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OBJECTIVES: The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. METHODS: To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose-response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of blaKPC. RESULTS: The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. CONCLUSIONS: Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp.
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Antibacterianos , Compostos Azabicíclicos , Proteínas de Bactérias , Ceftazidima , Modelos Animais de Doenças , Combinação de Medicamentos , Sinergismo Farmacológico , Infecções por Klebsiella , Klebsiella pneumoniae , Meropeném , Testes de Sensibilidade Microbiana , beta-Lactamases , Animais , Ceftazidima/farmacologia , Ceftazidima/uso terapêutico , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Compostos Azabicíclicos/farmacologia , Compostos Azabicíclicos/uso terapêutico , Meropeném/farmacologia , Meropeném/administração & dosagem , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Camundongos , beta-Lactamases/genética , Proteínas de Bactérias/genética , Feminino , Sequenciamento Completo do Genoma , Quimioterapia Combinada , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genéticaRESUMO
Bone disease is a common complication following liver transplantation, often overlooked in clinical practice. Clinical diagnosis of post-liver transplantation bone disease is challenging, and there have been few case report in the literature. This case report presents a patient who underwent two liver transplant surgeries, exhibited good daily activity, and did not display typical clinical symptoms such as fatigue, bone pain, or spinal deformities associated with prolonged sitting or standing. However, within the fifth year after the second liver transplant, the patient experienced two consecutive fractures. In March 2023, the patient underwent the first bone density test, which revealed osteoporosis. This case highlights the fact that severe fractures after liver transplantation may not necessarily be accompanied by typical symptoms of bone disease. Without timely examination and early prevention, serious consequences may arise. Therefore, this condition requires attention, proactive prevention, early detection, and timely treatment. Additionally, a retrospective analysis of the patient's previous laboratory data revealed persistent abnormalities in serum markers such as hypocalcemia and elevated alkaline phosphatase levels after liver transplantation, emphasizing the importance of monitoring these serum markers.
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Doenças Ósseas , Fraturas Ósseas , Fraturas Espontâneas , Transplante de Fígado , Humanos , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Densidade Óssea , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Fraturas Ósseas/etiologia , Doenças Ósseas/complicações , BiomarcadoresRESUMO
Single-atom catalysts (SACs) with high atom utilization and outstanding catalytic selectivity are useful for improving battery performance. Herein, atomically dispersed Ni-N4 and Fe-N4 dual sites coanchored on porous hollow carbon nanocages (Ni-Fe-NC) are fabricated and deployed as the sulfur host for Li-S battery. The hollow and conductive carbon matrix promotes electron transfer and also accommodates volume fluctuation during cycling. Notably, the high d band center of Fe in Fe-N4 site demonstrates strong polysulfide affinity, leading to an accelerated sulfur reduction reaction. Meanwhile, Li2S on the Ni-N4 site delivers a metallic property with high S 2p electron density of states around the Femi energy level, enabling a low sulfur evolution reaction barrier. The dual catalytic effect on Ni-Fe-NC endows sulfur cathode high energy density, prolonged lifespan, and low polarization.
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An up-conversion molecularly imprinted ratiometric fluorescent probe with a monodisperse nuclear-satellite structure and its test strip are designed which can avoid fluorescent background interference to detect Sudan I in chili powder highly selective and sensitive. The detection mechanism is based on the selective recognition of Sudan I by imprinted cavities on the surface of ratiometric fluorescent probe and the inner filter effect between Sudan I molecules and the emission of up-conversion materials (NaYF4:Yb,Tm). Under optimized experimental conditions, the response of fluorescent ratio signals (F475/F645) of this test strip show a good linear relationship in the range 0.02-50 µM Sudan I. The limits of detection and quantitation are as low as 6 nM and 20 nM, respectively. Sudan I is selectively detected in the presence of fivefold higher concentrations of interfering substances (imprinting factor up to 4.4). Detection of Sudan I in chili powder samples show ultra-low LOD (44.7 ng/g), satisfactory recoveries (94.99-105.5%) and low relative standard deviation (≤ 2.0%). This research offers a reliable strategy and promising scheme for highly selective and sensitive detection of illegal additives in complex food matrix via an up-conversion molecularly imprinted ratiometric fluorescent test strip.
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Impressão Molecular , Corantes Fluorescentes , Pós , Limite de DetecçãoRESUMO
This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 µm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 â, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 µL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 µmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
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Asteraceae , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Humanos , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Asteraceae/química , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Polypeptides and polypeptoids are promising materials in biomedical applications bearing α-amino acid repeating units, which are prepared from ring-opening polymerizations of α-amino acid N-carboxyanhydride (NCA) or N-thiocarboxyanydride (NTA) monomers. Detailed studies on monomer synthetic routes are essential to explore new α-amino acid NCA and NTA monomers as well as the corresponding poly(α-amino acid) materials. In this contribution, density functional theory (DFT) is applied to investigate the mechanism of the Leuchs approach including two possible pathways, precursor structure and racemization in the ring-closing reaction. According to DFT calculations, pathway 2 is preferred with lower ΔG than pathway 1, and the rate-determining step is recognized as an SN2 substitution with releasing equivalent halogenated hydrocarbon, which explains our experimental observations. Racemization results from the reaction between the NTA monomer and a strong protonic acid, which can be suppressed by low temperature and short reaction time. Racemization is inhibited by steric hindrance in those NTAs of α-amino acids containing high bulkiness at the ß-carbon, such as leucine-NTA.
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Aminoácidos/química , Oxazolidinonas/síntese química , Ciclização , Teoria da Densidade Funcional , Modelos Químicos , Estereoisomerismo , TermodinâmicaRESUMO
To establish and validate the design space of the Digeda-4 flavored decoction( DGD-4D) extraction process by using the quality by design( Qb D) concept. With DGD-4D decoction pieces as a model drug,with the transfer rate of aesculin,picroside I,picroside â ¡,geniposide and the yield of extract as critical quality attributes( CQAs),the single factor experiment design was used to determine the level of each factor; the Plackett-Burman experiment design was used to select the critical process parameters( CPPs);and the Box-Behnken experiment design was used to optimize the extraction process. The design space of the DGD-4D extraction process was established,and finally,four experimental points were selected to verify the established model. The single factor experiment determined the levels of each factor,including soaking time 60 min and 30 min,water adding volume 12 times and 8 times,extraction time 90 min and 30 min,number of extraction times 3 times and 1 time,as well as extraction temperature 100 â and 90 â.By Plackett-Burman experimental design,the DGD-4D water addition,extraction time and number of extraction times were determined to be CPPs. The Box-Behnken experimental variance analysis showed that P of the regression model was less than 0. 01 and the misstated value was more than 0. 01,indicating that the model had good predictive ability,and the operation space of CPPs in the DGD-4D extraction process was determined as follows: the amount of water addition was 10-12 times; extraction time 50-80 min; and number of extraction times was 3 times. The design space of DGD-4D extraction process based on the concept of Qb D is conducive to improving the stability of product quality and laying a foundation for the future development of DGD-4D.
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Química Farmacêutica/métodos , Medicamentos de Ervas Chinesas/química , Projetos de PesquisaRESUMO
BACKGROUND: Chronic radiation enteritis (CRE) is defined as loss of absorptive capacity after irradiation due to chronic inflammation and damage of intestinal mucosa, which may lead to varying degrees of malnutrition. The aim of this study was to evaluate the potential correlation between the nutritional status and systemic inflammation in patients with CRE. METHODS: Medical records of 92 patients with CRE and 184 age- and sex-matched controls in a single center from January 2010 to October 2015 were retrospectively reviewed. All enrolled subjects underwent nutritional status analysis, including three different nutritional indices: Nutritional Risk Screening-2002 (NRS-2002), Patient-generated Subjective Global Assessment (PG-SGA) and Controlling Nutritional Status (CONUT), bioelectrical impedance spectroscopy (BIS), and biochemical markers, within 24 h of admission. RESULTS: The results showed that NRS-2002, PG-SGA and CONUT were all positively correlated with neutrophil/lymphocyte ratio (NLR) (r = 0.304, 0.384 and 0.425, all p < 0.001) and C-reactive protein (CRP) (r = 0.357, 0.479 and 0.230, all p < 0.001), while negatively correlated with albumin (r = -0.612, -0.727 and -0.792, all p < 0.001) and total cholesterol (TC) (r = -0.485, -0.545 and -0.473, all p < 0.001) in patients with CRE, respectively. Body cell mass (BCM) has been deemed a key body composition parameter. It was positively correlated with albumin (r = 0.489, p < 0.001) and TC (r = 0.237, p < 0.001), while negatively correlated with NLR (r = -0.140, p = 0.02) and CRP (r = -0.215, p < 0.001). A multivariate linear regression analysis showed that values of intracellular water (ß coefficient = 0.760, p < 0.001), extracellular water (ß coefficient = 0.006, p = 0.011), protein (ß coefficient = 0.235, p < 0.001) and CRP (ß coefficient = 0.001, p = 0.009) were independent determinants of BCM. CONCLUSION: This study revealed that BIS combined with nutritional assessments and biochemical markers were appropriate methods to assess the nutritional and inflammatory status in patients with CRE. Furthermore, the nutritional status was verified to be significantly correlated with systemic inflammation.
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Biomarcadores/sangue , Composição Corporal , Enterite/sangue , Desnutrição/sangue , Avaliação Nutricional , Radioterapia/efeitos adversos , Adulto , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Colesterol/sangue , Doença Crônica , Creatinina/sangue , Impedância Elétrica , Enterite/complicações , Feminino , Humanos , Inflamação , Modelos Lineares , Linfócitos/citologia , Masculino , Desnutrição/etiologia , Pessoa de Meia-Idade , Análise Multivariada , Neutrófilos/citologia , Estado Nutricional , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/metabolismoRESUMO
Centenarians constitute a significant subpopulation in the Bama County of Guangxi province in China. The beneficial effects of intestinal microbiota, especially bifidobacteria of centenarians, have been widely accepted; however, knowledge about Bifidobacterium species in centenarians is not adequate. The aim of this study was to investigate the quantity and prevalence of fecal Bifidobacterium in healthy longevous individuals. Fecal samples from eight centenarians from Bama (aged 100 to 108 years), eight younger elderlies from Bama (aged 80 to 99 years), and eight younger elderlies from Nanning (aged 80 to 99 years) were analyzed using denaturing gradient gel electrophoresis, species-specific clone library, and quantitative polymerase chain reaction technology (qPCR). A total of eight different Bifidobacterium species were detected. B. dentium, B. longum, B. thermophilum, B. pseudocatenulatum/B. catenulatum, and B. adolescentis were common in fecal of centenarians and young elderly. B. minimum, B. saecularmay/B. pullorum/B. gallinarum, and B. mongoliense were found in centenarians but were absent in the younger elderlies. In addition, Bifidobacterium species found in centenarians were different from those found in Bama young elderly and Nanning young elderly, and the principal differences were the significant increase in the population of B. longum (P < 0.05) and B. dentium (P < 0.05) and the reduction in the frequency of B. adolescentis (P < 0.05), respectively. Centenarians tend to have more complex fecal Bifidobacterium species than young elderlies from different regions.
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Carga Bacteriana , Bifidobacterium/classificação , Bifidobacterium/isolamento & purificação , Fezes/microbiologia , Idoso de 80 Anos ou mais , Bifidobacterium/genética , China , Eletroforese em Gel de Gradiente Desnaturante , Humanos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The study is aimed to understand the resource and the current situation of the use of Cibotii Rhizoma and provide the basis for protecting and utilization. The method of literature survey, field survey and quality assessment were applied in the study. The results showed that all the Cibotii Rhizoma came from wild resource and was mainly founded in Fujian, Guangxi, Guizhou, Yunnan, Guangdong, Hunan, Jiangxi, Sichuan, Chongqing, Zhejiang, etc. It contains over 5 000 000 kg in the area which total is about 7 000 hm2. The annual output is over 850 000 kg. At present, there is no cultivated resources. Based on the investigation and market sampling analysis from various regions, the results showed that the quality of the collected crude drugs conformed with the regulations of the Chinese pharmacopoeia. However the qualification rate of decoction pieces of Cibotii Rhizoma in market was only 56.4%. At present, the resource of Cibotii Rhizoma could meet the needs of medinal uses. It is important to protect the wild resource which is less and less because of the environmental factors. It also need to make a standard of processing method to ensure the safety, and solve quality problem of the decoction pieces.
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Gleiquênias/química , Gleiquênias/crescimento & desenvolvimento , China , Conservação dos Recursos Naturais , Medicamentos de Ervas Chinesas/análise , Controle de Qualidade , Rizoma/química , Rizoma/crescimento & desenvolvimentoRESUMO
Thermal quenching is the core challenge that hinders the application of luminescent materials. Herein, a synergistic mechanism involving energy transfer and energy gap modulation is proposed based on the local crystal field regulation around sensitizers. The substitution of coordination cation V5+/P5+ weakens the crystal field strength of the sensitizer Bi3+, and the weakening of crystal field splitting causes an increase in the 3P1 energy level, thus increasing its energy gap. Compared with the YVO4:Bi3+,Eu3+ phosphor, the thermal stability of the YV0.25P0.75O4:Bi3+,Eu3+ phosphor is significantly improved, and the relative emission intensity of Eu3+ continuously increases with heating and reaches 1.24 times the original intensity at 523 K and does not show a decreasing trend in the studied temperature range. The anti-thermal quenching performance is mainly attributed to the increasing thermal quenching activation energy (ΔE) of the sensitizer by energy gap modulation, which enhances the energy transfer to compensate thermal quenching. Based on the thermal quenching characteristics of the materials, an optical thermometer is designed. The maximum relative sensitivity (Sr) and absolute sensitivity (Sa) are as high as 1.74% K-1 and 0.59 K-1, respectively, and the minimum temperature resolution reaches 0.288 K. The synergistic effect between energy gap modulation of the sensitizer and energy transfer enables the regulation of thermal quenching. Thus, this study provides a new strategy for exploiting high-performance luminescent materials.
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The addition of Sudan dyes with carcinogenic effects to food threatens human health. Herein, a ratiometric fluorescence strip consisting of core-shell upconversion particles (NaYF4:Yb,Tm@NaYF4:Yb,Er), metal-organic frameworks and dual-template molecularly imprinted polymers was developed to selectively and sensitively detect four Sudan dyes based on inner filter effect (detection time only takes 8 min). The high adsorption capacity of metal-organic frameworks and the greater overlap between the emission of NaYF4:Yb,Tm@NaYF4:Yb,Er and the absorbance of four Sudan dyes enable the signal responses to be more sensitive. The limits of detection in chilli powder samples are as low as 29.87 ng/g, 37.55 ng/g, 47.89 ng/g and 51.02 ng/g, with satisfactory recovery (93.32-103.4%) and minor relative standard deviations (≤4.3%). This method broadens the idea for low-cost and portable detection of multiple illegal additives in complex substrates with high selectivity and sensitivity based on one kind of fluorescent strip.
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Estruturas Metalorgânicas , Impressão Molecular , Humanos , Corantes , Fluorescência , AlimentosRESUMO
BACKGROUND/AIMS: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a serious health problem, and an effective treatment is needed for use in the clinical setting. METHODS: In this study, we first constructed ALI models in Adult Sprague-Dawley rats. We then used an herbal medicine, Houttuynia cordata (HC), to enhance the effect of endothelial progenitor cells (EPCs) on ALI. RESULTS: (1) HC improved the therapeutic effects of EPCs on lipopolysachharide-induced ALI in the rat model; (2) HC down-regulated the anti-inflammatory response by suppressing inflammatory cytokines; (3) the combination of EPC and HC reduced expression of iNOS and ET-1 and subsequently prevented lung injury. CONCLUSION: Combined EPC and HC therapy was more effective than either therapy alone. EPC and HC could be used in the clinical treatment of ALI.
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Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Células da Medula Óssea/citologia , Houttuynia/química , Lipopolissacarídeos , Substâncias Protetoras/uso terapêutico , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/cirurgia , Animais , Modelos Animais de Doenças , Regulação para Baixo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Endotelina-1/metabolismo , Medicina Herbária , Houttuynia/metabolismo , Interleucina-10/sangue , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Substâncias Protetoras/química , Ratos , Ratos Sprague-Dawley , Transplante de Células-Tronco , Células-Tronco/citologia , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: Adipose-derived stromal cells (ADSCs) are a good alternative to multipotent stem cells for regenerative medicine. Low tidal volume (LVT) has proved to be an effective ventilation strategy. However, it is not known if ADSCs and LVT can protect against ventilator-induced lung injury (VILI). This study was aimed to determine the potential of ADSCs and LVT to repair following VILI and to elucidate the mechanisms responsible for this section. METHODS: A total of 72 rats were randomly assigned into group I (sham group, n=18), group II (1 h of high tidal volume-ventilated (HVT) 40 mL/kg to peak airway pressures of approximately 35 cm H2O and 100% oxygen, n=18), group III (1 h of HVT followed by 6 h LVT 6 mL/kg to peak airway pressures of approximately 6 cm H2O and 100% oxygen, n=18) and group IV (1 h of HVT followed by intravenous injection of 5 × 106 ADSCs, n=18). All animals were sacrificed 7 after the experiments lasted for 7 hours. Bronchoalveolar lavage fluid (BALF) was collected and lungs were harvested for analysis. RESULTS: High tidal volume-ventilated (HVT) rats exhibited typical VILI features compared with sham rats. Lung edema, histological lung injury index, concentrations of total protein, total cell counts, number of neutrophils in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-10 and transforming growth factor-ß1 in BALF were significantly increased in HVT rats. Additionally, gene and protein levels of Na+ channel subunits, Na-K-ATPase pump activity and alveolar fluid clearance were significantly decreased in HVT rats. All these indices of VILI were significantly improved in rats treated with ADSCs. However, compared with ADSCs treatment, LVT strategy had little therapeutic effect in the present study. CONCLUSION: These results may provide valuable insights into the effects of ADSCs in acute lung injury.
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Tecido Adiposo/citologia , Lesão Pulmonar Induzida por Ventilação Mecânica/terapia , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar , Diferenciação Celular , Membrana Celular/metabolismo , Forma Celular , Quimiocinas/metabolismo , Canais Epiteliais de Sódio/genética , Canais Epiteliais de Sódio/metabolismo , Regulação da Expressão Gênica , Pulmão/enzimologia , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Infiltração de Neutrófilos , Ratos Sprague-Dawley , ATPase Trocadora de Sódio-Potássio/metabolismo , Células Estromais/transplante , Volume de Ventilação Pulmonar , Transplante Autólogo , Lesão Pulmonar Induzida por Ventilação Mecânica/fisiopatologiaRESUMO
Phthalate esters (PAEs), widely used as plasticizers, may pose a potential environmental and human hazard. The aim of this study was to compare the cytotoxicity of di(2-ethylhexyl) phthalates (DEHP) and dibutyl phthalate (DBP)) after their exposure to HepG2 cells alone or in combination. HepG2 cells treated with individual/combined DEHP and DBP at a dose of 10-2 M for 24 h were selected for metabolome and transcriptome analysis. The results demonstrated that exposure to the mixtures of DEHP and DBP caused enhanced or reduced toxic effects regarding 8 pathways with 1065 downregulated genes and 643 upregulated genes, in comparison with those of single chemicals. The combined toxicity of mixture revealed both synergistic and antagonistic interactions between DEHP and DBP. Besides, combined exposure to DEHP and DBP promoted TCA cycle, pyrimidine, and purine metabolism, while an antagonistic effect on fatty acid derangement should require further investigation. To summarize, our results suggest that DEHP exposed alone or combined with DBP caused a variety of metabolic disorders, and the type of combination effects varied among metabolic pathways.
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Dietilexilftalato , Ácidos Ftálicos , Humanos , Dietilexilftalato/análise , Transcriptoma , Ésteres/toxicidade , Células Hep G2 , Ácidos Ftálicos/toxicidade , Dibutilftalato/toxicidade , Dibutilftalato/metabolismo , Perfilação da Expressão GênicaRESUMO
The practical application of lithium-sulfur batteries (LSBs) is still hindered by several technical issues, including severe polysulfide shuttling and sluggish redox kinetics, which reduces the sulfur utilization and further results in low energy density. Herein, amorphous-crystalline heterostructured MnO2 (ACM) prepared through a simple calcination process was employed as the functional interlayer to play a double role as effective trapper and multifunctional electrocatalyst for LSBs. ACM not only combines the strong sulfur chemisorption of the amorphous MnO2 (AM) and fast Li+ transportation of the crystalline MnO2(CM) but also accelerates the interface charge transfer at the amorphous/crystalline interfaces. The LSBs with such unique interlayer exhibited an excellent rate performance of 1155.5 mAh·g-1 at 0.2 C and 692.9 mAh·g-1 at 3 C and a low decay rate of 0.071% per cycle over 500 cycles at 0.5 C. Even for a high sulfur loading of 5 mg·cm-2 at 0.1 C, a high capacity retention of 92.3% could also be achieved after 100 cycles. The concept of amorphous-crystalline heterostructures prepared by crystallization regulation might also be used for other electronic devices and catalyst designs.
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Rechargeable aqueous Zn-I2 batteries (ZIB) are regarded as a promising energy storage candidate. However, soluble polyiodide shuttling and rampant Zn dendrite growth hamper its commercial implementation. Herein, a hetero-polyionic hydrogel is designed as the electrolyte for ZIBs. On the cathode side, iodophilic polycationic hydrogel (PCH) effectively alleviates the shuttle effect and facilitates the redox kinetics of iodine species. Meanwhile, polyanionic hydrogel (PAH) toward Zn metal anode uniformizes Zn2+ flux and prevents surface corrosion by electrostatic repulsion of polyiodides. Consequently, the Zn symmetric cells with PAH electrolyte demonstrate remarkable cycling stability over 3000 h at 1 mA cm-2 (1 mAh cm-2 ) and 800 h at 10 mA cm-2 (5 mAh cm-2 ). Moreover, the Zn-I2 full cells with PAH-PCH hetero-polyionic hydrogel electrolyte deliver a low-capacity decay of 0.008 per cycle during 18 000 cycles at 8 C. This work sheds light on hydrogel electrolytes design for long-life conversion-type aqueous batteries.
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OBJECTIVE: We aimed to investigate the prevalence of covert hepatic encephalopathy (CHE) in cirrhotic patients in China and its risk factors. METHODS: A multicenter prospective observational study was conducted from January 2021 to March 2022 at 16 medical centers across China to investigate the risk factors of CHE and establish a prediction model for CHE episodes. RESULTS: A total of 528 patients were enrolled in the study. Based on both the psychometric hepatic encephalopathy score and Stroop test results, the prevalence of CHE was 50.4% (266/528), and the consistency between these two tests was 68.9%. Multivariate analysis showed that age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.022-1.063, P < 0.001), duration of education (OR 0.891, 95% CI 0.832-0.954, P = 0.001), comorbidities of cardiovascular diseases, hypertension, cerebral apoplexy or diabetes mellitus (OR 2.072, 95% CI 1.370-3.133, P < 0.001), Child-Pugh score (OR 1.142, 95% CI 1.029-1.465, P = 0.025), and blood urea nitrogen concentration (OR 1.126, 95% CI 1.038-1.221, P = 0.004) were associated with CHE episodes. According to the Chronic Liver Disease Questionnaire, CHE patients had lower scores for abdominal symptoms and systemic symptoms (P < 0.001), indicating a poor health-related quality of life. Based on a stepwise Cox regression hazard model, we established a nomogram for determining the probabilities of CHE episodes, and the area under the receiver operating characteristic curve was 0.733 (95% CI 0.679-0.788) and 0.713 (95% CI 0.628-0.797) in the training and validation cohorts. CONCLUSIONS: CHE is a common complication of cirrhosis in China. Large-scale studies with long-term follow-up are needed to determine the natural history of Chinese CHE patients.
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Encefalopatia Hepática , Humanos , Encefalopatia Hepática/etiologia , Qualidade de Vida , Prevalência , Fatores de Risco , Cirrose Hepática/complicações , ChinaRESUMO
The purpose of the present study is to define the role of sevoflurane (SEV) in hepatic ischemia-reperfusion (I/R) injury as well as its underlying mechanism. Initially, hepatic I/R animal models and I/R hepatocyte models were established in C57BL/6 mice and normal mouse hepatocytes (BNL CL.2) after SEV preconditioning, respectively, followed by detection of microRNA-124-3p (miR-124-3p), TRAF3, and CREB expression by RT-qPCR and Western blot analysis. In addition, miR-124-3p, TRAF3 and CREB expression in hepatocytes was altered to identify their roles in modulating the levels of glutathione transferase (GST), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and inflammation-related factors and hepatocyte apoptosis by ELISA and flow cytometry respectively. The effects of SEV on the miR-124-3p/TRAF3/CREB axis were also verified in vitro and in vivo. IP assay was performed to verify the effect of TRAF3 on CREB ubiquitination in BNL CL.2 cells, and the cycloheximide (CHX) intervention experiment to detect the stability of CREB protein. SEV augmented the miR-124-3p expression in I/R animal and cell models. Moreover, SEV was observed to suppress I/R-induced liver damage, GST, ALT, and AST levels, hepatocyte apoptosis and inflammation. Overexpression of miR-124-3p resulted in alleviation of hepatic I/R injury, which was countered by TRAF3 overexpression. miR-124-3p targeted TRAF3, while TRAF3 promoted CREB ubiquitination and reduced protein stability of CREB. SEV could impede I/R-induced liver damage, GST, ALT, and AST levels, hepatocyte apoptosis and inflammation via mediation of the miR-124-3p/TRAF3/CREB axis in vitro and in vivo. Collectively, SEV may upregulate miR-124-3p to inhibit TRAF3 expression, thereby reducing the ubiquitination and degradation of CREB, alleviating hepatic I/R injury.
RESUMO
As centenarians provide a paradigm of healthy aging, investigating the comprehensive metabolic profiles of healthy centenarians is of utmost importance for the pursuit of health and longevity. However, relevant reports, especially studies considering the dietary influence on metabolism, are still limited, mostly lacking the guidance of a model of healthy aging. Therefore, exploring the signatures of the integrative metabolic profiles of the healthy centenarians from a famous longevous region, Bama County, China, should be an effective way. The global metabolome in urine and the short-chain fatty acids (SCFAs) in the feces of 30 healthy centenarians and 31 elderly people aged 60−70 from the longevous region were analyzed by non-targeted metabolomics combined with metabolic target analysis. The results showed that the characteristic metabolites related to longevity were mostly summarized into phosphatidylserine, lyso-phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, bile acids, and amino acids (p < 0.05). Six metabolic pathways were found significant relevant to longevity. Furthermore, acetic acid, propionic acid, butyric acid, valeric acid, and total SCFA were significantly increased in the centenarian group (p < 0.05) and were also positively associated with the dietary fiber intake (p < 0.01). It was age-accompanied and diet-associated remodeling of phospholipid, amino acid, and SCFA metabolism that expressed the unique metabolic signatures related to exceptional longevity. This metabolic remodeling is suggestive of cognitive benefits, better antioxidant capacity, the attenuation of local inflammation, and health-span-promoting processes, which play a critical and positive role in shaping healthy aging.