Facile Multiple Graded Wrinkle Construction Strategy for Vastly Boosting the Sensing Performance of Ionic Skins.

The construction of surface microstructures (e.g., micropyramids and wrinkles) has been proven as the most effective means to boost the sensitivity of ionic skins (I-skins). However, the single-scale micronano patterns constructed by the common fabrication strategy generally lead to a limited pressure-response range. Here, a convenient repeated stretching/coordinating/releasing strategy is developed to controllably construct multiple graded wrinkles on the polyelectrolyte hydrogel-based I-skins for increasing their sensitivity over a broad pressure range. We find that the small wrinkles allow for high sensitivity yet small pressure detection range, while the large wrinkles can reduce structural stiffening to generate large pressure-response range but incur limited sensitivity. The multiple graded wrinkles can combine the merits of both the small and large wrinkles to simultaneously improve the sensitivity and broaden the pressure-response range. In particular, the sensing performance of multiple-wrinkle-based I-skins substantially outperforms the superposition of the sensing performance of different single-wrinkle-based I-skins. As a proof of concept, the triple-wrinkle-based I-skins can provide an extremely high sensitivity of 17,309 kPa-1 and an ultrawide pressure detection range of 0.38 Pa to 372 kPa. The approach and insight contribute to the future development of I-skins with a broader pressure-response range and higher sensitivity.

Screening and verification of hemostatic effective components group of Panax Notoginseng based on spectrum-effect relationships.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax Notoginseng (PN) can disperse blood stasis, hemostasis, and detumescence analgesic, which can be used for hemoptysis, hematemesis and another traumatic bleeding, and it is known as "A miracle hemostatic medicine". Studies show that the chemical composition of PN is relatively comprehensive, however, its hemostatic active ingredients have not been fully clarified. AIM OF STUDY: This study aimed to clarify the hemostatic effective components group (HECG) of PN, provide a foundation for the assessment of PN's quality and its comprehensive development, and for further studies on the pharmacodynamic material basis of other Traditional Chinese Medicines (TCMs). MATERIALS AND METHODS: UPLC-MS was used to establish the fingerprint and identify the common peaks in 44 batches of PN extracts (PNE). In addition, the plasma recalcification time and in vitro coagulation time were measured. For spectrum-effect analysis, bivariate correlation analysis (BCA) and partial least squares regression analysis (PLSR) were used to screen the hemostasis candidate active monomers of PN. The monomers were prepared by combining several preparative chromatography techniques. The efficacy was verified by plasma recalcification time, in vitro coagulation time, and a rat model of gastric hemorrhage. RESULTS: A total of 30 common peaks and hemostatic efficacy indexes of 44 batches of PNE were obtained. A total of 18 components were positively correlated with the comprehensive coagulation index by two statistical methods. Six and eleven monomers were obtained respectively by chromatographic preparation and procurement, and one monomer was eliminated due to preparation difficulty and other reasons. Seven active monomers with direct hemostatic effect and one active monomer with synergistic hemostatic effect were screened through plasma recalcification time, and their combinations were used as candidate HECG for hemostatic effect verification. The results of in vitro experiments showed that plasma recalcification time and in vitro coagulation time were significantly reduced (P < 0.05) in the HECG group, compared to the PNE group. The results of in vivo experiment also indicated that the hemostatic effect of HECG was comparable to that of PNE and PN powder. CONCLUSION: The composition and efficacy of the HECG of PN were screened and verified using the spectral correlation method and in vivo and in vitro efficacy verification; the HECG included Dencichine, Ginsenoside Rg1, Ginsenoside Rd, Ginsenoside Rh1, Ginsenoside F1, Notoginsenoside R1, Notoginsenoside Ft1 and Notoginsenoside Fe. These results laid a foundation for the quality evaluation of PN and provided a reference for the basic research of pharmacodynamic material basis of other TCMs.

Integrating serum pharmacochemistry and network pharmacology to reveal the active constituents and mechanism of Corydalis Rhizoma in treating Alzheimer's disease.

Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative condition. The search for multi-target traditional Chinese medicines or ingredients for treating AD has attracted much attention. Corydalis rhizome (CR) is a traditional Chinese medicine. Its main components are alkaloids, which have therapeutic effects that can potentially be used for treating AD. However, no systematic study has been conducted to explore the anti-AD efficacy of CR, as well as its active compounds and mechanisms of action. Objective: The present study aimed to clarify CR's active constituents and its pharmacological mechanisms in treating AD. Methods: A D-galactose & scopolamine hydrobromide-induced AD mouse model was used and CR was administered orally. The prototypical alkaloid components were identified in the serum. The core components, key targets, and possible mechanisms of action of these alkaloids were revealed through network pharmacology. Molecular docking of the key target was performed. Finally, the mechanism was validated by lipopolysaccharide (LPS)-induced activation of BV2 microglia. Results: The results showed that CR improved anxiety-like behavior, spatial and non-spatial recognition, and memory capacity in AD mice. It also achieved synergistic AD treatment by modulating neurotransmitter levels, anti-neuroinflammation, and anti-oxidative stress. The core components that enhance CR's efficacy in treating AD are protoberberine-type alkaloids. The CR may induce the polarization of LPS-activated BV2 microglia from phenotype M1 to M2. This is partially achieved by modulating the IL-6/JAK2/STAT3 signaling pathway, which could be the mechanism by which CR treats AD through anti-inflammation. Conclusion: The present study provided a theoretical and experimental basis for the clinical application of CR in treating AD. It also provides information that aids the secondary development, and precise clinical use of CR.

Biomimetic 3D Color-Changing Hydrogel Actuators Constructed Based on Soft Permeable Photonic Crystals.

The integration of photonic crystals and self-shaping actuators is a promising method for constructing powerful biomimetic color-changing actuators. The major barrier is that common photonic crystals generally block the transfer/orientation of monomers/fillers and hence hinder the formation of heterogeneous structures for programmed 3D deformations as well as degrade the deformation capacity and mechanical properties of actuators. Herein, we present the construction of complex and strong 3D color-changing hydrogel actuators by asymmetric photolithography based on soft, permeable photonic crystals. The soft permeable photonic crystals are assembled by hydrogel microspheres with an ultralow volume fraction. During the asymmetric photolithography, the monomers in precursor solutions can thus transfer freely to generate heterogeneous microstructures, spatially patterned internal stresses, and interpenetrating networks for programming the deformation trajectories and initial 3D configurations and enhancing mechanical properties of actuators. Various 3D color-changing hydrogel actuators (e.g., flower and scroll painting) are constructed for applications such as information encryption and display.

Cavity-enhanced and temporally multiplexed atom-photon entanglement interface.

Practical realization of quantum repeaters requires quantum memories with high retrieval efficiency, multi-mode storage capacities, and long lifetimes. Here, we report a high-retrieval-efficiency and temporally multiplexed atom-photon entanglement source. A train of 12 write pulses in time is applied to a cold atomic ensemble along different directions, which generates temporally multiplexed pairs of Stokes photons and spin waves via Duan-Lukin-Cirac-Zoller processes. The two arms of a polarization interferometer are used to encode photonic qubits of 12 Stokes temporal modes. The multiplexed spin-wave qubits, each of which is entangled with one Stokes qubit, are stored in a "clock" coherence. A ring cavity that resonates simultaneously with the two arms of the interferometer is used to enhance retrieval from the spin-wave qubits, with the intrinsic retrieval efficiency reaching 70.4%. The multiplexed source gives rise to a ∼12.1-fold increase in atom-photon entanglement-generation probability compared to the single-mode source. The measured Bell parameter for the multiplexed atom-photon entanglement is 2.21(2), along with a memory lifetime of up to ∼125 µs.

ß-Boron Effect Enables Regioselective and Stereospecific Electrophilic Addition to Alkenes.

Electrophilic addition to alkenes is a textbook-taught reaction, yet it is not always possible to control the regioselectivity of addition to unsymmetrical 1,2-disubstituted substrates. We report the observation and applications of the ß-boron effect that accounts for high regioselectivity in electrophilic addition reactions to allylic MIDA (N-methyliminodiacetic acid) boronates. While the well-established ß-silicon effect bears partial resemblance to the observed reactivity, the silyl group is typically lost during functionalization. In contrast, the boryl moiety is retained in the product when B(MIDA) is used as the nucleophilic stabilizer. Mechanistic studies elucidate the origin of this effect and demonstrate how σ(C-B) hyperconjugation helps stabilize the incipient carbocation. This transformation represents a rare example of the stereospecific hydrohalogenation of secondary allyl MIDA-boronates that proceeds in a syn-fashion.

Self-Powered Gradient Hydrogel Sensor with the Temperature-Triggered Reversible Adhension.

The skin, as the largest organ of human body, can use ions as information carriers to convert multiple external stimuli into biological potential signals. So far, artificial skin that can imitate the functionality of human skin has been extensively investigated. However, the demand for additional power, non-reusability and serious damage to the skin greatly limits applications. Here, we have developed a self-powered gradient hydrogel which has high temperature-triggered adhesion and room temperature-triggered easy separation characteristics. The self-powered gradient hydrogels are polymerized using 2-(dimethylamino) ethyl metharcylate (DMAEMA) and N-isopropylacrylamide (NIPAM) under unilateral UV irradiation. The prepared hydrogels achieve good adhesion at high temperature and detachment at a low temperature. In addition, according to the thickness-dependent potential of the gradient hydrogel, the hydrogels can also sense pressure changes. This strategy can inspire the design and manufacture of self-powered gradient hydrogel sensors, contributing to the development of complex intelligent artificial skin sensing systems in the future.

Effect of Different Mo Addition on Microstructure and Mechanical Properties of Cu-15Ni-8Sn Alloy.

In the present study, Mo was added to Cu-15Ni-8Sn alloy as the fourth element to solve the limitation of service performance of the alloy by composition design. The phase composition, microstructure transformation and mechanical properties of Cu-15Ni-8Sn-xMo (x = 0.3, 0.9, 1.5 wt.%) alloy were systematically studied by simulation calculation and experimental characterization. The results show that the addition of Mo can improve the as-cast structure of Cu-15Ni-8Sn alloy and reduce segregation and Cu-Mo phase precipitates on the surface with the increase in Mo contents. During solution treatment, Mo can partially dissolve into the matrix, which may be the key to improving the properties of the alloy. Furthermore, the discontinuous precipitation of Sn can be effectively inhibited by adding the appropriate amount of Mo to Cu-15Ni-8Sn alloy, and the hardness of alloy does not decrease greatly after a long-time aging treatment. When Mo content is 0.9 wt.%, the alloy reaches the peak hardness of 384 HV at 4 h of aging. These results provide new ideas for composition optimization of Cu-15Ni-8Sn alloy.

Regiocontrolled allylic functionalization of internal alkene via selenium-π-acid catalysis guided by boron substitution.

The selenium-π-acid-catalysis has received increasing attention as a powerful tool for olefin functionalization, but the regioselectivity is often problematic. Reported herein is a selenium-catalyzed regiocontrolled olefin transpositional chlorination and imidation reaction. The reaction outcome benefits from an allylic B(MIDA) substitution. And the stabilization of α-anion from a hemilabile B(MIDA) moiety was believed to be the key factor for selectivity. Broad substrate scope, good functional group tolerance and generally good yields were observed. The formed products were demonstrated to be valuable precursors for the synthesis of a wide variety of structurally complex organoborons.

FOXG1 sequentially orchestrates subtype specification of postmitotic cortical projection neurons.

The mammalian neocortex is a highly organized six-layered structure with four major cortical neuron subtypes: corticothalamic projection neurons (CThPNs), subcerebral projection neurons (SCPNs), deep callosal projection neurons (CPNs), and superficial CPNs. Here, careful examination of multiple conditional knockout model mouse lines showed that the transcription factor FOXG1 functions as a master regulator of postmitotic cortical neuron specification and found that mice lacking functional FOXG1 exhibited projection deficits. Before embryonic day 14.5 (E14.5), FOXG1 enforces deep CPN identity in postmitotic neurons by activating Satb2 but repressing Bcl11b and Tbr1. After E14.5, FOXG1 exerts specification functions in distinct layers via differential regulation of Bcl11b and Tbr1, including specification of superficial versus deep CPNs and enforcement of CThPN identity. FOXG1 controls CThPN versus SCPN fate by fine-tuning Fezf2 levels through diverse interactions with multiple SOX family proteins. Thus, our study supports a developmental model to explain the postmitotic specification of four cortical projection neuron subtypes and sheds light on neuropathogenesis.

Strong and tough self-wrinkling polyelectrolyte hydrogels constructed via a diffusion-complexation strategy.

Self-wrinkling hydrogels enable various engineering and biomedical applications. The major challenge is to couple the self-wrinkling technologies and enhancement strategies, so as to get rid of the poor mechanical properties of existing self-wrinkling gels. Herein we present a facile diffusion-complexation strategy for constructing strong and ultratough self-wrinkling polyelectrolyte hydrogels with programmable wrinkled structures and customizable 3D configurations. Driven by the diffusion of low-molecular-weight chitosan polycations into the polyanion hydrogels, the high-modulus polyelectrolyte complexation shells can form directly on the hydrogel surface. Meanwhile, the polyanion hydrogels deswell/shrink due to the low osmotic pressure, which applies an isotropous surface compressive stress for inducing the formation of polygonal wrinkled structures. When the diffusion-complexation reaction occurs on a pre-stretched hydrogel sheet, the long-range ordered wrinkled structures can form during the springback/recovery of the hydrogel matrix. Moreover, through controlling the regions of diffusion-complexation reaction on the pre-stretched hydrogels, they can be spontaneously transformed into various 3D configurations with ordered wrinkled structures. Notably, because of the introduction of plenty of electrostatic binding (i.e., sacrificial bonds), the as-prepared self-wrinkling gels possess outstanding mechanical properties, far superior to the reported ones. This diffusion-complexation strategy paves the way for the on-demand design of high-performance self-wrinkling hydrogels.

Self-Powered Multifunction Ionic Skins Based on Gradient Polyelectrolyte Hydrogels.

Human skin is the largest organ, and it can transform multiple external stimuli into the biopotential signals by virtue of ions as information carriers. Ionic skins (i-skins) that can mimic human skin have been extensively explored; however, the limited sensing capacities as well as the need of an extra power supply significantly restrict their broad applications. Herein, we develop self-powered humanlike i-skins based on gradient polyelectrolyte membranes (GPMs) that can directly and accurately perceive multiple stimuli. Prepared by a hydrogel-assisted reaction-diffusion method, the GPMs exhibit gradient-distributed charged groups across polymer networks, enabling one to generate a thickness-dependent and thermoresponsive self-induced potential in a hydrated situation and in a humidity-sensitive self-induced potential in a dehydrated/dried situation, respectively. Consequently, the GPM-based i-skins can precisely detect pressure, temperature, and humidity in a self-powered manner. The coupling of mechano-electric and thermo-electric effects inherent in GPMs provides a general strategy for developing innovative self-powered ion-based perception systems.

Integrative analysis reveals multiple modes of LXR transcriptional regulation in liver.

The nuclear receptors liver X receptor (LXR) α and ß play crucial roles in hepatic metabolism. Many genes induced in response to pharmacologic LXR agonism have been defined; however, the transcriptional consequences of loss of LXR binding to its genomic targets are less well characterized. Here, we addressed how deletion of both LXRα and LXRß from mouse liver (LXR double knockout [DKO]) affects the transcriptional regulatory landscape by integrating changes in LXR binding, chromatin accessibility, and gene expression. Many genes involved in fatty acid metabolism showed reduced expression and chromatin accessibility at their intergenic and intronic regions in LXRDKO livers. Genes that were up-regulated with LXR deletion had increased chromatin accessibility at their promoter regions and were enriched for functions not linked to lipid metabolism. Loss of LXR binding in liver reduced the activity of a broad set of hepatic transcription factors, inferred through changes in motif accessibility. By contrast, accessibility at promoter nuclear factor Y (NF-Y) motifs was increased in the absence of LXR. Unexpectedly, we also defined a small set of LXR targets for direct ligand-dependent repression. These genes have LXR-binding sites but showed increased expression in LXRDKO liver and reduced expression in response to the LXR agonist. In summary, the binding of LXRs to the hepatic genome has broad effects on the transcriptional landscape that extend beyond its canonical function as an activator of lipid metabolic genes.

Precisely Defining Local Gradients of Stimuli-Responsive Hydrogels for Complex 2D-to-4D Shape Evolutions.

The intellectualization and complication of existing self-shaping materials are limited by the inseparable monotonic relationship between their deformation rate and deformation degree (i.e., a higher deformation rate is accompanied by a high deformation degree). This causes that they can only deform from 2D to 3D states. Here, a simple yet versatile strategy to decouple the monotonic correlation between the deformation rate and deformation degree of self-shaping hydrogels is presented for achieving complex deformations from 2D to temporary 3D to 3D (2D-to-4D). It is demonstrated that when the gradient hydrogels prepared by photopolymerization possess dense polymer networks, the local regions with a high deformation rate can exhibit a low deformation degree. The resulting hydrogels can thus deform in a novel 2D-to-4D mode under external stimuli. During the deformation, they first transform into the temporary shapes induced by the local deformation rate difference, and then transform into the final shapes determined by the local deformation degree difference. Through controlling the ultraviolet irradiation direction and time to precisely program the local gradients of self-shaping hydrogels, they can be designed to produce various unprecedented yet controllable 2D-to-4D shape evolutions on demand, such as transformable origami, sequential gesture actions in finger-guessing games, mobile octopuses, time switch, etc.

Revealing the Effect of Phase Composition and Transformation on the Mechanical Properties of a Cu-6Ni-6Sn-0.6Si Alloy.

In the present study, a Cu-6Ni-6Sn-0.6Si alloy is fabricated through frequency induction melting, then subjected to solution treatment, rolling, and annealing. The phase composition, microstructure evolution, and transition mechanism of the Cu-6Ni-6Sn-0.6Si alloy are researched systematically through simulation calculation and experimental characterization. The ultimate as-annealed sample simultaneously performs with high strength and good ductility according to the uniaxial tensile test results at room temperature. There are amounts of precipitates generated, which are identified as belonging to the DO22 and L12 phases through the transmission electron microscope (TEM) analysis. The DO22 and L12 phase precipitates have a significant strengthening effect. Meanwhile, the generation of the common discontinuous precipitation of the γ phase, which is harmful to the mechanical properties of the copper-nickel-tin alloy, is inhibited mightily during the annealing process, possibly due to the existence of the Ni5Si2 primary phase. Therefore, the as-annealed sample of the Cu-6Ni-6Sn-0.6Si alloy possesses high tensile strength and elongation, which are 967 MPa and 12%, respectively.

Anti-Swelling Gradient Polyelectrolyte Hydrogel Membranes as High-Performance Osmotic Energy Generators.

Emerging asymmetric ionic membranes consisting of two different porous membranes show great superiority in harvesting clean and renewable osmotic energy. The main barriers constraining their applications are incompatible interfaces and a low interfacial ionic transport efficiency, which are detrimental to the long-term stability and improvement of the power density. Here, continuous-gradient all-polysaccharide polyelectrolyte hydrogel membranes prepared by ultrafast reaction/diffusion have been demonstrated to enable high-performance osmotic energy conversion. Besides an inherent high ion conductivity and excellent ion selectivity, the anti-swelling polyelectrolyte gradient membranes preserve the ionic diode effect of the asymmetric membranes to facilitate one-way ion diffusion but circumvent adverse interfacial effects. In consequence, they can present ultrahigh power densities of 7.87 W m-2 by mixing seawater and river water, far superior to state-of-the-art membranes.

Photochemical Radical C-H Halogenation of Benzyl N-Methyliminodiacetyl (MIDA) Boronates: Synthesis of α-Functionalized Alkyl Boronates.

α-Haloboronates are useful organic synthons that can be converted to a diverse array of α-substituted alkyl borons. Methods to α-haloboronates are limiting and often suffer from harsh reaction conditions. Reported herein is a photochemical radical C-H halogenation of benzyl N-methyliminodiacetyl (MIDA) boronates. Fluorination, chlorination, and bromination reactions were effective by using this protocol. Upon reaction with different nucleophiles, the C-Br bond in the brominated product could be readily transformed to a series of C-C, C-O, C-N, C-S, C-P, and C-I bonds, some of which are difficult to forge with α-halo sp2 -B boronate esters. An activation effect of B(MIDA) moiety was found.

Associations Between High-Altitude Residence and End-Stage Kidney Disease in Chinese Patients with Type 2 Diabetes.

Zhao, Lijun, Xi Wang, Tingli Wang, Wenxin Fan, Honghong Ren, Rui Zhang, Yutong Zou, Huan Xu, Jie Zhang, Yunhong Wu, and Fang Liu. Associations between high-altitude residence and end-stage kidney disease in Chinese patients with type 2 diabetes. High Alt Med Biol. 21:396-405, 2020. Background: This study investigated whether living at high altitude was associated with progression to end-stage kidney disease (ESKD) in Chinese patients with diabetic nephropathy (DN). Materials and Methods: This retrospective study included 369 patients with type 2 diabetes mellitus (T2DM) and biopsy-confirmed DN. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the influence of living at high altitude on ESKD. Results: Patients living at ≥2,000 m above sea level were more likely to be Tibetan, and they had higher mean body mass indexes, glycosylated hemoglobin, hemoglobin concentrations, and baseline estimated glomerular filtration rates than those living at lower altitudes. During a median follow-up period of 20 months, 141 (38%) patients progressed to ESKD. In multivariable Cox analysis adjusted for age, sex, ethnicity, and clinical and pathological parameters, living at high altitude was independently associated with progression to ESKD in Chinese DN patients [HR 2.83, 95% confidence interval (CI) 1.05-7.58]. Compared with Han Chinese, Tibetans were at a lower risk of progression to ESKD (HR 0.15, 95% CI 0.04-0.59). Conclusions: Living at high altitude was independently associated with renal outcome in Han Chinese patients with T2DM and DN, but not native Tibetans.

Precisely Controlling the Output Force of Hydrogel Actuator Based on Thermodynamic Nonequilibrium Temporary Deformation.

Self-shaping hydrogel actuators have promising applications in various fields. However, one hydrogel actuator can generally access only one specifically predefined deformation and output force, which are determined by its thermodynamic equilibrium swelling state under external stimuli. Here, we present a simple yet versatile strategy for precisely programming the output force/energy of dual-gradient hydrogel actuators. The strategy is based on thermodynamic nonequilibrium snapping deformations occurring during the recovery process of predeformed dual-gradient hydrogel actuators in low-temperature water. The output force/energy of such thermodynamic nonequilibrium snapping deformation is highly associated with predeformation conditions of the hydrogel actuators, which increases with the increase of the predeformation temperature or time. In consequence, just by adjusting the predeformation conditions of the dual-gradient hydrogel actuators, their output force, energy, and power can be modulated precisely and continuously during the snapping deformation. The as-prepared hydrogel actuators can not only be used as smart lifters and grippers with ultrahigh accuracy of weight identification but also act as smart switches in the timing circuits with precisely adjustable operating time, paving the way for the design of a new generation of actuation materials.

Spatial distribution patterns of planktonic ciliate communities in the East China Sea: Potential indicators of water masses.

The spatial distribution of planktonic ciliates over the coastal and continental shelf of the East China Sea were investigated using quantative protargol staining. Aloricate oligotrichs and choreotrichs were dominant in terms of species number, abundance and biomass. Ciliate densities varied between 3 and 2688 cells L-1 with higher values occurring in the coastal water and the mixing water than in the Yellow Sea coastal water and the Taiwan warm water. Ciliate biomass exhibited a similar pattern as abundance. A canonical analysis of principal coordinates demonstrated that the spatial patterns of ciliate community structure could be clearly discriminated in different water masses. Diversity parameters showed strong relationships with spatial changes in ciliate communities and might serve as predictors of water mass in future studies. Our findings provide evidence for using ciliate communtiy composition, supplemented with dominant species and diversity parameters, as potential indicators of water masses in complex marine environments.