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This experiment aimed to investigate the in vitro antimicrobial activity of danofloxacin against Escherichia coli (E. coli) isolated from pigeons, as well as the pharmacokinetics of danofloxacin in pigeons following oral (PO), intramuscular (IM), and intravenous (IV) administration. The minimum inhibitory concentration (MIC) of danofloxacin was first determined for 38 clinical E. coli strains using the micro broth dilution method. Subsequently, 30 healthy pigeons were weighed and randomly divided into 3 groups: IM, IV, and PO, with 10 pigeons in each group. Danofloxacin was given at 5 mg/kg body weight (BW) through 3 different routes. Blood was collected, and plasma was separated at various time points from 0 to 48 h. Plasma samples were analyzed for danofloxacin concentrations using a validated HPLC method. Pharmacokinetic analysis was performed using Phoenix software and a noncompartmental analytical (NCA) method. The results indicated that danofloxacin had a strong antibacterial effect on E. coli, with a MIC50 of 0.5 µg/mL. The noncompartmental analysis showed that after PO and IM administration at 5 mg/kg in pigeons, peak plasma concentrations (Cmax) of 0.61 and 1.62 µg/mL were reached at 4.5 and 0.53 h, respectively. The oral and intramuscular bioavailability (F) were 68.08% ± 24.82% and 87.82% ± 25.36%, respectively. Following IV administration, danofloxacin was widely distributed in pigeons, with volume of distribution (VZ) and volume of distribution at steady state (VSS) values of 6.11 ± 2.01 and 4.65 ± 1.62 L/kg, respectively, and was eliminated slowly, with an elimination half-life (t1/2λz) of 6.41 ± 2.15 h. Based on the calculated ratio values of AUC/MIC, the current IV, IM, and PO doses of 5 mg/kg of danofloxacin would be expected to effectively treat pigeons infected with E. coli strains with MIC values equal to or less than 0.5 µg/mL.
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China is facing a serious threat PAHs contaminated soil. To better understand the current state of soil PAH pollution in China and contribute to the development of feasible prevention and control measures and policies in the future. This study examines the spatiotemporal distributions of soil Polycyclic Aromatic Hydrocarbons (PAHs) pollution in China since 2000, and investigates the key factors influencing changes in levels of soil PAHs. The results of the survey on soil PAHs concentration levels in 716 areas were analyzed by visualization of ArcGIS pro data, correlation analysis and linear regression analysis, it was found that the increase in soil PAH pollution in China is concerning. The analysis indicates significant regional disparities, with pollution levels in the north being higher than in the south. Over the 20-year period, the median level of PAHs in soil increased by 476.8 µg/kg. Construction land areas that heavily rely on fossil fuels and industrial activities exhibit significantly higher concentrations of polycyclic aromatic hydrocarbons (PAHs) compared to other land use types. The study identifies key socio-economic factors linked to rising PAH levels, including energy consumption (notably coal and oil), industrial and domestic waste production. Coal consumption is highlighted as the leading factor in PAH concentration changes in 18 provinces, followed by industrial waste in 6 provinces. Future projections up to 2030 suggest continued influence of these factors on soil PAH levels. The research emphasizes the urgent necessity for comprehensive soil management policies to address the growing PAH pollution, offering insights into its dynamics and contributing factors in China.
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BACKGROUND: Arthroscopic treatment is recommended for hip synovial chondromatosis. However, evidence regarding long-term clinical outcomes is limited. PURPOSE: To evaluate long-term patient-reported outcomes (PROs) and survival, and to determine the potential effect of residual loose bodies, as evaluated by immediate postoperative computed tomography (CT), on clinical outcomes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A consecutive cohort of patients undergoing arthroscopic treatment and diagnosed with synovial chondromatosis between March 2010 and May 2015 were included in the study. Preoperative radiography, CT, and magnetic resonance imaging were performed. Preoperative, midterm (minimum of 4 years), and long-term (minimum of 8 years) PROs were collected for visual analog scale for pain, modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), and 12-item international Hip Outcome Tool (iHOT-12). The percentages achieving minimal clinically important difference (MCID) were calculated. PROs and survival were compared between patients with and without residual loose bodies evident on immediate postoperative CT scan. RESULTS: A total of 28 patients (20% of patients were lost to follow-up) were included in the study with a mean follow-up period of 104.9 months (range, 96-139 months). PROs including visual analog scale for pain (preoperative, 3.8 ± 1.2; midterm, 0.9 ± 1.7; long-term, 0.8 ± 1.4), mHHS (preoperative, 66.4 ± 14.4; midterm, 92.8 ± 12.3; long-term, 93.5 ± 10.5), NAHS (preoperative, 45.2 ± 16.2; midterm, 81.8 ± 15.3; long-term, 83.1 ± 12.9), and iHOT-12 (preoperative, 48.4 ± 15.6; midterm, 69.3 ± 11.7; long-term, 72.7 ± 11.4) were improved at both midterm and long-term follow-up (all with P < .001). In total, 27 (96.4%), 28 (100%), and 26 (92.9%) patients achieved MCID for mHHS, NAHS and iHOT-12, respectively, at the long-term follow-up. No significant difference was found in any of the PROs and the rate of achieving MCID between midterm and long-term follow-up (all with P > .05). One patient (3.6%) underwent revision surgery. Among the 23 patients who had loose bodies on preoperative CT or radiographs, 14 patients (60.9%) with residual loose bodies evident on immediate postoperative CT demonstrated lower NAHS (P = .045) and iHOT-12 (P = .037) scores but a comparable survival (P > .05) at long-term follow-up compared with those who did not have loose bodies. CONCLUSION: Arthroscopic treatment for hip synovial chondromatosis achieved satisfactory long-term clinical outcomes with strong survival. Most patients maintained or improved their overall functional status between midterm and long-term follow-up. Furthermore, patients with residual loose bodies had less favorable clinical outcomes, although the survival rate was comparable.
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Artroscopia , Condromatose Sinovial , Articulação do Quadril , Medidas de Resultados Relatados pelo Paciente , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Condromatose Sinovial/cirurgia , Condromatose Sinovial/diagnóstico por imagem , Seguimentos , Articulação do Quadril/cirurgia , Articulação do Quadril/diagnóstico por imagem , Corpos Livres Articulares/cirurgia , Corpos Livres Articulares/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Estudos Longitudinais , Resultado do Tratamento , Idoso , Imageamento por Ressonância Magnética , Medição da DorRESUMO
With the increasing attention paid to macrocyclic scaffolds in peptide drug development, genetically encoded peptide macrocycle libraries have become invaluable sources for the discovery of high-affinity peptide ligands targeting disease-associated proteins. The traditional phage display technique of constructing disulfide-tethered macrocycles by cysteine oxidation has the inherent drawback of reduction instability of the disulfide bond. Chemical macrocyclization solves the problem of disulfide bond instability, but the involved highly electrophilic reagents are usually toxic to phages and may bring undesirable side reactions. Here, we report a unique Sortase-mediated Peptide Ligation and One-pot Cyclization strategy (SPLOC) to generate peptide macrocycle libraries, avoiding the undesired reactions of electrophiles with phages. The key to this platform is to mine the unnatural promiscuity of sortase on the X residue of the pentapeptide recognition sequence (LPXTG). Low reactive electrophiles are incorporated into the X-residue side chain, enabling intramolecular cyclization with the cysteine residue of the phage-displayed peptide library. Utilizing the genetically encoded peptide macrocycle library constructed by the SPLOC platform, we found a high-affinity bicyclic peptide binding TEAD4 with a nanomolar KD value (63.9 nM). Importantly, the binding affinity of the bicyclic peptide ligand is 102-fold lower than that of the acyclic analogue. To our knowledge, this is the first time to mine the unnatural promiscuity of ligases to generate peptide macrocycles, providing a new avenue for the construction of genetically encoded cyclic peptide libraries.
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We describe a simple and robust oxidation strategy for preparing N-terminal thiazolidine-containing peptide thioesters from peptide hydrazides. We find for the first time that l-thioproline can be used as a protective agent to prevent the nitrosation of N-terminal thiazolidine during peptide hydrazide oxidation. The thioproline-based oxidation strategy has been successfully applied to the chemical synthesis of CC chemokine ligand-2 (69aa) and omniligase-C (113aa), thereby demonstrating its utility in hydrazide-based native chemical ligation.
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Oxirredução , Peptídeos , Tiazolidinas , Tiazolidinas/química , Tiazolidinas/síntese química , Estrutura Molecular , Peptídeos/química , Peptídeos/síntese química , Hidrazinas/química , Prolina/química , Ésteres/química , Compostos de Sulfidrila/químicaRESUMO
To solve the problem of unclear targeted inhibition of key free radicals by antioxidants, this paper took the hydroxyl radical with the highest oxidation activity of coal as the inhibition target and selected five antioxidants such as ethylene diamine tetraacetic acid, tea polyphenol, citric acid, vitamin C, and proanthocyanidins. Based on the theory of quantum chemistry, the characteristics and oxidation pathway of antioxidants inhibiting coal oxidation of hydroxyl radical were analyzed. Analyze the influence characteristics of antioxidants on the evolution of free radicals in coal through an electron paramagnetic resonance experiment (ESR). The results showed that the electron density of antioxidants was mainly distributed in the functional groups of carboxyl and hydroxyl, which played a key inhibitory role, and the vicinity of carboxyl and hydroxyl and other functional groups was positive potential, which was the active site of inhibiting hydroxyl radical. The order of inhibitory capacity of the five antioxidants was determined as GTP > PC > EDTA > CA > VC. It is concluded that the energy barrier of hydroxyl radical inhibition by citric acid is much lower than that of EDTA. For the hydrogen extraction reaction, VC inhibited the hydroxyl radical pathway with a higher energy barrier than the other three antioxidants. The mechanism of five antioxidants inhibiting â¢OH reaction was comprehensively analyzed. It was found that tea polyphenols have more active sites that can react with â¢OH to quench it, so the inhibition of tea polyphenols should be the most significant. When antioxidants inhibit coal spontaneous combustion, the type, complexity, concentration, and linewidth of free radicals in coal molecules are lower than those in raw coal, with GTP antioxidants having the best inhibitory effect. The research results have important theoretical and practical significance for revealing the mechanism of coal spontaneous combustion inhibition and developing directional coal spontaneous combustion inhibition technology.
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Antioxidantes , Carvão Mineral , Radical Hidroxila , Oxirredução , Radical Hidroxila/química , Antioxidantes/química , Antioxidantes/farmacologia , Espectroscopia de Ressonância de Spin EletrônicaRESUMO
Titanium (Ti), as a hard tissue implant, is facing a big challenge for rapid and stable osseointegration owing to its intrinsic bio-inertness. Meanwile, surface-related infection is also a serious threat. In this study, large-scale quasi-vertically aligned sodium titanate nanowire (SNW) arrayed coatings incorporated with bioactive Cu2+ ions were fabricated through a compound process involving acid etching, hydrothermal treatment (HT), and ion exchange (IE). A novel coating based on sustained ion release and a shape-preserving design is successfully obtained. Cu2+ substituted Na+ in sodium titanate lattice to generate Cu-doped SNW (CNW), which maintains the micro-structure and phase components of the original SNW, and can be efficiently released from the structure by immersing them in physiological saline (PS) solutions, ensuring superior long-term structural stability. The synergistic effects of the acid etching, bidirectional cogrowth, and solution-strengthening mechanisms endow the coating with higher bonding strengths. In vitro antibacterial tests demonstrated that the CNW coatings exhibited effective good antibacterial properties against both Gram-positive and Gram-negative bacteria based on the continuous slow release of copper ions. This is an exciting attempt to achieve topographic, hydrophilic, and antibacterial activation of metal implants, demonstrating a paradigm for the activation of coatings without dissolution and providing new insights into insoluble ceramic-coated implants with high bonding strengths.
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Persistent cadmium exposure poses significant health risks to the Chinese population, underscored by its prevalence as an environmental contaminant. This study leverages a machine-learning model, fed with a comprehensive dataset of environmental and socio-economic factors, to delineate trends in cadmium exposure from 1980 to 2040. We uncovered that urinary cadmium levels peaked at 1.09 µg/g Cr in the mid-2000 s. Encouragingly, a decline is projected to 0.92 µg/g Cr by 2025, tapering further to 0.87 µg/g Cr by 2040. Despite this trend, regions heavily influenced by industrialization, such as Hunan and Guizhou, as well as industrial counties in Jilin, report stubbornly high levels of exposure. Our demographic analysis reveals a higher vulnerability among adults & adolescents over 14, with males displaying elevated cadmium concentrations. Alarmingly, the projected data suggests that by 2040, an estimated 41% of the population will endure exposure beyond the safety threshold set by the European Food Safety Authority. Our research indicates disproportionate cadmium exposure impacts, necessitating targeted interventions and policy reforms to protect vulnerable groups and public health in China.
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Cádmio , Exposição Ambiental , Cádmio/urina , China , Humanos , Masculino , Adulto , Adolescente , Adulto Jovem , Feminino , Exposição Ambiental/análise , Criança , Pessoa de Meia-Idade , Pré-Escolar , Poluentes Ambientais/urina , Idoso , Lactente , Análise Espaço-Temporal , Aprendizado de MáquinaRESUMO
North China type coalfield are gradually mining deep, and the mixing of groundwater is intensified. Hydrogen and oxygen isotopes are important elements for tracing groundwater movement. The fractionation response mechanism under mining conditions is not clear. In this paper, combined with numerical simulation, MixSIAR isotope mixing model and other methods, according to the δD, δ18O and hydrochemical information of various water bodies, the impact of coal mining on hydrogen and oxygen isotope fractionation is analyzed from multiple perspectives. The results show that summer soil water is the main source of recharge for limestone water, accounting for 30.7%-41.5%, and the Zhan River is the main source of recharge for limestone water. Before groundwater recharge, evaporation leads to the increase of δ18O in surface water by 0.31-5.58, water loss by 1.81%-28.00%, the increase of δ18O in soil water by 0.47-6.33, and water loss by 2.74%-35.80%. Compared with the coal mining layer, the degree of hydrogen and oxygen isotope drift and water-rock interaction in the coal mine stopping layer are significantly improved. The results of numerical simulation show that the pumping activity reduces the 18O concentration in the mining layer. The ion ratio is used as a new variable to eliminate the influence of water-rock interaction when calculating the mixing ratio. The results show that the limestone water is in a state of receiving external recharge, and mixing effect increases the δ18O in limestone water by 0.86 on average, and the δD increases by 0.72 on average. The research results explain the controlled process of hydrogen and oxygen isotope fractionation under mining conditions, which is of great significance to coal mine safety production.
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Carbonato de Cálcio , Água Subterrânea , Isótopos de Oxigênio , Isótopos de Oxigênio/análise , Água Subterrânea/química , Água Subterrânea/análise , Carbonato de Cálcio/química , Carbonato de Cálcio/análise , Minas de Carvão , Deutério/análise , Fracionamento Químico , Mineração , Movimentos da Água , Monitoramento Ambiental/métodos , China , Hidrogênio/análise , Hidrogênio/químicaRESUMO
The current study aimed to investigate the pharmacokinetics of bromhexine hydrochloride in broilers after single intravenous (IV) and oral (PO) administration at 2.5 mg/kg body weight (BW). The trial adopted a randomized, parallel-controlled design, where 20 twelve-wk-old broilers were randomly assigned to either the PO or IV group. Blood samples were collected at predetermined time points, and plasma was further separated for analysis. The bromhexine hydrochloride concentrations in plasma samples were determined using an ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method. Noncompartmental analysis (NCA) using Phoenix software was conducted to analyze the concentration versus time data of bromhexine hydrochloride in every chicken. Subsequently, the main pharmacokinetic parameters between the 2 groups were statistically analyzed using SPSS software. Results from NCA revealed that after oral administration at 2.5 mg/kg BW, bromhexine hydrochloride exhibited slow absorption, reaching an average peak concentration of 32.72 ng/mL at 1.78 h. However, incomplete absorption was observed, with an absolute bioavailability of only 20.06% ± 10.84%. Additionally, bromhexine hydrochloride displayed wide distribution, with a steady-state distribution volume (VSS) of 22.55 ± 13.45 L/kg, and slow elimination, with a clearance (Cl) of 1.52 ± 0.38 L/h/kg. Furthermore, gender effects were assessed on the pharmacokinetics of bromhexine hydrochloride in broilers, revealing better absorption in male broilers compared to females. This disparity may be attributed to the faster blood flow and richer blood volume typically found in male broilers.
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Bromoexina , Galinhas , Animais , Masculino , Administração Oral , Feminino , Bromoexina/farmacocinética , Bromoexina/administração & dosagem , Injeções Intravenosas/veterinária , Espectrometria de Massas em Tandem/veterinária , Distribuição Aleatória , Disponibilidade Biológica , Administração Intravenosa/veterináriaRESUMO
NACs (NAMãATAF1/2ãCUC1/2), as a large family of plant transcription factors, are widely involved in abiotic stress responses. This study aimed to isolate and clone a novel stress-responsive transcription factor LpNAC5 from Lilium pumilum bulbs. Drought, salt, alkali, and ABA stresses induced the expression of LpNAC5. Transgenic tobacco plants overexpressing LpNAC5 were generated using the Agrobacterium-mediated method to understand the role of this factor in stress response. These plants exhibited increased tolerance to drought, salt, and alkali stresses. The tobacco plants overexpressing LpNAC5 showed strong drought, salt, and alkaline tolerance. Under the three abiotic stresses, the activities of antioxidant enzymes were enhanced, the contents of proline and chlorophyll increased, and the contents of malondialdehyde decreased. The functional analysis revealed that LpNAC5 enabled plants to positively regulate drought and salt stresses. These findings not only provided valuable insights into stress tolerance mechanisms in L. pumilum but also offered a potential genetic resource for breedi.
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Secas , Regulação da Expressão Gênica de Plantas , Lilium , Proteínas de Plantas , Plantas Geneticamente Modificadas , Tolerância ao Sal , Estresse Fisiológico , Lilium/genética , Lilium/metabolismo , Plantas Geneticamente Modificadas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tolerância ao Sal/genética , Estresse Fisiológico/genética , Nicotiana/genética , Nicotiana/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse SalinoRESUMO
To study thermal behaviour during spontaneous combustion of an open-pit coal mine, mixed slag (coal, oil shale, and coal gangue) was taken as the research object. Laser thermal conductivity analyser and differential scanning calorimetry were used to test thermophysical parameters and heat release characteristics of the minerals. The parameters can be employed to calculate the apparent activation energy using the Arrhenius equation and evaluate the thermal behaviour of open-pit mixed slag. The results indicate that thermophysical parameters have stage characteristics. Thermal diffusivity and thermal conductivity of minerals, especially mixed slag, have a strong correlation with temperature. Heat flow of minerals exhibits five characteristic stages, and heat flow of the samples is consistent with the change in heating rate. During the heating process, thermal diffusivity and heat flow of the mixed slag are between those of a single mineral. Except for the mixed slag at 15 and 20 °C/min, the initial exothermic temperature of the other samples is mainly concentrated at 50-80 °C. Thermal energy release of the sample is mainly concentrated in the accelerated exothermic stage and rapid exothermic stage. Thermal energy release of mixed slag in rapid exothermic stage is always greater than that in accelerated exothermic stage, and the proportion of thermal energy release in these two stages exceeds 98 %. The apparent activation energy during the accelerated exothermic stage is lower, making it easier to release heat, and rapid exothermic stage is relatively high, which can readily lead to heat accumulation. Thermal analysis reveals that the thermal behaviour of mixed slag is significantly different from that of a single mineral. Its unique exothermic characteristics can provide a more accurate theoretical basis for the prevention and control of environmental pollution caused by slag spontaneous combustion.
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Lead poisoning is globally concerning, yet limited testing hinders effective interventions in most countries. We aimed to create annual maps of county-specific blood lead levels in China from 1980 to 2040 using a machine learning model. Blood lead data from China were sourced from 1180 surveys published between 1980 and 2022. Additionally, regional statistical figures for 15 natural and socioeconomic variables were obtained or estimated as predictors. A machine learning model, using the random forest algorithm and 2973 generated samples, was created to predict county-specific blood lead levels in China from 1980 to 2040. Geometric mean blood lead levels in children (i.e., age 14 and under) decreased significantly from 104.4 µg/L in 1993 to an anticipated 40.3 µg/L by 2040. The number exceeding 100 µg/L declined dramatically, yet South Central China remains a hotspot. Lead exposure is similar among different groups, but overall adults and adolescents (i.e., age over 14), females, and rural residents exhibit slightly lower exposure compared to that of children, males, and urban residents, respectively. Our predictions indicated that despite the general reduction, one-fourth of Chinese counties rebounded during 2015-2020. This slower decline might be due to emerging lead sources like smelting and coal combustion; however, the primary factor driving the decline should be the reduction of a persistent source, legacy gasoline-derived lead. Our approach innovatively maps lead exposure without comprehensive surveys.
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Chumbo , Aprendizado de Máquina , Chumbo/sangue , China , Humanos , Feminino , Masculino , Criança , Adolescente , Exposição Ambiental , Intoxicação por Chumbo/epidemiologia , Intoxicação por Chumbo/sangueRESUMO
BACKGROUND: To evaluate the effectiveness of the computed tomographic (CT) volumetric analysis in postoperative lung function assessment and the predicting value for postoperative complications in patients who had segmentectomy for lung cancer. METHODS: CT scanning and pulmonary function examination were performed for 100 patients with lung cancer. CT volumetric analyses were performed by specific software, for the volume of the inspiratory phase (Vin), the mean inspiratory lung density (MLDin), the volume of expiratory phase (Vex), and the mean lung density at expiratory phase (MLDex). Pulmonary function examination results and CT volumetric analysis results were used to predict postoperative lung function. The concordance and correlations of these values were assessed by Bland-Altman analysis and Pearson correlation analysis, respectively. Multivariate binomial logistic regression analysis was executed to assess the associations of CT data with complication occurrence. RESULTS: Correlations between CT scanning data and pulmonary function examination results were significant in both pre- and post-operation (0.8083 ≤ r ≤ 0.9390). Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the ratio of FVC and FEV1 estimated by CT volumetric analyses showed high concordance with those detected by pulmonary function examination. Preoperative (Vin-Vex) and (MLDex- MLDin) values were identified as predictors for post-surgery complications, with hazard ratios of 5.378 and 6.524, respectively. CONCLUSIONS: CT volumetric imaging analysis has the potential to determine the pre- and post-operative lung function, as well as to predict post-surgery complication occurrence in lung cancer patients with pulmonary lobectomy.
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Neoplasias Pulmonares , Complicações Pós-Operatórias , Testes de Função Respiratória , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Pneumonectomia/efeitos adversos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Adulto , Período Pós-Operatório , Idoso de 80 Anos ou mais , Capacidade VitalRESUMO
Poa pratensis L. (Poaceae) is a valuable grass across the north hemisphere, inhabiting diverse environments with wide altitudinal span, where ubiquitous various kinds of stresses. Phytohormones would be helpful to improve tolerance to abiotic and biotic stresses, but the responses of transcriptome regulation of P. pratensis to exogenous phytohormones application remain unclear. In this study, we explored the alteration of plant physiological responses by the application of phytohormones. Aiming to achieve this knowledge, we got full-length transcriptome data 42.76 Gb, of which 74.9% of transcripts were completed. Then used 27 samples representing four treatments conducted at two time points (1 h and 6 h after application) to generate RNA-seq data. 371 and 907 common DEGs were identified in response to four phytohormones application, respectively, these DEGs were involved in "plant hormone signal transduction", "carbon metabolism" and "plant-pathogen interaction". Finally, P. pratensis basic research can gain valuable information regarding the responses to exogenous application of phytohormones in physiological indicators and transcriptional regulations in order to facilitate the development of new cultivars.
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Poa , Transcriptoma , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Reguladores de Crescimento de Plantas/farmacologia , Poa/genética , Estresse FisiológicoRESUMO
We report here an enzymatic strategy for asparaginyl endopeptidase-mediated peptide cyclization. Incorporation of chloroacetyl groups into the recognition sequence of OaAEP1 enabled intramolecular cyclization with Cys residues. Combining this strategy and phage display, we identified nanomolar macrocyclic peptide ligands targeting TEAD4. One of the bicyclic peptides binds to TEAD4 with a KD value of 139 nM, 16 times lower than its linear analogue, demonstrating the utility of this platform in discovering high-affinity macrocyclic peptide ligands.
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Bacteriófagos , Peptídeos , Ciclização , Peptídeos/química , Cisteína Endopeptidases , Ligantes , Bacteriófagos/metabolismo , Biblioteca de Peptídeos , Peptídeos Cíclicos/químicaRESUMO
Chemodynamic therapy (CDT) based on intracellular Fenton reaction to produce highly cytotoxic reactive oxygen species (ROS) has played an essential role in tumor therapy. However, this therapy still needs to be improved by weakly acidic pH and over-expression of glutathione (GSH) in tumor microenvironment (TEM), which hinders its future application. Herein, we reported a multifunctional bimetallic composite nanoparticle MnO2@GA-Fe@CAI based on a metal polyphenol network (MPN) structure, which could reduce intracellular pH and endogenous GSH by remodeling tumor microenvironment to improve Fenton activity. MnO2 nanoparticles were prepared first and MnO2@GA-Fe nanoparticles with Fe3+ as central ion and gallic acid (GA) as surface ligands were prepared by the chelation reaction. Then, carbonic anhydrase inhibitor (CAI) was coupled with GA to form MnO2@GA-Fe@CAI. The properties of the bimetallic composite nanoparticles were studied, and the results showed that CAI could reduce intracellular pH. At the same time, MnO2 could deplete intracellular GSH and produce Mn2+ via redox reactions, which re-established the TME with low pH and GSH. In addition, GA reduced Fe3+ to Fe2+. Mn2+ and Fe2+ catalyzed the endogenous H2O2 to produce high-lever ROS to kill tumor cells. Compared with MnO2, MnO2@GA-Fe@CAI could reduce the tumor weight and volume for the xenograft MDA-MB-231 tumor-bearing mice and the final tumor inhibition rate of 58.09 ± 5.77%, showing the improved therapeutic effect as well as the biological safety. Therefore, this study achieved the high-efficiency CDT effect catalyzed by bimetallic through reshaping the tumor microenvironment.
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Nanopartículas , Neoplasias , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Peróxido de Hidrogênio , Compostos de Manganês/farmacologia , Espécies Reativas de Oxigênio , Óxidos , Ácido Gálico , Glutationa , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
This study aimed to compare the residue depletion of gamithromycin in yellow-feather and white-feather broilers, using Sanhuang and Arbor Acres chickens as typical examples, respectively. Each breed (54 chickens) received a single subcutaneous dose of gamithromycin at 7.5 mg/kg bodyweight (BW). Tissues, including muscle, skin + fat, liver, kidney, and injection site, were collected at 6 h, 3, 5, 7, 10, 14, 21, 28, and 35 d postdrug administration. Gamithromycin concentrations in these tissues were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The kinetics of gamithromycin were analyzed in different tissues using a noncompartmental method in the Phoenix software. Differences were observed in gamithromycin concentrations and kinetic characteristics in both breeds of chickens, with higher residue concentrations and longer residue times found in yellow-feathered broilers. In Sanhuang broilers, the elimination rates of gamithromycin followed this order: injection site > muscle > liver > kidney > skin + fat. The corresponding elimination half-lives (t1/2λzs) in these samples were 1.22, 1.30, 1.71, 2.04, and 2.52 d, respectively. In contrast, in Arbor Acres broilers, a different order was noted: muscle > injection site > kidney > liver > skin + fat, with corresponding t1/2λzs of 1, 1.23, 1.88, 1.93, and 2.21 d, respectively. These differences may be related to variations in pigments in various tissues of chickens of the 2 breeds. However, further investigations are warranted to discern the underlying reasons.
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Antibacterianos , Galinhas , Resíduos de Drogas , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Antibacterianos/análise , Resíduos de Drogas/análise , Injeções Subcutâneas/veterinária , Plumas/química , Macrolídeos/administração & dosagem , Macrolídeos/farmacocinética , Macrolídeos/análise , Espectrometria de Massas em Tandem/veterinária , MasculinoRESUMO
Despite the significant threat of cadmium exposure in China, a national-level assessment has been conspicuously absent. This study bridges this critical gap by collecting, geospatial analyzing and multivariable regression analyzing published studies on urinary cadmium levels in Chinese from 1982 to 2021. Our research reveals a notable decline trend in cadmium exposure among Chinese populations. However, this trend varies by region, age and gender group, higher levels are seen in the South (1.04 µg/g cr) compared to the North (0.48 µg/g cr), and in adults (1.08 µg/g cr) relative to children (0.33 µg/g cr), with higher levels being more pronounced in females (6.17 µg/g cr). Urinary cadmium is significantly correlated with rice consumption (P < 0.001), while mining activities have been identified as the dominant factor for cadmium exposure in most regions of China, a trend that is evident both in past decades and is expected to continue into the next decade. These findings underscore the need for region-specific environmental and public health strategies, designed to effectively address the distinct cadmium exposure risks in various regions and among different population groups, thus enhancing protection against the adverse effects of cadmium.
Assuntos
Cádmio , Exposição Ambiental , Cádmio/urina , Cádmio/análise , China , Humanos , Feminino , Masculino , Criança , Exposição Ambiental/análise , Poluentes Ambientais/urina , Poluentes Ambientais/análise , Adulto , Pré-Escolar , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Lactente , Monitoramento AmbientalRESUMO
This study aimed to investigate the in vitro antibacterial activity of danofloxacin against Escherichia coli isolated from Gushi chickens, as well as the tissue distribution and residue depletion of danofloxacin in Gushi chickens following multiple oral administration. A total of 42 clinical E. coli strains were isolated from the cloaca of locally farmed Gushi chickens between August and October 2023. Then the minimum inhibitory concentration (MIC) of danofloxacin against these isolates was determined by broth microdilution method. Additionally, 42 healthy Gushi chickens were randomly divided into 6 groups, and danofloxacin was orally administered at a dose of 5 mg/kg body weight (BW) for 3 consecutive days. Plasma, intestinal content, and tissue samples, including muscle, skin + fat, liver, kidney, lung, and intestine, were collected at 4, 12, 24, 48, 72, and 120 h after the last administration. Danofloxacin concentrations in all samples were determined using a high-performance liquid chromatography (HPLC) method. The average concentration vs. time data were then subjected to noncompartmental analysis using Phoenix software, and withdrawal periods for danofloxacin in Gushi chickens were further determined with WT1.4 software, setting a 95% confidence interval. Results indicated a notable inhibitory effect of danofloxacin on E. coli, with an MIC50 of 0.5 µg/mL. Additionally, danofloxacin exhibited widespread distribution in Gushi chickens, detectable in all collected samples. Among all tissues, the liver exhibited the highest concentration, followed by the intestine. Even on the fifth day postadministration, danofloxacin persisted in skin + fat, liver, and lung. The elimination half-lives (t1/2λzs) of danofloxacin varied across samples: skin + fat (47.87 h), lung (30.61 h), liver (22.07 h), plasma (16.05 h), muscle (12.53 h), intestine (9.83 h), and kidney (6.34 h). Considering residue depletion and the maximum residue limit (MRL) of danofloxacin in poultry set by Chinese regulatory authorities, withdrawal periods for the kidney, muscle, liver, and skin + fat were determined as 1.03, 1.38, 3.34, and 5.85 d, respectively, rounded to a final withdrawal time of 6 d.