High Performance Nacre Fibers by Engineering Interfacial Entanglement.

Biological materials exhibit fascinating mechanical properties for intricate interactions at multiple interfaces to combine superb toughness with wondrous strength and stiffness. Recently, strong interlayer entanglement has emerged to replicate the powerful dissipation of natural proteins and alleviate the conflict between strength and toughness. However, designing intricate interactions in a strong entanglement network needs to be further explored. Here, we modulate interlayer entanglement by introducing multiple interactions, including hydrogen and ionic bonding, and achieve ultrahigh mechanical performance of graphene-based nacre fibers. Two essential modulating trends are directed. One is modulating dynamic hydrogen bonding to improve the strength and toughness up to 1.58 GPa and 52 MJ/m3, simultaneously. The other is tailoring ionic coordinating bonding to raise the strength and stiffness, reaching 2.3 and 253 GPa. Modulating various interactions within robust entanglement provides an effective approach to extend performance limits of bioinspired nacre and optimize multiscale interfaces in diverse composites.

Function analysis of transcription factor OSR1 regulating osmotic stress resistance in maize.

BACKGROUND: Maize is a major cereal crop world widely, however, the yield of maize is frequently limited by dehydration and even death of plants, which resulted from osmotic stress such as drought and salinity. Dissection of molecular mechanisms controlling stress tolerance will enable plant scientists and breeders to increase crops yield by manipulating key regulatory components. METHODS: The candidate OSR1 gene was identified by map-based cloning. The expression level of OSR1 was verified by qRT-PCR and digital PCR in WT and osr1 mutant. Electrophoretic mobility shift assay, transactivation activity assay, subcellular localization, transcriptome analysis and physiological characters measurements were conducted to analyze the function of OSR1 in osmotic stress resistance in maize. RESULTS: The osr1 mutant was significantly less sensitive to osmotic stress than the WT plants and displayed stronger water-holding capacity, and the OSR1 homologous mutant in Arabidopsis showed a phenotype similar with maize osr1 mutant. Differentially expressed genes (DEGs) were identified between WT and osr1 under osmotic stress by transcriptome analysis, the expression levels of many genes, such as LEA, auxin-related factors, PPR family members, and TPR family members, changed notably, which may primarily involve in osmotic stress or promote root development. CONCLUSIONS: OSR1 may serve as a negative regulatory factor in response to osmotic stress in maize. The present study sheds new light on the molecular mechanisms of osmotic stress in maize.

Highly Flexible and Superelastic Graphene Nanofibrous Aerogels for Intelligent Sign Language.

Highly flexible and superelastic aerogels at large deformation have become urgent mechanical demands in practical uses, but both properties are usually exclusive. Here a trans-scale porosity design is proposed in graphene nanofibrous aerogels (GNFAs) to break the trade-off between high flexibility and superelasticity. The resulting GNFAs can completely recover after 1000 fatigue cycles at 60% folding strain, and notably maintain excellent structural integrity after 10000 cycles at 90% compressive strain, outperforming most of the reported aerogels. The mechanical robustness is demonstrated to be derived from the trans-scale porous structure, which is composed of hyperbolic micropores and porous nanofibers to enable the large elastic deformation capability. It is further revealed that flexible and superelastic GNFAs exhibit high sensitivity and ultrastability as an electrical sensors to detect tension and flexion deformation. As proof, The GNFA sensor is implemented onto a human finger and achieves the intelligent recognition of sign language with high accuracy by multi-layer artificial neural network. This study proposes a highly flexible and elastic graphene aerogel for wearable human-machine interfaces in sensor technology.

NSCGRN: a network structure control method for gene regulatory network inference.

Accurate inference of gene regulatory networks (GRNs) is an essential premise for understanding pathogenesis and curing diseases. Various computational methods have been developed for GRN inference, but the identification of redundant regulation remains a challenge faced by researchers. Although combining global and local topology can identify and reduce redundant regulations, the topologies' specific forms and cooperation modes are unclear and real regulations may be sacrificed. Here, we propose a network structure control method [network-structure-controlling-based GRN inference method (NSCGRN)] that stipulates the global and local topology's specific forms and cooperation mode. The method is carried out in a cooperative mode of 'global topology dominates and local topology refines'. Global topology requires layering and sparseness of the network, and local topology requires consistency of the subgraph association pattern with the network motifs (fan-in, fan-out, cascade and feedforward loop). Specifically, an ordered gene list is obtained by network topology centrality sorting. A Bernaola-Galvan mutation detection algorithm applied to the list gives the hierarchy of GRNs to control the upstream and downstream regulations within the global scope. Finally, four network motifs are integrated into the hierarchy to optimize local complex regulations and form a cooperative mode where global and local topologies play the dominant and refined roles, respectively. NSCGRN is compared with state-of-the-art methods on three different datasets (six networks in total), and it achieves the highest F1 and Matthews correlation coefficient. Experimental results show its unique advantages in GRN inference.

Determination of interaction parameters in a bottom-up approach employed in reactive dissipative particle dynamics simulations for thermosetting polymers.

The limitations in previous dissipative particle dynamics (DPD) studies confined simulations to a narrow resin range. This study refines DPD parameter calculation methodology, extending its application to diverse polymer materials. Using a bottom-up approach with molecular dynamics (MD) simulations, we evaluated solubility parameters and bead number density governing nonbonded interactions via the Flory-Huggins parameter and covalent-bonded interactions. Two solubility parameter methods, Hildebrand and Krevelen-Hoftyzer, were compared for DPD simulations. The Hildebrand method, utilizing MD simulations, demonstrates higher consistency and broader applicability in determining solubility parameters for all DPD particles. The DPD/MD curing reaction process was examined in three epoxy systems: DGEBA/4,4'-DDS, DGEBA/MPDA and DGEBA/DETA. Calculations for the curing profile, gelation point, radial distribution function and branch ratio were performed. Compared to MD data for DGEBA/4,4'-DDS, the maximum deviation in secondary reactions between epoxy and amine groups according to DPD simulations with Krevelen-Hoftyzer was 14.8%, while with the Hildebrand method, it was 1.7%. The accuracy of the DPD curing reaction in reproducing the structural properties verifies its expanded application to general polymeric material simulations. The proposed curing DPD simulations, with a short run time and minimal computational resources, contributes to high-throughput screening for optimal resins and investigates mesoscopic inhomogeneous structures in large resin systems.

Nickel(II)/Lewis acid catalysed olefin hydroamination and hydroarylation under mild conditions.

Aniline derivatives are important nitrogen-containing compounds with wide applications in chemicals, pharmaceuticals and agrochemicals. In the work described herein, nickel(II)/Lewis acid (LA) catalysed olefin hydroamination with anilines was explored for use in aniline derivative syntheses. The Ni(II)/LA catalysis proceeded smoothly under mild conditions, whereas using Ni(OAc)2 alone, the catalyst was inactive. Remarkably, the Markovnikov addition type products were obtained when substituted styrenes were used as the olefin source, while the anti-Markovnikov addition type products were obtained when the electron-deficient olefins such as acrylonitrile and acrylates were used. The mechanistic studies revealed that hydroamination of the styrene derivates proceeded via the amino-Ni(II)/LA attacking the carbocation intermediate which was generated by the protonation of the olefin, whereas for acrylonitrile and acrylates, it proceeded by a direct amino-Ni(II)/LA attack on the olefin by nucleophilic addition. In addition, the hydroarylation product was generated by the Hofmann-Martius rearrangement of the hydroamination product.

Pd(II)/LA-catalyzed acetanilide olefination with dioxygen.

Transition-metal-catalyzed aromatic olefination through direct C-H activation represents an atom and step-economic route for versatile pharmaceutical syntheses, and in many cases, different stoichiometric oxidants are frequently employed for achieving a reasonable catalytic efficiency of the transition metal ions. Herein, we report a Lewis acid promoted Pd(II)-catalyzed acetanilide olefination reaction with atmospheric dioxygen as the oxidant source. The linkage of the Lewis acid to the Pd(II) species through a diacetate bridge significantly improved its catalytic efficiency, and independent kinetic studies on the olefination step revealed that adding the Lewis acid significantly accelerated the olefination rate as well as the C-H activation step. A strong basicity of the internal base in the Pd(II) salt also benefited the olefination reaction plausibly through base-assisted ß-hydride elimination.

Longitudinal Adaptive Optics Scanning Laser Ophthalmoscopy Reveals Regional Variation in Cone and Rod Photoreceptor Loss in Stargardt Disease.

PURPOSE: To investigate the temporal sequence of changes in the photoreceptor cell mosaic in patients with Stargardt disease type 1 (STGD1), using adaptive optics scanning laser ophthalmoscopy (AOSLO). METHODS: Two brothers with genetically confirmed STGD1 underwent comprehensive eye exams, spectral-domain optical coherence tomography (SD-OCT), fundus auto fluorescence (FAF) and AOSLO imaging 3 times over the course of 28 months. Confocal images of the cones and rods were obtained from the central fovea to 10 degrees inferiorly. Photoreceptors were counted in sampling windows at 100 µm intervals of 200 µm × 200 µm for cones and 50 µm × 50 µm for rods, using custom cell marking software with manual correction. Photoreceptor density and spacing were measured and compared across imaging sessions using one-way ANOVA. RESULTS: AOSLO revealed the younger brother had a 30% decline in foveal cone density after 8 months, followed by complete loss of foveal cones at 28 months; the older brother had no detectable foveal cones at baseline. In the peripheral macula, cone and rod spacings were greater than normal in both patients. The ratio of the cone spacing to rod spacing was greater than normal across all eccentricities, with a greater divergence closer to the foveal center. CONCLUSIONS: Cone cell loss may be an early pathogenetic step in Stargardt disease. AOSLO provides the capability to track individual photoreceptor changes longitudinally in Stargardt disease. SUMMARY STATEMENT: The pathogenetic mechanism of Stargardt disease remains poorly understood. We used high resolution AOSLO to track the progression of the disease and found cone cell loss may be an early pathogenetic step in Stargardt disease.

High-efficiency reflective terahertz cross-polarization converter with broadband and wide-angle response.

In this paper, a broadband terahertz metasurface dedicated to cross-polarization conversion was designed, fabricated, and assessed. The metasurface, comprising two nested double-split rings, features an inherent insensitivity to the angle of incidence. Simulations reveal that the converter achieves a >99% polarization conversion efficiency across the 90-140 GHz range. Moreover, it maintains a >90% polarization conversion ratio (PCR), even at a 50° incidence angle. The sample, featuring 50×70 arrays, was fabricated, and the relevant experimental results align closely with the simulated outcomes. The metasurface characteristics can markedly enhance the performance of cross-polarization converters operating in the terahertz range.

Superior Strong and Tough Nacre-Inspired Materials by Interlayer Entanglement.

Natural materials teach that mechanical dissipative interactions relieve the conflict between strength and toughness and enable fabrication of strong yet tough artificial materials. Replicating natural nacre structure has yielded rich biomimetic materials; however, stronger interlayer dissipation still waits to be exploited to extend the performance limits of artificial nacre materials. Here, we introduce strong entanglement as a new artificial interlayer dissipative mechanism and fabricate entangled nacre materials with superior strength and toughness, across molecular to nanoscale nacre structures. The entangled graphene nacre fibers achieved high strength of 1.2 GPa and toughness of 47 MJ/m3, and films reached 1.5 GPa and 25 MJ/m3. Experiments and simulations reveal that strong entanglement can effectively dissipate interlayer energy to relieve the conflict between strength and toughness, acting as natural folded proteins. The strong interlayer entanglement opens up a new path for designing stronger and tougher artificial materials to mimic but surpass natural materials.

SYTL2 promotes metastasis of prostate cancer cells by enhancing FSCN1-mediated pseudopodia formation and invasion.

BACKGROUND: Metastatic prostate cancer (mPCa) has a poor prognosis with limited treatment options. The high mobility of tumor cells is the key driving characteristic of metastasis. However, the mechanism is complex and far from clarified in PCa. Therefore, it is essential to explore the mechanism of metastasis and discover an intrinsic biomarker for mPCa. METHODS: Transcriptome sequencing data and clinicopathologic features of PCa from multifarious public databases were used to identify novel metastatic genes in PCa. The PCa tissue cohort containing 102 formalin-fixed paraffin-embedded (FFPE) samples was used to evaluate the clinicopathologic features of synaptotagmin-like 2 (SYTL2) in PCa. The function of SYTL2 was investigated by migration and invasion assays and a 3D migration model in vitro and a popliteal lymph node metastasis model in vivo. We performed coimmunoprecipitation and protein stability assays to clarify the mechanism of SYTL2. RESULTS: We discovered a pseudopodia regulator, SYTL2, which correlated with a higher Gleason score, worse prognosis and higher risk of metastasis. Functional experiments revealed that SYTL2 promoted migration, invasion and lymph node metastasis by increasing pseudopodia formation in vitro and in vivo. Furthermore, SYTL2 induced pseudopodia formation by enhancing the stability of fascin actin-bundling protein 1 (FSCN1) by binding and inhibiting the proteasome degradation pathway. Targeting FSCN1 enabled rescue and reversal of the oncogenic effect of SYTL2. CONCLUSIONS: Overall, our study established an FSCN1-dependent mechanism by which SYTL2 regulates the mobility of PCa cells. We also found that the SYTL2-FSCN1-pseudopodia axis may serve as a pharmacological and novel target for treating mPCa.

Kv1.3 mediates ox-LDL-induced vascular smooth muscle cell proliferation through JAK2/STAT3 signaling pathway.

Kv1.3 channel has been shown to participate in regulating inflammatory activation, proliferation and apoptosis in several cell types. However, most of those existing studies focused on the ion-conducting properties of Kv1.3 in maintaining the resting potential and regulating Ca2+ influx. The aim of our study was to explore whether the Kv1.3-JAK2/STAT3 signaling pathway was involved in oxidized low density lipoprotein (ox-LDL) induced vascular smooth muscle cell (VSMC) proliferation. VSMCs from mouse aorta were cultured and treated with ox-LDL (25 µg/mL). The cell counting kit-8 was used to assess cell proliferation, and western blotting was performed to detect expression levels of Kv1.3, JAK2/STAT3, phosphorylated JAK2/STAT3, cyclin B1 and cyclin D1 in treated VSMCs. VSMCs were transfected with Kv1.3 small interfering RNA (Kv1.3-siRNA) or infected with a Kv1.3 lentiviral expression vector (Lv-Kv1.3) and treated with a JAK2 inhibitor LY2784544 to assess the role of Kv1.3 and JAK2/STAT3 signaling in mediating VSMC proliferation induced by ox-LDL. Ox-LDL induced cell proliferation and upregulated the expression of Kv1.3 in mouse VSMCs. In VSMCs transfected with Kv1.3-siRNA, ox-LDL was not efficient in inducing cell proliferation or the levels of proliferation associated proteins, cyclin B1 and cyclin D1. However, cell proliferation, cyclin B1 and cyclin D1 levels increased in VSMCs infected with Lv-Kv1.3. Levels of phosphorylated JAK2 and STAT3 were increased in ox-LDL-treated VSMCs, and this increase was prevented in VSMCs transfected with Kv1.3-siRNA. Treatment with the JAK2 inhibitor LY2784544 also prevented the increase in VSMCs proliferation treated with ox-LDL. Our findings demonstrated that Kv1.3 promoted proliferation of VSMCs treated with ox-LDL, and that this effect might be mediated through activation of the JAK2/STAT3 signaling pathway.

Engineering Double Sulfur-Vacancy in CoS1.097@MoS2 Core-Shell Heterojunctions for Hydrogen Evolution in a Wide pH Range.

Heterostructured nanomaterials have arisen as electrocatalysts with great potential for hydrogen evolution reaction (HER), considering their superiority in integrating different active components but are plagued by their insufficient active site density in a wide pH range. In this report, double sulfur-vacancy-decorated CoS1.097@MoS2 core-shell heterojunctions are designed, which contain a primary structure of hollow CoS1.097 nanocubes and a secondary structure of ultrathin MoS2 nanosheets. Taking advantage of the core-shell type heterointerfaces and double sulfur-vacancy, the CoS1.097@MoS2 catalyst exhibits pH-universal HER performance, achieving the overpotentials at 10 mA cm-2 of 190, 139, and 220 mV in 0.5 M H2SO4, 1.0 M KOH, and 1.0 M PBS, respectively. Systematic theoretical results show that the double sulfur-vacancy can endow the CoS1.097@MoS2 core-shell heterojunctions with promoted electron/mass transfer and enhanced reactive kinetics, thus boosting HER performance. This work clearly demonstrates an indispensable role of double sulfur-vacancy in enhancing the electrocatalytic HER performance of core-shell type heterojunctions under a wide pH operating condition.

Morphology, Solid Structure and Antioxidant Activity in Vitro of Angelica sinensis Polysaccharide-Ce(IV).

Angelica Sinensis polysaccharide cerium (ASP-Ce) was prepared by Angelica Sinensis polysaccharide (ASP) and cerium ammonium nitrate (NH4 )2 Ce(NO3 )6 . and its morphology, and solid structure was investigated. The antioxidant activity of the ASP-Ce complex in vitro was evaluated. The antioxidant activity of ASP-Ce complex in vitro was evaluated by the scavenging activity of 2,2-diphenyl-1-picrylhyrazyl radical (DPPH), hydroxyl radical (⋅OH) and superoxide anion radical ( O 2 - ${{{\rm O}}_{2}^{-}}$ ⋅). The results showed that the ASP-Ce had the more ordered structure for inserting the Ce4+ into the polymer chain of ASP and there was little change in the conformation of the polysaccharide from Ce4+ . Three free radical scavenging experiments proved that ASP-Ce had better antioxidant capacity than of ASP, especially on DPPH, and then on O 2 - ${{{\rm O}}_{2}^{-}}$ ⋅. The scavenging rate of ASP-Ce at 1.0 mg/mL on DPPH reached 71.6 %. Therefore, these results provide references for the further development and utilization of rare earth-polysaccharide.

Probing membrane protein interactions and signaling molecule homeostasis in plants by Förster resonance energy transfer analysis.

Membrane proteins have key functions in signal transduction, transport, and metabolism. Therefore, deciphering the interactions between membrane proteins provides crucial information on signal transduction and the spatiotemporal organization of protein complexes. However, detecting the interactions and behaviors of membrane proteins in their native environments remains difficult. Förster resonance energy transfer (FRET) is a powerful tool for quantifying the dynamic interactions and assembly of membrane proteins without disrupting their local environment, supplying nanometer-scale spatial information and nanosecond-scale temporal information. In this review, we briefly introduce the basic principles of FRET and assess the current state of progress in the development of new FRET techniques (such as FRET-FLIM, homo-FRET, and smFRET) for the analysis of plant membrane proteins. We also describe the various FRET-based biosensors used to quantify the homeostasis of signaling molecules and the active state of kinases. Furthermore, we summarize recent applications of these advanced FRET sensors in probing membrane protein interactions, stoichiometry, and protein clustering, which have shed light on the complex biological functions of membrane proteins in living plant cells.

Observing the Agostic Hydrogen in Pd(II)-Catalyzed Aromatic C-H Activation.

Direct C-H activation and functionalization offer a convenient protocol for pharmaceutical and material syntheses. Although versatile mechanisms have been proposed to depict transition-metal-catalyzed C-H activation, to date, the shared key agostic hydrogen intermediate in several major mechanisms has not been observed yet, which apparently puzzles the mechanism-based catalyst design. This work reports the direct observations of this intermediate in Pd(II)/Sc(III)-catalyzed C-H activation of acetanilides, and its stability and reactivity in C-H activation are investigated. Remarkably, this intermediate is only observed in electron-rich acetanilides, and the meta-substituent with increased σm constant generally accelerates C-H activation, a characteristic of the base-assisted C-H activation mechanism. This study has unveiled the masks of this intermediate with an understanding of its first-hand physicochemical properties, shedding new light on mechanism-based catalyst design.

Pd(II)/Lewis Acid Catalyzed Intramolecular Annulation of Indolecarboxamides with Dioxygen through Dual C-H Activation.

Transition-metal ion catalyzed intramolecular dual C-H activation to construct polycyclic heteroarene skeletons is merited for its step and atom-economic advantages in organic synthesis. However, in most cases, stoichiometric oxidants, elevated temperature, and other harsh conditions were commonly faced for this reaction, which apparently block the synthetic applications. Herein, we report a Pd(II)/LA (LA: Lewis acid) catalyzed intramolecular dual C-H activation to construct indoloquinolinone derivatives under mild conditions with dioxygen as the sole oxidant. It was found that adding LA such as Sc3+ to Pd(OAc)2 sharply improved its catalytic efficiency, whereas Pd(OAc)2 alone was very sluggish. The activity improvement was attributed to the linkage of the Sc3+ cation to the Pd(II) species through a diacetate bridge that significantly enhanced the electrophilic properties of Pd(II) for dual C-H activation.

Palladium(II)/Lewis Acid-Catalyzed Olefination of Arylacetamides with Dioxygen.

The present work introduces Pd(II)/LA-catalyzed (LA: Lewis acid) olefination of arylacetamides with dioxygen as the oxidant source. This protocol tolerates with different functional groups on the substrates, and the catalytic efficiency is highly Lewis acidity-dependent on added LA, that is, a stronger LA provided a better promotional effect. The 1H NMR studies of the semireaction between the arylacetamide and the Pd(II)/Sc(III) catalyst in HOAc-d4 disclosed the formation of a palladacycle intermediate, and the C-H activation step was reversible, which led to the formation of the deuterated arylacetamide substrate and the palladacycle intermediate. Further semireaction between the palladacycle intermediate and the olefin disclosed that it was a clean and much faster reaction than the C-H activation step, thus revealing multiple mechanistic information for Pd(II)-catalyzed C-H activation.

Pd(II)/Lewis acid catalyzed regioselective olefination of indole with dioxygen.

Transition metal ion catalyzed indole olefination through C-H activation is a convenient protocol to synthesize versatile bioactive vinylindole compounds; however, in most cases, stoichiometric amounts of oxidants were necessary to accomplish the catalytic cycle. The present study describes a Pd(II)/LA (LA: Lewis acid) catalyzed indole olefination with dioxygen as the sole oxidant. The olefination reaction with electron-rich olefins proceeded smoothly through the pyrrolyl N-carboxamide group directed remote C-H activation at the C3 position of the indole with the Pd(II)/LA catalyst, whereas Pd(II) alone was a very sluggish catalyst under identical conditions. For the electron-deficient olefins, the directing N-carboxamide group was not essential for olefination with this Pd(II)/LA catalyst, demonstrating a different olefination pathway from that of electron-rich olefins. Remarkably, 1H NMR kinetics disclosed that olefination proceeded much faster with electron-rich olefins than with electron-deficient ones.

Integration of an Intensive Care Unit Visualization Dashboard (i-Dashboard) as a Platform to Facilitate Multidisciplinary Rounds: Cluster-Randomized Controlled Trial.

BACKGROUND: Multidisciplinary rounds (MDRs) are scheduled, patient-focused communication mechanisms among multidisciplinary providers in the intensive care unit (ICU). OBJECTIVE: i-Dashboard is a custom-developed visualization dashboard that supports (1) key information retrieval and reorganization, (2) time-series data, and (3) display on large touch screens during MDRs. This study aimed to evaluate the performance, including the efficiency of prerounding data gathering, communication accuracy, and information exchange, and clinical satisfaction of integrating i-Dashboard as a platform to facilitate MDRs. METHODS: A cluster-randomized controlled trial was performed in 2 surgical ICUs at a university hospital. Study participants included all multidisciplinary care team members. The performance and clinical satisfaction of i-Dashboard during MDRs were compared with those of the established electronic medical record (EMR) through direct observation and questionnaire surveys. RESULTS: Between April 26 and July 18, 2021, a total of 78 and 91 MDRs were performed with the established EMR and i-Dashboard, respectively. For prerounding data gathering, the median time was 10.4 (IQR 9.1-11.8) and 4.6 (IQR 3.5-5.8) minutes using the established EMR and i-Dashboard (P<.001), respectively. During MDRs, data misrepresentations were significantly less frequent with i-Dashboard (median 0, IQR 0-0) than with the established EMR (4, IQR 3-5; P<.001). Further, effective recommendations were significantly more frequent with i-Dashboard than with the established EMR (P<.001). The questionnaire results revealed that participants favored using i-Dashboard in association with the enhancement of care plan development and team participation during MDRs. CONCLUSIONS: i-Dashboard increases efficiency in data gathering. Displaying i-Dashboard on large touch screens in MDRs may enhance communication accuracy, information exchange, and clinical satisfaction. The design concepts of i-Dashboard may help develop visualization dashboards that are more applicable for ICU MDRs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04845698; https://clinicaltrials.gov/ct2/show/NCT04845698.