleavage by asparagine endopeptidase (AEP) were examined on a preclinical murine model of chronic restraint stress (CRS)-induced depression. CRS activated IL-1ß-C/EBPß-AEP pathway in mice hippocampus, accompanied by elevated TrkB 1-486 fragment generated by AEP. Specifi.c overexpression or suppression of AEP-TrkB axis in hippocampal CaMKIIα-positive cells aggravated or relieved depressive-like behaviors, respectively. Mechanistically, in addition to facilitating AMPARs internalization, TrkB 1-486 interacted with peroxisome proliferator-activated receptor-δ (PPAR-δ) and sequestered it in cytoplasm, repressing PPAR-δ-mediated transactivation and mitochondrial function. Moreover, co-administration of 7,8-dihydroxyflavone and a peptide disrupting the binding of TrkB 1-486 with PPAR-δ attenuated depression-like symptoms not only in CRS animals, but also in Alzheimer's disease and aged mice. These findings reveal a novel role for TrkB cleavage in promoting depressive-like phenotype.
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Depressão , Hipocampo , Estresse Psicológico , Animais , Hipocampo/metabolismo , Camundongos , Depressão/metabolismo , Masculino , Estresse Psicológico/metabolismo , Receptor trkB/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Comportamento Animal/fisiologia , Transdução de Sinais/fisiologia , Doença de Alzheimer/metabolismo , Glicoproteínas de Membrana/metabolismoRESUMO
ABSTRACT: In this study, we investigated the safety and efficacy of fondaparinux sodium in postpercutaneous coronary intervention (PCI) anticoagulation therapy for patients with ST-segment elevation myocardial infarction. There are a total of 200 patients with ST segment elevation myocardial infarction underwent PCI and anticoagulation therapy. They were randomly split into experimental (n = 108) and control groups (n = 92). The experimental group received postoperative fondaparinux sodium (2.5 mg q.d), while the control group received enoxaparin (4000 IU q12 h). We did not use a loading dose for enoxaparin. Bleeding incidence and major adverse cardiovascular/cerebrovascular events were monitored during hospitalization, and at 1, 3, and 6 months postsurgery. The primary end points, including bleeding, mortality, and myocardial infarction during hospitalization, were not significantly different between the 2 groups. For secondary end points, the incidence of combined end point events at 1 month, 3 months, and 6 months after surgery in the experimental group was lower than in the control group (P < 0.05). According to Cox regression analysis, the risk of bleeding in the experimental group was significantly lower than that in the control group [hazard ratios: 0.506, 95% confidence interval (CI): 0.284-0.900] (P = 0.020). The risk of mortality in the experimental group was significantly lower than in the control group (hazard ratio: 0.188, 95% CI: 0.040-0.889) (P = 0.035). In summary, perioperative use of fondaparinux sodium during PCI in patients with STEMI in this study was associated with a lower risk of bleeding and death compared with enoxaparin use in the absence of loading dose.
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Enoxaparina , Fondaparinux , Hemorragia , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Fondaparinux/uso terapêutico , Fondaparinux/efeitos adversos , Fondaparinux/administração & dosagem , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , China/epidemiologia , Resultado do Tratamento , Hemorragia/induzido quimicamente , Enoxaparina/efeitos adversos , Enoxaparina/administração & dosagem , Enoxaparina/uso terapêutico , Fatores de Risco , Fatores de Tempo , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/uso terapêutico , Estudos ProspectivosRESUMO
The objective of this study was to assess the quality and consistency of recommendations in clinical practice guidelines (CPGs) and expert consensus on paediatric cow's milk protein allergy (CMPA) to serve as a foundation for future revisions and enhancements of clinical guidelines and consensus documents. We conducted a comprehensive literature search across several databases, including the Chinese Biomedical Literature Database (CBM), PubMed, Embase, Web of Science, UpToDate, ClinicalKey, DynaMed Plus and BMJ Best Practice. We spanned the search period from the inception of each database through October 1, 2023. We integrated subject headings (MeSH/Emtree) and keywords into the search strategy, used the search methodologies of existing literature and developed it in collaboration with a librarian. Two trained researchers independently conducted the literature screening and data extraction. We evaluated methodological quality and recommendations by using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) and AGREE-Recommendations for Excellence (AGREE-REX) tools. Moreover, we compared and summarized key recommendations from high-quality CPGs. Our study included 27 CPGs and expert consensus documents on CMPA. Only four CPGs (14.8%) achieved a high-quality AGREE II rating. The four high-quality CPGs consistently provided recommendations for CMPA. The highest scoring domains for AGREE II were 'scope and purpose' (77 ± 12%) and 'clarity of presentation' (75 ± 22%). The lowest scoring domains were 'stakeholder involvement' (49 ± 21%), 'rigor of development' (34 ± 20%) and 'applicability' (12 ± 20%). Evaluation with AGREE-REX generally demonstrated low scores across its domains. Conclusion: Recommendations within high-quality CPGs for the paediatric CMPA showed fundamental consistency. Nevertheless, the methodology and recommendation content of CPGs and the expert consensus exhibited low quality, thus indicating a substantial scope for enhancement. Guideline developers should rigorously follow the AGREE II and AGREE-REX standards in creating CPGs or expert consensuses to guarantee their clinical efficacy in managing paediatric CMPA. What is Known: ⢠The quality of clinical practice guidelines and expert consensus on paediatric cow's milk protein allergy (CMPA) remains uncertain. ⢠There is a lack of clarity regarding the consistency of crucial recommendations for CMPA management. What is New: ⢠Improving the methodological quality of guidelines and consensus on CMPA requires greater emphasis on stakeholder engagement, rigorous development processes, and practical applicability. ⢠The recommendations from four high-quality guidelines align. However, addressing clinical applicability, integrating values and preferences, and ensuring actionable implementation are critical to improving the quality of all guidelines.
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Consenso , Hipersensibilidade a Leite , Guias de Prática Clínica como Assunto , Hipersensibilidade a Leite/diagnóstico , Humanos , Criança , Proteínas do LeiteRESUMO
Ion migration activated by illumination is a critical factor responsible for the performance decline and stability degradation of perovskite solar cells (PSCs). While ion migration has been widely believed to be much slower than charge transport, recent research suggests that, despite the lack of understanding of the mechanism, it may also be involved in a series of rapid photoelectric responses of PSCs. Here, we report an improved circuit-switched transient photoelectric technique with nanosecond temporal resolution, which enables quantitative characterization of ion migration dynamics in PSCs across a fairly broad time window. Specifically, ion migration occurring within microseconds after illumination (corresponding to a diffusion length of â¼10-7 cm) is unambiguously identified. In conjunction with the composition engineering protocol, we justify that it arises from the short-range migration of halide anions and organic cations around the contact/perovskite interface. The rapid ion migration kinetics revealed in this work strongly complement the well-established ion migration model, which offers new insights into the mechanism of ion-carrier interaction in PSC devices.
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BACKGROUND: Medical service efficiency is an important indicator for measuring the equity of medical services. Therefore, this study primarily focuses on investigating the spatiotemporal domain to explore both spatial and temporal characteristics, as well as influencing factors that affect medical service efficiency across diverse provinces in China. METHODS: The super Epsilon-based Measure (EBM) unexpected model has previously been utilized to quantify energy eco-efficiency, carbon emission efficiency, and green development efficiency. However, limited studies have applied this method to assess the efficiency of healthcare services. Therefore, this study investigates the application of the super-EBM-unexpected model in evaluating medical service efficiency, and further integrates spatial econometric models to explore the influencing factors of medical service efficiency and aims to identify potential avenues for improvement. RESULTS: The average efficiency of medical services in the 31 provinces of China ranges from 0.6 to 0.7, indicating predominantly low efficiency values. However, economically developed coastal areas exhibit relatively high efficiency levels above 1. Conversely, regions with relatively lower levels of economic development demonstrate lower efficiency rates at approximately 0.3. Evidently, substantial regional disparities exist. For the influencing factors, the enhancement of residents' living standards can effectively foster the medical service efficiency, while residential living standards of nearby areas can also exert an impact in this region. The influence of educational attainment on medical service efficiency exhibits a significant inhibitory effect. CONCLUSIONS: The majority of China's 31 provinces exhibit suboptimal medical service efficiency, with notable regional disparities. Future policy initiatives should be tailored to address the unique challenges faced by regions with lower levels of economic development, prioritizing enhancements in both the efficacy and quality of their healthcare systems.
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Eficiência Organizacional , Análise Espaço-Temporal , China , Humanos , Modelos EconométricosRESUMO
Four new prenylated acetophenone derivatives, including one acetophenone dimer [acronyrone D (1)] and three acetophenone monomers [acronyrones E-G (2-4)], along with seven known analogues (5-11) were obtained from the leaves of Acronychia pedunculata. Their structures and absolute configurations were established by analysis of HRMS and NMR data, single crystal X-ray diffraction studies and quantum chemical calculations. In addition, the isolates were tested for their anti-proliferative acivity against HCT-116, RKO and SW480 cancer cell lines. Remarkably, compound 5 exhibited significant anti-proliferative effects on the three cell lines, with IC50 values ranging from 0.24 to 5.3 µM.
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Abscisic acid (ABA) is one of the many naturally occurring phytohormones widely found in plants. This study focused on refining APAn, a series of previously developed agonism/antagonism switching probes. Twelve novel APAn analogues were synthesized by introducing varied branched or oxygen-containing chains at the C-6' position, and these were screened. Through germination assays conducted on A. thaliana, colza, and rice seeds, as well as investigations into stomatal movement, several highly active ABA receptor antagonists were identified. Microscale thermophoresis (MST) assays, molecular docking, and molecular dynamics simulation showed that they had stronger receptor affinity than ABA, while PP2C phosphatase assays indicated that the C-6'-tail chain extending from the 3' channel effectively prevented the ligand-receptor binary complex from binding to PP2C phosphatase, demonstrating strong antagonistic activity. These antagonists showed effective potential in promoting seed germination and stomatal opening of plants exposed to abiotic stress, particularly cold and salt stress, offering advantages for cultivating crops under adverse conditions. Moreover, their combined application with fluridone and gibberellic acid could provide more practical agricultural solutions, presenting new insights and tools for overcoming agricultural challenges.
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Ácido Abscísico , Germinação , Simulação de Acoplamento Molecular , Ácido Abscísico/química , Germinação/efeitos dos fármacos , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Reguladores de Crescimento de Plantas/química , Reguladores de Crescimento de Plantas/farmacologia , Sementes/efeitos dos fármacos , Sementes/química , Sementes/crescimento & desenvolvimento , Oryza/efeitos dos fármacos , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Proteínas de Arabidopsis/antagonistas & inibidores , Proteínas de Arabidopsis/metabolismo , Simulação de Dinâmica Molecular , Agricultura/métodos , Giberelinas/química , Giberelinas/metabolismo , PiridonasRESUMO
Ion migration is a major issue hindering the long-term stability of perovskite solar cells (PSCs). As an intrinsic characteristic of metal halide perovskite materials, ion migration is closely related to the atomic arrangement and coordination, which are the basic characteristic differences among various facets. Herein, we report the facet-related ion migration, and then achieve the inhibition of ion migration in perovskite through finely modulating the facet orientation. We show that the (100) facet is substantially more vulnerable to cationic migration than the (111) facet. The main reason for this difference in migration is that the cationic migration route in the (111) facet deviates from that in the (100) facet, which increases the active migration energy and weakens the contribution from the electric field during operation. We prepare a (111)-dominated perovskite film by incorporating a facile and green addition of water (H2O) into the antisolvent, further achieving a power conversion efficiency (PCE) of 26.0 % (25.4 % certification) on regular planar PSCs and 25.8 % on inverted PSCs. Moreover, the unencapsulated PSCs can maintain 95 % of their initial PCE after 3500-hours operation under simulated AM1.5 illumination at the maximum power point.
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Rare earth (RE) addition to steels to produce RE steels has been widely applied when aiming to improve steel properties. However, RE steels have exhibited extremely variable mechanical performances, which has become a bottleneck in the past few decades for their production, utilization and related study. Here in this work, we discovered that the property variation of RE steels stems from the presence of oxygen-based inclusions. We proposed a dual low-oxygen technology, and keeping low levels of oxygen content in steel melts and particularly in the raw RE materials, which have long been ignored, to achieve impressively stable and favourable RE effects. The fatigue life is greatly improved by only parts-per-million-level RE addition, with a 40-fold improvement for the tension-compression fatigue life and a 40% enhancement of the rolling contact fatigue life. We find that RE appears to act by lowering the carbon diffusion rate and by retarding ferrite nucleation at the austenite grain boundaries. Our study reveals that only under very low-oxygen conditions can RE perform a vital role in purifying, modifying and micro-alloying steels, to improve the performance of RE steels.
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Oxigênio , Aço , Ligas , CarbonoRESUMO
An electricity-promoted method for Friedel-Crafts acylation of biarylcarboxylic acids is described in this research. Various fluorenones can be accessed in up to 99% yields. During the acylation, electricity plays an essential role, which might motivate the chemical equilibrium by consuming the generated TFA. This study is predicted to provide an avenue to realize Friedel-Crafts acylation in a more environmentally friendly process.
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Biofilms are used widely to remove nitrogen from wastewater; however, most biofilm carriers (i.e. polyurethane foam, PUF) are hydrophobic organic materials with millimetre-scale apertures, ineffective attachment, and unstable colonization of microorganisms. To address these limitations, hydrophilic sodium alginate (SA) mixed with zeolite powder (Zeo) was cross-linked in PUF to form a micro-scale hydrogel (PAS) with a well-organized and reticular cellular structure. Scanning electron microscopy revealed that immobilized cells were entrapped in the interior of hydrogel filaments and rapidly formed a stable biofilm on the surface. The biofilm generated was 10.3-fold greater than the film developed on PUF. Kinetics and isotherm studies revealed that the as-developed carrier, because of the presence of Zeo, effectively improved the adsorption of NH4+-N by 53%. The PAS carrier achieved total nitrogen removal in excess of 86% for low carbon-to-nitrogen ratio wastewater treated for 30 d, indicating that this novel modification-encapsulation technology has potential for wastewater treatment.
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Hidrogéis , Zeolitas , Desnitrificação , Águas Residuárias , Bactérias , Alginatos , Biofilmes , NitrogênioRESUMO
Drought stress profoundly affects plant growth and development, posing a significant challenge that is extensively researched in the field. Thioredoxins (TRXs), small proteins central to redox processes, are crucial to managing both abiotic and biotic stresses. In this research, the VyTRXy gene, cloned from wild Yanshan grapes, was validated as a functional TRX through enzyme activity assays. VyTRXy was found to bolster photosynthesis, augment levels of osmotic regulators, stimulate antioxidant enzyme activities, and strengthen drought resilience in transgenic plants. These enhancements were evidenced by higher survival rates, optimized photosynthetic metrics, increased proline levels, augmented chlorophyll concentration, reduced electrolyte leakage, and decreased malondialdehyde and hydrogen peroxide (H2O2) levels. Furthermore, there was a surge in the activities of enzymes such as catalase, ascorbate peroxidase, glutathione peroxidase, dehydroascorbate reductase, and glutathione reductase, along with an increased expression of TRX peroxidase. Notably, under drought stress, there was a marked elevation in the expression of stress-responsive genes, including the adversity stress-inducible expression gene (NtRD29A) and DRE-binding protein (NtDREB), in transgenic tobacco. This investigation is pivotal in the quest for drought-resistant grapevine varieties and provides significant insights into the molecular functionality of VyTRXy in enhancing grapevine drought tolerance.
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Antioxidantes , Resistência à Seca , Antioxidantes/metabolismo , Peróxido de Hidrogênio/metabolismo , Fotossíntese , Estresse Fisiológico/genética , Plantas Geneticamente Modificadas/metabolismo , Secas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Domestication and breeding have reshaped the genomic architecture of chicken, but the retention and loss of genomic elements during these evolutionary processes remain unclear. We present the first chicken pan-genome constructed using 664 individuals, which identified an additional approximately 66.5-Mb sequences that are absent from the reference genome (GRCg6a). The constructed pan-genome encoded 20,491 predicated protein-coding genes, of which higher expression levels are observed in conserved genes relative to dispensable genes. Presence/absence variation (PAV) analyses demonstrated that gene PAV in chicken was shaped by selection, genetic drift, and hybridization. PAV-based genome-wide association studies identified numerous candidate mutations related to growth, carcass composition, meat quality, or physiological traits. Among them, a deletion in the promoter region of IGF2BP1 affecting chicken body size is reported, which is supported by functional studies and extra samples. This is the first time to report the causal variant of chicken body size quantitative trait locus located at chromosome 27 which was repeatedly reported. Therefore, the chicken pan-genome is a useful resource for biological discovery and breeding. It improves our understanding of chicken genome diversity and provides materials to unveil the evolution history of chicken domestication.
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Galinhas , Estudo de Associação Genômica Ampla , Animais , Tamanho Corporal/genética , Galinhas/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Locos de Características QuantitativasRESUMO
BACKGROUND: Colorectal cancer (CRC) is prevalent worldwide and is often challenged by treatment failure and recurrence due to resistance to radiotherapy. Here, we aimed to identify the elusive underlying molecular mechanisms of radioresistance in CRC. METHODS: Weighted gene co-expression network analysis was used to identify potential radiation-related genes. Colony formation and comet assays and multi-target single-hit survival and xenograft animal models were used to validate the results obtained from the bioinformatic analysis. Immunohistochemistry was performed to examine the clinical characteristics of ALDH1L2. Co-immunoprecipitation, immunofluorescence and flow cytometry were used to understand the molecular mechanisms underlying radioresistance. RESULTS: Bioinformatic analysis, in vitro, and in vivo experiments revealed that ALDH1L2 is a radiation-related gene, and a decrease in its expression induces radioresistance in CRC cells by inhibiting ROS-mediated apoptosis. Patients with low ALDH1L2 expression exhibit resistance to radiotherapy. Mechanistically, ALDH1L2 interacts with thioredoxin (TXN) and regulates the downstream NF-κB signaling pathway. PX-12, the TXN inhibitor, overcomes radioresistance due to decreased ALDH1L2. CONCLUSIONS: Our results provide valuable insights into the potential role of ALDH1L2 in CRC radiotherapy. We propose that the simultaneous application of TXN inhibitors and radiotherapy would significantly ameliorate the clinical outcomes of patients with CRC having low ALDH1L2.
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Neoplasias Colorretais , NF-kappa B , Animais , Apoptose , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Regulação Neoplásica da Expressão Gênica , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Tolerância a Radiação/genética , Transdução de Sinais , Tiorredoxinas/genética , Tiorredoxinas/metabolismo , Tiorredoxinas/uso terapêuticoRESUMO
Epithelial-mesenchymal transition (EMT) is a crucial process for cancer cells to acquire metastatic potential, which primarily causes death in gastric cancer (GC) patients. Bone morphogenetic protein 4 (BMP4) is a member of the TGF-ß family that plays an indispensable role in human cancers. However, little is known about its roles in GC metastasis. In this study, BMP4 was found to be frequently overexpressed in GC tissues and was correlated with poor patient's prognosis. BMP4 was upregulated in GC cell lines and promoted EMT and metastasis of GC cells both in vitro and in vivo, whereas knockdown of BMP4 significantly inhibited EMT and metastasis of GC cells. Furthermore, the inhibitor of DNA binding 1 (also known as DNA-binding protein inhibitor ID1) was identified as a downstream target of BMP4 using PCR arrays and was upregulated via SMAD1/5/8 phosphorylation. ID1 knockdown attenuated BMP4-induced EMT and invasion in GC cells. Moreover, ID1 overexpression in BMP4 knockdown cells restored the promotion of EMT and cell invasion. In summary, BMP4 induced EMT and promoted GC metastasis by upregulating ID1 expression. Antagonizing BMP4 could be a potential therapeutic strategy for GC metastasis.
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Transição Epitelial-Mesenquimal , Neoplasias Gástricas , Proteína Morfogenética Óssea 4/genética , Linhagem Celular Tumoral , Movimento Celular , Humanos , Proteína 1 Inibidora de Diferenciação/genética , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias Gástricas/genéticaRESUMO
Lysophosphatidic acid (LPA) is a common glycerol phospholipid and an important extracellular signaling molecule. LPA binds to its receptors and mediates a variety of biological effects, including the pathophysiological process underlying ischemic brain damage and traumatic brain injury. However, the molecular mechanisms mediating the pathological role of LPA are not clear. Here, we found that LPA activates cyclin-dependent kinase 5 (CDK5). CDK5 phosphorylates tau, which leads to neuronal cell death. Inhibition of LPA production or blocking its receptors reduced the abnormal activation of CDK5 and phosphorylation of tau, thus reversing the death of neurons. Our data indicate that the LPA-CDK5-Tau pathway plays an important role in the pathophysiological process after ischemic stroke. Inhibiting the LPA pathway may be a potential therapeutic target for treating ischemic brain injury.
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Quinase 5 Dependente de Ciclina , Proteínas tau , Quinase 5 Dependente de Ciclina/metabolismo , Quinase 5 Dependente de Ciclina/farmacologia , Humanos , Isquemia , Lisofosfolipídeos , Neurônios , Reperfusão , Proteínas tau/metabolismoRESUMO
Magnetic resonance imaging (MRI) has become one of the most important medical imaging techniques in the clinic due to its high degree of soft tissue resolution and no radiation damage, and it plays an important role in the early diagnosis and treatment of tumors. This article mainly studies the analysis of no-reflow in patients with acute ST-segment elevation myocardial infarction after PCI and the effect of coronary nicorandil on CoO nanoparticles combined with MRI. In this paper, the synthesized water-soluble nanoparticles are dispersed in a 2% xanthan gum or agarose solution. In an MRI analyzer, the T1 value is tested with the inversion recovery sequence, and the T2 value is tested with the hard pulse CPMG sequence. The gyroscope imaging sequence performs T1-weighted and T2-weighted imaging tests. Calculated densitometry (QCA) was used to measure the stenosis of the coronary lesions, the length of the lesions and the diameter of the lumen before stent implantation. In order to facilitate the collection of urine samples, this article adopts the method of inserting a catheter to drain the patient for sampling. From the baseline state at the time of enrollment to 150 minutes after PCI, polyethylene containing 0.1% butylated hydroxyanisole is used. Urine samples were taken from the test tube every 30 minutes, a total of 6 times were collected, and the collected urine samples were stored in a low-temperature refrigerator at -80â for the final inspection. This paper uses calculation software to calculate the risk of death and death/myocardial infarction in the hospital and at 6 months after discharge. The data showed that the postoperatively detected CKMB and cTnI were higher than those before the operation, but the peak value of the nicorandil group was lower than that of the control group, but there was still no statistical difference (P>0.05). The results show that nicorandil can significantly improve the no-reflow phenomenon in AMI patients during PCI.
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Infarto do Miocárdio , Nanopartículas , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Arritmias Cardíacas , Humanos , Imageamento por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/tratamento farmacológico , Nicorandil/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Resultado do TratamentoRESUMO
We conduct a molecular study on the structural chirality in Langmuir monolayers composed of dipalmitoylphosphatidylcholine (DPPC) using in situ nonlinear optical spectroscopies, including second harmonic generation (SHG) and sum frequency generation (SFG). Chiral SHG response is observed from L-DPPC monolayers at moderate surface pressures and almost vanishes at a high surface pressure. SFG spectra of L-DPPC monolayers show chiral features that can be assigned to the terminal CH3 groups and the CH2 groups attached to the chiral center atom. This means that these achiral moieties form chiral superstructures at the interface. Along with increasing surface pressure, the structural chirality of CH3 groups shows a similar trend as that of chiral SHG, but CH2 chirality increases monotonically. Furthermore, in a racemic DPPC monolayer with a moderate surface pressure, both chiral SHG and chiral SFG of CH3 groups are absent, whereas chiral SFG of CH2 groups is clearly present, indicating that L- and D-DPPC are diastereomers at the air/water interface and interfacial CH2 prefers a certain orientation regardless of the molecular handedness. A molecular mechanism is proposed to explain the origin of the structural chirality in DPPC monolayers.
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Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder manifested in hepatic fat accumulation (hepatic steatosis) in the absence of heavy alcohol use. NAFLD consists of four major stages ranging from simple steatosis or non-alcoholic fatty liver (NAFL) to more advanced stages, non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. NFLAD may further advance to hepatocellular carcinoma (HCC). Primary causes of NAFLD are obesity and obesity-associated insulin resistance (IR). As a result of the obesity pandemic, NAFLD has become one of the most common liver disorders worldwide and both the incidence and mortality rate of HCC that develops from NAFLD are increasing steadily. As treatment options are not available for advanced NAFLD, a better understanding of the molecular mechanisms for NAFLD development and progression is urgently needed. Emerging evidence suggests that dysregulation of the metabolism of sphingolipids contributes to development and progression of NAFLD and NAFLD-associated HCC. The present chapter summarizes roles of bioactive sphingolipids, ceramides, sphingosine, and sphingosine-1-phosphate (S1P) and their metabolizing enzymes in NAFLD and HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Carcinoma Hepatocelular/patologia , Ceramidas , Progressão da Doença , Fibrose , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/patologia , Esfingolipídeos/metabolismoRESUMO
OBJECTIVE: To investigate the effects of sacubitril/valsartan (S/V) on cardiopulmonary function and blood pressure response to exercise during hospitalization in patients with acute myocardial infarction (AMI) based on the cardiopulmonary exercise test (CPET). METHODS: A total of 265 AMI patients were treated with either perindopril or S/V within 24 hours of admission. CPET was completed for all patients before discharge. There were 182 cases in the perindopril group and 83 cases in the S/V group. RESULTS: The proportion of exercise oscillatory ventilation (EOV) was higher in the S/V group than in the perindopril group (10.8% vs 1.6%, X2 = 11.148, P = .001). The resting heart rate (HR), resting diastolic blood pressure (DBP), and warm-up DBP were lower in the S/V group than in the perindopril group (P < .05). The resting systolic blood pressure (SBP) was 9.0 mmHg lower (115.7 ± 17.5 vs 106.7 ± 15.0, P < .001), the SBP during warm-up was 9.5 mmHg lower (124.8 ± 23.7 vs 115.3 ± 22.5,P = .002), the SBP at the anaerobic threshold (AT) was 10.5 mmHg lower (135.3 ± 24.8 vs 127.1 ± 25.1,P = .021),the SBP at max watts was 11.5 mmHg lower (148.9 ± 26.4 vs 137.4 ± 26.4,P = .001), and the SBP during one-minute recovery was 12.3 mmHg lower (146.5 ± 27.1 vs 134.2 ± 24.4, P = .001)in the S/V group than in the perindopril group. The S/V group had a higher oxygen ventilation equivalent and carbon dioxide ventilation equivalent (VE/VCO2) at AT and a lower oxygen uptake-work rate relationship during max watts (P < .05). The differences in the oxygen pulse, stroke volume, peak oxygen uptake (VO2 peak), and VE/VCO2 slope were not statistically significant between the two groups. CONCLUSION: Treatment with S/V was able to reduce the exercise blood pressure in patients with AMI during hospitalization, but did not significantly improve the VO2 peak, VE/VCO2 slope, or exercise tolerance.