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The prediction of major histocompatibility complex (MHC)-peptide binding affinity is an important branch in immune bioinformatics, especially helpful in accelerating the design of disease vaccines and immunity therapy. Although deep learning-based solutions have yielded promising results on MHC-II molecules in recent years, these methods ignored structure knowledge from each peptide when employing the deep neural network models. Each peptide sequence has its specific combination order, so it is worth considering adding the structural information of the peptide sequence to the deep model training. In this work, we use positional encoding to represent the structural information of peptide sequences and validly combine the positional encoding with existing models by different strategies. Experiments on three datasets show that the introduction of position-coding information can further improve the performance built upon the existing model. The idea of introducing positional encoding to this field can provide important reference significance for the optimization of the deep network structure in the future.
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Antígenos de Histocompatibilidad Clase I , Péptidos , Péptidos/metabolismo , Secuencia de Aminoácidos , Redes Neurales de la Computación , Unión ProteicaRESUMEN
BACKGROUND: The sharp increase in fungal infections, insufficient diagnostic and treatment capabilities for fungal infections, poor prognosis of patients with fungal infections as well as the increasing drug resistance of fungi are serious clinical problems. It is necessary to explore the implementation and evaluation methods of antifungal stewardship (AFS) to promote the standardized use of antifungal drugs. METHODS: The AFS programme was implemented at a tertiary first-class hospital in China using a plan-do-check-act (PDCA) quality management tool. A baseline investigation was carried out to determine the utilization of antifungal drugs in pilot hospitals, analyse the existing problems and causes, and propose corresponding solutions. The AFS programme was proposed and implemented beginning in 2021, and included various aspects, such as team building, establishment of regulations, information construction, prescription review and professional training. The management effectiveness was recorded from multiple perspectives, such as the consumption of antifungal drugs, the microbial inspection rate of clinical specimens, and the proportion of rational prescriptions. The PDCA management concept was used for continuous improvement to achieve closed-loop management. RESULTS: In the first year after the implementation of the AFS programme, the consumption cost, use intensity and utilization rate of antifungal drugs decreased significantly (P < 0.01). The proportion of rational antifungal drug prescriptions markedly increased, with the proportion of prescriptions with indications increasing from 86.4% in 2019 to 97.0% in 2022, and the proportion of prescriptions with appropriate usage and dosage increased from 51.9 to 87.1%. In addition, after the implementation of the AFS programme, physicians' awareness of the need to complete microbial examinations improved, and the number of fungal cultures and serological examinations increased substantially. Statistics from drug susceptibility tests revealed a decrease in the resistance rate of Candida to fluconazole. CONCLUSION: This study indicated that the combination of AFS and the PDCA cycle could effectively reduce antifungal consumption and promote the rational use of antifungal drugs, providing a reference for other health care systems to reduce the overuse of antifungal drugs and delay the progression of fungal resistance.
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Antifúngicos , Programas de Optimización del Uso de los Antimicrobianos , Micosis , Centros de Atención Terciaria , Antifúngicos/uso terapéutico , Humanos , China , Micosis/tratamiento farmacológico , Micosis/microbiología , Farmacorresistencia Fúngica , Utilización de Medicamentos/normas , Utilización de Medicamentos/estadística & datos numéricosRESUMEN
PURPOSE: Hypoxia is one of the most frequent adverse events under deep sedation in the semiprone position. We hypothesized that supraglottic jet oxygenation and ventilation (SJOV) via Wei nasal jet tube (WNJ) can reduce the incidence of hypoxia in patients under deep sedation during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A total of 171 patients were divided into three groups: N group, supplementary oxygen via a nasopharyngeal airway (4-6 L/min); W group, supplementary oxygen via WNJ (4-6 L/min); WS group, SJOV via WNJ. The primary outcome was the incidence of adverse events, including sedation-related adverse events [SRAEs, hypoxemia (SpO2 = 75-89% lasted less than 60 s); severe hypoxemia (SpO2 < 75% at any time or SpO2 < 90% lasted more than 60 s] and subclinical respiratory depression (SpO2 = 90-95%). Other intraoperative and post-operative adverse events were also recorded as secondary outcomes. RESULTS: Compared with the N group, the incidence of hypoxemia and subclinical respiratory depression in the WS group was significantly lower (21% vs. 4%, P = 0.005; 27% vs. 6%, P = 0.002). Compared with Group W, the incidence of hypoxemia and subclinical respiratory depression in Group WS was also significantly less frequent (20% vs. 4%, P = 0.009; 21% vs. 6%, P = 0.014). No severe hypoxia occurred in the group WS, while four and one instances were observed in the group N and group W respectively. There were no significant differences in other adverse events among the three groups. CONCLUSION: SJOV can effectively improve oxygenation during ERCP in deeply sedated semiprone patients.
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Anestesia , Insuficiencia Respiratoria , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Hipoxia/etiología , Hipoxia/prevención & control , Hipoxia/epidemiología , Oxígeno , Insuficiencia Respiratoria/complicaciones , Anestesia/efectos adversosRESUMEN
The most common construction material used in Taiwan is concrete, potentially contaminated by geologic heavy metals (HMs). Younger children spend much time indoors, increasing HM exposure risks from household dust owing to their behaviors. We evaluated arsenic (As), cadmium (Cd), and lead (Pb) concentrations in fingernails among 280 preschoolers between 2017 and 2023. We also analyzed HM concentrations, including As, Cd, Pb, chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), iron (Fe), and manganese (Mn), in 90 household dust and 50 road dust samples from a residential area where children lived between 2019 and 2021 to deepen the understanding of sources and health risks of exposure to HMs from household dust. The average As, Cd, and Pb concentrations in fingernails were 0.12 ± 0.06, 0.05 ± 0.05, and 0.95 ± 0.77 µg/g, respectively. Soil parent materials, indoor construction activities, vehicle emissions, and mixed indoor combustion were the pollution sources of HMs in household dust. Higher Cr and Pb levels in household dust may pose non-carcinogenic risks to preschoolers. Addressing indoor construction and soil parent materials sources is vital for children's health. The finding of the present survey can be used for indoor environmental management to reduce the risks of HM exposure and avoid potential adverse health effects for younger children.
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Arsénico , Metales Pesados , Humanos , Preescolar , Cadmio , Monitoreo del Ambiente , Polvo/análisis , Plomo , Metales Pesados/análisis , Cromo , Medición de Riesgo , Suelo , China , CiudadesRESUMEN
Multi-walled carbon nanotubes (MWCNTs) with one-dimensional nanostructure are an ideal support for oxygen reduction reaction (ORR) catalysts thanks to their intrinsic outstanding electrical conductivity and high specific surface area. Iron and nitrogen doping could alter the local electronic structure and therefore enhance the ORR activity of MWCNTs, but the preparation process always includes complicated growth conditions and post-treatment. Herein, an iron and nitrogen co-modified multi-walled carbon nanotubes (Fe-N-MWCNTs) with hierarchical nanostructure is engineered and synthesized via a simple two-step pyrolysis approach. Large specific surface area, low resistivity, and intensified charge density near the Fermi level synergistically endow the Fe-N-MWCNTs with outstanding ORR activity. The optimal Fe-N-MWCNTs exhibit a higher onset potential value of 0.92 V (versus RHE) and half-wave potential (E1/2) of 0.85 V (versus RHE) in 0.1 M KOH medium, which exceeds the benchmark Pt/C electrocatalyst (E1/2= 0.84 V). This strategy of modifying MWCNTs support by a simple calcination process provides a feasible method to prepare cost-efficient ORR electrocatalysts.
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The all-trans conformation (ß-phase) possesses a significant impact on the piezoelectric polymer polyvinylidene fluoride (PVDF). Inducing more molecular chain [-CH2-CF2-]nto form all-trans conformation is one of the biggest obstacles for manufacturing high-performance piezoelectric sensing devices. Herein, the continuous vacuum technology is used to modulate the polarity of binary solvents by the proportion of the lower solvent. The regulated solvent forms a high dipole moment, an interaction between the dipole ofß-phase and the dipole moment makes the phase reversal in PVDF. Fourier transform infrared spectroscopy, piezoelectric constant test and other characterization results show that when the weakly polar acetone and the strongly polar solvent DMF reach a ratio of 4:6, the pure PVDF film possesses high piezoelectricity (d33â¼ -44.8 pC N-1) and strong self-polarization. Additionally, the A4D6device exhibits high sensitivity (S1= 0.182 V/N, 0.5 N â¼ 30 N), driven capability (0.49 mW m-2), and reliability during the electrical tests as a pressure device. This work provides an effective and cost-effective route of optimizing the solvent's polarity to improve the piezoelectric characteristics of the polymer.
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Allergic inflammation is the foundation of multiple allergic disorders, such as allergic rhinitis and asthma. Mast cells are effector cells that initiate inflammatory response. 5-hydroxymethylfurfural (5-HMF), a furfural compound, is the heat-processed product of various fruit, foods, drinks, as well as some Chinese herbal medicines. 5-HMF was previously reported to inhibit mast cell activation. Our study aimed to explore the functions of 5-HMF in both phorbol 12-mystate 13-acetate (PMA) plus calcium ionophore (A23187)-induced allergic inflammation in human mast cell line HMC-1 and ovalbumin (OVA)-induced asthma mouse models. HMC-1 cells were pretreated with 5-HMF and then stimulated by PMA+A23187. The cytotoxicity of 5-HMF on HMC-1 cells was evaluated by MTT assay. Histamine content in cell supernatants was measured by the o-phthaldialdehyde spectrofluorometric procedure. Intracellular calcium was determined using the fluorescent dye Fura-2AM. The production and expression of pro-inflammatory cytokines were detected by ELISA and RT-qPCR. Caspase-1 colorimetric assay was employed to examine the enzymatic activity of caspase-1. Asthma mouse models were induced by OVA sensitization. The bronchoalveolar lavage fluid (BALF) and blood samples were collected for the detection of total and differential cell count as well as aspartate aminotransferase (AST), alanine aminotransferase (ALT), OVA-immunoglobulin E (OVA-IgE), OVA-immunoglobulin G1 (OVA-IgG1), and pro-inflammatory cytokine levels. The left lung of mouse was dissected for histopathological examination by hematoxylin and eosin (H&E) staining. The protein expression of pro-caspase-1 and the phosphorylation of NF-κB and MAPK pathway-associated molecules were assessed by Western blotting. Our findings revealed that 5-HMF efficiently suppressed the PMA+A23187-induced enhancement in histamine production and intracellular calcium in HMC-1 cells. Pro-inflammatory cytokine production and expression in HMC-1 cells were elevated after PMA plus A23187 stimulation, which, however, were inhibited by pretreatment of 5-HMF. Additionally, 5-HMF suppressed the activity of caspase-1 and the phosphorylation of NF-κB and MAPK-associated molecules including p65 NF-κB, p38 MAPK, ERK, and JNK in HMC-1 cells. In vivo experiments demonstrated that 5-HMF treatment reduced the lung/body weight index and total and differential (macrophages, neutrophils, lymphocytes, and eosinophils) cell counts in BALF of asthmatic mice, but exerted no influence on serum AST and ALT levels. Besides, 5-HMF reduced serum OVA-IgE and OVA-IgG1 levels, mitigated lung inflammation, and inhibited the NF-κB and MAPK signaling pathways in asthma mouse models. 5-HMF mitigates allergic inflammation in asthma by inactivating caspase-1 and NF-κB and MAPK signaling pathways.
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Health risk assessments of exposure to mercury (Hg) from soils via ingestion and inhalation are indispensable for Taiwanese people living in the vicinity of Hg-contaminated sites. In this study, anthropogenic soils were collected from various polluted sources in Taiwan. In vitro oral and inhalation bioaccessible fractions of Hg were analyzed to avoid from overestimating the exposure risk. Discrepancies in oral and inhalation bioaccessible levels of Hg in soils were found using different in vitro assays with different pH levels and chemical compositions. The freshly contaminated soil (soil S7) polluted by chlor-alkali production activity sampled before the site was remediated had the highest total Hg concentration of 1346 mg/kg, with the highest oral bioaccessibility of 26.2% as analyzed by SW-846 Method 1340 and inhalation bioaccessibility of 30.5% as analyzed by modified Gamble's solution. The lesser extent of aging of Hg in soil S7 increased the Hg availability for humans, which was also found based on results of a sequential extraction procedure. Results of the hazard quotient showed that soil ingestion was the main pathway causing non-carcinogenic risks for children and adults. Children were also exposed to higher risks than were adults due to higher frequencies of hand-to-mouth behaviors and lower body weights. Furthermore, hazard index results adjusted for oral and inhalation bioaccessible Hg were lower than those obtained based on the total Hg content; however, an unacceptable value of the non-carcinogenic risk (> 1) for children living near soil S7 was still observed. This study suggests that children living near sites polluted for a short period of time may suffer potential renal effects regardless of the bioaccessibility. Our findings provide suggestions for decision makers on setting new strategies for managing risks of Hg-contaminated soils in Taiwan.
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Mercurio , Contaminantes del Suelo , Adulto , Niño , Humanos , Mercurio/análisis , Taiwán , Contaminación Ambiental/análisis , Suelo/química , Medición de Riesgo , Riñón , Contaminantes del Suelo/análisis , Monitoreo del AmbienteRESUMEN
BACKGROUND: Rice (Oryza sativa L.) is one of the most widely grown food crops, and its yield and quality are particularly important for a warm-saturated diet. Cold stress restricts rice growth, development, and yield; however, the specific mechanism of cold tolerance in rice remains unknown. RESULTS: The analysis of leaf physiological and photosynthetic characteristics showed that the two rice varieties were significantly affected by cold stress, but the cold-tolerant variety KY131 had more stable physiological characteristics, maintaining relatively good photosynthetic capacity. To better explore the transcriptional regulation mechanism and biological basis of rice response to cold stress, a comprehensive analysis of the rice transcriptome and lipidome under low temperature and control temperature conditions was carried out. The transcriptomic analysis revealed that lipid metabolism, including membrane lipid and fatty acid metabolism, may be an important factor in rice cold tolerance, and 397 lipid metabolism related genes have been identified. Lipidomics data confirmed the importance of membrane lipid remodeling and fatty acid unsaturation for rice adaptation to cold stress. This indicates that the changes in the fluidity and integrity of the photosynthetic membrane under cold stress lead to the reduction of photosynthetic capacity, which could be relieved by increased levels of monogalactosyldiacylglycerol that mainly caused by markedly increased expression of levels of 1,2-diacylglycerol 3-beta-galactosyltransferase (MGD). The upregulation of phosphatidate phosphatase (PAP2) inhibited the excessive accumulation of phosphatidate (PA) to produce more phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG), thereby preventing of membrane phase transition under cold stress. In addition, fatty acid ß-oxidation is worth further study in rice cold tolerance. Finally, we constructed a metabolic model for the regulatory mechanism of cold tolerance in rice, in which the advanced lipid metabolism system plays a central role. CONCLUSIONS: Lipidome analysis showed that membrane lipid composition and unsaturation were significantly affected, especially phospholipids and galactolipids. Our study provides new information to further understand the response of rice to cold stress.
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Aclimatación , Metabolismo de los Lípidos , Lipidómica , Oryza/genética , Oryza/metabolismo , Aclimatación/genética , Frío , Perfilación de la Expresión Génica , Fotosíntesis , Especificidad de la EspecieRESUMEN
Mercury (Hg) is a well-known toxicant that can affect children's neurodevelopment. This study attempted to evaluate the internal dose of Hg in hair and fingernails and external Hg exposure from dietary consumption in 283 pairs of mothers and their children aged under 6 years in Taiwan. Mean Hg levels in hair and fingernail samples were 1.07 ± 0.67 and 0.42 ± 0.34 µg/g for mothers, and 1.11 ± 1.22 and 0.36 ± 0.26 µg/g for children, respectively. Our results showed that 42% of mothers and 41% of children had hair Hg levels exceeding the US Environmental Protection Agency recommended value of 1 µg/g. Hg exposure in children was greater than that of their mothers. Estimated daily intake (EDI) levels of Hg among preschool children were 3.3-times higher than those of their mothers. A sensitivity analysis indicated that fish consumption was the main potential factor of Hg exposure among both mothers and their children. External Hg exposure using estimated daily dietary ingestion by mothers was a surrogate for internal hair Hg concentrations. However, poor correlations were found between EDI Hg levels and hair Hg levels among children aged 4-6 years. Exposure sources from food and other media, such as soil and dust, need to be considered to arrive at more-valid risk assessments for younger children's exposure to Hg. Children of mothers who did not have food safety-related risk perceptions or protective behaviors had significantly higher hair Hg concentrations compared to children whose mothers had risk perceptions and protective behaviors. Hg exposure of women of childbearing age and preschool children in Taiwan is still an area of great concern. Providing food safety information and risk-benefits of fish consumption for mothers may avoid harm to the developing nervous systems of their children.
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Mercurio , Animales , Preescolar , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente , Femenino , Peces , Contaminación de Alimentos/análisis , Inocuidad de los Alimentos , Cabello/química , Humanos , Mercurio/análisisRESUMEN
Elaborating the sensitization effects of different noble metals on In2O3has great significance in providing an optimum method to improve ethanol sensing performance. In this study, long-range ordered mesoporous In2O3has been fabricated through replicating the structure of SBA-15. Different noble metals (Au, Ag, Pt and Pd) with the same doping amount (1 at%) have been introduced by anin situdoping routine. The results of the gas sensing investigation indicate that the gas responses towards ethanol can be obviously increased by doping different noble metals. In particular, the best sensing performance towards ethanol detection can be achieved through Pd doping, and the sensors based on Pd-doped In2O3not only possess the highest response (39.0-100 ppm ethanol) but also have the shortest response and recovery times at the optimal operating temperature of 250 °C. The sensing mechanism of noble metal doped materials can be attributed to the synergetic effect combining 'catalysis' and 'electronic and chemical sensitization' of noble metals. In particular, the chemical state of the noble metal also has a great influence on the gas sensing mechanism. A detailed explanation of the enhancement of gas sensing performance through noble metal doping is presented in the gas sensing mechanism part of the manuscript.
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Large-scale and well-alignedin situgrowth SnO2nanotube (NT) arrays have been synthesized directly on the surface of the Al2O3ceramic tube by a cost-effective template self-etching method. The morphology ofin situSnO2NTs can be adjusted by changing the concentration of urea. The structure and morphology characteristics of SnO2NT were examined via x-ray diffraction, BET, and scanning electron microscopy, respectively. A series of detections were carried out to evaluate the gas sensing performances. The results indicated thatin situgrowth SnO2NT arrays sensor exhibited an excellent response (S = 20.3), good linearity under the concentration range of ppm level (5-300 ppm), and outstanding selectivity to 100 ppm of acetone gas. Compared with the sensors fabricated by a slurry-coating method, the controllablein situassembled SnO2NT arrays exhibited a more stable structure and easier fabrication process. The high acetone sensing performance might due to the unique hollow structure and favorable orientation growth. The dominant sensing mechanism about thein situgrowth SnO2NT arrays sensor has been discussed in detail. It is expected thatin situgrowth SnO2NT arrays sensor with the general working principle and controllable growth strategy will become a promising functional material in monitoring and detecting acetone.
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This study focuses on estimating the probabilistic soil and dust ingestion rates for children under 3 years old by the Stochastic Human Exposure and Dose Simulation Soil and Dust (SHEDS-S/D) model developed by the U.S. Environmental Protection Agency. The health risk of children's exposure to heavy metals through soil and dust ingestion and dermal absorption was then assessed in three exposure scenarios. In the exposure scenario of direct contact with soil, the average soil and dust ingestion rates for children aged 24 to 36 months were 90.7 and 29.8 mg day-1 in the sand and clay groups, respectively. Hand-to-mouth soil ingestion was identified as the main contributor to soil and dust ingestion rates, followed by hand-to-mouth dust ingestion and object-to-mouth dust ingestion. The soil-to-skin adherence factor was the most influential factor increasing the soil and dust ingestion rate based on a sensitivity analysis in the SHEDS-S/D model. Furthermore, the modeled soil and dust ingestion rates based on the SHEDS-S/D model were coincident with results calculated by the tracer element method. Our estimates highlight the soil ingestion rate as the key parameter increasing the risk for children, while a higher frequency of hand washing could potentially reduce the risk.
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Polvo , Suelo , Niño , Preescolar , Polvo/análisis , Ingestión de Alimentos , Exposición a Riesgos Ambientales/análisis , Humanos , Medición de Riesgo , TaiwánRESUMEN
The CdS interlayer plays an important role as the seed layer and energy barrier in photovoltaic performance enhancement of CdSe quantum-dot sensitized solar cells (QDSCs). However, the CdS (CdS-CBD) interlayer is generally synthesized by the chemical bath deposition method (CBD) and suffers from excessive Cd2+ due to the poor controllability of interfacial chemical reactions. Here, we employed a sol-gel method to prepare a CdS interlayer (CdS-SG) with a stoichiometric ratio of Cd2+ to S2- on a TiO2 mesoporous photoanode and then fabricated CdSe QDSCs. A power conversion efficiency of 3.37% was obtained in the CdS-SG QDSCs (Cell-SG), which is higher than that of 2.64% in the CdS-CBD QDSCs (Cell-CBD) under AM 1.5G solar illumination of 100 mW cm-2. Charge extraction measurements showed that the Cell-SG contained fewer trap states than the Cell-CBD. A comprehensive study of the electron dynamics based on open-circuit voltage decay (OCVD), electrochemical impedance spectroscopy (EIS), intensity-modulated voltage spectroscopy (IMVS), and intensity-modulated photocurrent spectroscopy (IMPS) measurements revealed that the stoichiometric CdS-SG interlayer significantly reduced the charge recombination and prolonged the lifetime of photogenerated electrons in contrast to the CdS-CBD interlayer in the QDSCs.
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BACKGROUND: Sepsis leads to severe acute lung injury/acute respiratory distress syndrome (ALI/ARDS) that is associated with enhanced endoplasmic reticulum (ER) stress. Heme oxygenase-1 (HO-1), an ER-anchored protein, exerts antioxidant and protective functions under ALI. However, the role of HO-1 activation in the development of endoplasmic reticulum (ER) stress during sepsis remains unknown. METHODS: Cecal ligation and puncture (CLP) model was created to induce septic ALI. Lung tissue ER stress was measured 18 hours after CLP. The effects of HO-1 on ER stress during septic ALI were investigated in vivo using HO-1 agonist hemin and antagonist ZnPP. RESULTS: Compared with the sham group, ER stress in septic lung increased significantly 18 hours after CLP, which was significantly reduced by pretreatment with the ER inhibitor 4-phenylbutyrate (4-PBA). The lung injury score and the lung wet to dry (W/D) ratio in lungs were significantly reduced in septic rats after ER stress inhibition. Similarly, lung ER stress-related genes' (PERK, eIF2-α, ATF4, and CHOP) levels were attenuated after ER stress inhibition. Furthermore, HO-1 activation by hemin reduced p-PERK, p-eIF2-α, ATF4, and CHOP protein expression and oxidative stress and lung cell apoptosis. Additionally, HO-1 antagonist could aggregate the ER stress-related ALI. CONCLUSIONS: ER stress was activated during CLP-induced ALI, which may represent a mechanism by which CLP induces ALI. HO-1 activation could inhibit CLP-induced lung ER stress and attenuate CLP-induced ALI.
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Lesión Pulmonar Aguda/metabolismo , Estrés del Retículo Endoplásmico , Retículo Endoplásmico/metabolismo , Hemo Oxigenasa (Desciclizante)/metabolismo , Sepsis/metabolismo , Animales , Antioxidantes/metabolismo , Ciego/patología , Hemina/farmacología , Pulmón/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Agua/químicaRESUMEN
Objective To determine whether the myotoxic side effects of statin simvastatin affect skeletal muscle's sensitivity to caffeine and halothane.Methods Primary cultured neonate rat skeletal myotubes were treated with 0.01-5.0 µmol/L simvastatin for 48 hours. MTT was used to evaluate cellular viability. The gross morphology and microstructure of the myotubes were observed with a light and electron microscope, respectively. The intracellular calcium concentrations ([Ca2+]i) at rest and in response to caffeine and halothane were investigated by fluorescence calcium imaging. Data were analyzed by analysis of variance (ANOVA) test.Results Simvastatin (0.01-5.0 µmol/L) decreased myotube viability, changed their morphological features and microstructure, and increased the resting [Ca2+]i in a dose-dependent manner. Simvastatin did not change myotube's sensitivity to low doses of caffeine (0.625-2.5 mmol/L) or halothane (1.0-5.0 mmol/L). In response to high-dose caffeine (10.0 mmol/L, 20.0 mmol/L) and halothane (20.0 mmol/L, 40.0 mmol/L), myotubes treated with 0.01 µmol/L simvastatin showed a significant increase in sensitivity, but those treated with 1.0 µmol/L and 5.0 µmol/L simvastatin showed a significant decrease. The sarcoplasmic reticulum Ca2+ storage peaked in the myotubes treated with 0.01 µmol/L simvastatin, but it decreased when cells were treated with higher doses of simvastatin (0.1-5.0 µmol/L).Conclusions The myotoxic side effect of simvastatin was found to change the sensitivity of myotubes in response to high-dose caffeine and halothane. When dose was low, sensitivity increased mainly because of increased Ca2+ content in the sarcoplasmic reticulum, which might explain why some individuals with statin-induced myotoxic symptoms may show positive caffeine-halothane contracture test results. However, when the dose was high and the damage to the myotubes was severer, sensitivity was lower. It is here supposed that the damage itself might put individuals with statin-induced myotoxic symptoms at greater risks of presenting with rhabdomyolysis during surgery or while under anesthesia.
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Músculo Esquelético , Animales , Cafeína , Calcio , Relación Dosis-Respuesta a Droga , Halotano , Ratas , SimvastatinaRESUMEN
Histamine H2 receptor (HRH2) was previously suggested to affect the proliferation of breast cancer cells and disease-free survival of breast cancer patients. Furthermore, a common polymorphism, rs2067474, was identified in an enhancer element of the HRH2 gene promoter and was reported to be associated with various diseases including cancer. However, the relationship between this polymorphism and breast cancer risk and malignant degree remains unclear. The aim of this study was to clarify the clinical association of rs2067474 polymorphism with breast cancer. A total of 201 unrelated Chinese Han breast cancer patients and 238 ethnicity-matched health controls were recruited and rs2067474 polymorphism was genotyped. Logistic regression analyses were performed to calculate the odds ratios (ORs) as a measure of association of genotype with breast cancer according to 3 genetic models (dominant, recessive, and additive). Although the percentage of hormone receptor negative cases tended to be higher in AA genotypes, we did not find any significant associations of rs2067474 polymorphism with breast cancer risk or with related clinicopathological parameters in the present study, which indicates that rs2067474 polymorphism of HRH2 gene might not be a risk factor in the development of breast cancer in Chinese Han population.
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Pueblo Asiatico/genética , Neoplasias de la Mama/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Receptores Histamínicos H2/genética , Adulto , Alelos , Biomarcadores de Tumor , Neoplasias de la Mama/patología , Estudios de Casos y Controles , China , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de RiesgoRESUMEN
Herein we selected the model organic donor-acceptor dye C218 and modulated the self-organization of dye molecules on the surface of titania by changing the dyeing solvent from chlorobenzene to a mixture of acetonitrile and tert-butanol. We further unveiled the relationship between the microstructure of a dye layer and the multichannel charge-transfer dynamics that underlie the photovoltaic performance of dye-sensitized solar cells.
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BACKGROUND: To detect and analyze risk signals of the drug-related adverse events (AEs) of 4 gadolinium-based contrast agents (GBCAs) (gadopentetate dimeglumine (Gd-DTPA), gadobenate dimeglumine (Gd-BOPTA), gadoteridol (Gd-HP-DO3A), and gadobutrol (Gd-BT-DO3A)) according to the US Food and Drug Administration Adverse Event Reporting System (FAERS) database and ensure the clinical safety. RESEARCH DESIGN AND METHODS: The AEs that are associated with the 4 GBCAs were collected from the FAERS database from 2004Q1 to 2022Q3. The risk signals were mined using reporting odds ratio (ROR) and proportional reporting ratio (PRR). RESULTS: 424 risk signals were excavated, in which 151 risk signals were associated with Gd-DTPA, 93 risk signals were related to Gd-BOPTA, 79 risk signals were relevant to Gd-HP-DO3A, and 101 risk signals were associated with Gd-BT-DO3A. The AE signals involved 20 system organ classes (SOCs). Two of the top four SOCs were identical, namely 'skin and subcutaneous tissue disorders' and 'general disorders and administration site conditions.' CONCLUSIONS: The safety signals of 4 GBCAs were detected, and the SOCs associated with the AEs of the 4 GBCAs were different. Besides, some AEs obtained in this study were not mentioned in the package inserts, which need more attention and research to ensure the clinical safety.
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Medios de Contraste , Gadolinio DTPA , Compuestos Heterocíclicos , Meglumina/análogos & derivados , Compuestos Organometálicos , Estados Unidos , Humanos , Medios de Contraste/efectos adversos , Gadolinio DTPA/efectos adversos , Gadolinio/efectos adversos , United States Food and Drug Administration , Minería de DatosRESUMEN
In the present prospective cohort research, we aimed to explore the serum levels of Acyl-CoA synthetase long-chain family member 4 (ACSL4) in patients with ST-segment elevation myocardial infarction (STEMI) and its association with 1-year major adverse cardiovascular events (MACE). This prospective cohort study recruited 507 patients who underwent percutaneous coronary intervention for the treatment of STEMI at our hospital during August 2019 to July 2022. The serum ACSL4, tumor necrosis factor-α, interleukin (IL)-6, IL-1ß, and C-reactive protein levels were measured by enzyme-linked immunosorbent assay. Demographic and clinical statistics were also collected. In addition, all patients were followed up for 1 year, and patients with MACE were defined as poor prognosis group. All data used SPSS 26.0 to statistical analyses. The poor prognosis group had significantly higher age and low-density leptin cholesterol (LDLC) levels compared to the favorable prognosis group (Pâ <â .05). STEMI patients exhibited significantly elevated serum levels of ACSL4, tumor necrosis factor-α, IL-6, IL-1ß, and C-reactive protein (Pâ <â .05). Serum ACSL4 and IL-1ß levels in the poor prognosis group were remarkably enhanced compared to the favorable prognosis group. Curvilinear regression analysis demonstrated that ACSL4 was associated with LDLC and IL-1ß. Moreover, ACSL4 (Bâ =â 0.138, 95% CI 1.108-1.189, Pâ <â .001), LDLC (Bâ =â 2.317, 95% CI 5.253-19.603, Pâ <â .001), and IL-1ß (Bâ =â 0.061, 95%CI 1.008-1.122, Pâ =â .025) levels were the risk factors for STEMI patients with 1-year MACE. This study showed that the serum ACSL4 levels was remarkably elevated in STEMI patients. This study might provide new targets and a comprehensive approach to cardiovascular protection in STEMI patients.