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Lipid droplets (LDs) and lysosomes are vital organelles that play crucial roles in various physiological and pathological processes. However, simultaneous two-color visualization of these two organelles using a single probe for cell homeostasis monitoring remains a challenge due to the lack of rational design strategies. To address this issue, we have developed an aggregation-induced emission (AIE) fluorescent probe named TPE-NDI-Mor with an electron donor (D)-acceptor (A) structure, which can stain both LDs and lysosomes with high selectivity through green and red fluorescence imaging, respectively. A detailed mechanism study revealed that TPE-NDI-Mor, with a twisted intramolecular charge transfer (TICT) effect, shows a high affinity for a polar microenvironment. Additionally, the probe also demonstrates good stability, high anti-interference performance and a large Stokes shift, making it suitable for visualizing cell homeostasis and further disease diagnosis by tracking the dynamic changes of LDs and lysosomes.
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Recharging primary batteries is of great importance for increasing the energy density of energy storage systems to power electric aircraft and beyond. Carbon fluoride (CFx) cathodes are characterized by high specific capacity and energy density (865 mAh g-1 and 2180 Wh kg-1, respectively). Preventing the crystallization of LiF with an intermediate and lowering the energy barrier from LiF to CFx is expected to render the Li/CFx battery reversible. In this study, taking the advantage of a high-voltage-stable all-fluorinated electrolyte containing the boron-based anion receptor tris(trimethylsilyl)borate (TMSB), a rechargeable Li/CFx battery was realized with a reversible capacity of 465.9 mAh g-1 and an energy density of 1183.9 Wh kg-1, approximately 53% of that in the first discharge. After the first discharge, the charge-discharge profile featured rechargeable characteristics. In situ X-ray diffraction, ex situ soft X-ray absorption spectroscopy, pair distribution function analysis, and other measurements confirmed the generation and decomposition of Li-F and C-F bonds during cycling. Density functional theory calculations and nuclear magnetic resonance spectroscopy confirmed that TMSB serves as an anion carrier through the generation of a [TMSB-F]- complex, facilitating the conversion reactions during cycling. This study demonstrated a facile and low-cost approach for realizing high-energy-density, reversible Li/CFx batteries.
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Disinfection efficiency and disinfection byproduct (DBP) formation are two important aspects deserving careful consideration when evaluating different disinfection protocols. However, most of the previous studies on the selection of disinfection methods by comparing DBP formation were carried out under the same initial/residual dose and contact time of different disinfectants, and such a practice may cause overdose or underdose of a certain disinfectant, leading to the inaccurate evaluation of disinfection. In this study, a comprehensive and quantitative comparison of chlorine (Cl2) and chlorine dioxide (ClO2) disinfection was conducted with regard to their DBP formation under equal disinfection efficiency. The microbial inactivation models as well as the Cl2 and ClO2 demand models were developed. On such basis, the integral CT (ICT) values were determined and used as a bridge to connect disinfection efficiency and DBP formation. For 3-log10 and 4-log10 reductions of Pseudomonas aeruginosa, ClO2 had 1.5 and 5.8 times higher inactivation ability than Cl2, respectively. In the premise of equal disinfection efficiency (i.e., the ICT ratios of Cl2 to ClO2 = 1.5 and 5.8), the levels of total organic chlorine, total organic bromine, and total organic halogen formed in the Cl2 disinfection were significantly higher than those formed in the ClO2 disinfection. Among the 35 target aliphatic DBPs, trihalomethanes (THMs) and haloacetic acids (HAAs) were the dominant species formed in both Cl2 and ClO2 disinfection. The total THM levels formed in Cl2 disinfection were 14.6 and 30.3 times higher than those in ClO2 disinfection, respectively. The total HAA levels formed in Cl2 disinfection were 3.5 and 5.4 times higher than those in ClO2 disinfection, respectively. Formation of the target 48 aromatic DBPs was much favored in Cl2 disinfection than that in ClO2 disinfection, and the formation levels was dominated by contact time. This study demonstrated that ClO2 had significant advantages over Cl2, especially at higher microorganism inactivation and lower DBP formation requirements.
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Compuestos de Cloro , Cloro , Desinfectantes , Desinfección , Agua Potable , Óxidos , Purificación del Agua , Compuestos de Cloro/farmacología , Compuestos de Cloro/química , Óxidos/farmacología , Óxidos/química , Cloro/farmacología , Cloro/química , Desinfección/métodos , Desinfectantes/farmacología , Desinfectantes/química , Agua Potable/microbiología , Agua Potable/química , Pseudomonas aeruginosa/efectos de los fármacosRESUMEN
RATIONALE: Diffuse multivessel coronary artery spasm (DMV-CAS) was defined as a severe and reversible diffuse spasm occurring in more than 2 major coronary arteries, which is rare in clinical practice. Due to a wide lesion scope, DMV-CAS often occurs in the form of complications. It is not easy to be clinically diagnosed because it is too brief to be caught. Here, we report a rare case of spontaneous subtotal occlusion of 3 major coronary arteries induced by Vasalva action, which was confirmed in real-time by CAG. PATIENT CONCERNS: A 68-year-old man had sudden chest pain after forced defecation during hospitalization. The electrocardiogram showed transient ST segment elevation of the inferior wall lead, inversion of the anterior wall, and lateral wall leads T waves. Emergency CAG revealed elongated vessel beds in 3 coronary arteries and multiple diffuse stenosis, but none of the coronary arteries were completely occlusive. DIAGNOSES: Diagnoses of DMV-CAS were made based on CAG findings and postmedication response. INTERVENTIONS: Nitroglycerin was administered in the coronary arteries. The anti-vasospasm, antiplatelet aggregation and lipid-regulating drugs were administered orally. OUTCOMES: The patient was discharged on the 7th day with complete resolution of symptoms and normalization of the electrocardiography findings. No ischemic events occurred during a follow-up for 5 months. LESSONS: This case highlights the identification of multivessel diffuse coronary spasm and acute myocardial infarction, and the prevention of CAS triggers, which requires the attention of clinicians.
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Vasoespasmo Coronario , Infarto del Miocardio , Masculino , Humanos , Anciano , Vasos Coronarios/diagnóstico por imagen , Angiografía Coronaria/efectos adversos , Vasoespasmo Coronario/complicaciones , Vasoespasmo Coronario/diagnóstico , Infarto del Miocardio/complicaciones , Nitroglicerina/uso terapéutico , Electrocardiografía , Arritmias Cardíacas/tratamiento farmacológicoRESUMEN
Photocatalytic oxidation desulfurization (PODS) has emerged as a promising, ecofriendly alternative to traditional, energy-intensive fuel desulfurization methods. Nevertheless, its progress is still hindered due to the slow sulfide oxidation kinetics in the current catalytic systems. Herein, we present a MoOx decorated on a Cu2O@CuO core-shell catalyst, which enables a new, efficient PODS pathway by in situ generation of hydrogen peroxide (H2O2) with saturated moist air as the oxidant source. The photocatalyst delivers remarkable specific activity in oxidizing dibenzothiophene (DBT), achieving a superior rate of 7.8 mmol g-1 h-1, while maintaining a consistent performance across consecutive reuses. Experimental investigations reveal that H2O2 is produced through the two-electron oxygen reduction reaction (ORR), and both H2O2 and the hydroxyl radicals (â¢OH) generated from it act as the primary reactive species responsible for sulfide oxidation. Importantly, our catalyst accomplishes complete PODS of real diesel fuel, underscoring an appealing industrial prospect for our photocatalyst.
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Sequential recommendation uses contrastive learning to randomly augment user sequences and alleviate the data sparsity problem. However, there is no guarantee that the augmented positive or negative views remain semantically similar. To address this issue, we propose graph neural network-guided contrastive learning for sequential recommendation (GC4SRec). The guided process employs graph neural networks to obtain user embeddings, an encoder to determine the importance score of each item, and various data augmentation methods to construct a contrast view based on the importance score. Experimental validation is conducted on three publicly available datasets, and the experimental results demonstrate that GC4SRec improves the hit rate and normalized discounted cumulative gain metrics by 1.4% and 1.7%, respectively. The model can enhance recommendation performance and mitigate the data sparsity problem.
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Benchmarking , Aprendizaje , Redes Neurales de la ComputaciónRESUMEN
BACKGROUND: Heat shock protein 90 (HSP90) appears to have a pivotal function in ischemic preconditioning. Pioglitazone preconditioning (PioC) attenuates myocardial ischemia/reperfusion (I/R) injuries. OBJECTIVES: The current study aims to investigate the role of HSP90, complement C3 and C5a, and nuclear factor kappa-B (NF-κB) in PioC-induced cardioprotection. MATERIAL AND METHODS: A total of 80 rats were randomly categorized into 4 groups, as follows: sham, I/R, PioC, and PioC+HSP90 inhibitor geldanamycin (PioC+GA). The sham group rats had a thoracotomy, in which the ligature was passed by the heart with no ligation (150 min). The other 3 groups were exposed to ischemia (30 min) followed by reperfusion (2 h). In the PioC group, pioglitazone (3 mg/kg) was administered intravenously 24 h before ischemia. In the PioC+GA group, after being pretreated with pioglitazone, GA was administered (intraperitoneally, 1 mg/kg) 30 min before ischemia. Myocardial infarct sizes (ISs), apoptosis rates, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin I (cTnI) serum levels were determined. The HSP90, C3, NF-κB, C5a, B-cell lymphoma-2 (Bcl-2), and Bax expression levels, as well as interleukin (IL)-1ß, IL-6, intercellular cell adhesion molecule-1 (ICAM-1), and tumor necrosis factor alpha (TNF-α) mRNA levels were measured. RESULTS: The myocardial ISs, serum CK-MB, cTnI and LDH levels, apoptosis rates, IL-1ß, IL-6, TNF-α, ICAM-1 release, as well as Bax, C5a, C3, and NF-κB protein expression were considerably lower in the PioC group than in the I/R group (p < 0.05). The Bcl-2 and HSP90 expression was higher in the PioC group than in the I/R group (p < 0.05). Geldanamycin inhibited the effects of PioC. These data strongly demonstrate that the PioC-induced is dependent upon HSP90 activity. CONCLUSIONS: The HSP90 is indispensable for PioC-mediated cardioprotection. The HSP90 attenuates I/R-induced ISs, apoptosis of cardiomyocytes and myocardial inflammation through C3, C5a and NF-κB activation inhibition.
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Infarto del Miocardio , Daño por Reperfusión Miocárdica , Animales , Ratas , Proteína X Asociada a bcl-2/metabolismo , Activación de Complemento , Proteínas de Choque Térmico , Molécula 1 de Adhesión Intercelular , Interleucina-1beta , Interleucina-6/metabolismo , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/patología , FN-kappa B/metabolismo , Pioglitazona/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The flexibility of the joint drive system of an industrial robot can cause vibration at the end part, which can lead to motion errors. A method to predict the vibration during the motion of the robot arm is proposed considering the robot joint flexibility. The method combines the internal transfer function of the drive system and the identification of parameters under external excitation. Firstly, the dynamics of the robot joint system are modeled by a double inertia elastic system. The joint system transfer function from the electromagnetic torque to the arm vibration is obtained according to the dynamics model. To solve the unknown parameters in the transfer function, a vibration dynamics model of the joint arm under the external forces on the arm is developed. According to this model, the equivalent stiffness, damping and load inertia of the joint can be obtained by the direct parametric method. Then, the vibration spectrum of the robot arm is derived from the motor electromagnetic torque and joint dynamics models were used to predict the vibration spectrum of the robot arm. The experiments were conducted on a single-joint robot testbed, and on an articulated industrial robot. In both experiments, the key parameters in the system were determined by impact experiments. Then, the vibration signal of the arm during the robot motion was obtained by electromagnetic torque prediction. The predicted vibration signals are analyzed in comparison with the actual vibration signals. The experimental results both show the validity of the vibration prediction.
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Procedimientos Quirúrgicos Robotizados , Vibración , Movimiento , Rango del Movimiento Articular , TorqueRESUMEN
How the ocean circulation changes in a warming climate is an important but poorly understood problem. Using a global ocean model, we decompose the problem into distinct responses to changes in sea surface temperature, salinity, and wind. Our results show that the surface warming effect, a robust feature of anthropogenic climate change, dominates and accelerates the upper ocean currents in 77% of the global ocean. Specifically, the increased vertical stratification intensifies the upper subtropical gyres and equatorial currents by shoaling these systems, while the differential warming between the Southern Ocean upwelling zone and the region to the north accelerates surface zonal currents in the Southern Ocean. In comparison, the wind stress and surface salinity changes affect regional current systems. Our study points a way forward for investigating ocean circulation change and evaluating the uncertainty.
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OBJECTIVE: We previously showed that HSP90 is involved in postconditioning cardioprotection by inhibiting complement C5a. Here, we investigated whether HSP90-mediated C5a/NF-κB inhibition is responsible for the cardioprotection conferred by liraglutide. METHODS: Rat hearts underwent a 30 min occlusion of the anterior descending coronary artery, after which reperfusion was performed for 2 h. A total of 100 rats were randomly assigned to the following groups: ischemia/reperfusion (I/R), sham, liraglutide preconditioning (LP, liraglutide, 0.18 mg/kg, intravenously, 12 h before ischemia), HSP90 inhibitor geldanamycin (GA, 1 mg/kg, intraperitoneally, 30 min before ischemia) plus LP, and C5a receptor antagonist PMX53 (1 mg/kg, intravenously, 30 min before ischemia) plus LP. Cardiac injury, C5a/NF-κB activation, and inflammation were investigated. RESULTS: LP significantly attenuated I/R-induced cardiomyocyte apoptosis, infarct size, and secretion of creatine kinase-MB, lactate dehydrogenase and cardiac troponin I. These effects were complemented by decreased C5a levels, nuclear factor (NF)-κB signaling, inflammatory cytokine expression, and increased HSP90 levels. GA, an HSP90 inhibitor, promotes C5a activation, NF-κB signaling, and inflammation and suppresses cardioprotection by LP. By contrast, PMX53, a C5a inhibitor, suppressed C5a activation, NF-κB signaling, and inflammation, and enhanced cardioprotection by LP. CONCLUSION: HSP90 markedly contributes to LP cardioprotection by inhibiting inflammatory responsesand C5a/NF-κB signaling , ultimately attenuating I/R-induced cardiomyocyte apoptosis by suppressing the proapoptotic factor Bax, and inducing the anti-apoptotic factor Bcl2.
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Liraglutida , FN-kappa B , Animales , Inflamación , Liraglutida/farmacología , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
The design of the light-weight infill structure is a hot research topic in additive manufacturing. In recent years, various infill structures have been proposed to reduce the amount of printing material. However, 3D models filled with them may have very different structural performances under different loading conditions. In addition, most of them are not self-supporting. To mitigate these issues, a novel light-weight infill structure based on the layer construction is proposed in this article. The layers of the proposed infill structure continuously and periodically transform between triangles and hexagons. The geometries of two adjacent layers are controlled to be self-supporting for different 3D printing technologies. The machine code (Gcode) of the filled 3D model is generated in the construction of the infill structure for 3D printers. That means 3D models filled with the proposed infill structure do not need an extra slicing process before printing, which is time consuming in some cases. Structural simulations and physical experiments demonstrate that our infill structure has comparable structural performance under different loading conditions. Furthermore, the relationship between the structural stiffness and the parameters of the infill structure is investigated, which will be helpful for non-professional users.
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BACKGROUND: Activation of the complement component 5a (C5a) and nuclear factor κB (NF-κB) signaling is an important feature of myocardial ischemia/reperfusion (I/R) injury and recent studies show that morphine postconditioning (MP) attenuates the myocardial injury. However, the mediating cardioprotective mechanisms remain unclear. The present study explores the role and interaction of heat shock protein 90 (HSP90), Akt, C5a, and NF-κB in MP-induced cardioprotection. METHODS: Male Sprague Dawley rats (n = 160) were randomized into eight groups (n = 20 per group). Rats in the sham group underwent thoracotomy, passing the ligature through the heart but without tying it (150 min), and the other seven groups were subjected to 30 min of anterior descending coronary artery occlusion followed by 2 h of reperfusion and the following treatments: I/R (30 min of ischemia and followed by 2 h of reperfusion); ischemic postconditioning (IPostC, 30 s of ischemia altered with 30 s of reperfusion, repeated for three cycles, and followed by reperfusion for 2 h); MP (0.3 mg/kg morphine administration 10 min before reperfusion); MP combined with the HSP90 inhibitor geldanamycin (GA, 1 mg/kg); MP combined with the Akt inhibitor GSK-690693 (GSK, 20 mg/kg); and MP combined with the C5a inhibitor PMX205 (PMX, 1 mg/kg/day, administration via drinking water for 28 days) and MP combined with the NF-κB inhibitor EVP4593 (QNZ, 1 mg/kg). All inhibitors were administered 10 min before morphine and followed by 2 h reperfusion. RESULTS: MP significantly reduced the I/R-induced infarct size, the apoptosis, and the release of cardiac troponin I, lactate dehydrogenase (LDH), and creatine kinase-MB. These beneficial effects were accompanied by increased expression of HSP90 and p-Akt, and decreased expression of C5a, NF-κB, tumor necrosis factor α, interleukin-1ß, and intercellular cell adhesion molecule 1. However, HSP90 inhibitor GA or Akt inhibitor GSK increased the expression of C5a and NF-κB and prevented MP-induced cardioprotection. Furthermore, GA inhibited the MP-induced upregulation of p-Akt, while GSK did not affect HSP90, indicating that p-Akt acts downstream of HSP90 in MP-induced cardioprotection. In addition, C5a inhibitor PMX enhanced the MP-induced downregulation of NF-κB, while NF-κB inhibitor QNZ had no effect on C5a, indicating that the C5a/NF-κB signaling pathway is involved in MP-induced cardioprotection. CONCLUSION: HSP90 is critical for MP-mediated cardioprotection possibly by promoting the phosphorylation of Akt and inhibiting the activation of C5a and NF-κB signaling and the subsequent myocardial inflammation, ultimately attenuating the infarct size and cardiomyocyte apoptosis.
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Important state parameters, such as torque and angle obtained from the servo control and drive system, can reflect the operating condition of the equipment. However, there are two problems with the information obtained through the network from the control and drive system: the low sampling rate, which does not meet the sampling theorem and the nonuniformity of the sampling points. By combing equivalent sampling and nonuniform signal reconstruction theory, this paper proposes a reconstruction method for signal obtained from servo system in periodic reciprocating motion. Equivalent sampling combines the low rate and nonuniform samples from multiple periods into one single period, so that the equivalent sampling rate is far increased. Then, the nonuniform samples with high density are further resampled to meet the reconstruction conditions. This step can avoid the amplitude error in the reconstructed signal and increase the possibility of successful reconstruction. Finally, the reconstruction formula derived from basis theory is applied to recover the signal. This method has been successfully verified by the simulation signal of the robot swing process and the actual current signal collected on the robot arm testbed.
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BACKGROUND: Myocardial inflammation mediated by toll-like receptor 4 (TLR4) plays an active role in myocardial ischemia/reperfusion (I/R) injury. Studies show that heat shock protein 90 (HSP90) is involved in ischemic postconditioning (IPostC) cardioprotection. This study investigates the roles of TLR4 and HSP90 in IPostC. METHODS: Rats were subjected to 30âmin ischemia, then 2âh reperfusion. IPostC was applied by three cycles of 30âs reperfusion, then 30âs reocclusion at reperfusion onset. Sixty rats were randomly divided into four groups: sham, I/R, IPostC, and geldanamycin (GA, HSP90 inhibitor, 1âmg/kg) plus IPostC (IPostCâ+âGA). RESULTS: IPostC significantly reduced I/R-induced infarct size (40.2±2.1% versus 28.4±2.4%; Pâ<â0.05); the release of cardiac Troponin T, creatine kinase-MB, and lactate dehydrogenase (191.5±3.1 versus 140.6±3.3âpg/ml, 3394.6±132.7 versus 2880.7±125.5âpg/ml, 2686.2±98.6 versus 1848.8±90.1âpg/ml, respectively; Pâ<â0.05); and cardiomyocyte apoptosis (40.3±2.2% versus 27.0±1.6%; Pâ<â0.05). Further, local and circulating IL-1ß, IL-6, TNF-α, and ICAM-1 levels decreased; TLR4 expression and nuclear factor-KB (NF-κB) signaling decreased; and cardiac HSP90 expression increased. Blocking HSP90 function with GA inhibited IPostC protection and anti-inflammation, suggesting that IPostC has a HSP90-dependent anti-inflammatory effect. CONCLUSION: HSP90 may play a role in IPostC-mediated cardioprotection by inhibiting TLR4 activation, local and systemic inflammation, and NF-kB signaling.
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Proteínas HSP90 de Choque Térmico/uso terapéutico , Inflamación/metabolismo , Poscondicionamiento Isquémico/métodos , Receptor Toll-Like 4/metabolismo , Animales , Proteínas HSP90 de Choque Térmico/farmacología , Humanos , Masculino , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
Toll-like receptor 2 (TLR2)-mediated myocardial inflammation serves an important role in promoting myocardial ischemic/reperfusion (I/R) injury. Previous studies have shown that miR499 is critical for cardioprotection after ischemic postconditioning (IPostC). Therefore, the present study evaluated the protective effect of IPostC on the myocardium by inhibiting TLR2, and also assessed the involvement of microRNA (miR)499. Rat hearts were subjected to 30 min of ischemia and 2 h of reperfusion. The IPostC was 3 cycles of 30 sec of reperfusion and 30 sec of reocclusion prior to reperfusion. In total, 90 rats were randomly divided into six groups (n=15 per group): Sham; I/R; IPostC; miR499 negative control adenoassociated virus (AAV) vectors + IPostC; miR499 inhibitor AAV vectors + IPostC; and miR499 mimic AAV vectors + IPostC. It was identified that IPostC significantly decreased the I/Rinduced cardiomyocyte apoptotic index (29.4±2.03% in IPostC vs. 42.64±2.27% in I/R; P<0.05) and myocardial infarct size (48.53±2.49% in IPostC vs. 66.52±3.1% in I/R; P<0.05). Moreover, these beneficial effects were accompanied by increased miR499 expression levels (as demonstrated by reverse transcriptionquantitative PCR) in the myocardial tissue and decreased TLR2, protein kinase C (PKC), interleukin (IL)1ß and IL6 expression levels (as demonstrated by western blotting and ELISA) in the myocardium and serum. The results indicated that IPostC + miR499 mimics significantly inhibited inflammation and the PKC signaling pathway and enhanced the antiinflammatory and antiapoptotic effects of IPostC. However, IPostC + miR499 inhibitors had the opposite effect. Therefore, it was speculated that IPostC may have a miR499dependent cardioprotective effect. The present results suggested that miR499 may be involved in IPostCmediated ischemic cardioprotection, which may occur via local and systemic TLR2 inhibition, subsequent inhibition of the PKC signaling pathway and a decrease in inflammatory cytokine release, including IL1ß and IL6. Moreover, these effects will ultimately lead to a decrease in the myocardial apoptotic index and myocardial infarct size via the induction of the antiapoptotic protein Bcl2, and inhibition of the proapoptotic protein Bax in myocardium.
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Poscondicionamiento Isquémico , MicroARNs/genética , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/terapia , Receptor Toll-Like 2/análisis , Regulación hacia Arriba , Animales , Regulación hacia Abajo , Poscondicionamiento Isquémico/métodos , Masculino , Daño por Reperfusión Miocárdica/sangre , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Ratas Sprague-Dawley , Receptor Toll-Like 2/sangreRESUMEN
PURPOSE: To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). METHODS: The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1ß and c-Jun N-terminal kinase (JNK) were assessed. RESULTS: Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1ß, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. CONCLUSION: HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.
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Benzoquinonas/farmacología , Proteínas del Sistema Complemento/metabolismo , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Lactamas Macrocíclicas/farmacología , Infarto del Miocardio/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Animales , Forma MB de la Creatina-Quinasa/metabolismo , Mediadores de Inflamación , Poscondicionamiento Isquémico/métodos , Masculino , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Computerized detection is a promising method for monitoring adverse drug events (ADEs); however, this method is currently in its infancy and is a new area of exploration in China. This study aimed to develop a computerized ADE alarm and assessment system to help pharmacists effectively detect, assess, and analyze possible ADEs in patients in China. METHODS: Based on the clinical characteristics of these adverse drug events, we designed combined multiparameters as ADE alert rules to be assembled into detection configurations. We also developed system function modules by extracting data from the People's Liberation Army (PLA) general hospital information system (electronic medical records). Positive predictive values were calculated for the alert. RESULTS: Five function modules were created in this platform: automatic screening, assisted evaluation, risk characteristic analysis, report generation into SRS (spontaneous reporting system), and a dictionary database. Four ADE alert configurations were set in our ADE alarm and assessment system: drug-related thrombocytopenia, anemia, liver injury, and kidney injury. The positive predictive values of the 4 monitored ADEs were approximately 44.4% to 95.8%. CONCLUSIONS: An automatic ADE screening system was established for hospitalized patients in Chinese medical institutions. Compared with previous studies, combined drug-event alerts and a system-assisted assessment interface performed better than alerts based only on laboratory values. Furthermore, this platform's assisted-layered evaluation and risk factor analysis functions could save considerable time for professionals and improve early prevention of potentially serious ADEs. To date, this system has been applied in 10 large-scale medical institutions.
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Sistemas de Registro de Reacción Adversa a Medicamentos , Sistemas de Computación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hospitales , China , Humanos , Pacientes InternosRESUMEN
The concentrations of persistent organic pollutants (POPs) in sediments from the Eastern Indian Ocean were analyzed by GC-MS/MS to explore the status of contamination, distribution and their potential sources and risk. The average (±SD) concentrations of total polycyclic aromatic hydrocarbons (∑16PAHs), polybrominated diphenyl ethers (∑10PBDEs), dechlorane plus (∑2DP), organochlorine pesticides (∑22OCPs) and polychlorinated biphenyls (∑31PCBs) in sediments were 79,900 ± 31,400, 173 ± 62, 42 ± 24, 1051 ± 305 and 147 ± 24 pg g-1 dw (or 11,200 ± 7200, 28 ± 26, 6 ± 6, 168 ± 121 and 24 ± 17 ng g-1 organic carbon), respectively. The concentrations of POPs in sediments were generally at low to median levels compared to those recorded in other ocean sediments. Composition analyses suggest that PAHs originate from both petrogenic and pyrogenic sources, while dichlorodiphenyltrichloroethane (DDT) mainly comes from technical-DDT, hexachlorocyclohexane (HCH) from lindane, and chlordane from fresh inputs. The risk assessments show that the targeted chemicals except for chlordane and naphthalene in sediments do not pose potential biological effects to the organisms in the Eastern Indian Ocean. The present study contributes to the very rare data on PAHs, PBDEs, DP, OCPs and PCBs in the vast deep-ocean and will deepen our knowledge of the fate of POPs in ocean environments.
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Kai-Xin-San consists of Ginseng Radix, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria at a ratio of 3:3:2:2. Kai-Xin-San has been widely used for the treatment of emotional disorders in China. However, no studies have identified the key proteins implicated in response to Kai-Xin-San treatment. In this study, rat models of chronic mild stress were established using different stress methods over 28 days. After 14 days of stress stimulation, rats received daily intragastric administrations of 600 mg/kg Kai-Xin-San. The sucrose preference test was used to determine depression-like behavior in rats, while isobaric tags were used for relative and absolute quantitation-based proteomics to identify altered proteins following Kai-Xin-San treatment. Kai-Xin-San treatment for 2 weeks noticeably improved depression-like behaviors in rats with chronic mild stress. We identified 33 differentially expressed proteins: 7 were upregulated and 26 were downregulated. Functional analysis showed that these differentially expressed proteins participate in synaptic plasticity, neurodevelopment, and neurogenesis. Our results indicate that Kai-Xin-San has an important role in regulating the key node proteins in the synaptic signaling network, and are helpful to better understand the mechanism of the antidepressive effects of Kai-Xin-San and to provide objective theoretical support for its clinical application. The study was approved by the Ethics Committee for Animal Research from the Chinese PLA General Hospital (approval No. X5-2016-07) on March 5, 2016.
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Abstract Purpose To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). Methods The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed. Results Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. Conclusion HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.