RESUMEN
Recently, CrSe2, a new ferromagnetic van der Waals two-dimensional material, was discovered to be highly stable under ambient conditions, making it an attractive candidate for fundamental research and potential device applications. Here, we study the interlayer interactions of bilayer CrSe2using first-principles calculations. We demonstrate that the interlayer interaction depends on the stacking structure. The AA and AB stackings exhibit antiferromagnetic (AFM) interlayer interactions, while the AC stacking exhibits ferromagnetic (FM) interlayer interaction. Furthermore, the interlayer interaction can be further tuned by tensile strain and charge doping. Specifically, under large tensile strain, most stacking structures exhibit FM interlayer interactions. Conversely, under heavy electron doping, all stacking structures exhibit AFM interlayer interactions. These findings are useful for designing spintronic devices based on CrSe2.
RESUMEN
Lead (Pb) can disrupt plant gene expression, modify metabolite contents, and influence the growth of plants. Cuminum cyminum L. is highly adaptable to adversity, but molecular mechanism by which it responds to Pb stress is unknown. For this study, transcriptomic and metabolomic sequencing was performed on root tissues of C. cyminum under Pb stress. Our results showed that high Pb stress increased the activity of peroxidase (POD), the contents of malondialdehyde (MDA) and proline by 80.03 %, 174.46 % and 71.24 %, respectively. Meanwhile, Pb stress decreased the activities of superoxide dismutase (SOD) and catalase (CAT) as well as contents of soluble sugars and GSH, which thus affected the growth of C. cyminum. In addition, Pb stress influenced the accumulation and transport of Pb in C. cyminum. Metabolomic results showed that Pb stress affected eight metabolic pathways involving 108 differentially expressed metabolites, primarily amino acids, organic acids, and carbohydrates. The differentially expressed genes identified through transcriptome analysis were mainly involved the oxidation reductase activity, transmembrane transport, phytohormone signaling, and MAPK signaling pathway. The results of this study will help to understand the molecular mechanisms of C. cyminum response to Pb stress, and provide a basis for screening seeds with strong resistance to heavy metals.
Asunto(s)
Antioxidantes , Cuminum , Antioxidantes/metabolismo , Cuminum/química , Cuminum/metabolismo , Plomo/toxicidad , Metabolómica , Perfilación de la Expresión GénicaRESUMEN
Background: Plant growth-promoting rhizobacteria (PGPR) have a specific symbiotic relationship with plants and rhizosphere soil. The purpose of this study was to evaluate the effects of PGPR on blueberry plant growth, rhizospheric soil nutrients and the microbial community. Methods: In this study, nine PGPR strains, belonging to the genera Pseudomonas and Buttiauxella, were selected and added into the soil in which the blueberry cuttings were planted. All the physiological indexes of the cuttings and all rhizospheric soil element contents were determined on day 6 after the quartic root irrigation experiments were completed. The microbial diversity in the soil was determined using high-throughput amplicon sequencing technology. The correlations between phosphorus solubilization, the auxin production of PGPR strains, and the physiological indexes of blueberry plants, and the correlation between rhizospheric microbial diversity and soil element contents were determined using the Pearson's correlation, Kendall's tau correlation and Spearman's rank correlation analysis methods. Results: The branch number, leaf number, chlorophyllcontentand plant height of the treated blueberry group were significantly higher than those of the control group. The rhizospheric soil element contents also increased after PGPR root irrigation. The rhizospheric microbial community structure changed significantly under the PGPR of root irrigation. The dominant phyla, except Actinomycetota, in the soil samples had the greatest correlation with phosphorus solubilization and the auxin production of PGPR strains. The branch number, leaf number, and chlorophyllcontent had a positive correlation with the phosphorus solubilization and auxin production of PGPR strains and soil element contents. In conclusion, plant growth could be promoted by the root irrigation of PGPR to improve rhizospheric soil nutrients and the microenvironment, with modification of the rhizospheric soil microbial community. Discussion: Plant growth could be promoted by the root irrigation of PGPR to improve rhizospheric soil nutrients and the microenvironment, with the modification of the rhizospheric soil microbial community. These data may help us to better understand the positive effects of PGPR on blueberry growth and the rhizosphere soil microenvironment, as well as provide a research basis for the subsequent development of a rhizosphere-promoting microbial fertilizer.
Asunto(s)
Alphaproteobacteria , Arándanos Azules (Planta) , Suelo/química , Rizosfera , Plantas , Ácidos Indolacéticos , FósforoRESUMEN
Mitosis is a crucial biological process where a parental cell undergoes precisely controlled functional phases and divides into two daughter cells. Some drugs can inhibit cell mitosis, for instance, the anti-cancer drugs interacting with the tumor cell proliferation and leading to mitosis arrest at a specific phase or cell death eventually. Combining machine learning with microfluidic impedance flow cytometry (IFC) offers a concise way for label-free and high-throughput classification of drug-treated cells at single-cell level. IFC-based single-cell analysis generates a large amount of data related to the cell electrophysiology parameters, and machine learning helps establish correlations between these data and specific cell states. This work demonstrates the application of machine learning for cell state classification, including the binary differentiations between the G1/S and apoptosis states and between the G2/M and apoptosis states, as well as the classification of three subpopulations comprising a subgroup insensitive to the drug beyond the two drug-induced states of G2/M arrest and apoptosis. The impedance amplitudes and phases used as input features for the model training were extracted from the IFC-measured datasets for the drug-treated tumor cells. The deep neural network (DNN) model was exploited here with the structure (e.g., hidden layer number and neuron number in each layer) optimized for each given cell type and drug. For the H1650 cells, we obtained an accuracy of 78.51% for classification between the G1/S and apoptosis states and 82.55% for the G2/M and apoptosis states. For HeLa cells, we achieved a high accuracy of 96.94% for classification between the G2/M and apoptosis states, both of which were induced by taxol treatment. Even higher accuracy approaching 100% was achieved for the vinblastine-treated HeLa cells for the differentiation between the viable and non-viable states, and between the G2/M and apoptosis states. We also demonstrate the capability of the DNN model for high-accuracy classification of the three subpopulations in a complete cell sample treated by taxol or vinblastine.
RESUMEN
Breezes are a common source of renewable energy in the natural world. However, effectively harnessing breeze energy is challenging with conventional wind generators. These generators have a relatively high start-up wind speed requirement due to their large and steady rotational inertia. This study puts forth the idea of an autoregulatory driving arm (ADA), utilizing a stretchable arm for every wind cup and an elastic thread to provide adjustable rotational inertia and a low start-up speed. The self-adjustable rotational inertia of the harvester is achieved through coordinated interaction between the centrifugal and elastic forces. As the wind speed varies, the arm length of the wind cup automatically adjusts, thereby altering the rotational inertia of the harvester. This self-adjustment mechanism allows the harvester to optimize its performance and adapt to different wind conditions. By implementing the suggested ADA harvester, a low start-up speed of 1 m/s is achieved due to the small rotational inertia in its idle state. With the escalation of wind speed, the amplified centrifugal force leads to the elongation of the driving arms. When compared to a comparable harvester with a constant driving arm (CDA), the ADA harvester can generate more power thanks to this stretching effect. Additionally, the ADA harvester can operate for a longer time than the CDA harvester even after the wind has stopped. This extended operation time enables the ADA harvester to serve as a renewable power source for sensors and other devices in natural breeze environments. By efficiently utilizing and storing energy, the ADA harvester ensures a continuous and reliable power supply in such settings.
RESUMEN
Chemotherapeutic drugs such as paclitaxel and vinblastine interact with microtubules and thus induce complex cell states of mitosis arrest at the G2/M phase followed by apoptosis dependent on drug exposure time and concentration. Microfluidic impedance cytometry (MIC), as a label-free and high-throughput technology for single-cell analysis, has been applied for viability assay of cancer cells post drug exposure at fixed time and dosage, yet verification of this technique for varied tumor cell states after anticancer drug treatment remains a challenge. Here we present a novel MIC device and for the first time perform impedance cytometry on carcinoma cells exhibiting progressive states of G2/M arrest followed by apoptosis related to drug concentration and exposure time, after treatments with paclitaxel and vinblastine, respectively. Our results from impedance cytometry reveal increased amplitude and negative phase shift at low frequency as well as higher opacity for HeLa cells under G2/M mitotic arrest compared to untreated cells. The cells under apoptosis, on the other hand, exhibit opposite changes in these electrical parameters. Therefore, the impedance features differentiate the HeLa cells under progressive states post anticancer drug treatment. We also demonstrate that vinblastine poses a more potent drug effect than paclitaxel especially at low concentrations. Our device is fabricated using a unique sacrificial layer-free soft lithography process as compared to the existing MIC device, which gives rise to readily aligned parallel microelectrodes made of silver-PDMS embedded in PDMS channel sidewalls with one molding step. Our results uncover the potential of the MIC device, with a fairly simple and low-cost fabrication process, for cellular state screening in anticancer drug therapy.
Asunto(s)
Antineoplásicos , Vinblastina , Humanos , Vinblastina/farmacología , Plata/farmacología , Células HeLa , Impedancia Eléctrica , Microelectrodos , Antineoplásicos/farmacología , Mitosis , Paclitaxel/farmacología , ApoptosisRESUMEN
A series of spiro[pyrrolidine-2,3'-quinoline]-2'-one derivatives were designed and synthesized for the discovery of novel antifungal drugs. The bioactivities of all derivatives were screened by evaluating their inhibitory effects against chitin synthase (CHS) and antimicrobial activities in vitro. Enzyme inhibition experiments showed that all the synthesized compounds inhibited the chitin synthase. Compounds 4d, 4k, 4n and 4o showed inhibitory effects against CHS with IC50 values which were close to that of the control drug (polyoxin B). The results of enzyme kinetics experiment showed that these compounds were non-competitive inhibitors of chitin synthase (Ki of compound 4o is 0.14 mM). Antimicrobial experiments showed that these compounds exhibited moderate to excellent antifungal activity against pathogenic fungal strains while the compounds showed little potency against bacteria. Among them, compounds 4d, 4f, 4k and 4n showed stronger antifungal activities against C. albicans than those of fluconazole and polyoxin B. Compounds 4f, 4n and 4o showed better antifungal activities against A. flavus than those of fluconazole and polyoxin B. Compound 4d showed similar activity to that of fluconazole and stronger activity than those of polyoxin B against C. neoformans and A. fumigatus. It is also showed that these compounds have the potency against drug-resistant fungal variants. The results of sorbitol protection assay and evaluation of antifungal activity against micafungin-resistant strains experiment further illustrated that these compounds inhibited the synthesis of chitin of fungal cell wall. Drug combination experiments showed that these compounds had synergistic or additive effects when combined with fluconazole or polyoxin B. The synergistic effects with polyoxin B further confirmed the compounds were non-competitive inhibitors of chitin synthase. Additionally, docking studies showed that these compounds had strong affinity with chitin synthase from C. albicans (CaChs2). These results indicate that the target of these synthesized compounds is chitin synthase, and these compounds had excellent antifungal activity while possessed the potency against drug-resistant fungal variants.
Asunto(s)
Cryptococcus neoformans , Quinolinas , Antifúngicos/farmacología , Fluconazol , Quitina Sintasa , Quitina , Candida albicans , PiperazinasRESUMEN
The dynamic characteristics of sandwich panels with a hierarchical hexagonal honeycomb (SP-HHHs) show significant improvements due to their distinct hierarchy configurations. However, this also increases the complexity of structural analysis. To address this issue, the variational asymptotic method was utilized to homogenize the unit cell of the SP-HHH and obtain the equivalent stiffness, establishing a two-dimensional equivalent plate model (2D-EPM). The accuracy and effectiveness of the 2D-EPM were then verified through comparisons with the results from a detailed 3D FE model in terms of the free vibration and frequency- and time-domain forced vibration, as well as through local field recovery analysis at peak and trough times. Furthermore, the tailorability of the typical unit cell was utilized to perform a parametric analysis of the effects of the length and thickness ratios of the first-order hierarchy on the dynamic characteristics of the SP-HHH under periodic loading. The results reveal that the vertices serve as weak points in the SP-HHH, while the vertex cell pattern significantly influences the specific stiffness and stiffness characteristics of the panel. The SP-HHH with hexagonal vertex cells has superior specific stiffness compared to panels with circular and rectangular vertex cells, resulting in a more lightweight design and enhanced stiffness.
RESUMEN
Breeze energy is a widely distributed renewable energy source in the natural world, but its efficient exploitation is very difficult. The conventional harvester with fixed arm length (HFA) has a relatively high start-up wind speed owing to its high and constant rotational inertia. Therefore, this paper proposes a harvester with a helix s-type vertical axis (HSVA) for achieving random energy capture in the natural breeze environment. The HSVA is constructed with two semi-circular buckets driven by the difference of the drag exerted, and the wind energy is transferred into mechanical energy. Firstly, as the wind speed changes, the HSVA harvester can match the random breeze to obtain highly efficient power. Compared with the HFA harvester, the power coefficient is significantly improved from 0.15 to 0.2 without additional equipment. Furthermore, it has more time for energy attenuation as the wind speeds dropped from strong to moderate. Moreover, the starting torque is also better than that of HFA harvester. Experiments showed that the HSVA harvester can improve power performance on the grounds of the wind speed ranging in 0.8-10.1 m/s, and that the star-up wind speed is 0.8 m/s and output peak power can reach 17.1 mW. In comparison with the HFA harvester, the HSVA harvester can obtain higher efficient power, requires lower startup speed and keeps energy longer under the same time. Additionally, as a distributed energy source, the HSVA harvester can provide a self-generating power supply to electronic sensors for monitoring the surrounding environment.
RESUMEN
A series of spiro-quinazolinone scaffolds were constructed based on the bioactivity of quinazolinone and the inherent feature of spirocycle to design novel chitin synthase inhibitors that possess mode of action different from that of the currently used antifungal agents. Among them, the spiro[thiophen-quinazolin]-one derivatives containing α, ß-unsaturated carbonyl fragments had shown inhibitory activities against chitin synthase and antifungal activities. The enzymatic experiments showed that among the sixteen compounds, compounds 12d, 12g, 12j, 12l and 12m exhibited inhibitions against chitin synthase with IC50 values of 116.7 ± 19.6 µM, 106.7 ± 14.2 µM, 102.3 ± 9.6 µM, 122.7 ± 22.2 µM and 136.8 ± 12.4 µM, respectively, which were comparable to that of polyoxin B (IC50 = 93.5 ± 11.1 µM). The assays of enzymatic Kinetic parameters showed that compound 12g was a non-competitive inhibitor of chitin synthase. The antifungal assays showed that compounds 12d, 12g, 12j, 12l and 12m exhibited a broad-spectrum of antifungal activity against the four strains tested in vitro. In which, compounds 12g and 12j had stronger antifungal activity against four tested strains than that of polyoxin B and similar to that of fluconazole, while compounds 12d, 12l and 12m showed antifungal activity comparable to that of polyoxin B against four tested strains. Meanwhile, compounds 12d, 12g, 12j, 12l and 12m exhibited good antifungal activity against fluconazole-resistant and micafungin-resistant fungi variants with MIC values ranging from 4 to 32 µg/mL while the MIC values of reference drugs were above 256 µg/mL. Furthermore, the results of drug-combination experiments showed that compounds 12d, 12g, 12j, 12l and 12m had synergistic or additive effects with fluconazole or polyoxin B. The results of sorbitol protection experiment and the experiment of antifungal activity against micafungin-resistant fungi further demonstrated that these compounds target chitin synthase. The result of cytotoxicity assay showed that compound 12g had low toxicity toward human lung cancer A549 cells and the ADME analysis in silico displayed that compound 12g possessed promising pharmacokinetic properties. The molecular docking indicated that compound 12g formed multiple hydrogen bond interactions binding to chitin synthase, which might be conductive to increasing the binding affinity and inhibiting the activity of chitin synthase. The above results indicated that the designed compounds were chitin synthase inhibitors with selectivity and broad-spectrum antifungal activity and could be act as the lead compounds against drug-resistant fungi.
Asunto(s)
Antifúngicos , Quitina Sintasa , Humanos , Antifúngicos/química , Relación Estructura-Actividad , Inhibidores Enzimáticos/química , Quinazolinonas/farmacología , Fluconazol , Micafungina , Quitina , Simulación del Acoplamiento Molecular , Pruebas de Sensibilidad Microbiana , Hongos/metabolismo , Diseño de FármacosRESUMEN
On the basis of star-shaped core sandwich panel, a novel sandwich panel with petal-triangle core (SP-PSC) was proposed to improve the negative Poisson's ratio (NPR) effect while retaining the characteristics of light weight and high strength. To study the complex structure more conveniently and quickly, a variational asymptotic method-based equivalent two-dimensional model (2D-EPM) was developed. The accuracy and efficiency of 2D-EPM were verified by the three-point bending experiment data and the 3D FE model results under different boundary and load conditions. The effects of the geometric parameters on the equivalent stiffness, buckling, natural frequency and NPR effect were also investigated. To increase the NPR of SP-PSC, the material of facesheet was changed from isotropic material to unidirectional CFPR material, and the influence of the material anisotropy on the NPR effect of SP-PSC was investigated. It is found that the NPR of SP-PSC increased first and then decreased with the increase in the fiber angle, reaching the maximum value at 40-50∘. At the same time, this law is applicable to SP-PSC with different material or geometric parameters. Finally, two improved cores, petal star-triangular core with X-shaped ligaments (PSC-X) and double-arc star-shaped core (DSC), were proposed and compared with SP-PSC in equivalent stiffness and recovered local fields to demonstrate their advantages. Compared with the original plate, the stress concentration and equivalent stiffness of the two improved PSCs significantly improved.
RESUMEN
Due to their complex microstructures, the research on the static and dynamic behaviors of triangular honeycomb sandwich panels (triangular HSPs) is limited. In this study, the effective plate properties of triangular HSP was obtained by the homogenizing of the unit cell, and then the input to a VAM-based two-dimensional equivalent plate model (2D-EPM) to perform static and dynamic analyses. The accuracy of the proposed model for predicting the equivalent stiffness of the triangular HSP was verified by three-point bending experiments of 3D-printed specimens. Then, the static displacement, global buckling, and free vibrations predicted by 2D-EPM were verified with the results from three-dimensional finite element model simulations under various boundary conditions. The influences of structural parameters (including angle, core wall thickness, and cell side length of the unit cell) on the static and dynamic characteristics of triangular HSPs were also investigated, which can provide a useful tool for the modeling and evaluation of triangular HSPs under different conditions.
RESUMEN
Chalcocite-dominant secondary copper ore with a high pyrite content had a rapidly increased iron concentration in the middle and later periods of bioleaching, which increased the difficulty of separating copper and iron ions in the leaching solution. In the two aspects of microbial community succession and energy band theory, the selective dissolution mechanism of chalcocite in this type of copper ore was analyzed and illustrated using experiments and first-principles calculations. The results showed that controlling the solution potential at a lower level was beneficial to the selective leaching of chalcocite, while bacteria promoted the leaching of pyrite and chalcocite simultaneously by oxidizing Fe2+ to Fe3+ in the solution. Below 700 mV of solution potential, the bacterial community, mainly consisting of Acidithiobacillus and Sulfobacillus, had a stronger promotion on the selective dissolution of chalcocite. The solution energy level of bioleaching was higher than ideal pyrite but lower than ideal chalcocite, which resulted in the accumulation of electrons on the surface of pyrite and the formation of holes at the top of the chalcocite valence band. When bacteria assisted the oxidation of Fe2+ to Fe3+ and caused the raise of the solution potential, the difference between the solution energy level and the top of the pyrite valence band would be smaller than the width of the pyrite energy gap. Below 700 mV, the assistance of Acidithiobacillus and Sulfobacillus on the oxidation of Fe2+ was weak. Chalcocite would be selectively dissolved by oxygen and a small amount of Fe3+ in the solution. Because of the existence of Fe, Cu, and S vacancies in real minerals, the atomic activity in the Cu-S bond and the Fe-S bond enhanced, and the reaction difficulty between chalcocite, pyrite, and electron acceptors in the solution reduced. The solution potential should be controlled at 600 mV or less to ensure the selective dissolution of chalcocite.
RESUMEN
Shigella species possess a type III secretion system (T3SS), which is required for human infection and that delivers effector proteins into target host cells. Here, we show that the effector, IpaH4.5 dampens the pro-inflammatory cytokine response. In both the Sereny test and a murine lung infection model, the Shigella ΔipaH4.5 mutant strain caused more severe inflammatory responses and significantly induced higher pro-inflammatory cytokine levels (MIP-2 and TNF-α) in the lung homogenates of wild type-infected mice. Moreover, there was a threefold decrease in bacterial colonization of the mutant compared with the WT and ΔipaH4.5/ipaH4.5-rescued strains. Yeast two-hybrid screening showed that IpaH4.5 specifically interacts with the p65 subunit of NF-κB. Ten truncated versions of IpaH4.5 and p65 spanning different regions were constructed and expressed to further map the IpaH binding sites with p65. The results revealed thatthe p65 region spanning amino acids 1-190 of p65 interacted with the IpaH4.5/1-293 N-terminal region. In vitro, IpaH4.5 displayed ubiquitin ligase activity towards ubiquitin and p65. Furthermore, the transcriptional activity of NF-κB was shown to be inhibited by IpaH4.5 utilizing a dual-luciferase reporter gene detection system containing NF-κB promoter response elements. Thus, we conclude that the IpaH4.5 protein is an E3 ubiquitin ligase capable of directly regulating the host inflammatory response by inhibiting the NF-κB signalling pathway.