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Microplastics (MPs) have become a significant concern for their potential toxicity. However, the correlation between the size of plastic particles and their toxicity remains inconclusive. Here, we investigate the toxic effects of different sizes (80 nm, 800 nm, 8 µm and 80 µm) polystyrene MPs (PS-MPs) on the model organism Nile tilapia (Oreochromis niloticus). The results of bioluminescent imaging indicate that the 80 nm PS-MPs are more likely to invade the body. H&E staining shows severe damage on the intestinal villi and distinct hepatic steatosis in the 80 nm group. EdU labeling shows that the proliferation activity of intestinal and liver cells reduces significantly in the 80 nm group. The gut microbiome analysis shows a severe imbalance of gut microbiota homeostasis in the 80 nm group. The analysis of liver transcriptomics and metabolomics shows that the liver lipid metabolism is disordered in the 80 nm group. In conclusion, this study confirms that the 80 nm PS-MPs are more likely to induce intestinal and liver toxicity. All the above lay the foundation for further study on the pathological damage of MPs to other organisms.
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Ciclídeos , Poluentes Químicos da Água , Animais , Poliestirenos/toxicidade , Poliestirenos/metabolismo , Microplásticos/toxicidade , Plásticos , Ciclídeos/metabolismo , Água , Fígado/metabolismo , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismoRESUMO
STUDY OBJECTIVE: The incidence of pruritus from neuraxial opioids is about 60%. Pruritus causes discomfort and decreases the quality of recovery. This randomized double-blinded clinical trial was aimed to evaluate the prophylactic effects of a single dose IV nalmefene on the incidence and severity of epidural opioid-induced pruritus within 24 h after surgeries. DESIGN: A two-center, randomized, double blinded, controlled clinical trial. SETTING: The study was conducted from March 2022 to February 2023 at two tertiary care hospitals in China. PATIENTS: Patients aged between 18 and 80 years-old who underwent elective surgeries and received epidural analgesia intra- and post-operatively were screened for study enrollment. A total of 306 patients were enrolled, 302 patients underwent randomization and 296 patients were included in the final analysis. INTERVENTIONS: The nalmefene group was prophylactically given 0.5 µg/kg nalmefene intravenously while the control group was given the same volume of saline. MEASUREMENTS: The primary endpoint was the incidence of pruritus within 24 h after surgeries. The secondary endpoints included time of the first patient-reported pruritus, severity of pruritus after surgeries, severity of acute pain scores after surgeries and other anesthesia/analgesia related side effects. MAIN RESULTS: Pruritus occurred in 51 of the 147 (34.69%) patients in the control group and 35 of the 149 (23.49%) patients in the nalmefene group (odds ratio, 0.58; 95% CI, 0.35 to 0.96; P = 0.034) within 24 h postoperatively. Nalmefene group demonstrated delayed onset of pruritus, reduced severity of pruritus and decreased vomiting within 24 h after surgery. There were no significant differences in postoperative analgesia and the incidence of other anesthesia/analgesia associated side effects. CONCLUSIONS: A single dose of 0.5 µg/kg nalmefene intravenously significantly reduced the incidence and severity of epidural-opioid induced pruritus within 24 h after surgery without affecting the efficacy of epidural analgesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn) and the registration number is ChiCTR2100050463. Registered on August 27th, 2021.
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Analgesia Epidural , Analgésicos Opioides , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Morfina , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Prurido/induzido quimicamente , Prurido/epidemiologia , Prurido/prevenção & controle , Analgesia Epidural/efeitos adversos , Método Duplo-CegoRESUMO
Flooding time and external nitrogen (N) input have been projected to be the main threats to marsh ecosystems in the scenario of more intense flooding events and N deposition. How flooding and N addition experienced at different growth stages interact in determining phenotypic change remains scarce. We established a controlled experiment (3 flooding time treatments x 5 N addition levels) using two herbaceous marsh species (Phragmites australis and Bolboschoenus planiculmis) to assess the responses of six key traits to environmental changes and the indication of plant performance. Early flooding reduced plant height and aboveground biomass of P. australis and below/aboveground biomass ratio of B. planiculmis and increased below/aboveground biomass ratio of P. australis and root biomass of B. planiculmis, whereas late flooding reduced root biomass of P. australis and ramet number and aboveground biomass of B. planiculmis. The combination of flooding and high N (16 and 32 g N m-2) exerted negative effects on ramet number of both plant species. The interaction of early flooding and low-medium N (8 and 16 g N m-2) inhibited clonal/belowground biomass ratio of both plant species. The combination of early flooding and low N (0, 4 and 8 g N m-2) promoted root biomass and below/aboveground biomass ratio of P. australis. Ramet number, plant height, and root biomass explained 80-90 % of aboveground biomass variation of both plant species, and the contribution of ramet number was greater than that of the other two traits. These results highlight that the influence of flooding time and external N input on the performance of marsh plants depends on species identity. Meanwhile, the ramet number-plant height-root biomass (RHR) strategy is supposed to be the adaptation strategy of wetland clonal plants to environmental changes, and clonal reproductive traits should be incorporated into vegetation dynamics models for marsh plants.
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Cyperaceae , Poaceae , Áreas Alagadas , Ecossistema , Nitrogênio , Plantas , BiomassaRESUMO
Quantum storage and distribution of entanglement are the key ingredients for realizing a global quantum internet. Compatible with existing fiber networks, telecom-wavelength entangled photons and corresponding quantum memories are of central interest. Recently, 167Er3+ ions have been identified as a promising candidate for an efficient telecom quantum memory. However, to date, no storage of entangled photons, the crucial step of quantum memory using these promising ions, 167Er3+, has been reported. Here, we demonstrate the storage and retrieval of the entangled state of two telecom photons generated from an integrated photonic chip. Combining the natural narrow linewidth of the entangled photons and long storage time of 167Er3+ ions, we achieve storage time of 1.936 µs, more than 387 times longer than in previous works. Successful storage of entanglement in the crystal is certified using entanglement witness measurements. These results pave the way for realizing quantum networks based on solid-state devices.
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Keloid formation is a pathological consequence resulting from cutaneous irritation and injury, primarily attributed to excessive collagen matrix deposition and fibrous tissue proliferation. Chronic inflammation, left uncontrolled over an extended period, also stands as a substantial contributing factor. The precise mechanisms underlying keloid formation remain unclear. Therefore, this study aimed to identify key genes for diagnostic purposes. To achieve this, we used two Gene Expression Omnibus (GEO) data sets to identify differentially expressed genes. We identified one particular gene, homeobox C9 (HOXC9), using a thorough strategy involving two algorithms (least absolute shrinkage and selection operator and support vector machine-recursive feature elimination) and weighted gene co-expression network analysis. We then assessed its expression in normal and keloid tissues. In addition, we explored its temporal expression patterns via Mfuzz time clustering analysis. In our comprehensive analysis, we observed that immune infiltration, as well as cell proliferation, are crucial to keloid formation. Thus, we investigated immune cell infiltration in the keloid and normal groups, as well as the correlation between HOXC9 and these immune cells. It was found that HOXC9 was closely associated with the immune microenvironment of keloids. This shows that HOXC9 can serve as a potential biomarker and therapeutic target for keloids.
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Queloide , Humanos , Queloide/genética , Algoritmos , Biomarcadores , Proliferação de Células/genética , Biologia Computacional , InflamaçãoRESUMO
BACKGROUND: Compelling evidences indicated that circular RNA (circRNA) was a novel class of non-coding RNA that played critical and distinct roles in various human cancers. Their roles and underlying mechanisms, however, in bladder cancer (BC) remained largely unknown. METHODS: A novel circRNA derived from oncogene FSCN1, namely circFSCN1, was selected from a microarray analysis. The phenotypic alterations were assessed with functional experiments in vitro and in vivo. RNA immunoprecipitation, RNA pull-down, luciferase reporter assay, and rescue experiments were sequentially proceeded to clarify the interactions among circFSCN1, miR-145-5p, MDM2, and p53. RESULTS: We observed that the expression of circFSCN1 was elevated in BC cell lines and tissues. Next, we validated the fundamental properties of circFSCN1. In the meanwhile, we noticed that elevated circFSCN1 level, pathological T stage, and tumor grade were identified as independent factors associated with cancer-specific survivals of patients with BCï¼as determined by univariate and multivariable COX regression analyses. Phenotype studies demonstrated the promoting effects of circFSCN1 on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of BC cells. Mechanistically, we elucidated that circFSCN1, primarily localized in the cytoplasm, upregulated the expression of MDM2, a well-known inhibitor of p53, by directly binding to miR-145-5p. CONCLUSIONS: Elevated circFSCN1 induces tumor progression and EMT in BC via enhancing MDM2-mediated silencing of p53 by sponging miR-145-5p. Targeting circFSCN1, a novel identified target, may be conducive in impeding BC progression and providing survival benefits for patients with BC.
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ABSTRACT: A 52-year-old woman with medical history of surgery for left malignant phyllodes breast tumor found a mass on the left chest 3 months ago. A suspicion of recurrent malignant phyllodes breast tumor was made. The patient was enrolled in the clinical trial of 18F-FAPI PET/CT in recurrent sarcoma (no. NCT05485792). 18F-FAPI PET/CT and 18F-FDG PET/CT were performed, and the images demonstrated intense uptake in a huge mass in the left anterior chest wall. Then the patient underwent extended resection of left chest wall tumor. The tumor proved to be recurrent malignant phyllodes breast tumor pathologically.
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Carbapenem-resistant Acinetobacter baumannii (CRAB) strains are prevalent worldwide and represent a major threat to public health. However, treatment options for infections caused by CRAB are very limited as they are resistant to most of the commonly used antibiotics. Consequently, understanding the mechanisms underlying carbapenem resistance and restoring bacterial susceptibility to carbapenems hold immense importance. The present study used gas chromatography-mass spectrometry (GC-MS)-based metabolomics to investigate the metabolic mechanisms of antibiotic resistance in clinically isolated CRAB. Inactivation of the pyruvate cycle and purine metabolism is the most typical characteristic of CRAB. The CRAB exhibited a reduction in the activity of enzymes involved in the pyruvate cycle, proton motive force, and ATP levels. This decline in central carbon metabolism resulted in a decrease in the metabolic flux of the α-ketoglutarate-glutamate-glutamine pathway toward purine metabolism, ultimately leading to a decline in adenine nucleotide interconversion. Exogenous adenosine monophosphate (AMP) and adenosine triphosphate (ATP) enhance the killing efficacy of Meropenem against CRAB. The combination of ATP and Meropenem also has a synergistic effect on eliminating CRAB persisters and the biofilm, as well as protecting mice against peritonitis-sepsis. This study presents a novel therapeutic modality to treat infections caused by CRAB based on the metabolism reprogramming strategy.
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BACKGROUND: Individuals with chronic kidney disease tend to have sedentary behavior and decreased physical activity, both are independent predictors of mortality in general population. While physical inactivity correlates to adverse health outcomes in patients with reduced kidney function, it is unclear whether this relationship remains significant for sedentary behavior. Our study purpose is to evaluate the association of sedentary lifestyle with mortality risk in individuals with renal insufficiency. METHODS: The study population were adult participants of 2007-2016 National Health and Nutrition Examination Survey (NHANES) with estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m 2 or self-reporting receiving dialysis (N=1419). Sedentary lifestyle was defined as sedentary time > 6 hours per day. Outcome of interest was all-cause and cardiovascular disease (CVD)- or cancer-related mortality. RESULTS: We observed that non-Hispanic Whites, and individuals with younger age and higher educational level were more likely to have sedentary lifestyle. During a median follow-up of 99 (interquartile range 70 to 128) months, a total of 458 participants died (3.98 deaths per 1000 person-months); 120 died from CVD and 92 from cancer, respectively. The crude analysis showed that individuals with sedentary lifestyle have higher risk of all-cause and CVD-related but not cancer-related mortality compared with the non-sedentary population. After adjusting for potential confounders, we showed that all-cause mortality and CVD-related mortality were 1.64-fold (95% CI 1.26-2.12) and 1.66-fold (95% CI 1.03-2.67) higher, respectively, in the sedentary population compared with the non-sedentary population. Similar results were observed in the sensitive analyses, in which we excluded individuals with dialysis, eGFR < 15 ml/min/1.73 m 2 , or mobility disability. CONCLUSIONS: Our findings suggest that sedentary lifestyle correlated to greater risk of all-cause and CVD-related mortality among individuals with reduced kidney function. Interventions targeting the individuals with risky behaviors may have practical importance for public health.
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This research aimed to examine the effects of dietary rutin supplementation on growth, body composition, serum biochemical indexes, liver enzyme activities and antioxidant-related genes expression, intestinal morphology, and microbiota composition of juvenile yellow catfish (Pelteobagrus fulvidraco). Rutin was added to the basal diets at doses of 0 (control), 100 mg/kg, and 500 mg/kg. Each diet was fed randomly into three tanks, each tank containing 30 fish with an initial body mass of (10.27 ± 0.62) g. The feeding trial was conducted in an indoor recirculating aquiculture system at 28 °C for 56 days. According to the findings, the inclusion of 100 mg/kg rutin significantly improved the growth performance of yellow catfish and reduced the feed conversion ratio; however, the growth promotion effect was diminished when the diet was supplemented with 500 mg/kg of rutin. The inclusion of 500 mg/kg rutin in the diet significantly reduced the level of crude lipid and protein of the whole fish. Serum activities of alkaline phosphatase, albumin, and total protein were all significantly increased when fish were fed the diet supplemented with 500 mg/kg rutin, while serum glucose was significantly lower compared to the control group. Meanwhile, dietary rutin at a concentration of 500 mg/kg significantly induced the hepatic mRNA expressions of antioxidant-related genes (including Cu/Zn-SOD, Mn-SOD, CAT, GPx) and inflammatory-associated genes (including TNFα, IL-10, LYZ). Incorporating rutin at doses of 100 mg/kg and 500 mg/kg into the diets resulted in a notable increase in superoxide dismutase (SOD) activity, while simultaneously reducing malondiadehyde (MDA) content in the liver and intestine. Intestinal villus height, villus width, muscular thickness, and lumen diameter were significantly increased with the administration of 500 mg/kg of dietary rutin. Gut microbial diversity analysis indicated that supplementing diets with 100 mg/kg and 500 mg/kg rutin significantly enhanced the abundance of Cetobacterium while decreasing Plesiomonas richness. In conclusion, dietary rutin levels at 100 mg/kg could enhance the growth, antioxidant capability, and intestinal health of yellow catfish under present experimental conditions.
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The redox-active metal ions, especially Cu2+, are highly correlated to Alzheimer's disease (AD) by causing metal ion-mediated oxidative stress and toxic metal-bound ß-amyloid (Aß) aggregates. Numerous pieces of evidence have revealed that the regulation of metal homeostasis could be an effective therapeutic strategy for AD. Herein, in virtue of the interaction of both amino-containing silane and ethylenediaminetetraacetic acid disodium salt for Cu2+, the silicon-carbon dots (SiCDs) are deliberately prepared using these two raw materials as the cocarbon source; meanwhile, to realize the local enrichment of SiCDs and further maximize the chelating ability to Cu2+, the SiCDs are feasibly loaded to the biocompatible mesoporous silica nanoparticles (mSiO2) with the interaction between residual silane groups on SiCDs and silanol groups of mSiO2. Thus-obtained nanocomposites (i.e., mSiO2@SiCDs) could serve as an efficient Cu2+ chelator with satisfactory metal selectivity and further modulate the enzymic activity of free Cu2+ and the Aß42-Cu2+ complex to alleviate the pathological oxidative stress with an anti-inflammatory effect. Besides, mSiO2@SiCDs show an inspiring inhibitory effect on Cu2+-mediated Aß aggregation and further protect the neural cells against the toxic Aß42-Cu2+ complex. Moreover, the transgenic Caenorhabditis elegans CL2120 assay demonstrates the protective efficacy of mSiO2@SiCDs on Cu2+-mediated Aß toxicity in vivo, indicating its potential for AD treatment.
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IgA nephropathy is the most common primary glomerulonephritis worldwide. However, its exact cause remains unclear, with known genetic factors explaining only 11% of the variation. Recently, researchers have turned their attention to epigenetic abnormalities in immune-related diseases, recognizing their significance in IgA nephropathy's development and progression. This emerging field has revolutionized our understanding of epigenetics in IgA nephropathy research. Though in its early stages, studying IgA nephropathy's epigenetics holds promise for unraveling its pathogenesis and identifying new biomarkers and therapies. This review aims to comprehensively analyze epigenetics' role in IgA nephropathy's development and suggest avenues for potential therapeutic interventions. In the future, assessing and modulating epigenetics may become integral in diagnosing, tailoring treatments and assessing prognoses for IgA nephropathy.
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Epigênese Genética , Glomerulonefrite por IGA , Humanos , Epigenômica , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/terapiaRESUMO
Multidrug-resistant bacteria present a major threat to public health that urgently requires new drugs or treatment approaches. Here, we conduct integrated proteomic and metabolomics analyses to screen for molecular candidates improving survival of mice infected with Vibrio parahaemolyticus, which indicate that L-Alanine metabolism and phagocytosis are strongly correlated with mouse survival. We also assess the role of L-Alanine in improving mouse survival by in vivo bacterial challenge experiments using various bacteria species, including V. parahaemolyticus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Functional studies demonstrate that exogenous L-Alanine promotes phagocytosis of these multidrug-resistant pathogen species. We reveal that the underlying mechanism involves two events boosted by L-Alanine: TLR4 expression and L-Alanine-enhanced TLR4 signaling via increased biosynthesis and secretion of fatty acids, including palmitate. Palmitate enhances binding of lipopolysaccharide to TLR4, thereby promoting TLR4 dimer formation and endocytosis for subsequent activation of the PI3K/Akt and NF-κB pathways and bacteria phagocytosis. Our data suggest that modulation of the metabolic environment is a plausible approach for combating multidrug-resistant bacteria infection.
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[This retracts the article DOI: 10.3892/etm.2020.8540.].
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Powder ramjets are a kind of vehicle propulsion system with high specific impulse and efficiency. They provide significant benefits in terms of extended propulsion and thrust adjustment. The pursuit of a highly reactive fuel appropriate for powder ramjets is likely to stimulate advancements in innovative propulsion systems, which are crucial for deep space exploration and long-term space missions. This work presents experimental studies on the thermal oxidation and laser ignition performance of aluminum-magnesium-lithium powders at atmospheric pressure. TG-DSC curves of powders in three heating rates were obtained. The ignition processes and ignition delay times were recorded by a CO2 laser ignition experiment system at a laser power of 10~60 W. The results show that at a lower heating rate of 10 K/min, the powder's thermal hysteresis is less, and the powder energy released in stage I is more concentrated. However, the degree of heat release concentration approached a similar level at heating rates of 30 K and 50 K. The ignition delay time decreased as the laser flux density increased. When the laser flux density exceeds 80 W/cm2, the effect of laser power on the ignition delay time decreases. At atmospheric pressure, the mathematical relationship between ignition delay time and laser flux density is given. Finally, the powder ignition processes at different laser powers are represented graphically.
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In this paper, the effects of initial electrons generation approaches on nanosecond pulsed breakdown characteristics are analyzed. Based on the numerical simulations with a 3D PIC-MCC model, the impacts of field-enhancement factor and initial electron concentration on nanosecond pulsed breakdown characteristics are investigated. Three types of switches are designed and subjected to testing under pulse voltages with rise times of 40, 70, and 120 ns, respectively. The results can be summarized as follows. First, the field-enhancement factor and initial electron concentration have significant influences on the development of the discharge channel. Second, the cathode-grooved self-triggered switch exhibits lower breakdown time delay jitter than the hemispherical self-breakdown switch at low pressure, while the differences in jitter between the two switches become negligible at high pressure. Third, the cathode-grooved self-triggered switch shows a lower breakdown time delay jitter compared to the pre-ionization self-triggered switch for pulse voltages with rise times of 40 and 70 ns. Conversely, this trend reverses for pulse voltage with a rise time of 120 ns. Finally, the breakdown time delay jitter for both the cathode-grooved self-triggered switch and the pre-ionization self-triggered switch has been reduced, and both switches are suitable for different operating requirements and conditions.
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High-quality soda ash (Na2CO3) is mainly produced using the ammonia-alkaline method, generating a significant amount of industrial waste called soda residue. In China, the annual production of soda residue exceeds 10 million tons. The large-scale open-air storage of soda residue not only occupies land but also causes severe pollution to the surrounding environment. Soda residue displays characteristics such as strong alkalinity, high reactivity, and a well-developed pore structure, making it a valuable raw material for producing environmentally functional materials. This article provided an overview and summary of soda residue, including its sources and hazards, basic properties, applications in environmental management (wastewater treatment, flue gas desulfurization, and soil remediation), and associated risks. The limitations of using soda residue in "waste to waste" technologies were also analyzed. Based on this analysis, the article suggests focusing on simultaneous removal of heavy metal ions using soda residue, safely disposing of and acquiring resources from metal-laden sludge, efficiently dechlorinating soda residue, using soda residue for contaminated soil solidification, stabilization, and assisted remediation, controlling pollution via green and circular utilization approaches, and assessing long-term risk.
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The synthetic biology has employed the synthetic gene networks through engineering to construct various functions in biological systems. However, the use of gene circuits to create sensors for detecting low-abundance targets has been limited due to the lack of signal amplification strategies beyond direct output of detection signals. To address this issue, we introduce a novel method utilizing Selective Recognition Proximity Ligation and signal amplification with T7 Transcription and CRISPR/Cas12a system (SRPL-TraCs), which permits the incorporation of cell-free gene circuits with signal amplification and enables the construction of high-order cascade signal amplification strategy to detect biomarkers in homogeneous systems. Specifically, the SRPL-TraCs utilizes selective recognition proximity ligation with high-fidelity T4 DNA ligase and generates a unique crRNA via T7 transcription, along with target-activated Cas12a/crRNA system to achieve excellent specificity for HIV-1 DNA. With this straightforward synthetic biology-based method, the proposed SRPL-TraCs has the potential to detect numerous other interesting targets beyond the nucleic acids.