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Osteomyelitis is an osseous infectious disease that primarily affects children and the elderly with high morbidity and recurrence. The conventional treatments of osteomyelitis contain long-term and high-dose systemic antibiotics with debridements, which are not effective and lead to antibiotic resistance with serious side/adverse effects in many cases. Hence, developing novel antibiotic-free interventions against osteomyelitis (especially antibiotic-resistant bacterial infection) is urgent and anticipated. Here, a bone mesenchymal stem cell membrane-constructed nanocell (CFE@CM) was fabricated against osteomyelitis with the characteristics of acid-responsiveness, hydrogen peroxide self-supplying, enhanced chemodynamic therapeutic efficacy, bone marrow targeting and cuproptosis induction. Notably, mRNA sequencing was applied to unveil the underlying biological mechanisms and found that the biological processes related to copper ion binding, oxidative phosphorylation, peptide biosynthesis and metabolism, etc., were disturbed by CFE@CM in bacteria. This work provided an innovative antibiotic-free strategy against osteomyelitis through copper-enhanced Fenton reaction and distinct cuproptosis, promising to complement the current insufficient therapeutic regimen in clinic.
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Cobre , Osteomielitis , Osteomielitis/tratamiento farmacológico , Animales , Cobre/química , Cobre/farmacología , Concentración de Iones de Hidrógeno , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Ratones , Peróxido de Hidrógeno/metabolismo , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/química , Humanos , Staphylococcus aureus/efectos de los fármacosRESUMEN
Acinetobacter baumannii poses a serious threat to human health. Pathogenic bacterial lipopolysaccharides (LPSs) are potent immunogens for the development of antibacterial vaccines. To investigate the antigenic properties of A. baumannii LPS, five well-defined core oligosaccharide fragments from the LPS of A. baumannii SMAL and ATCC 19606 were synthesized. A divergent synthesis strategy based on orthogonally protected α-(2 â 5)-linked Kdo dimer 6 was developed. Selective exposure of different positions in this key precursor and then elongation of sugar chains via stereocontrolled formation of both 1,2-trans and 1,2-cis-2-aminoglycosidic linkages permitted the efficient synthesis of the targets. The synthetic route also highlights a 4-O and then 7-O glycosylation sequence for assembly of the novel 4,7-branched Kdo framework. Antigenicity assay using the glycan microarray technique disclosed that tetrasaccharide 3 featuring both 4,7-branch and α-(2 â 5)-Kdo-Kdo structural elements was a potential antigenic determinant.
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In recent years, the issue of PM2.5-O3 compound pollution has become a significant global environmental concern. This study examines the spatial and temporal patterns of global PM2.5-O3 compound pollution and exposure risks, firstly at the global and urban scale, using spatial statistical regression, exposure risk assessment, and trend analyses based on the datasets of daily PM2.5 and surface O3 concentrations monitored in 120 cities around the world from 2019 to 2022. Additionally, on the basis of the common emission sources, spatial heterogeneity, interacting chemical mechanisms, and synergistic exposure risk levels between PM2.5 and O3 pollution, we proposed a synergistic PM2.5-O3 control framework for the joint control of PM2.5 and O3. The results indicated that: (1) Nearly 50% of cities worldwide were affected by PM2.5-O3 compound pollution, with China, South Korea, Japan, and India being the global hotspots for PM2.5-O3 compound pollution; (2) Cities with PM2.5-O3 compound pollution have exposure risk levels dominated by ST + ST (Stabilization) and ST + HR (High Risk). Exposure risk levels of compound pollution in developing countries are significantly higher than those in developed countries, with unequal exposure characteristics; (3) The selected cities showed significant positive spatial correlations between PM2.5 and O3 concentrations, which were consistent with the spatial distribution of the precursors NOx and VOCs; (4) During the study period, 52.5% of cities worldwide achieved synergistic reductions in annual average PM2.5 and O3 concentrations. The average PM2.5 concentration in these cities decreased by 13.97%, while the average O3 concentration decreased by 19.18%. This new solution offers the opportunity to construct intelligent and healthy cities in the upcoming low-carbon transition.
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This study focuses on investigating the strength recovery of fire-damaged fly ash concrete (FAC) with a low substitution rate of 10% through post-fire curing. The chemical and microstructural changes were analyzed using X-ray diffraction (XRD), derivative thermogravimetry (DTG), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), and nitrogen adsorption. The findings indicate that the incorporation of fly ash slightly enhanced the strength after exposure to 400 °C; this was attributed to improved pozzolanic reactions, which were not observed at higher temperatures of 600 °C and 800 °C. Moreover, a positive effect on the recovery of compressive strength was observed due to the pozzolanic reaction. However, due to the relatively low fly ash content, depletion occurred at a later age, resulting in the inability to inhibit microstructural damage caused by the production of portlandite, thereby weakening the compressive strength. Interestingly, fly ash influenced the morphology of calcium carbonate and calcium silicate hydrate crystals, which is potentially ascribed to the role of high aluminum content acting as a crystallization-guiding agent.
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Recently, virtual staining techniques have attracted more and more attention, which can help bypass the chemical staining process of traditional histopathological examination, saving time and resources. Meanwhile, as an emerging tool to characterize specific tissue structures in a label-free manner, the Mueller matrix microscopy can supplement more structural information that may not be apparent in bright-field images. In this Letter, we propose the Mueller matrix guided generative adversarial networks (MMG-GAN). By integrating polarization information provided by the Mueller matrix microscopy, the MMG-GAN enables the effective transformation of input H&E-stained images into corresponding Masson trichrome (MT)-stained images. The experimental results demonstrate the accuracy of the generated images by MMG-GAN and reveal the potential for more stain transformation tasks by incorporating the Mueller matrix polarization information, laying the foundation for future polarimetry-assisted digital pathology.
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Procesamiento de Imagen Asistido por Computador , Procesamiento de Imagen Asistido por Computador/métodos , Redes Neurales de la Computación , Coloración y Etiquetado , Humanos , Microscopía de Polarización/métodosRESUMEN
Thermochemical conversion, including hydrothermal processing, pyrolysis and incineration, has become a promising technology for sewage sludge (SS) treatment and disposal. Furthermore, acid leaching is considered as an effective method to recover phosphorus (P) from SS and its thermochemical treatment products. This study has investigated the potential of P reclamation from SS and its thermochemical derivatives, including hydrochar (HC), biochar (BC), and SS incinerated ash (SA). Comparative analyses of physicochemical properties of these derivatives revealed a decrease in hydroxyl and aromatic groups and an increase in aliphatic and oxygen-containing functional groups in HC and BC. Leaching experiments using 1 M sulfuric acid (H2SO4) and 1 M oxalic acid (C2H2O4) suggested that H2SO4 slightly outperformed C2H2O4 in terms of P leaching efficiency. HC achieved 79.1 % optimal leaching efficiency in 60 min using H2SO4, while BC, SS, and SA required 360 min to achieve comparable efficiency. SS and BC reached optimal leaching efficiency at 74.1 % and 76.2 % in H2SO4, while SA achieved 80.9 % in C2H2O4. Importantly, HC and SA are more favorable for P extraction using acid leaching, whereas BC tends to be a potential P carrier. Time-dependent kinetics revealed a two-stage leaching process, i.e., fast and slow reaction stages. Shrinking core model indicates product layer diffusion as the primary rate-limiting step in both stages. Overall, these fundamental insights play an important role in practical P recovery through acid leaching of SS derived residues after thermochemical treatment.
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Glycosylation is an important post-modification reaction in plant secondary metabolism, and contributes to structural diversity of bioactive natural products. In plants, glycosylation is usually catalyzed by UDP-glycosyltransferases. Flavonoid 2'-O-glycosides are rare glycosides. However, no UGTs have been reported, thus far, to specifically catalyze 2'-O-glycosylation of flavonoids. In this work, UGT71AP2 was identified from the medicinal plant Scutellaria baicalensis as the first flavonoid 2'-O-glycosyltransferase. It could preferentially transfer a glycosyl moiety to 2'-hydroxy of at least nine flavonoids to yield six new compounds. Some of the 2'-O-glycosides showed noticeable inhibitory activities against cyclooxygenase 2. The crystal structure of UGT71AP2 (2.15 Å) was solved, and mechanisms of its regio-selectivity was interpreted by pK a calculations, molecular docking, MD simulation, MM/GBSA binding free energy, QM/MM, and hydrogenâdeuterium exchange mass spectrometry analysis. Through structure-guided rational design, we obtained the L138T/V179D/M180T mutant with remarkably enhanced regio-selectivity (the ratio of 7-O-glycosylation byproducts decreased from 48% to 4%) and catalytic efficiency of 2'-O-glycosylation (k cat/K m, 0.23 L/(s·µmol), 12-fold higher than the native). Moreover, UGT71AP2 also possesses moderate UDP-dependent de-glycosylation activity, and is a dual function glycosyltransferase. This work provides an efficient biocatalyst and sets a good example for protein engineering to optimize enzyme catalytic features through rational design.
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High-frequency oscillatory activity in cognition-related neural circuits during wakefulness consistently induces the growth of dendritic spines and axonal terminals. Although these structural changes are essential for cognitive functions, it is hypothesized that if these newly expanded structures fail to establish functional connections, they may become superfluous. Sleep is believed to facilitate the reduction of such redundant structures to maintain neural homeostasis. However, the mechanisms underlying this pruning process during sleep remain poorly understood. In this study, that melatonin type 3 receptors (MT3Rs) are selectively expressed in the stellate neurons of the medial entorhinal cortex (MEC) is demonstrated, an area where high melatonin levels are detected during sleep. Activation of MT3Rs during sleep initiates the shrinkage of dendritic spines in stellate neurons by downregulating neural network activity and dephosphorylating synaptic proteins in the MEC. This process is disrupted when MT3R expression is knocked down or when MT3Rs are blocked during sleep. Notably, interference with MT3Rs in the MEC during sleep impairs the acquisition of spatial memory but does not affect object memory acquisition following sleep. These findings reveal novel molecular mechanisms involving melatonin and MT3Rs in the regulation of dendritic spine shrinkage during sleep, which is crucial for the acquisition and consolidation of spatial memory.
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The incidence of intrahepatic cholangiocarcinoma (ICC) is steadily rising, and it is associated with a high mortality rate. Clinical samples were collected to detect the expression of HSPB8 and BAG3 in ICC tissues. ICC cells were cultured and transfected with plasmids that overexpressed or silenced specific genes to investigate the impact of gene expression alterations on cell function. qPCR and Western blot techniques were utilized to measure gene and protein expression levels. A wound healing assay was conducted to assess cell migration ability. The Transwell assay was used to assess cell invasion ability. Co-IP was used to verify the binding relationship between HSPB8 and BAG3. The effects of HSPB8 and BAG3 on lung metastasis of tumors in vivo were verified by constructing a metastatic tumor model. Through the above experiments, we discovered that the expressions of HSPB8 and BAG3 were up-regulated in ICC tissues and cells, and their expressions were positively correlated. The metastatic ability of ICC cells could be promoted or inhibited by upregulating or downregulating the expression of BAG3. Furthermore, the HSPB8-BAG3 chaperone complex resulted in the abnormal degradation of Filamin A by activating autophagy. Increased expression of Filamin A inhibits the migration and invasion of ICC cells. Overexpression of HSPB8 and BAG3 in vivo promoted the lung metastasis ability of ICC cells. The HSPB8-BAG3 chaperone complex promotes ICC cell migration and invasion by regulating CASA-mediated degradation of Filamin A, offering insights for enhancing ICC therapeutic strategies.
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Proteínas Adaptadoras Transductoras de Señales , Proteínas Reguladoras de la Apoptosis , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Filaminas , Chaperonas Moleculares , Invasividad Neoplásica , Colangiocarcinoma/patología , Colangiocarcinoma/metabolismo , Colangiocarcinoma/genética , Humanos , Filaminas/metabolismo , Filaminas/genética , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genética , Animales , Ratones , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Movimiento Celular , Línea Celular Tumoral , Masculino , Femenino , Ratones Desnudos , Regulación Neoplásica de la Expresión GénicaRESUMEN
Hydrothermal carbonization (HTC) for the recovery of phosphorus (P) from biomass wastes has attracted considerable attention, while migration of P to the liquid phase greatly weakened P recovery efficiency and elevated the environmental risk. Therefore, a systematic scheme was proposed in this work to accomplish the complete reclamation of P from wetland plant (Ceratophyllum demersum) through coupling liquid-recirculated HTC mediated by H2O or H2SO4 with precipitation, and the migration and speciation of P during this process was determined by P K-edge X-ray absorption near edge structure, 31P nuclear magnetic resonance, and the modified sequential extraction. The P concentration in the liquid phase increased with the recirculation of HTC process water, and reached up to 550.6 mg L-1. >98.1 % of P in the recirculated liquid products was recovered in the forms of hydroxyapatite and struvite with the HTC mediums of H2O and H2SO4, respectively, without the addition of exogenous metals. In addition to the production of P compounds, P-enriched hydrochar was simultaneously obtained during this process. The HTC medium and liquid recirculation had profound impact on the hydrochar characteristics and the transformation of P. Hydroxyapatite and magnesium phosphate were the dominant P species in the hydrochars derived from H2O-mediated HTC, while FePO4 and other Ca-P species [Ca3(PO4)2 and Ca(H2PO4)2] dominated the P compounds in the H2SO4-mediated hydrochar. These results suggest that coupling liquid-recirculated HTC and precipitation could be a promising strategy for P reclamation, which could provide new insights into the P recovery from biomass waste.
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Biomasa , Fósforo , Humedales , Fósforo/química , Contaminantes Químicos del Agua/química , Precipitación QuímicaRESUMEN
To date, although the high-carbohydrate (HC) feed has been extensively adopted in the aquaculture industry, its effects on the intestinal function and development of aquatic animals still remain unclear. In addition, the corresponding nutritional intervention is still barely reported. This study aimed to evaluate the influence of xylooligosaccharides (XOS) on the intestinal health of Megalobrama amblycephala subjected to a HC feeding. Fish (average weight: 44.55 ± 0.15 g) were randomly offered 3 diets, including a control one (29 % carbohydrate), a HC one (41 % carbohydrate), and a XOS supplemented one (HC + 1.0 % XOS, HCX) respectively for 12 weeks. The HC feeding caused morphological abnormalities of intestine, an increased intestinal permeability, and the intestinal immunosuppression, all of which were markedly reversed by XOS administration. In addition, compared with the HC group, HCX feeding remarkably promoted the intestinal activities of digestive and brush border enzymes, and the expressions of cell proliferation-related proteins (Wnt10b and Cyclin D1). The 16s rDNA sequencing also revealed that XOS administration increased the abundance of beneficial bacteria, and decreased that of pathogenic ones. In conclusion, dietary supplementation of XOS improved the intestinal histomorphology, barrier function, cell proliferation and bacterial communities of carbohydrate-overloaded fish Megalobrama amblycephala.
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Carpas , Microbioma Gastrointestinal , Glucuronatos , Intestinos , Oligosacáridos , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Oligosacáridos/farmacología , Glucuronatos/farmacología , Carpas/microbiología , Carpas/crecimiento & desarrollo , Intestinos/efectos de los fármacos , Intestinos/patología , Intestinos/microbiología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Alimentación Animal , Carbohidratos de la Dieta/farmacología , Carbohidratos de la Dieta/efectos adversos , Suplementos DietéticosRESUMEN
Melatonin (MLT) is an important circadian signal for sleep regulation, but the neural circuitries underlying the sleep-promoting effects of MLT are poorly understood. The paraventricular thalamus (PVT) is a critical thalamic area for wakefulness control and expresses MLT receptors, raising a possibility that PVT neurons may mediate the sleep-promoting effects of MLT. Here, we found that MLT receptors were densely expressed on PVT neurons and exhibited circadian-dependent variations in C3H/HeJ mice. Application of exogenous MLT decreased the excitability of PVT neurons, resulting in hyperpolarization of membrane potential and reduction of action potential firing. MLT also inhibited the spontaneous activity of PVT neurons at both population and single-neuron levels in freely behaving mice. Furthermore, pharmacological manipulations revealed that local infusion of exogeneous MLT into the PVT promoted non-rapid eye movement (NREM) sleep and increased NREM sleep duration, whereas MLT receptor antagonists decreased NREM sleep. Moreover, we found that selectively knocking down endogenous MLT receptors in the PVT decreased NREM sleep and correspondingly increased wakefulness, with particular changes shortly after the onset of the dark or light phase. Taken together, these results demonstrate that PVT is an important target of MLT for promoting NREM sleep.
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Melatonina , Ratones Endogámicos C3H , Núcleos Talámicos de la Línea Media , Animales , Ratones , Núcleos Talámicos de la Línea Media/fisiología , Núcleos Talámicos de la Línea Media/efectos de los fármacos , Melatonina/farmacología , Melatonina/metabolismo , Vigilia/fisiología , Vigilia/efectos de los fármacos , Masculino , Receptores de Melatonina/metabolismo , Receptores de Melatonina/genética , Sueño/fisiología , Sueño/efectos de los fármacos , Ritmo Circadiano/efectos de los fármacos , Ritmo Circadiano/fisiología , Neuronas/fisiología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Sueño de Onda Lenta/fisiologíaRESUMEN
Identifying priority pollutants in wastewater treatment plant (WWTP) effluents is crucial for optimizing monitoring efforts, improving regulations, and developing targeted mitigation strategies. Despite the presence of numerous trace organic pollutants in WWTP effluents, a comprehensive prioritization scheme is lacking, hindering effective control. This study screened 216 micropollutants, including pharmaceuticals, pesticides, and industrial chemicals, which had been detected in effluents from 46 WWTPs across China. A multi-criteria prioritization method was developed, considering exposure potential based on median concentrations and detection frequencies, as well as hazard potential determined by persistence, bioaccumulation, in vitro toxicity, and in vivo toxicity. Pollutants with low exposure or hazard potential were filtered out, and a priority index was calculated to rank the remaining 59 substances. The top 15 priority pollutants included regulated persistent organic pollutants like perfluorooctanoic acid and their alternatives such as perfluorobutane sulfonate, pesticide transformation products, and emerging contaminants such as bisphenol A, which are not currently regulated in WWTP effluents. This study provides a systematic approach to identify priority pollutants and generates a guiding framework for monitoring, regulation, and control of both well-recognized and overlooked contaminants in WWTP effluents.
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Monitoreo del Ambiente , Aguas Residuales , Contaminantes Químicos del Agua , China , Contaminantes Químicos del Agua/análisis , Aguas Residuales/química , Eliminación de Residuos Líquidos , Ecosistema , Contaminantes Orgánicos PersistentesRESUMEN
INTRODUCTION: Benign prostatic hyperplasia (BPH) is a common condition in older men, marked by the noncancerous enlargement of the prostate gland. Inflammation of the prostate plays a significant role in the progression of BPH and the symptoms it causes. The objective of this study was to create a predictive model for prostatic inflammation in men with BPH based on important clinical factors. METHODS: A retrospective cohort study was conducted with 137 patients diagnosed with BPH. Data collected included various factors such as age, prostate volume (PV), preoperative international prostate symptom score, preoperative maximum urine flow rate (Qmax), preoperative post-void residue, weight of the excised tissue, body mass index, fasting blood glucose (FBG), cholesterol levels, prostate-specific antigen, blood calcium, blood phosphorus, blood uric acid, triglycerides, hypertension status, and presence of prostate calcifications. Multivariate logistic regression and LASSO regression analyses were performed to identify significant predictors and develop a nomogram. The model's performance was evaluated using receiver operating characteristic curves, calibration plots, and decision curve analysis (DCA). RESULTS: Among the patients, 9.49% showed no signs of prostatic inflammation, while 22.63% had mild, 47.45% had moderate, and 20.44% had severe inflammation. Factors such as PV, FBG, and prostate calcification were identified as important predictors of prostatic inflammation. The predictive model developed exhibited strong discrimination and calibration, as evidenced by a high area under the curve value, indicating reliable predictive accuracy. DCA further validated the clinical usefulness of the nomogram. CONCLUSION: The developed nomogram, incorporating PV, FBG, and prostate calcification, effectively predicts prostatic inflammation in men with BPH. This tool can aid in early intervention and targeted treatment, potentially improving patient outcomes. Further validation in diverse populations is recommended to enhance its generalizability and clinical applicability.
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Mitochondrial function can be regulated by ion channels. Mitochondrial RNA splicing 2 (Mrs2) is a magnesium ion (Mg2+) channel located in the inner mitochondrial membrane, thereby mediating the Mg2+ influx into the mitochondrial matrix. However, its potential role in regulating the Mg homeostasis and mitochondrial function in aquatic species is still unclear. This study molecularly characterizes the gene encoding Mrs2 in fish M. amblycephala with its functions in maintaining the Mg homeostasis and mitochondrial function verified. The mrs2 gene is 2133 bp long incorporating a 1269 bp open reading frame, which encodes 422 amino acids. The Mrs2 protein includes two transmembrane domains and a conserved tripeptide Gly-Met-Asn, and has a high homology (65.92-97.64%) with those of most vertebrates. The transcript of mrs2 was relatively high in the white muscle, liver and kidney. The inhibition of mrs2 reduces the expressions of Mg2+ influx/efflux-related proteins, mitochondrial Mg content, and the activities of mitochondrial complex I and V in hepatocytes. However, the over-expression of mrs2 increases the expressions of Mg2+ influx/efflux-related proteins, mitochondrial Mg content, and the complex V activity, but decreases the activities of mitochondrial complex III and IV and citrate synthase in hepatocytes. Collectively, Mrs2 is highly conserved among different species, and is prerequisite for maintaining Mg homeostasis and mitochondrial function in fish.
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Secuencia de Aminoácidos , Clonación Molecular , Homeostasis , Magnesio , Mitocondrias , Animales , Magnesio/metabolismo , Mitocondrias/metabolismo , Mitocondrias/genética , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Cyprinidae/genética , Cyprinidae/metabolismo , Filogenia , Secuencia de Bases , Empalme del ARNRESUMEN
Microwave thermotherapy (MWTT), as a treatment for tumors, lacks specificity and requires sensitizers. Most reported microwave sensitizers are single metal-organic frameworks (MOFs), which must be loaded with ionic liquids to enhance the performance in MWTT. Meanwhile, MWTT is rarely combined with other treatment modalities. Here, we synthesized a novel Fe-Cu bimetallic organic framework FeCuMOF (FCM) by applying a hydrothermal method and further modified it with methyl polyethylene glycol (mPEG). The obtained FCM@PEG (FCMP) showed remarkable heating performance under low-power microwave irradiation; it also acted as a novel nanospheres enzyme to catalyze H2O2 decomposition, producing abundant reactive oxygen species (ROS) to deplete glutathione (GSH) and prevent ROS clearance from tumor cells during chemodynamic treatment. The FCMP was biodegradable and demonstrated excellent biocompatibility, allowing it to be readily metabolized without causing toxic effects. Finally, it was shown to act as a suitable agent for T2 magnetic resonance imaging (MRI) in vitro and in vivo. This new bimetallic nanostructure could successfully realize two tumor treatment modalities (MWTT and chemodynamic therapy) and dual imaging modes (T2 MRI and microwave thermal imaging). Our findings represent a breakthrough for integrating the diagnosis and treatment of tumors and provides a reference for developing new microwave sensitizers.
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Individual optical addressing in chains of trapped atomic ions requires the generation of many small, closely spaced beams with low cross-talk. Furthermore, implementing parallel operations necessitates phase, frequency, and amplitude control of each individual beam. Here, we present a scalable method for achieving all of these capabilities using a high-performance integrated photonic chip coupled to a network of optical fibre components. The chip design results in very low cross-talk between neighbouring channels even at the micrometre-scale spacing by implementing a very high refractive index contrast between the channel core and cladding. Furthermore, the photonic chip manufacturing procedure is highly flexible, allowing for the creation of devices with an arbitrary number of channels as well as non-uniform channel spacing at the chip output. We present the system used to integrate the chip within our ion trap apparatus and characterise the performance of the full individual addressing setup using a single trapped ion as a light-field sensor. Our measurements showed intensity cross-talk below ~10-3 across the chip, with minimum observed cross-talk as low as ~10-5.
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SCOPE: Chalcones are widely present in most plants and have various health beneficial functions. This study investigates the suppressive effect of 13 natural and synthetic chalcones on transformation of aryl hydrocarbon receptor (AhR) induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene (3-MC) in a cell-free system, Hepa-1c1c7 cells, and liver of ICR mice. METHODS AND RESULTS: In the cell-free system, cardamonin dose-dependently inhibits AhR transformation. Chalcones with substitution on 2' and/or 6' position is important for the suppressive effect, while the substitution on 4' position is negatively for the effect. Moreover, cardamonin and 2'-hydroxychalcone competitively inhibit the binding of [3H]-3-MC to the AhR. In Hepa-1c1c7 cells, cardamonin inhibits AhR transformation and expression of cytochrome P4501A1 (CYP1A1) in a dose-dependent manner through suppressing TCDD-induced phosphorylation of both AhR and AhR nuclear translocator, heterodimerization of them, and nuclear translocation of AhR. In the liver of mice, oral administered cardamonin also inhibits 3-MC-induced AhR translocation and expression of CYP1A1. CONCLUSION: Among used chalcones, a natural chalcone cardamonin competitively binds to AhR and suppresses its transformation. Thus, cardamonin is an effective food factor for suppression of the dioxin-caused biochemical alterations and toxicities.
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BACKGROUND: The prognosis comparison between endoscopic therapy + partial splenic embolization (PSE) and Hassab's operation is unclear in the treatment of esophageal variceal bleeding in patients with liver cirrhosis. This study aimed to compare the outcome of endoscopic therapy + PSE (EP) with a combination of splenectomy + pericardial devascularization procedure, known as Hassab's operation (SH) for esophageal variceal bleeding in patients with liver cirrhosis with hypersplenism. METHODS: We enrolled 328 patients, including 125 and 203 patients who underwent EP and SH, respectively. Each group consisted of 110 patients after propensity score matching (PSM). Subsequently, we recorded and analyzed bleeding episodes and mortality in 6 months and 1, 2, and 5 years after therapies. RESULTS: The median follow-up time in the EP and SH groups was 53 and 64 months, respectively. Bleeding incidence 6 months after therapies in the EP group was lower than that in the SH group (1.8% vs. 10.0%, P = 0.010). Additionally, complications in the perioperative period were not significantly different (0% vs. 3.6%, P = 0.008). However, the bleeding rate between the two groups was not significantly different at 1, 2, and 5 years after therapies (7.3% vs. 12.7%, P = 0.157; 10.9% vs. 16.4%, P = 0.205; 30.6% vs. 31.8%, P = 0.801), as well as mortality rate (4.5% vs 7.3%, P = 0.571). CONCLUSION: Compared with SH therapy, the bleeding rate 6 months after EP therapy was lower, but the long-term bleeding rate was similar.