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The interaction between light and moiré superlattices presents a platform for exploring unique light-matter phenomena. Tailoring these optical properties holds immense potential for advancing the utilization of moiré superlattices in photonics, optoelectronics, and valleytronics. However, the control of the optical polarization state in moiré superlattices, particularly in the presence of moiré effects, remains elusive. Here, we unveil the emergence of optical anisotropy in moiré superlattices by constructing twisted WSe2/WSe2/SiP heterostructures. We report a linear polarization degree of â¼70% for moiré excitons, attributed to the spatially nonuniform charge distribution, corroborated by first-principles calculations. Furthermore, we demonstrate the modulation of this linear polarization state via the application of a magnetic field, resulting in polarization angle rotation and a magnetic-field-dependent linear polarization degree, influenced by valley coherence and moiré potential effects. Our findings demonstrate an efficient strategy for tuning the optical polarization state of moiré superlattices using heterointerface engineering.
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IV-V two-dimensional materials have emerged as key contenders for polarization-sensitive and angle-resolved devices, given their inherent anisotropic physical properties. While these materials exhibit intriguing high-pressure quasi-particle behavior and phase transition, the evolution of quasi-particles and their interactions under external pressure remain elusive. Here, employing a diamond anvil cell and spectroscopic measurements coupled with first-principles calculations, we unveil rarely observed pressure-induced phonon-phonon coupling in layered SiP flakes. This coupling manifests as an anomalous phonon hardening behavior for the A1 mode within a broad wavenumber phonon softening region. Furthermore, we demonstrate the effective tuning of exciton emissions in SiP flakes under pressure, revealing a remarkable 63% enhancement in the degree of polarization (DOP) within the pressure range of 0-3.5 GPa. These findings contribute to our understanding of high-pressure phonon evolution in SiP materials and offer a strategic approach to manipulate the anisotropic performance of in-plane anisotropic 2D materials.
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Radiation-induced skin injury is a common side effect of radiotherapy, but there are few therapeutic drugs available for prevention or treatment. In this study, we demonstrate that 18ß-Glycyrrhetinic acid (18ß-GA), a bioactive component derived from Glycyrrhiza glabra, substantially reduces the accumulation of reactive oxygen species (ROS) and inhibits apoptosis in HaCaT cells after ionizing radiation (IR), thereby mitigating radiation-induced skin injury. Mechanistically, 18ß-GA promotes the nuclear import of Nrf2, leading to activation of the Nrf2/HO-1 signaling pathway in response to IR. Importantly, Nrf2 silencing increases cell apoptosis and reverse the protective effect of 18ß-GA on radiation-induced skin injury. Furthermore, 18ß-GA preserves skin tissue structure after irradiation, inhibits inflammatory cell infiltration, and alleviates radiation dermatitis. In conclusion, our results suggest that 18ß-GA reduces intracellular ROS production and apoptosis by activating the Nrf2/HO-1 signaling pathway, leading to amelioration of radiation dermatitis.
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Ácido Glicirretínico , Hemo-Oxigenasa 1 , Factor 2 Relacionado con NF-E2 , Especies Reactivas de Oxígeno , Transducción de Señal , Ácido Glicirretínico/farmacología , Ácido Glicirretínico/análogos & derivados , Factor 2 Relacionado con NF-E2/metabolismo , Humanos , Transducción de Señal/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Animales , Especies Reactivas de Oxígeno/metabolismo , Piel/efectos de los fármacos , Piel/efectos de la radiación , Piel/metabolismo , Piel/patología , Apoptosis/efectos de los fármacos , RatonesRESUMEN
Healing of chronic wounds has been critically limited by prolonged inflammation. Carbon monoxide (CO) is a biologically active molecule with high potential based on its efficacy in modulating inflammation, promoting wound healing and tissue remodeling. Strategies to use CO as a gaseous drug to chronic wounds have emerged, but controlling the sustained release of CO at the wound site remains a major challenge. In this work, a porphyrin-Fe based metal organic frameworks, TPyP-FeMOFs was prepared. The synthesized TPyP-FeMOFs was high-temperature vacuum activated (AcTPyP-FeMOFs) and AcTPyP-FeMOFs had a relatively high Fe (II) content. CO sorption isotherms showed that AcTPyP-FeMOFs chemisorbed CO and thus CO release was sustained and prolonged. In vitro evaluation results showed that CO@TPyP-FeMOFs reduced the inflammatory level of lipopolysaccharide (LPS) activated macrophages, polarized macrophages to M2 anti-inflammatory phenotype, and promoted the proliferation of fibroblasts by altering the pathological microenvironment. In vivo study confirmed CO@TPyP-FeMOFs promoted healing in a LPS model of delayed cutaneous wound repair and reduced macrophages and neutrophils recruitment. Both in vitro and in vivo studies verified that CO@TPyP-FeMOFs acted on macrophages by modulating phenotype and inflammatory factor expression. Thus, CO release targeting macrophages and pathological microenvironment modulation presented a promising strategy for wound healing.
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Monóxido de Carbono , Inflamación , Macrófagos , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Inflamación/tratamiento farmacológico , Células RAW 264.7 , Masculino , Fenotipo , Lipopolisacáridos/farmacología , Ratones Endogámicos C57BL , Hierro/química , Hierro/metabolismoRESUMEN
Vascular stent implantation remains the major therapeutic method for cardiovascular diseases currently. We here introduced crucial biological functional biological function factors (SDF-1α, VEGF) and vital metal ions (Zn2+) into the stent surface to explore their synergistic effect in the microenvironment. The combination of the different factors is known to effectively regulate cellular inflammatory response and selectively regulate cell biological behavior. Meanwhile, in the implemented method, VEGF and Zn2+ were loaded into heparin and poly-l-lysine (Hep-PLL) nanoparticles, ensuring a controlled release of functional molecules with a multi-factor synergistic effect and excellent biological functions in vitro and in vivo. Notably, after 150 days of implantation of the modified stent in rabbits, a thin and smooth new intima was obtained. This study offers a new idea for constructing a modified surface microenvironment and promoting tissue repair.
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Citocinas , Zinc , Animales , Conejos , Zinc/farmacología , Factor A de Crecimiento Endotelial Vascular , Preparaciones de Acción Retardada/farmacología , StentsRESUMEN
In 2019, a serious dengue virus (DENV) infection broke out in the Xishuangbanna Dai Autonomous Prefecture, China. Therefore, we conducted a molecular epidemiological analysis in people that contracted DENV serotype 1 (DENV-1) during this year. We analyzed the molecular epidemiology of six DENV-1 epidemic strains in 2019 by full-length genome sequencing, amino acid mutation site analysis, evolutionary tree analysis, and recombination site comparison analysis. Through the analysis of amino acid mutation sites, it was found that DENV-1 strain (MW386867) was different from the other five epidemic DENV-1 strains in Xishuangbanna in 2019. MW386867 had unique mutation sites at six loci. The six epidemic DENV-1 strains in Xishuangbanna in 2019 were divided into two clusters. MW386867 was highly similar to the MG679800 (Myanmar 2017), MG679801 (Myanmar 2017), and KC172834 (Laos 2008), and the other five strains were highly similar to JQ045660 (Vietnam 2011), FJ176780 (GuangDong 2006). Genetic recombination analysis revealed that there was no recombination signal in the six epidemic DENV-1 strains in Xishuangbanna in 2019. We speculate that the DENV-1 epidemic in 2019 has a co-epidemic of local strains and cross-border strains.
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Virus del Dengue , Dengue , Humanos , Virus del Dengue/genética , Dengue/epidemiología , Filogenia , Genotipo , Brotes de Enfermedades , Serogrupo , China/epidemiologíaRESUMEN
The grinding grooves of material removal machining and the residues of a machining tool on the key component surface cause surface stress concentration. Thus, it is critical to carry out precise measurements on the key component surface to evaluate the stress concentration. Based on white-light interferometry (WLI), we studied the measurement distortion caused by the reflected light from the steep side of the grinding groove being unable to return to the optical system for imaging. A threshold value was set to eliminate the distorted measurement points, and the cubic spline algorithm was used to interpolate the eliminated points for compensation. The compensation result agrees well with the atomic force microscope (AFM) measurement result. However, for residues on the surface, a practical method was established to obtain a microscopic 3D micro-topography point cloud and a super-depth-of-field fusion image simultaneously. Afterward, the semantic segmentation network U-net was adopted to identify the residues in the super-depth-of-field fusion image and achieved a recognition accuracy of 91.06% for residual identification. Residual feature information, including height, position, and size, was obtained by integrating the information from point clouds and super-depth-of-field fusion images. This work can provide foundational data to study surface stress concentration.
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Artificial H2 O2 photosynthesis by covalent organic frameworks (COFs) photocatalysts is promising for wastewater treatment. The effect of linkage chemistry of COFs as functional basis to photoelectrochemical properties and photocatalysis remains a significant challenge. In this study, three kinds of azoles-linked COFs including thiazole-linked TZ-COF, oxazole-linked OZ-COF and imidazole-linked IZ-COF were successfully synthesized. More accessible channels of charge transfer were constructed in TZ-COF via the donor-π-acceptor structure between thiazole linkage and pyrene linker, leading to efficient suppression of photoexcited charge recombination. Density functional theory calculations support the experimental studies, demonstrating that the thiazole linkage is more favorable for the formation of *O2 intermediate in H2 O2 production than that of the oxazole and imidazole linkages. The real active sites in COFs located at the benzene ring fragment between pyrene unit and azole linkage.
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One key reason for T cell exhaustion is continuous antigen exposure. Early exhausted T cells can reverse exhaustion and differentiate into fully functional memory T cells if removed from persisting antigen stimulation. Therefore, this study viewed T cell exhaustion as an over-activation status induced by chronic antigen stimuli. This study hypothesized that blocking TCR signal intermittently to terminate over-activation signal can defer the developmental process of T cell exhaustion. In this study, melanoma-bearing mice were treated with tacrolimus (FK506) every 5 days. The tumor size and tumor-infiltrating lymphocytes (TILs) were analyzed. We found that intermittent administration of tacrolimus significantly inhibited tumor growth, and this effect was mediated by CD8+T cells. Intermittent tacrolimus treatment facilitated the infiltration of CD8+TILs. RNA-seq and quantitative RT-PCR of sorted CD8+TILs showed the expression of Nr4a1 (an exhaustion-related transcription factor) and Ctla4 (a T cell inhibitory receptor) was remarkably downregulated. These results indicated that intermittently blocking TCR signal by tacrolimus can promote anti-tumor immunity and inhibit the tumor growth in melanoma-bearing mice, inhibiting the transcription of several exhaustion-related genes, such as Nr4a1 and Ctla4.
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Melanoma , Tacrolimus , Animales , Linfocitos T CD8-positivos , Antígeno CTLA-4/metabolismo , Linfocitos Infiltrantes de Tumor , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Ratones , Tacrolimus/metabolismo , Tacrolimus/farmacologíaRESUMEN
Surface modification manipulates the application performance of materials, and thrombosis caused by material contact is a key risk factor of biomaterials failure in blood-contacting/implanting devices. Therefore, building a safe and effective hemocompatibility platform is still urgent. Owing to the unique properties of polyamidoamine (PAMAM) dendrimers, in this study, modified surfaces with varying dendrimer densities were interacted with elements maintaining blood homeostasis. These included the plasma proteins bovine serum albumin and fibrinogen, cells in blood (platelets and erythrocyte), as well as endothelial cells (ECs), and the objective was to evaluate the blood compatibility of the chosen materials. Whole blood test and dynamic blood circulation experiment by the arteriovenous shunt mode of rabbit were also conducted, based on the complexity and fluidity of blood. The PAMAM-modified substrates, particularly that with a high density of PAMAM (N1.0), adsorbed proteins with lessened fibrinogen adsorption, reduced platelet activation and aggregation, and suppressed clotting in whole blood and dynamic blood testing. Furthermore, the designed PAMAM dendrimer densities were safe and showed negligible erythrocyte lysis. Concurrently, PAMAM modification could maintain EC growth and did not trigger the release of procoagulant factors. These results suggest that the PAMAM-modified materials are compatible for maintaining blood homeostasis. Thus, PAMAM dendrimers can work as excellent surface modifiers for constructing a hemocompatibility platform and even a primer layer for desired functional design, promoting the service performance of blood-contacting devices.
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Dendrímeros , Animales , Conejos , Dendrímeros/química , Células Endoteliales/metabolismo , Diálisis Renal , FibrinógenoRESUMEN
Background: Radiation-induced pulmonary fibrosis (RIPF) is a serious complication in patients treated with transthoracic irradiation. To date, there are no effective drugs for RIPF treatment. In this study, we attempted to explore the function of miR-761 in RIPF, further investigate its potential mechanism and evaluate its effectiveness in the treatment of RIPF. Methods: qRT-PCR analysis was used to detect miR-761 and peroxisome proliferator-activated receptor gamma (PPARg) coactivator-1 (PGC-1α) expression. Western Blot (WB) assay was applied to verify the regulation of PGC-1α by miR-761 and the expression of fibrosis-related proteins. Gel contraction assay was performed to demonstrate the level of fibroblast activation in vitro. A mouse RIPF model was used to validate the anti-fibrotic effect of Antagomir761. Bioinformatics analysis and dual-luciferase reporter assays were utilized to confirm the regulation relationship between miR-761 and PGC-1α. Results: The results showed that miR-761 was significantly elevated in irradiated mice lungs and fibroblasts. Overexpression of miR-761 in vitro promoted fibroblast activation. Whereas inhibition of miR-761 attenuated the degree of RIPF and inhibited fibroblast activation. Mechanistically, PGC-1α was a direct and functional target of miR-761, overexpression of PGC-1α inhibited irradiation-induced fibroblast activation, and knockdown of PGC-1α caused miR-761 inhibitor loses its anti-activation ability in irradiated cells. Conclusion: Our findings demonstrated that miR-761 regulated RIPF by targeting PGC-1α. Inhibition of miR-761 restored PGC-1α expression and attenuated RIPF damage, and miR-761 was a potential target for preventing the development of RIPF.
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MicroARNs , Fibrosis Pulmonar , Animales , Regulación hacia Abajo , Fibrosis , Pulmón/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Fibrosis Pulmonar/genéticaRESUMEN
Epilepsy is a neurological disorder with recurrent seizures, which convey complex dynamical characteristics including chaos and randomness. Until now, the underlying mechanism has not been fully elucidated, especially the bistable property beneath the epileptic random induction phenomena in certain conditions. Inspired by the recent finding that astrocyte GTPase-activating protein (G-protein)-coupled receptors could be involved in stochastic epileptic seizures, we proposed a neuron-astrocyte network model, incorporating the noise of the astrocytic second messenger, inositol triphosphate (IP3) that is modulated by G-protein-coupled receptor activation. Based on this model, we have statistically analyzed the transitions of epileptic seizures by performing repeatable simulation trials. Our simulation results show that the increase in the IP3 noise intensity induces depolarization-block epileptic seizures together with an increase in neuronal firing frequency, consistent with corresponding experiments. Meanwhile, the bistable states of the seizure dynamics were present under certain noise intensities, during which the neuronal firing pattern switches between regular sparse spiking and epileptic seizure states. This random presence of epileptic seizures is absent when the noise intensity continues to increase, accompanying with an increase in the epileptic depolarization block duration. The simulation results also shed light on the fact that calcium signals in astrocytes play significant roles in the pattern formations of the epileptic seizure. Our results provide a potential pathway for understanding the epileptic randomness in certain conditions.
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Astrocitos , Convulsiones , Humanos , Fosfatos de Inositol , NeuronasRESUMEN
This study aimed to explore the effects of recombinant serine protease treatment on the development of post-harvest loquat diseases, fruit quality, and disease resistance enzyme activities. It also sought to analyze differential genes expression using RNA-seq technology. Transcriptomics analysis revealed 708 and 398 differentially expressed genes (DEGs) in loquat fruits treated with serine protease for 24 and 48 h. Furthermore, 2198 DEGs were obtained between 24 and 48 h after treatment. The genes encoding JAZ, MYC2 and ERF in the plant signal transduction pathway were significantly up-regulated. The resistance-related genes, such as PPO, PAL, TLP, WRKY, and transcription factors were also significantly up-regulated. These results indicated that the recombinant serine protease can induce plant signal transduction pathway in loquat fruit. The expression of some resistance-related genes enhanced the disease resistance of loquat fruit and revealed the molecular mechanism of loquat fruit resistance induced by recombinant serine protease.
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Eriobotrya , Eriobotrya/genética , Eriobotrya/metabolismo , Frutas/genética , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica de las Plantas , Serina Proteasas/genética , Serina Proteasas/metabolismo , TranscriptomaRESUMEN
The process of full-thickness skin regeneration is complex and has many parameters involved, which makes it difficult to use a single dressing to meet the various requirements of the complete regeneration at the same time. Therefore, developing hydrogel dressings with multifunction, including tunable rheological properties and aperture, hemostatic, antibacterial and super cytocompatibility, is a desirable candidate in wound healing. In this study, a series of complex hydrogels were developed via the hydrogen bond and covalent bond between chitosan (CS) and alginate (SA). These hydrogels exhibited suitable pore size and tunable rheological properties for cell adhesion. Chitosan endowed hemostatic, antibacterial properties and great cytocompatibility and thus solved two primary problems in the early stage of the wound healing process. Moreover, the sustained cytocompatibility of the hydrogels was further investigated after adding FGF and VE-cadherin via the co-culture of L929 and EC for 12 days. The confocal 3D fluorescent images showed that the cells were spherical and tended to form multicellular spheroids, which distributed in about 40-60 µm thick hydrogels. Furthermore, the hydrogel dressings significantly accelerate defected skin turn to normal skin with proper epithelial thickness and new blood vessels and hair follicles through the histological analysis of in vivo wound healing. The findings mentioned above demonstrated that the CS/SA hydrogels with growth factors have great potential as multifunctional hydrogel dressings for full-thickness skin regeneration incorporated with hemostatic, antibacterial, sustained cytocompatibility for 3D cell culture and normal skin repairing.
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Antígenos CD/farmacología , Cadherinas/farmacología , Factores de Crecimiento de Fibroblastos/farmacología , Piel/metabolismo , Alginatos/química , Animales , Antibacterianos/química , Vendas Hidrocoloidales , Línea Celular , China , Quitosano/química , Hemostáticos/química , Hidrogeles/síntesis química , Hidrogeles/química , Masculino , Conejos , Ratas , Ratas Sprague-Dawley , Piel/efectos de los fármacos , Fenómenos Fisiológicos de la Piel/efectos de los fármacos , Cicatrización de Heridas/fisiologíaRESUMEN
Vascular stent service involves complex service environments and performance requirements, among which the histocompatibility of the stent could seriously affect the therapeutic effect. In the pathology of vascular disease, the thin fiber cap is easily ruptured, exposing the necrotic core below, and triggering a series of dangerous biochemical reactions. In contrast, the thin neointima, considered an essential structure growing on the stent, may evolve into vulnerable plaque structures due to lesions induced by the stent. Therefore, the reduction of necrosis around the stent below the thin neointima is indispensable. In this work, different cell model experiments suggested that the content of endogenous labile Zn positively correlated with cell injury. Zinquin-Zn fluorescence experiments and zinc ion channels research suggested that the change in the content of endogenous labile Zn in smooth muscle cells is affected by different stent coatings. The content of endogenous labile Zn in cells negatively correlated with cell viability. Animal experiments indirectly verified the increase in endogenous labile Zn by detecting the expression of Zn regulatory protein (metallothionein) in the necrotic tissues. Reducing the content of endogenous labile Zn may favor a reduction in smooth muscle cell injury and necrosis. This biochemical mechanism is effective in improving the therapeutic effect of vascular stents.
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Miocitos del Músculo Liso , Neointima , Animales , Miocitos del Músculo Liso/metabolismo , Necrosis/metabolismo , Neointima/metabolismo , Stents , Zinc/metabolismoRESUMEN
BACKGROUND: Alginate oligosaccharides (AOS), with various physiological effects, have been widely used in the food, agricultural, and pharmaceutical industries. The biological enzymatic method of preparing AOS, using alginate lyase, has more advantages compared with physical and chemical methods. Cloning and heterologously expressing alginate lyase are therefore very important. RESULTS: A novel alginate lyase, BY17PV7, from Microbulbifer sp. BY17, isolated from Gracilaria, was cloned and expressed in Escherichia coli BL21(DE3). BY17PV7 was about 27 KDa. BY17PV7 showed the greatest activity (150.42 ± 3.32 U/mg) at 43 °C and pH 8.9. It could be activated by Ca2+ , Mn2+ , Co2+ , Fe3+ , Na+ , and inhibited by Mg2+ , Zn2+ , Ba2+ , Cu2+ , sodium dodecyl sulfate (SDS), ethylene diamine tetraacetic acid (EDTA). BY17PV7 had a wide range of substrate specificity and good degradation effects for poly ß-D-mannuronate (polyM) and poly α-L-guluronate (polyG), demonstrating that it is a bifunctional alginate lyase. The kinetic parameters showed that BY17PV7 had a greater affinity for polyG. BY17PV7 released AOS with a degree of polymerization (DP) of 3-4 in an endolytic manner from sodium alginate. Alginate oligosaccharides showed strong antioxidant ability of reducing Fe3+ and scavenging radicals such as hydroxyl, 2,2-azion-bia (3-ethylbenzo-thiazoline-6-sulfonic acid diammonium salt) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH). CONCLUSION: A novel bifunctional alginate lyase, BY17PV7, was expressed and characterized in Escherichia coli BL21(DE3). The results were helpful for the analysis of the molecular mechanisms of degrading patterns in the polysaccharide lyase (PL) family. © 2022 Society of Chemical Industry.
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Alginatos , Polisacárido Liasas , Alginatos/metabolismo , Proteínas Bacterianas/metabolismo , Clonación Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Concentración de Iones de Hidrógeno , Oligosacáridos/metabolismo , Polisacárido Liasas/química , Polisacárido Liasas/genética , Especificidad por SustratoRESUMEN
Furfural residue (FR), a solid waste, was applied as the precursor to prepare activated carbon by steam activation. The Box-Behnken design (BBD) approach-based response surface methodology (RSM) was utilized to optimize the preparation conditions to evaluate their effects on the performance of activated carbon from furfural residue (FRAC). The optimum preparation conditions of FRAC were found as follows: activation temperature of 922 °C, activation time of 62 min, and the mass ratio of char to H2O of 1:4.5, resulting in 1,501.84 mg/g of iodine adsorption capacity and 1,662.41 m2/g of specific surface area. The FRAC was characterized and then the adsorption performance of bisphenol S (BPS) on FRAC was investigated. Langmuir and Koble-Corrigan isotherm models were well fitted to the experimental data, and the adsorption kinetics process was perfectly described by the pseudo-second-order model. Thermodynamic parameters showed that the adsorption of BPS was a spontaneous exothermic process. Besides, the regeneration efficiency of FRAC was over 97% after five consecutive cycles. The maximum monolayer adsorption capacity of FRAC for BPS was 3.2848 mmol/g at 298 K, indicating that the FRAC was an excellent adsorbent for the removal of BPS from aqueous solutions.
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Carbón Orgánico , Contaminantes Químicos del Agua , Adsorción , Furaldehído , Concentración de Iones de Hidrógeno , Cinética , Fenoles , Sulfonas , Termodinámica , Contaminantes Químicos del Agua/análisisRESUMEN
A novel N-doped activated carbon (NAC) derived from shaddock peel was investigated to remove norfloxacin (NFX) from aqueous solution. The Box-Behnken central composite design (BBD) was used to optimize the preparation conditions of NAC. The specific surface area of NAC was 2,481.81 m2 g-1, which was obtained at 1,106 K activation temperature, 2.4 h residence time, and 2.3:1 mass ratio of KOH to hydrochar. Moreover, the equilibrium data were perfectly represented by Langmuir and Koble-Corrigan isotherms, and the adsorption process was precisely described by the pseudo-second-order kinetic model. Besides, the adsorption of NFX on NAC was mainly controlled by π-π electron-donor-acceptor (EDA) interaction, hydrophobic effect, hydrogen-bonding, electrostatic interaction and Lewis acid-base effect. The maximum monolayer adsorption capacity of NFX was 746.29 mg g-1 at 298 K, implying that NAC was a promising adsorbent for the removal of NFX from aqueous solution.
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Norfloxacino , Contaminantes Químicos del Agua , Adsorción , Carbón Orgánico/química , Agua , Contaminantes Químicos del Agua/químicaRESUMEN
A dengue virus serotype 1 (DENV-1) epidemic occurred from October to December 2018 in Xishuangbanna, Yunnan, Southwest China, neighboring Myanmar, Laos, and Vietnam. In this study, we investigated the molecular characteristics, evolution, and potential source of DENV from Xishuangbanna. The C (capsid), prM (premembrane), and E (envelope) genes of DENV isolated from 87 serum samples obtained from local patients were amplified and sequenced, and the sequences were evaluated by identification of mutations, phylogenetic and homologous recombination analysis, and secondary structure prediction. Phylogenetic analysis showed that all of the epidemic DENV strains from Xishuangbanna could be grouped in a branch with DENV-1 isolates, and were most similar to the Fujian 2005 (China, DQ193572) and Singapore 2016 (MF314188) strains. When compared with DENV-1SS (the standard strain), there were 31 non-synonymous mutations, but no obvious homologous recombination signal was found. Secondary structure prediction showed that some changes had occurred in a helical region in proteins of the MN123849 and MN123854 strains, but there were few changes in the disordered region. This study reveals the molecular characteristics of the structural genes of the Xishuangbanna epidemic strains in 2018 and provides a reference for molecular epidemiology, infection, and pathogenicity research and vaccine development.
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Proteínas de la Cápside/genética , Virus del Dengue/genética , Dengue/epidemiología , Proteínas del Envoltorio Viral/genética , Secuencia de Aminoácidos , China/epidemiología , Virus del Dengue/clasificación , Virus del Dengue/aislamiento & purificación , Brotes de Enfermedades , Genotipo , Humanos , Epidemiología Molecular , Filogenia , ARN Viral/genética , Alineación de Secuencia , Análisis de Secuencia de ARN , SerogrupoRESUMEN
BACKGROUND: An unexpected dengue outbreak occurred in Hunan Province in 2018. This was the first dengue outbreak in this area of inland China, and 172 cases were reported. METHODS: To verify the causative agent of this outbreak and characterise the viral genes, the genes encoding the structural proteins C/prM/E of viruses isolated from local residents were sequenced followed by mutation and phylogenetic analysis. Recombination, selection pressure, potential secondary structure and three-dimensional structure analyses were also performed. RESULTS: Phylogenetic analysis revealed that all epidemic strains were of the cosmopolitan DENV-2 genotype and were most closely related to the Zhejiang strain (MH010629, 2017) and then the Malaysia strain (KJ806803, 2013). Compared with the sequence of DENV-2SS, 151 base substitutions were found in the sequences of 89 isolates; these substitutions resulted in 20 non-synonymous mutations, of which 17 mutations existed in all samples (two in the capsid protein, six in the prM/M proteins, and nine in the envelope proteins). Moreover, amino acid substitutions at the 602nd (E322:Q â H) and 670th (E390: N â S) amino acids may have enhanced the virulence of the epidemic strains. One new DNA binding site and five new protein binding sites were observed. Two polynucleotide binding sites and seven protein binding sites were lost in the epidemic strains compared with DENV-2SS. Meanwhile, five changes were found in helical regions. Minor changes were observed in helical transmembrane and disordered regions. The 429th amino acid of the E protein switched from a histamine (positively charged) to an asparagine (neutral) in all 89 isolated strains. No recombination events or positive selection pressure sites were observed. To our knowledge, this study is the first to analyse the genetic characteristics of epidemic strains in the first dengue outbreak in Hunan Province in inland China. CONCLUSIONS: The causative agent is likely to come from Zhejiang Province, a neighbouring province where dengue fever broke out in 2017. This study may help clarify the intrinsic geographical relatedness of DENV-2 and contribute to further research on pathogenicity and vaccine development.