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Kushneria phosphatilytica YCWA18T (= CGMCC 1.9149T = NCCB 100306T) was isolated from sediment collected in a saltern on the eastern coast of Yellow Sea in China. The genome was sequenced and comprised of one circular chromosome with the size of 3,624,619 bp and DNA G + C content of 59.13%. A total of 3267 protein-coding genes, 64 tRNA genes and 12 rRNA genes were obtained. Genomic annotation indicated that the genome of K. phosphatilytica YCWA18T had 34 genes involved in phosphorus (P) solubilization/metabolism, e.g., gdh, pqq, phoA, phoD and phoX, which products can convert insoluble P-containing compounds to more bio-available dissolved inorganic P. Comparative genomic analysis of Kushneria strains revealed that gdh, pqq, phoA, phoD and phoX were widely distributed in these strains, indicating the genus Kushneria may play an important role in the P cycle. Additionally, a multitude of salt tolerance genes were detected in the genome of K. phosphatilytica YCWA18T. This study and the genome sequence data will be available for further research and will provide insights into potential biotechnological and agricultural applications of Kushneria strains.
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Genoma Bacteriano , Fósforo , Secuenciación Completa del Genoma , Fósforo/metabolismo , ChinaRESUMEN
The shuttle effect of lithium polysulfides (LiPSs) and the sluggish reaction kinetics of LiPSs conversion pose serious challenges to the commercial feasibility of lithium-sulfur (Li-S) batteries. To address these obstacles, herein, we construct CeO2/Co heterostructures in hollow necklace-like carbon fibers (CeO2/Co-CNFs) as the cathode host material for Li-S batteries. The specific surface area of fibers is significantly enhanced by using a template, thereby promoting the utilization efficiency of sulfur. Meanwhile, CeO2/Co-CNFs show strong conductivity, effective adsorption to LiPSs, and robust catalytic activity for LiPSs conversion. As a result, the Li-S battery with CeO2/Co-CNFs displays 961 mAh g-1 at 0.2 C, with an 86 % capacity retention rate after 100 cycles. At 2.0 C current density, the composite cathode maintains an initial discharge capacity of 782 mAh g-1, with a mere 0.044 % capacity loss per cycle. Furthermore, in situations with limited electrolytes, high sulfur loading, and high areal mass loading, the composite cathode can provide a high areal capacity of 6.2 mg cm-2 over 100 cycles. This work provides a useful approach for investigating high-performance Li-S battery cathodes.
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Novel eye-sensitive Ba3Nb2O2F12(H2O)2:Tb3+ green and Ba3Nb2O2F12(H2O)2:Mn4+ red oxyfluoride phosphors with extremely strong absorption in the UV region were designed and synthesized by simple co-precipitation strategy. Particularly, Tb3+ ions were doped in this matrix for the first time, which greatly improves their absorption efficiency in the near ultraviolet region (367 nm) and emits sharp green light (544 nm). In addition, the Ba3Nb2O2F12(H2O)2:Mn4+ red phosphors have strong zero phonon line (ZPL) emission at 625 nm, which is conducive to improving the sensitivity of human eye and color purity. Meanwhile, the optical properties of the red phosphor are significantly enhanced via doping K+ cations as charge compensators. Crystal field environment and nephelauxetic effect of the as-prepared phosphors before and after K+ cation doping were systematically analyzed. Moreover, these synthesized red/green phosphors have good thermal stability and moisture resistance. Remarkably, the as-prepared Ba3Nb2O2F12(H2O)2:5%Mn4+ or K0.9Ba2.1Nb2O2F12(H2O)2:5%Mn4+ red phosphors can be directly mixed with the as-synthesized Ba3Nb2O2F12(H2O)2:13%Tb3+ green phosphor coating on 365 nm near-ultraviolet LED chip to package WLED devices with excellent electroluminescence performance. These findings are conducive to opening an avenue for screening the unique structure of optical materials.
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Lead halide perovskite quantum dots (QDs) are promising semiconductors for next-generation photoelectric devices. However, the development of perovskite QDs-based multifunctional materials still needs to be addressed in order to further advance the application of perovskite QDs. Herein, a successful synthesis of Janus microfibers array Janus membrane (JMAJM) with up-down structure and multifunction of luminescence, magnetism and electroconductivity is firstly achieved based on CsPbBr3 QDs through a parallel electrospinning. JMAJM comprises up-down two layers tightly bonded together. The up-layer of JMAJM is luminescence/magnetism Janus microfibers array (L/M-JMAJM) constructed by [CsPbBr3/polymethyl methacrylate (PMMA)]//[CoFe2O4/PMMA] Janus microfibers as building elements. The down-layer of JMAJM is luminescence/electroconductivity Janus microfibers array (L/E-JMAJM) fabricated by [CsPbBr3/PMMA]//[polyaniline (PANI)/PMMA] Janus microfibers as building elements. Two independent microcosmic regions are designed and realized in a Janus microfiber, confining luminescence with magnetic or conductive substances into their respective regions, thus minimizing adverse effects of other dark-colored functional substances on the fluorescence of CsPbBr3 QDs. This peculiar Janus microfiber enables the effective separation and high integration of CsPbBr3 QDs with other functional substances. The up-down structure of JMAJM ensures a high integration of luminescence, magnetism and conductivity. Meanwhile, JMAJM addresses the environmental instability of CsPbBr3 QDs while simultaneously endows perovskite QDs-based materials with additional functions to realize multifunction. Under ultraviolet excitation, fluorescence characteristics of the CsPbBr3 QDs in JMAJM are maintained, exhibiting a vibrant green emission at 517 nm. Meanwhile, JMAJM achieves a maximum saturation magnetization of 20.32 emu·g-1, high conductance of 10-2 S and aeolotropic electroconductivity degree of 107. The combination of micro-partition with macro-partition in JMAJM receives superior concurrent luminescence-magnetic-conductive multifunction. This work provides a novel idea and strategy for advancing perovskite QDs-based multifunctional materials.
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A new type of self-supporting multi-channel Janus carbon fibers with efficient water splitting has been successfully manufactured using a specially designed parallel spinneret through electrospinning technology and subsequent carbonization technique. Every single Janus fiber composes of a half side of Mo2C and the other half side of Ni components as Mo2C, Ni embedded in N-doped multi-channel Janus carbon fibers ([Mo2C/C]//[Ni/C]-NMCFs) for overall water splitting. Under optimized condition, the hydrogen evolution reaction overpotential of [Mo2C/C]//[Ni/C]-NMCFs (62 mV) is just 24 mV higher than 20 wt% Pt/C (38 mV) at a current density of 10 mA cm-2. Furthermore, it achieves current density of 10 mA cm-2 to require an overpotential of 324 mV for oxygen evolution reaction. Additionally, the cell assembled by the identical [Mo2C/C]//[Ni/C]-NMCFs catalyst as both the cathode and anode needs only 1.607 V at a current density of 10 mA cm-2, which is only 0.022 V higher than that of Pt/C-IrO2 electrodes. Moreover, [Mo2C/C]//[Ni/C]-NMCFs catalyst also exhibits a long-term stability. The synergistic effect and unique heterostructure of Mo2C and Ni enhance the catalytic activity.
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The shuttle effect of lithium polysulfides (LiPSs) severely hinders the development and commercialization of lithium-sulfur batteries, and the design of high-conductive carbon fiber-host material has become a key solution to suppress the shuttle effect. In this work, a unique Co/CoN-carbon nanocages@TiO2-carbon nanotubes structure (NC@TiO2-CNTs) is constructed using an electrospinning and nitriding process. Lithium-sulfur batteries using NC@TiO2-CNTs as cathode host materials exhibit high sulfur utilization (1527 mAh g-1 at 0.2 C) and can still maintain a discharge capacity of 663 mAh g-1 at a high current density of 5 C, and the capacity loss is only 0.056% per cycle during 500 cycles at 1 C. It is worth noting that even under extreme conditions (sulfur-loading = 90%, surface-loading = 5.0 mg cm-2 (S), and E/S = 6.63 µL mg-1), the lithium-sulfur batteries can still provide a reversible capacity of 4 mAh cm-2. Throughdensity functional theory calculations, it has been found that the Co/CoN heterostructures can adsorb and catalyze LiPSs conversion effectively. Simultaneously, the TiO2 can adsorb LiPSs and transfer Li+ selectively, achieving dual confinement for the shuttle effect of LiPSs (nanocages and nanotubes). The new findings provide a new performance enhancement strategy for the commercialization of lithium-sulfur batteries.
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Poor water stability and single luminous color are the major drawbacks of the most phosphors reported. Therefore, it is important to realize multicolor luminescence in a phosphor with single host and single activator as well as moisture resistance. LaF3 :Pr3+ @SiO2 yolk-shell nanospheres are facilely obtained by a designing new technology of a simple and cost-effective electrospray ionization combined with a dicrucible fluorating technique without using protective gas. In addition, tunable photoluminescence, especially white-light emission, is successfully obtained in LaF3 :Pr3+ @SiO2 yolk-shell nanospheres by adjusting Pr3+ ion concentrations, and the luminescence mechanism of Pr3+ ion is advanced. Compared with the counterpart LaF3 :Pr3+ nanospheres, the water stability of LaF3 :Pr3+ @SiO2 yolk-shell nanospheres is improved by 15% after immersion in water for 72 h, and the fluorescence intensity can be maintained at 86% of the initial intensity. Furthermore, by treating the yolk-shell nanospheres with hydrofluoric acid, it is not only demonstrated that the shell-layer is SiO2 but also core-LaF3 :Pr3+ nanospheres are obtained. Particularly, only fluorination procedure among the halogenation can produce such special yolk-shell nanospheres, the formation mechanism of yolk-shell nanospheres is proposed detailedly based on the sound experiments and a corresponding new technology is built. These findings broaden practical applications of LaF3 :Pr3+ @SiO2 yolk-shell nanospheres.
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Herein, a new organic cationic matrix [N(CH3)4]3MoO3F3 suitable for Mn4+ doping was constructed. Due to the large steric hindrance of N[CH3]4+ (TMA), charge compensation defects can be effectively prevented in the heterovalent Mn4+-doping process, and a high IQE (91.05%) was obtained. Through the cation co-doping strategy, Mg2+/Zn2+/Li+ cations were introduced into the Mo6+ cationic site, which improved the crystallinity of the matrix and reduced energy losses, so as to improve luminescence intensity, QE, thermal stability, water stability and other spectral properties. Meanwhile, [N(CH3)4]2TiF6:Mn4+ phosphors with the same TMA organic cation and equivalent Mn4+ doping were synthesized for comparison, and the effects of the Mg2+ cation co-doping strategy on the spectral properties of phosphors with different matrix types (fluoride/oxyfluoride) and substitution types (equivalent/non-equivalent) were analyzed. These findings provide the basis for the preparation of new luminescent materials. Furthermore, according to the optical properties exhibited by these phosphors, they are packaged into WLED devices with excellent photoelectric properties, which are suitable for indoor lighting and display fields.
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The Piwi-interacting RNA (piRNA) pathway has been shown to be involved in the antiviral defense against RNA viruses, especially in mosquitoes, but its universality has been questioned. Here, we used the Bombyx mori nucleopolyhedrovirus (BmNPV) -infected silkworm as a model to explore the effects of the key factors of piRNA pathway, BmAgo3 and Siwi, on replication of a large DNA virus (belonging to the family of Baculoviridae). We demonstrated that BmAgo3 and Siwi could promote the replication of BmNPV through both overexpression and knockdown experiments in BmN cell lines and silkworm larvae. In addition, we also studied the effect of PIWI-class genes on Autographa californica nucleopolyhedrovirus (AcMNPV) replication in the Spodoptera frugiperda cell line Sf9. By knocking down the expression of PIWI-class genes in Sf9, we found that Piwi-like-1 and Piwi-like-2-3 could inhibit AcMNPV replication, while Piwi-like-4-5 promoted virus replication. Our study provides compelling evidence that the piRNA pathway affects host infection by exogenous viruses in Lepidoptera. Also, our results reflect the diversity of the roles of PIWI-class genes in virus infection of the host across species. This study is the first to explore the interaction of PIWI-class proteins with DNA viruses, providing new insights into the functional roles of the piRNA pathway.
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A novel [uniaxial needle]//[coaxial needle]//[uniaxial needle] parallel spinneret is first innovatively designed and manufactured by inserting a coaxial needle into the middle of a bi-axial parallel needle, and the corresponding spinning device is established. With the aid of the distinctive-structured spinneret and the spinning device, a novel and brand-new flexible one-dimensional nanobelt//coaxial nanobelt//nanobelt tri-strand parallel nanobelt, very much like a tricolor flag and named a pseudo-tricolor typed nanobelt, is successfully prepared by electrospinning technology for the first time. Microscopically, partition of four independent domains in the pseudo-tricolor typed nanobelt is realized, and such a partitioned structure can assemble various functions and helps reduce detrimental interactions among various functions to acquire excellent poly-functions of multifunctional nanomaterials. As a case study, {anthracene/Eu(2-thenoyltrifluoroacetone)3(triphenylphosphine oxide)2 [Eu(TTA)3(TPPO)2]/polymethylmethacrylate (PMMA)}//{[CoFe2O4/PMMA]@[polyaniline (PANI)/PMMA]}//{coumarin-6/PMMA} pseudo-tricolor typed nanobelts and arrays (abbreviated as [B + R]//[M@C]//[G] PNA) are designed and constructed via electrospinning. Each pseudo-tricolor typed nanobelt is composed of left and right sides of blue and red fluorescent [anthracene/Eu(TTA)3(TPPO)2/PMMA] nanobelts and green fluorescent [coumarin-6/PMMA] nanobelts, respectively, and the middle of the [CoFe2O4/PMMA]@[PANI/PMMA] coaxial nanobelt with magnetic-conductive bifunctionality using the CoFe2O4/PMMA nanobelt as the core and PANI/PMMA as the shell. Luminescence-magnetic-conductive polyfunctionalities are highly integrated but also mutually separated in the pseudo-tricolor typed nanobelt, and thus, both segregation and integration of the functions are actualized in the pseudo-tricolor typed nanobelt. A pseudo-tricolor typed nanobelt as the building unit ensures strong fluorescence and high conductive anisotropy of the array. Moreover, energy transfer between dyes is controlled by the special structure of the nanobelt and thus white light emission is realized by the combination of europium complexes with the dyes. The conductive anisotropy and magnetism of the array are tuned by changing the content of PANI and CoFe2O4, respectively. The formation mechanism of the pseudo-tricolor typed nanobelt is proposed, and new techniques for constructing nanobelts and arrays are established. This kind of pseudo-tricolor typed nanobelt with four functional subareas possesses important implications as a building unit to construct other polyfunctional nanostructures. More importantly, the design philosophy and the construction techniques for the novel pseudo-tricolor typed nanobelt and array afford some guidance for the development of other multifunctional materials.
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A novel three-dimensional (3D) S-scheme S-gC3N4/TiO2/SiO2/PAN aerogel heterojunction photocatalyst (denoted as S-gTAHP) is rationally devised and manufactured by combining electrospinning, calcination, hydrothermal and freeze-drying techniques. The synthesized S-gC3N4 molecule is different from traditional g-C3N4, which has a small molecular structure similar to melamine. S-gC3N4 is embedded in the interwoven network structure of TiO2/PAN short fibers, and the catalytic system of the S-scheme heterojunction is formed with SiO2 as a crosslinking agent. S-gTAHP achieves perfect tri-functional photocatalytic capability, including remarkable hydrogen release capacity (806.7 µmolâh-1âg-1), efficient removal of three colored dyes with removal efficiencies up to 99.43% (MB, 15 min), 96.13% (RhB, 30 min) and 91.32% (MO, 40 min), and a degradation rate of the colorless antibiotic TCH reaching 84.20% in 40 min driven by simulated sunlight. Meanwhile, the effects of pH values and concentrations of contaminant solutions on the removal rates are explored, and the S-scheme mechanism of S-gTAHP strengthening photocatalytic activity is elucidated. The apparently heightened photocatalytic activities of S-gTAHP can be ascribed to the fact that the 3D hierarchical porous structure of the aerogel endows more active centers and enhanced light-harvesting capacity, and the S-scheme heterojunction supplies effective charge migrating channels, thereby affording the carriers with strong redox capability. Furthermore, S-gTAHP holds prominent reusability and is light weight. Hence, efficient and recyclable 3D aerogel photocatalysts with S-scheme heterojunctions have broad application prospects in practical sewage treatment and energy conversion fields.
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Antibacterianos , Colorantes , Dióxido de Silicio , Aguas del Alcantarillado , HidrógenoRESUMEN
Compared to single functional materials, multifunctional materials with electrical conduction, magnetism, and luminescence are more attractive and promising, so it has become an important subject. A distinctive sandwich-type composite film (STCF) with dual-color up- and down-conversion luminescence, magnetism, and aeolotropic conduction is prepared by layer-by-layer electrospinning technology. Macroscopically, STCF is assembled by three tightly bonded layers, including a [polypyrrole (PPy)/poly(methyl methacrylate) (PMMA)]//[NaYF4:Yb3+, Er3+/PMMA] Janus nanobelt array layer as the first layer, a CoFe2O4/polyacrylonitrile (PAN) nanofiber nonarray layer as the second layer, and a Na2GeF6:Mn4+/polyvinylpyrrolidone (PVP) nanofiber nonarray layer as the third layer. This unique macropartition effectually confines conductive aeolotropy, magnetism, and luminescence in different layers. Microscopically, a Janus nanobelt is used as a construction unit to restrict the luminescent and conductive materials to their microregions, thus achieving highly conductive aeolotropy and green luminescence. The high integration of the micro-subarea and macro-subarea in the STCF can efficaciously avoid the mutual disadvantageous effects among different materials to obtain splendid polyfunctional performance. The conductive anisotropy and magnetism of the STCF can be adjusted by changing the contents of PPy and CoFe2O4. When the PPy content reaches 70%, the conductance ratio in the conductive direction to insulative direction is 108. The 2D STCF can be crimped by four different methods, and the 3D TWTs have the same excellent polyfunctional performances as 2D STCF. This unique design idea and construction technology can be applied to the preparation of other multifunctional materials to avoid harmful interference among various functions.
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Both spherical MnO as adsorbent and Ni nanoparticles as catalyzer, with highly exposed contact surface area in the carbon nanofibers, are successfully synthesized via electrospinning technology combined with carbothermal reduction. Compared with typical electrospun carbon nanofiber composites, the as-prepared C@Ni/MnO composite fibers as interlayer enable MnO and Ni to contact fully with polysulfides rather than provide local contact surface. With the sulfur loading of 1.6 mg cm-2 and the approximately 0.1 g composite fibers as interlayer, the cathode shows initial capacity of 687.36 mAh g-1 at 0.5C and superior capacity retention of 70%. This simple technical route leads a way to prepare nanoparticles with highly exposed contact surfaces partially embedded in the carbon nanofibers, which can be applied in electrocatalysis.
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Detection of copper plays a prominent role in the environmental protection and human health. Herein, we firstly design and construct an "off-on" upconversion fluorescence resonance energy transfer (UFRET) probe with low toxicity for the Cu2+ determination by using NaYF4: Yb3+, Er3+ upconversion nanoparticles (UCNPs) and Au NPs. UCNPs with positive charge and Au NPs with negative charge are respectively employed as the donor and acceptor, and bound together to form UFRET probe. The upconversion fluorescence quenching of UCNPs occurs by Au NPs through FRET (defined as "off" state). When Cu2+ exists in samples, Cu2+ reacts with 4-mercaptobenzoic acid (4-MBA) capped on the surface of Au NPs to make Au NPs detach from UCNPs, leading to the termination of FRET and the recovery of upconversion fluorescence (defined as "on" state). "Off-on" typed UFRET probe has excellent sensing performances, including linear range of 0.02-1 µM Cu2+ concentration, the limit of detection of 18.2 nM, high selectivity to Cu2+ and good recovery. The probe has been successfully used to determine Cu2+ in spiked tap water with satisfactory results. The probe will provide theoretical and technical support for the design of new sensitive heavy metal ion detection probe.
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Transferencia Resonante de Energía de Fluorescencia , Nanopartículas , Cobre , Transferencia Resonante de Energía de Fluorescencia/métodos , Oro , Humanos , AguaRESUMEN
Outbreak updates are an integral part of crisis communication during epidemics. Regarding the COVID-19 crisis communication, localities in China present different strategies for managing outbreak updates, which largely determine the effect of crisis communication and the evolution of social psychology. Depending on the analysis of the update texts from 31 provincial (autonomous regions and municipalities directly under the central government) health committees in China, the study found the differences among the provincial outbreak updates and summarizes 12 innovative crisis communication ways. A coupling analysis was applied using the equilibrium-cognitive-psychosocial transition model to further expound on the psychological connotation and intervention potential of the crisis communication innovations. Coupling crisis communication with interventions has a positive effect on designing crisis communication strategies by taking into account psychological factors. It can help construct and optimize the public crisis communication systems and emphasize "care" in modernizing the emergency management capacity.
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Triboelectric nanogenerators (TENGs) have opened a new direction in the field of flexible devices. Here, a fluorescent TENG-JNA constructed with a flexible Janus nanobelt array (JNA) and PVDF/PVP nanofibers membrane by electro-spinning is reported for the first time. The building unit of JNA is the [PANI/CNTs/PMMA]//[Tb(BA)3phen/PMMA] Janus nanobelts, which demonstrate green fluorescence and electrical conduction bi-function, where two independent partitions are microscopically realized in the Janus nanobelts. In TENG-JNA, JNA concurrently gains excellent charge-trapping ability and charge-generating capability by optimizing the PANI content; therefore, JNA serves as both a charge-generating layer and charge-trapping layer. The interface between TB(BA)3phen and PMMA, the existence of aromatic ring structures in the PANI main chain and the interface between PANI and PMMA are conducive to trap a large number of triboelectric charges in time to prevent the triboelectric charges from combining with induced charges, which can significantly improve the output performance of TENG-JNA. The maximum output current and voltage of TENG-JNA are 6.20 µA and 155 V, respectively. The introduction of Tb(BA)3phen ensures the strong fluorescence of TENF-JNA, and this fluorescence can be used to judge whether TENF-JNA works normally or is out of order in a dark environment. TENG-JNA possesses other compelling features, such as prominent flexibility, good hydrophobicity, durability and light weight, which provides the premise for TENG-JNA to be used as a flexible device in a wet environment or for warning functions. The Janus nanobelt was firstly used to assemble a TENG, which provides theoretical, material and technical support for the development of new building units of TENGs and paves a pathway for designing and assembling new TENGs.
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Sensitive detection and effective removal of copper ions (Cu2+) from water are still arduous tasks required to protect public health and environmental safety because of the serious impacts of Cu2+ on humans and other organisms. Herein, we report the design and fabrication of self-supporting flexible amidated polyacrylonitrile/branched polyethyleneimine nanofiber membranes (abbreviated as aPAN/BPEI NMs) via facile electrospinning and a subsequent hydrothermal method, which are used not only as strips for the visual detection of Cu2+ but also as effective adsorbents for the removal of Cu2+ from water. Because aPAN/BPEI NMs are self-supporting, they can be easily removed from the solution to reduce secondary pollution to the environment. Based on the high Cu2+ binding capacity of BPEI, Cu2+ ions are adsorbed on the aPAN/BPEI NMs, which leads to the appearance of new absorbance bands at 280 and 636 nm and a color change from yellow to blue. aPAN/BPEI NMs are utilized for the visual detection of Cu2+ with a linear range of 50-700 µM and limits of detection of 11.5 and 4.8 µM (absorption peaks at 280 and 636 nm). More importantly, aPAN/BPEI NMs exhibit excellent selectivity and certain recovery with a simple treatment. Furthermore, by utilizing the adsorption characteristics of Cu2+ in aqueous media, it can be effectively removed by aPAN/BPEI NMs with a remarkable adsorption capacity of 209.53 mg·g-1. Additionally, the removal of Cu2+ by aPAN/BPEI NMs does not exhibit interference by other foreign ions. The adsorption process conforms well to the pseudo-second order (PSO) kinetic model and Jovanovich model, proving that adsorption occurs via chemical and monolayer adsorption mechanisms. Accordingly, this work will provide theoretical and technical support for the design and fabrication of novel heavy metal ion detection-removal integrated materials exhibiting high sensitivity and strong adsorption.
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A series of IDO1 inhibitors containing a decahydroquinoline, decahydro-1,6-naphthyridine, or octahydro-1H-pyrrolo[3,2-c]pyridine scaffold were identified with good cellular and human whole blood activity against IDO1. These inhibitors contain multiple chiral centers and all diastereomers were separated. The absolute stereochemistry of each isomers were not determined. Compounds 15 and 27 stood out as leads due to their good cellular as well as human whole blood IDO1 inhibition activity, low unbound clearance, and reasonable mean residence time in rat cassette PK studies.
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Inhibidores Enzimáticos/farmacología , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Naftiridinas/farmacología , Pirroles/farmacología , Quinolinas/farmacología , Animales , Dominio Catalítico , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacocinética , Células HeLa , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/química , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Simulación del Acoplamiento Molecular , Naftiridinas/síntesis química , Naftiridinas/metabolismo , Naftiridinas/farmacocinética , Pirroles/síntesis química , Pirroles/metabolismo , Pirroles/farmacocinética , Quinolinas/síntesis química , Quinolinas/metabolismo , Quinolinas/farmacocinética , Ratas , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
A novel series of IDO1 inhibitors have been identified with good IDO1 Hela cell and human whole blood activity. These inhibitors contain an indoline or a 3-azaindoline scaffold. Their structure-activity-relationship studies have been explored. Compounds 37 and 41 stood out as leads due to their good potency in IDO1 Hela assay, good IDO1 unbound hWB IC50s, reasonable unbound clearance, and good MRT in rat and dog PK studies.
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Compuestos Aza/farmacología , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Indoles/farmacología , Animales , Compuestos Aza/síntesis química , Compuestos Aza/química , Perros , Relación Dosis-Respuesta a Droga , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Indoles/síntesis química , Indoles/química , Masculino , Estructura Molecular , Ratas , Ratas Wistar , Relación Estructura-ActividadRESUMEN
A series of unique macrocyclic HDACs 1, 2, and 3 selective inhibitors were identified with good enzymatic activity and high selectivity over HDACs 6 and 8. These macrocyclic HDAC inhibitors used an ethyl ketone as the zinc-binding group. Compounds 25 and 26 stood out as leads due to their low double-digit nM EC50s in the 2C4 cell-based HIV latency reactivation assay. The PK profiles of these macrocyclic HDAC inhibitors still needed improvement.