Using a wet chemical process, a continuous network of silver nanowires was buried at the surface of a transparent polymer (PVA) to form a flexible transparent conductor, which shows high optical ...transparency, low sheet resistance, a smooth surface, and superior mechanical, thermal and chemical stabilities. The composite is a competitive choice for transparent electrodes in OLED and thin film solar cells.
Aim
Novel long‐acting drugs for type 2 diabetes mellitus may optimize patient compliance and glycaemic control. Exendin‐4‐IgG4‐Fc (E4F4) is a long‐acting glucagon‐like peptide‐1 receptor agonist. ...This first‐in‐human study investigated the safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of a single subcutaneous injection of E4F4 in healthy subjects.
Methods
This single‐centre, randomized, double‐blind, placebo‐controlled phase 1 clinical trial included 96 subjects in 10 sequential cohorts that were provided successively higher doses of E4F4 (0.45, 0.9, 1.8, 3.15, 4.5, 6.3, 8.1, 10.35, 12.6 and 14.85 mg) or placebo (ChinaDrugTrials.org.cn: ChiCTR2100049732). The primary endpoint was safety and tolerability of E4F4. Secondary endpoints were pharmacokinetic, pharmacodynamic and immunogenicity profiles of E4F4. Safety data to day 15 after the final subject in a cohort had been dosed were reviewed before commencing the next dose level.
Results
E4F4 was safe and well tolerated among healthy Chinese participants in this study. There was no obvious dose‐dependent relationship between frequency, severity or causality of treatment‐emergent adverse events. Cmax and area under the curve of E4F4 were dose proportional over the 0.45‐14.85 mg dose range. Median Tmax and t1/2 ranged from 146 to 210 h and 199 to 252 h, respectively, across E4F4 doses, with no dose‐dependent trends. For the intravenous glucose tolerance test, area under the curve of glucose in plasma from time 0 to 180 min showed a dose‐response relationship in the 1.8‐10.35 mg dose range, with an increased response at the higher doses.
Conclusion
E4F4 exhibited an acceptable safety profile and linear pharmacokinetics in healthy subjects. The recommended phase 2 dose is 4.5‐10.35 mg once every 2 weeks.
Ethylene response factor (ERF) has been widely studied in regulating fruit ripening in tomato, apple, banana and kiwifruit, but little is known in pear. In this study 1‐methylcyclopropene (1‐MCP) ...treatment, an inhibitor of ethylene perception, was conducted at approximately 30 days before harvest to delay fruit ripening in a climacteric white pear cultivar Yali. Transcriptome libraries were constructed and sequenced in pre‐ripening, ripening, and 1‐MCP treated fruits. Data analysis showed that 73 candidate genes related to fruit ripening were induced by 1‐MCP, among which two were positively related, namely 1‐aminocyclopropane‐1‐carboxyla oxidase and an ERF gene (designated as ACO54 and ERF24). Transient transformations in pear fruit revealed that over‐expression of ACO54 enhance transcription level of ERF24 and most ripening‐related genes. Meanwhile, over‐expression of ERF24 raises expression level of ACO54 and partially ripening‐related genes. Moreover, dual‐luciferase and yeast‐one‐hybrid assays unravel an interaction between ERF24 and the ACO54 promoter. Therefore, the ERF24 could directly regulate ACO54 expression by binding to its promoter. These results suggested that the first identified ERF24 is involved in regulating fruit ripening in Chinese white pear.
SUMMARY
Gametophytic self‐incompatibility (GSI) has been widely studied in flowering plants, but studies of the mechanisms underlying pollen tube growth arrest by self S‐RNase in GSI species are ...limited. In the present study, two leucine‐rich repeat extensin genes in pear (Pyrus bretschneideri), PbLRXA2.1 and PbLRXA2.2, were identified based on transcriptome and quantitative real‐time PCR analyses. The expression levels of these two LRX genes were significantly higher in the pollen grains and pollen tubes of the self‐compatible cultivar ‘Jinzhui’ (harboring a spontaneous bud mutation) than in those of the self‐incompatible cultivar ‘Yali’. Both PbLRXA2.1 and PbLRXA2.2 stimulated pollen tube growth and attenuated the inhibitory effects of self S‐RNase on pollen tube growth by stabilizing the actin cytoskeleton and enhancing cell wall integrity. These results indicate that abnormal expression of PbLRXA2.1 and PbLRXA2.2 is involved in the loss of self‐incompatibility in ‘Jinzhui’. The PbLRXA2.1 and PbLRXA2.2 promoters were directly bound by the ABRE‐binding factor PbABF.D.2. Knockdown of PbABF.D.2 decreased PbLRXA2.1 and PbLRXA2.2 expression and inhibited pollen tube growth. Notably, the expression of PbLRXA2.1, PbLRXA2.2, and PbABF.D.2 was repressed by self S‐RNase, suggesting that self S‐RNase can arrest pollen tube growth by restricting the PbABF.D.2–PbLRXA2.1/PbLRXA2.2 signal cascade. These results provide novel insight into pollen tube growth arrest by self S‐RNase.
Significance Statement
PbLRXA2.1 and PbLRX.A2.2 mediate pollen tube growth and attenuate the inhibitory effects of self S‐RNase on pollen tube growth by stabilizing the actin cytoskeleton and enhancing cell wall integrity. Self S‐RNase can arrest pollen tube growth by restricting the PbABF.D.2–PbLRXA2.1/PbLRXA2.2 signal cascade.
•The immunomodulatory properties of mesenchymal stem cells (MSCs).•The interaction between MSCs and those critical immune cells in human innate and adaptive immune systems.•MSCs-mediated ...immunomodulation is highly plastic depending on the inflammatory status in microenvironment of diseases
Mesenchymal stem cells (MSCs) exist in almost all tissues with the capability to differentiate into several different cell types and hold great promise in tissue repairs in a cell replacement manner. The study of the bidirectional regulation between MSCs and immune response has ushered an age of rethinking of tissue regeneration in the process of stem cell-based tissue repairs. By sensing damaged signals, both endogenous and exogenous MSCs migrate to the damaged site where they involve in the reconstitution of the immune microenvironment and empower tissue stem/progenitor cells and other resident cells, whereby facilitate tissue repairs. This MSC-based therapeutic manner is conferred as cell empowerment. In this process, MSCs have been found to exert extensive immunosuppression on both innate and adaptive immune response, while such regulation needs to be licensed by inflammation. More importantly, the immunoregulation of MSCs is highly plastic, especially in the context of pathological microenvironment. Understanding the immunoregulatory properties of MSCs is necessary for appropriate application of MSCs. Here we review the current studies on the crosstalk of MSCs and immune response in disease pathogenesis and therapy.
Facile and effective access for the asymmetric construction of the useful and important skeleton of the bicyclic N,O‐acetals is described. CuII/SaBOX could catalyze the reaction of β,γ‐unsaturated ...α‐ketoesters with cyclic enamines efficiently, thus affording the desired products in excellent yields with excellent stereoselectivities (21 examples; up to 99 % yields; up to >95:5 d.r.; and 95–99 % ee). This reaction can be well performed on gram scale, even with only 1 mol % catalyst loading. The single‐crystal structures of the copper complexes lead to a good understanding of the stereo‐synergistic effects of the sidearm.
N,O skeletons: A protocol for the enantioselective construction of useful and important bicyclic N,O‐acetal skeletons is described. Excellent yields and excellent stereoselectivities were obtained for a broad scope of substrates, and even with only a 1 mol % catalyst loading on gram scale.
Selective electron beam melting (SEBM) is considered to be a promising method to fabricate TiAl alloy components with complex geometries. In this work, the effect of annealing on the microstructure ...and anisotropy of tensile properties of SEBM-produced Ti–47Al–2Cr–2Nb alloys was systematically investigated. The results indicated that the SEBM-produced TiAl alloy samples exhibited equiaxed and elongated grains in the transverse and longitudinal directions, respectively, and presented anisotropy of the tensile properties. For the sample produced at an energy density of 24.07 J/mm3, the microstructure in the vertical cross section presented an elongated lamellar structure consisting of (α2/γ) lamellar colonies, after annealing at 1310 °C for 3 h; on the other hand, for the same sample, elongated grains were almost invisible after annealing at 1370 °C for 2 h. Further, for the sample produced at an energy density of 35 J/mm3, the elongated grains remained after annealing at 1370 °C for 2 h and were destroyed by cyclic heat treatment. The texture intensity and anisotropy of the tensile properties of the two samples fabricated with different processing parameters were weakened by annealing at 1370 °C for a duration of 2 h and cyclic heat treatment between the α+β+γ and α phase regions, respectively. Both the tensile strength and elongation increased as a result of heat treatment. Moreover, the phase transformation during annealing was analyzed.
Hydromechanical behaviour of unsaturated expansive soils is complex, and current constitutive models failed to accurately reproduce it. Different from conventional modelling, this study proposes a ...novel physics-informed neural networks (PINN)-based model utilising long short-term memory as the baseline algorithm and incorporating a physical constraint (water retention) to modify the loss function. Firstly, a series of laboratory tests on Zaoyang expansive clay, including wetting and drying cycle tests and triaxial tests, was compiled into a dataset and subsequently fed into the PINN-based model. Subsequently, a specific equation representing the soil water retention curve (SWRC) for expansive clay was derived by accounting for the influence of the void ratio, which was integrated into the PINN-based model as a physical law. The ultimate predictions from the PINN-based model are compared with experimental data of unsaturated expansive clay with excellent agreement. This study demonstrates the capability of the proposed PINN in modelling the hydromechanical response of unsaturated soils and provides an innovative approach to establish constitutive models in the unsaturated soil mechanics field.
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•LiAl LDH nanoflakes is used to modify the PP membrane for Li metal batteries.•Homogeneous interfacial Li flux is regulated through the modified PP separator.•Ultra-stable battery ...cycling performance is achieved with the modified PP separator.
Lithium metal batteries have attracted remarkable attention because of their high theoretic specific capacity and low redox potential. However, the issues, including uncontrollable dendritic formation and the highly reactive nature of Li anodes hinder the practical application of lithium metal batteries. Herein, LiAl layered double hydroxide (LiAl LDH) modified separators (LiAl LDH@PP) are prepared by simply coating LiAl2(OH)6Cl nanoflakes onto polypropylene (PP) membranes. LiAl LDH nanoflakes with plenty of octahedral vacancies and abundant lithium ion diffusion pathways improve the ionic conductivity, surface electrolyte wettability and mechanical robustness of the separators. The modified separator promotes the interfacial lithium ionic flux, suppressing the dendrite formation and consequently increasing the cycling stability of lithium metal batteries. Even at an ultrahigh current density of 20 mA cm−2, the Li|Li symmetric batteries with the LiAl LDH@PP separators can be charged/discharged for more than 3000 h, demonstrating the remarkably high cycling stability. This work provides a feasible and efficient strategy for enhancing the cycling performance and safety of lithium metal batteries.
Various experiments and computational methods have been conducted to describe the mechanical behaviours of frozen soils. However, due to high nonlinearity and uncertainty of responses, modelling the ...stress-strain behaviours of frozen soils remains challenging. Accordingly, we first propose a novel data-driven method based on Long Short-Term Memory (LSTM) to model the mechanical responses of frozen soil. A compiled database on the stress-strain of a frozen silty sandy soil is employed to feed into the LSTM model, where the mechanical behaviours under various temperatures and confining pressures are measured through triaxial tests. Subsequently, uncertainty of the stress-strain relations (i.e., deviatoric stress and volumetric strain to axial strain) is investigated and considered in LSTM-based modelling with Monte Carlo dropout (LSTM-MCD). Results demonstrate that the LSTM model without uncertainty can capture the stress-strain responses of the frozen soil with considerable predictive accuracy. Uncertainty analysis from LSTM-MCD reveals that the model with uncertainty can be applied to evaluate the mechanical responses of frozen soil with 95% confidence intervals. This study sheds light on the advantage of the data-driven model with uncertainty in predicting mechanical behaviours of frozen soils and provides references for permafrost construction.
•A data-driven method is proposed to model the mechanical behaviour of frozen soil.•LSTM with dropout is developed for considering the uncertainty in modelling.•Confidence intervals are provided for reliability evaluation in practice.
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