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BACKGROUND: Stress hyperglycemia and glycemic variability (GV) can reflect dramatic increases and acute fluctuations in blood glucose, which are associated with adverse cardiovascular events. This study aimed to explore whether the combined assessment of the stress hyperglycemia ratio (SHR) and GV provides additional information for prognostic prediction in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU). METHODS: Patients diagnosed with CAD from the Medical Information Mart for Intensive Care-IV database (version 2.2) between 2008 and 2019 were retrospectively included in the analysis. The primary endpoint was 1-year mortality, and the secondary endpoint was in-hospital mortality. Levels of SHR and GV were stratified into tertiles, with the highest tertile classified as high and the lower two tertiles classified as low. The associations of SHR, GV, and their combination with mortality were determined by logistic and Cox regression analyses. RESULTS: A total of 2789 patients were included, with a mean age of 69.6 years, and 30.1% were female. Overall, 138 (4.9%) patients died in the hospital, and 404 (14.5%) patients died at 1 year. The combination of SHR and GV was superior to SHR (in-hospital mortality: 0.710 vs. 0.689, p = 0.012; 1-year mortality: 0.644 vs. 0.615, p = 0.007) and GV (in-hospital mortality: 0.710 vs. 0.632, p = 0.004; 1-year mortality: 0.644 vs. 0.603, p < 0.001) alone for predicting mortality in the receiver operating characteristic analysis. In addition, nondiabetic patients with high SHR levels and high GV were associated with the greatest risk of both in-hospital mortality (odds ratio [OR] = 10.831, 95% confidence interval [CI] 4.494-26.105) and 1-year mortality (hazard ratio [HR] = 5.830, 95% CI 3.175-10.702). However, in the diabetic population, the highest risk of in-hospital mortality (OR = 4.221, 95% CI 1.542-11.558) and 1-year mortality (HR = 2.013, 95% CI 1.224-3.311) was observed in patients with high SHR levels but low GV. CONCLUSIONS: The simultaneous evaluation of SHR and GV provides more information for risk stratification and prognostic prediction than SHR and GV alone, contributing to developing individualized strategies for glucose management in patients with CAD admitted to the ICU.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Hiperglucemia , Humanos , Femenino , Anciano , Masculino , Enfermedad de la Arteria Coronaria/diagnóstico , Estudios Retrospectivos , Glucemia/análisis , Factores de RiesgoRESUMEN
In our research on naturally occurring sesquiterpenes, eight shizukaol-type dimers, one chlorahololide-type dimer, and one sarcanolide-type dimer were isolated from the roots of Chloranthus fortunei. As the project was implemented, we accidentally discovered that shizukaol-type dimers can be converted into peroxidized chlorahololide-type dimers. This potential change was discovered after simulations of the changes in corresponding shizukaols showed that three peroxide products were generated (1-3), indicating that peroxidation reactions occurred. HPLC-HR-MS analysis results obtained for the shizukaol derivatives further demonstrate that the reaction occurred, and the type of substituent of small organic ester moieties at positions C-15' and C-13' of unit B were not decisively related to the reaction. Quantum chemical calculations of the mode dimer further demonstrated this phenomenon. The highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy of the precursor and production revealed the advantageous yield of 4ß-hydroperoxyl production. Additionally, the potential reaction mechanism was speculated and validated using the free energy in the reaction which successfully explained the feasibility of the reaction. Finally, the anti-inflammatory activity of the precursors and products was evaluated, and the products of peroxidation showed better anti-inflammatory activity.
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Artefactos , Sesquiterpenos , Antiinflamatorios/farmacología , Sesquiterpenos/químicaRESUMEN
Helicity-resolved Raman spectroscopy (HRRS) can effectively distinguish the Raman modes of two-dimensional (2D) layered materials by phonon symmetry. In this paper, we systematically investigated the phonon helicity selection of basal and edge planes of MoS2 bulk by HRRS. We find that the symmetry of the crystal structure changes the helicity selection of the E1g, E1 2g, and A1g modes in the edge plane. The theoretical calculation results confirm that the E1 2g and A1g modes of the basal plane exhibit a perfect helicity exchange, and the helicity selections of the E1 2g and A1g modes of the edge plane are eliminated or weakened. Our study provides references for phonon helicity selection of 2D layered materials represented by MoS2.
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Prolamins, proteins derived from plants, have extensive applications in pharmaceutics and food science. Jiuzao is a byproduct of the Baijiu brewing industry, and is a great source of prolamin. Despite its importance, knowledge regarding the extraction techniques and the properties of prolamin derived from Baijiu Jiuzao (PBJ) remains limited. Reverse micelles (RMs) extraction offers an efficient and cost-effective method for purifying proteins. In the present study, prolamin was extracted from Baijiu Jiuzao using RMs extraction and subsequently characterized in terms of its secondary structure, morphology, and particle size distribution. Our findings indicate that the purified prolamin extracted using further RMs extraction possessed higher α-helix content (+13.25%), forming a large-scale protein network, and narrower particle size distributions compared to the crude prolamin obtained by NaOH-ethanol method. This research suggests that RMs extraction has potential applications in extracting prolamin from brewing industry byproducts, offering an environmentally friendly approach to Baijiu Jiuzao recycling.
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Liver fibrosis scores have been demonstrated to be associated with poor prognosis after percutaneous coronary intervention (PCI). However, no studies have compared the prognostic value of these scores in acute myocardial infarction (AMI) patients with and without diabetes. We retrospectively enrolled 1576 AMI patients who underwent PCI. There were 177 all-cause deaths and 111 cardiac deaths during follow-up (median 3.8 years). The non-alcoholic fatty liver disease fibrosis score (NFS) showed a better prognostic value than the fibrosis-8 (FIB-8) score (Harrell's C-index: 0.703 vs 0.671, P = .014) and the fibrosis-4 (FIB-4) score (Harrell's C-index: 0.703 vs 0.648, P < .001) in the overall population. In the time-dependent receiver operating characteristic analysis, the NFS also had the highest area under the curve across all time points. Consistent results were observed in diabetic and non-diabetic populations. Adding the NFS to traditional cardiovascular risk factors significantly improved the prediction both for all-cause mortality (Harrell's C-index: 0.806 vs 0.771, P < .001) and cardiac death (Harrell's C-index: 0.800 vs 0.771, P = .014). The NFS showed a better prognostic value than the FIB-8 score and the FIB-4 score in patients with AMI undergoing PCI, which might be preferable for estimating the risk of mortality regardless of the presence or absence of diabetes.
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Diabetes Mellitus Tipo 2 , Infarto del Miocardio , Enfermedad del Hígado Graso no Alcohólico , Intervención Coronaria Percutánea , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Pronóstico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Estudios Retrospectivos , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapiaRESUMEN
AIMS: The stress hyperglycemia ratio (SHR) is significantly associated with short-term adverse cardiovascular events. However, the association between SHR and mortality after the acute phase of acute coronary syndrome (ACS) remains controversial. METHODS: This study used data from the Medical Information Mart for Intensive Care-IV database. Patients with ACS hospitalized in the intensive care unit (ICU) were retrospectively enrolled. RESULTS: A total of 2668 ACS patients were enrolled. The incidence of in-hospital and 1-year mortality was 4.7 % and 13.2 %, respectively. The maximum SHR had a higher prognostic value for predicting both in-hospital and 1-year mortality than the first SHR. Adding the maximum SHR to the SOFA score could significantly improve the prognostic prediction. In the landmark analysis at 30 days, the maximum SHR was a risk factor for mortality within 30 days regardless of whether patients had diabetes. However, it was no longer associated with mortality after 30 days in patients with diabetes after adjustment (HR = 1.237 per 1-point increment, 95 % CI 0.854-1.790). CONCLUSIONS: The maximum SHR was significantly associated with mortality in patients with ACS hospitalized in the ICU. However, caution is warranted if it is used for predicting mortality after 30 days in patients with diabetes.
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Síndrome Coronario Agudo , Diabetes Mellitus , Hiperglucemia , Humanos , Estudios Retrospectivos , Síndrome Coronario Agudo/complicaciones , Hiperglucemia/complicaciones , Hospitalización , PronósticoRESUMEN
AIMS: Variability of metabolic parameters, such as glycemic variability (GV) and systolic blood pressure variability (SBPV), are associated with adverse cardiovascular outcomes. However, whether these parameters have additive effects on mortality in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU) remains unclear. METHODS: We retrospectively enrolled patients with CAD from the Medical Information Mart for Intensive Care-IV database. The highest tertile of variability was defined as high variability. A variability scoring system was established, which assigned 0 points to tertile 1, 1 point to tertile 2, and 2 points to tertile 3 for GV and SBPV. RESULTS: Among 4237 patients with CAD, 400 patients died in hospital, and 967 patients died during 1-year follow-up. High GV and high SBPV were associated with an increased risk of mortality. The effects of GV and SBPV on in-hospital mortality were partially mediated by ventricular arrhythmias (18.0 % and 6.6 %, respectively). The risk of mortality gradually increased with the number of high-variability parameters and increasing variability scores. CONCLUSIONS: GV and SBPV have additive effects on the risk of mortality in patients with CAD hospitalized in the ICU. Ventricular arrhythmias partially mediate the effects of GV and SBPV on in-hospital mortality.
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Enfermedad de la Arteria Coronaria , Humanos , Enfermedad de la Arteria Coronaria/complicaciones , Presión Sanguínea/fisiología , Glucemia , Estudios Retrospectivos , Mortalidad HospitalariaRESUMEN
BACKGROUND: The Age-D-dimer-Albumin (ADA), the CREDO-Kyoto, and the PARIS scores have been established to predict thrombotic events. However, the prognostic performance of these scores compared to the GRACE score in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) has not been reported. METHODS: Consecutive AMI patients treated with PCI were retrospectively enrolled at a teaching hospital in China from January 2016 to December 2019. The primary endpoint was all-cause mortality and the secondary endpoint was cardiac death. Harrell's C-index and net reclassification improvement (NRI) were used to compare the prognostic value of these scores with the GRACE score for mortality. RESULTS: Of the 1,578 patients enrolled, the mean age was 62.5 years, and 23.5% were female. During a median follow-up of 3.8 years, 146 all-cause deaths and 80 cardiac deaths occurred. The ADA score showed a better prognostic performance than the GRACE (Harrell's C-index: 0.800 vs. 0.749; p = 0.003), the CREDO-Kyoto (Harrell's C-index: 0.800 vs. 0.765; NRI = 0.348, p < 0.001), and the PARIS scores (Harrell's C-index: 0.800 vs. 0.694; NRI = 0.556, p < 0.001). In the multivariable Cox regression analysis, the ADA score was independently associated with all-cause mortality (hazard ratio [HR] = 1.641 per 10-point increment, 95% confidence interval [CI]: 1.397-1.929) and cardiac death (HR = 1.636 per 10-point increment, 95% CI: 1.325-2.020). The risk of all-cause mortality and cardiac death increased with the rising of the ADA score. CONCLUSION: The ADA score showed a better prognostic performance than the GRACE, the CREDO-Kyoto, and the PARIS scores in patients with AMI undergoing PCI, which was a potential predictive tool for mortality.
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Síndrome Coronario Agudo , Productos de Degradación de Fibrina-Fibrinógeno , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Femenino , Persona de Mediana Edad , Masculino , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Infarto del Miocardio/etiología , Muerte , Síndrome Coronario Agudo/terapiaRESUMEN
The total partition function was calculated for carbon monoxide with approximation. Using the dipole moment function and the wave function with Morse approximation, we computed the matrix elements of vibrational-rotational transition and absorption coefficient at normal and high temperature. The computed results agreed with the HITRAN database and literature, which shows that the calculation of total partition function and matrix elements of vibrational-rotational transition is reliable. Furthermore, the absorption coefficient and radiant spectrum are also presented at higher temperature of 4 000 and 6 000 K.
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Eleven previously unreported compounds (1-11), including five diterpenoids (1-5) and six sesquiterpenoids (6-11), together with two known diterpenoids (12-13), have been isolated from the roots of Salvia prattii. Their structures were comprehensively elucidated through spectroscopic methods, and their configurations were established using computational 13C nuclear magnetic resonance and electronic circular dichroism. Compound 1 was found to be an abietane-type diterpenoid with a novel rearrangement generated from the cleavage of the C-4/5 chemical bond, 20-methyl shift, and the rearrangement of the C-10 side chain. Compounds 2-3 were the third and fourth examples of arrangement seco-norabietanes with a spiro-lactone ring. We evaluated all compounds for their protective effects against alcoholic liver diseases (ALD). Compound 2 exhibited potential protective activity and hence can be used as a novel anti-ALD candidate.
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Diterpenos , Salvia , Terpenos/farmacología , Estructura Molecular , Salvia/química , Diterpenos/farmacología , Diterpenos/química , Abietanos/farmacología , Abietanos/químicaRESUMEN
Many studies have proven that autophagy plays a pivotal role in the development of depression and it also affects the expression of GLUT4 in the hypothalamus. Xiaoyaosan has been shown to exert antidepressant effects in a variety of ways, but its underlying mechanism by which Xiaoyaosan regulates autophagy as well as GLUT4 in the hypothalamus remains unclear. Thus, in this study, we established a mouse model of depression induced by chronic unpredictable mild stress (CUMS), and set up autophagy blockade as a control to explore whether Xiaoyaosan exerts antidepressant effect by affecting autophagy. We examined the effects of Xiaoyaosan on behaviors exhibited during the open field test, tail suspension test and sucrose preference test, and the changes in autophagy in hypothalamic neurons as well as changes in GLUT4 and the related indicators of glucose metabolism in CUMS-induced depressive mouse model. We found that CUMS- and 3-MA-induced mice exhibited depressive-like behavioral changes, with decreased LC3 expression and increased p62 expression, suggesting decreased levels of autophagy in the mouse hypothalamus. The expression of GLUT4 was also decreased, and it was closely related to the level of autophagy through Rab8 and Rab10. Nevertheless, after the intervention of Xiaoyaosan, the above changes were effectively reversed. These results show that Xiaoyaosan can regulate the autophagy in hypothalamic neurons and the expression of GLUT4 in depressed mice.
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BACKGROUND: Dahuang Zhechong pill (DHZCP) improves the inhibitory immune status of mice with hepatocellular carcinoma (HCC) by regulating Treg/Th1 balance. HYPOTHESIS/PURPOSE: To study the multi-material basis and multi-mechanisms of DHZCP against HCC by regulating Treg/Th1 balance in vitro and in vivo. METHODS: UPLC-MS/MS was used to detect the dynamic changes in 29 characteristic components of different polar parts of DHZCP. H&E and TUNEL were used to check pathological condition in HCC mice. The number of CD4+T, CD8+T, Treg, Th1, and Th1-like Treg cells was counted by flow cytometry. TGF-ß, IL-10, IFN-γ, and TNF-α content were detected by ELISA. α-Ketoglutarate and glutamine levels were detected by Trace1310/TSQ8000 GC-MS/MS. p-Smad2, and p-Smad3 protein levels were detected by WB, mRNA expression of Smad2, alanine-serine-cysteine transporter-2, glutaminase, and glutamate dehydrogenase were detected by RT-PCR. Simca-p multivariate data analysis software was used to evaluate the relationship between the different polar parts of DHZCP and the proportion of Treg cells. RESULTS: Water-soluble (PW) and ethyl acetate (PE) polar parts of DHZCP affected the HCC immune system by inhibiting the differentiation of Tregs, reversing the balance of Treg/Th1, and significantly reduced the tumor volume and weight. However, petroleum ether and n-butanol polar parts had no above actions. The changes in emodin, chrysophanol, aloe vera emodin, emodin-8-O-ß-D-glycoside, gallic acid, naringenin, baicalein, wogonin, norwogonin, apigenin, chrysin, glycyrrhizin, formononetin, and palmitic acid were closely related to the changes of Treg cells, which is the main material basis of DHZCP inhibition of Treg differentiation. Additionally, PW mainly inhibit the differentiation of Treg cells by affecting the metabolism of hepatoma cells, improving tumor microenvironment acidity, and glutamine depletion. However, PE inhibited the differentiation of Treg cells mainly by regulating the TGF-ß/Smad pathway. CONCLUSION: In this study, accurate analysis of multi-component was combined with pharmacodynamic evaluations to identify the pharmacodynamic substances of DHZCP in regulating Treg/Th1 balance, and clarified the multi-target mechanism of DHZCP to improve tumor immunity. The study style offers a novel approach for pharmacological research on TCM.
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Carcinoma Hepatocelular , Emodina , Neoplasias Hepáticas , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Medicamentos Herbarios Chinos , Glutamina , Neoplasias Hepáticas/tratamiento farmacológico , Ratones , Linfocitos T Reguladores , Espectrometría de Masas en Tándem , Factor de Crecimiento Transformador beta , Microambiente TumoralRESUMEN
Tracing the characters of very ancient proteins represents one of the biggest challenges in the study of origin of life. Although there are no primitive protein fossils remaining, the characters of very ancient proteins can be traced by molecular fossils embedded in modern proteins. In this paper, first the prior findings in this area are outlined and then a new strategy is proposed to address the intriguing issue. It is interesting to find that various molecular fossils and different protein datasets lead to similar conclusions on the features of very ancient proteins, which can be summarized as follows: (i) the architectures of very ancient proteins belong to the following folds: P-loop containing nucleoside triphosphate hydrolases (c.37), TIM beta/alpha-barrel (c.1), NAD(P)-binding Rossmann-fold domains (c.2), Ferredoxin-like (d.58), Flavodoxin-like (c.23) and Ribonuclease H-like motif (c.55); (ii) the functions of very ancient proteins are related to the metabolisms of purine, pyrimidine, porphyrin, chlorophyll and carbohydrates; (iii) a certain part of very ancient proteins need cofactors (such as ATP, NADH or NADPH) to work normally.
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Evolución Molecular , Variación Genética/genética , Modelos Genéticos , Origen de la Vida , Proteoma/química , Proteoma/genética , Factores de TiempoRESUMEN
@#Abstract: Objective To construct SARS-CoV-2 receptor binding domain molecular probe for monoclonal memory B cell sorting and obtain RBD specific neutralizing antibodies from peripheral blood mononuclear cells (PBMCs) of COVID-19 convalescents by single-cell sorting. Methods The SARS-CoV-2 RBD sequence was downloaded from GenBank, and the Avi tag and 6-histidine tags were added at the C-terminal. After codon optimization, it was chemically synthesized, cloned into the pDRVI1.0 vector, expressed after transfection of 293F cells, and biotinylated consequently. RBD-specific B cells were sorted out with this probe1 from the PBMCs of convalescents recovered from COVID-19. After B cells were lysed, the variable regions of heavy chain and light chain were amplified, cloned into the antibody expression vector, and transfected into 293F cells to express the antibody. Then the antibody was purified from the supernatant using protein A column and SARS-CoV-2 pseudovirus was used to test their neutralizing activity. Results RBD-Avi probe was produced and successfully biotinylated sequentially with an efficiency of 30%-50%. Western blot analysis revealed that the biotinylated probe was recognized by the antibodies purified from COVID-19 convalescent plasma. Using this probe, 7 and 16 RBD-specific memory B cells were successfully isolated from the PBMCs of two convalescent individuals, accounting for 0.24% and 0.17% of the total cell population, respectively. After amplifying the variable regions of antibody heavy and light chains from the lysed B cells, 7 and 12 pairs of antibody heavy-light chains were obtained. A total of 16 antibodies were expressed in the convalescent individuals, and most of the purified antibodies showed neutralizing activity against the pseudovirus, with IC50 values of 6 antibodies below 1 μg/mL. The IC50 values of XJ-A9 and SCF-F1 against the wild-type pseudovirus were 0.07 μg/mL and 0.35 μg/mL, respectively. Conclusion The SARS-CoV-2 RBD molecular probe constructed in this study has good antigenicity, and the isolated antibodies present neutralizing activity against wild-type SARS-CoV-2 pseudovirus.
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In this study, we decided to use low doses of memantine pretreatment to examine the roles of the immune function in cocaine-supported conditioning. Cocaine-induced conditioned place preference (CPP) was used to assess the hedonic value and/or reinforcing efficacy of cocaine and cocaine-supported conditioning. Systemic pretreatment with memantine (20, 2.0, 0.2, and 0.02 mg/kg/injection) 30 min before each cocaine and saline conditioning trial abolished the acquisition of cocaine-induced CPP in mice. Even a total of 0.12 mg/kg memantine pretreatment in three days was effective in diminishing cocaine-induced CPP. Three consecutive days of cocaine conditioning increased interleukin-6 (IL-6) but decreased tumor necrosis factor (TNF-α) levels in medial prefrontal cortex (mPFC) and nucleus accumbens (Acb). Interestingly, pretreatment with memantine at the lowest effective dose (0.02 mg/kg/injection) reversed cocaine conditioning-enhanced IL-6 and -decreased TNF-α levels in these brain regions. Nevertheless, such a memantine dosing regimen did not affect dopamine metabolism in mPFC and Acb. Single memantine (0.02 mg/kg) injection did not acutely affect mouse locomotor activity or cocaine-increased locomotor activity. Similar memantine dosing regimen was ineffective to affect the maintenance of cocaine-induced CPP. Finally, intra-mPFC infusion of recombinant IL-6, but not thalidomide, reversed memantine (0.02 mg/kg/injection × 6)-decreased cocaine-induced CPP. These results, taken together, suggest that cocaine conditioning-enhanced IL-6 in mPFC may be, in part, involved in the acquisition of cocaine-induced CPP. Moreover, an extremely low dose of memantine may decrease the acquisition of cocaine-induced CPP by reversing cocaine conditioning-increased IL-6 levels in mPFC.