Efficacy and safety of Tongxin formula after stent implantation for acute coronary syndrome: A multicenter, double-blind, placebo-controlled randomized trial.

OBJECTIVE: The aim of this study is to comprehensively evaluate both the efficacy and safety profile of integrating the Tongxin formula with optimal medical therapy (OMT) for patients experiencing acute coronary syndromes subsequent to coronary stenting, over the course of one year. METHODS: We enrolled 150 patients diagnosed with acute coronary syndromes who had received stent placement within one month and exhibited a TCM syndrome characterized by Qi deficiency and blood stasis. This group comprised patients with unstable angina, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction. The participants were divided equally, allocating 75 to the Tongxin formula group and 75 to a placebo-controlled group. After undergoing percutaneous coronary intervention (PCI) surgery, both groups received conventional Western medical care, including dual antiplatelet therapy and lipid-lowering medications. The placebo-controlled group received a placebo, while the Tongxin formula group were administered Tongxin formula granules orally. Both study cohorts were monitored for a duration of 6 months. The primary endpoints included the occurrence of major adverse cardiovascular events and the rate of lumen diameter reduction post-treatment in both groups, with the Seattle Angina Scale serving as a secondary assessment tool. Safety evaluations encompassed the measurement of liver and kidney function, coagulation parameters, and other relevant indicators. RESULTS: The rate of adverse cardiovascular events in the placebo-controlled group was 42.46 % within a year of surgery, whereas it was 16.90 % in the Tongxin formula group (P < 0.05). Comparing the Tongxin formula group to the placebo-controlled group, there was a decrease in the frequency of unstable angina and readmission due to cardiovascular events (P < 0.05). Coronary angiography performed 6 months after surgery revealed that the Tongxin formula group had considerably less lumen loss than the placebo-controlled group in a number of segments, including the entire segment, within the stent, at the proximal end, and at the distal end (P < 0.05). Six months after surgery, the Seattle angina score was higher in the Tongxin formula group than in the placebo-controlled group (P < 0.05). There were no significant changes in indicators such as liver and renal function as well as coagulation indexes in both groups within the first 12 months after surgery (P > 0.05). CONCLUSION: Tongxin formula has been shown to lower the occurrence of major adverse cardiovascular events, minimize narrowing of blood vessel lumen, enhance clinical symptoms, and enhance the quality of life of patients following PCI surgery, all while maintaining a good safety profile.

Core-shell heterostructured Ni(OH)2@activation Zn-Co-Ni layered double hydroxides electrode for flexible all-solid-state coaxial fiber-shaped asymmetric supercapacitors.

The increasing requirements for wearable and portable electronics are driving the interests of high performance fiber supercapacitor. Layered double hydroxide (LDH) is broadly used in electrode materials, owing to the adjustability of components and the unique lamellar structure. However, limited active sites and poor electrical conductivity hinder its applications. Herein, the core-shell heterostructured Ni(OH)2@activation Zn-Co-Ni layered double hydroxides (Ni(OH)2@A-ZnCoNi-LDH) electrode was fabricated by loading pseudocapacitance material on the A-ZnCoNi-LDH to improve the electrochemical performance. Significantly, benefits from the synergistic effect of the multi-metal ions and the core-shell heterostructure, the electrodes demonstrated a capacitance of 2405 mF·cm-2 at 1 mA·cm-2. Furthermore, Ni(OH)2@A-ZnCoNi-LDH was used as the core electrode and carbon nanotube (CNT) film coated with Fe2O3@reduced graphene oxide (rGO) was wrapped around the core electrode to assemble coaxial fiber asymmetric supercapacitor, which illustrated an ultrahigh energy density of 177.7 µWh·cm-2 at 0.75 mW·cm-2. In particular, after consecutive charging and discharging 7000 cycles, the capacitance retention of the device was 95 %, indicating the excellent cycling stability. Furthermore, the device with high flexibility can be woven into textiles in different shapes. The fabricated device has an excellent development prospect as an energy source in wearable electronic devices.

Lightweight, flame retardant Janus carboxymethyl cellulose aerogel with fire-warning properties for smart sensor.

Lightweight, flame retardant biomass aerogels combining with multi-functionalities are promising for thermal insulation, noise absorption and smart sensors. However, high flammability hinders the application of these aerogels in extreme condition. Herein, lightweight, flame retardant aerogel with fire-warning properties fabricated from resource-abundant graphite and green carboxymethyl cellulose (CMC) is reported. During sonicating expandable graphite (EG) in CMC solution, CMC not only fabricates the downsizing process via hydrogen bonding effect but also forms stable dispersions. Then biomass aerogel is fabricated by freeze-drying strategy and enhanced by metal ionic cross-linking method. This aerogel demonstrates Janus properties for electrical conductivity and thermal conductivity. Due to the synergistic flame retardant effect of graphite nanocomposite and metal ions with a barrier effect and catalytic carbonization capacity, the flame retardancy of these aerogels are enhanced with fire-warning properties. Furthermore, these aerogels are used for monitoring physical deformations as smart sensors, which provides inspiration and a sustainable solution for developing low-cost biomass aerogel with multifunction.

Measurement of the [Formula: see text]Ta([Formula: see text]) cross sections up to stellar s-process temperatures at the CSNS Back-n.

The neutron capture cross section of [Formula: see text]Ta is relevant to s-process of nuclear astrophysics, extraterrestrial samples analysis in planetary geology and new generation nuclear energy system design. The [Formula: see text]Ta([Formula: see text]) cross section had been measured between 1 eV and 800 keV at the back-streaming white neutron facility (Back-n) of China spallation neutron source(CSNS) using the time-of-flight (TOF) technique and [Formula: see text] liquid scintillator detectors. The experimental results are compared with the data of several evaluated libraries and previous experiments in the resolved and unresolved resonance region. Resonance parameters are extracted using the R-Matrix code SAMMY in the 1-700 eV region. The astrophysical Maxwell average cross section(MACS) from kT = 5 to 100 keV is calculated over a sufficiently wide range of neutron energies. For the characteristic thermal energy of an astrophysical site, at kT = 30keV the MACS value of [Formula: see text]Ta is 834 ± 75 mb, which shows an obvious discrepancy with the Karlsruhe Astrophysical Database of Nucleosynthesis in Stars (KADoNiS) recommended value 766 ± 15 mb. The new measurements strongly constrain the MACS of [Formula: see text]Ta([Formula: see text]) reaction in the stellar s-process temperatures.

Versatile Liquid Metal/Alginate Composite Fibers with Enhanced Flame Retardancy and Triboelectric Performance for Smart Wearable Textiles.

Liquid metal (LM) shows the superiority in smart wearable devices due to its biocompatibility and electromagnetic interference (EMI) shielding. However, LM based fibers that can achieve multifunctional integrated applications with biodegradability remain a daunting challenge. Herein, versatile LM based fibers are fabricated first by sonication in alginate solution to obtain LM micro/nano droplets and then wet-spinning into LM/alginate composite fibers. By mixing with high-concentration alginate solution (4-6 wt.%), the LM micro/nano droplets stability (colloidal stability for > 30 d and chemical stability for > 45 d) are not only improved, but also facilitate its spinning into fibers through bimetallic ions (e.g., Ga3+ and Ca2+ ) chelation strategy. These resultant fibers can be woven into smart textiles with excellent flexibility, air permeability, water/salt resistance, and high temperature tolerance (-196-150 °C). In addition, inhibition of smoldering result from the LM droplets and bimetallic ions is achieved to enhance flame retardancy. Furthermore, these fibers combine the exceptional properties of LM droplets (e.g., photo-thermal effect and EMI shielding) and alginate fibers (e.g., biocompatibility and biodegradability), applicable in wearable heating devices, wireless communication, and triboelectric nanogenerator, making it a promising candidate for flexible smart textiles.

Endothelial PHACTR1 Promotes Endothelial Activation and Atherosclerosis by Repressing PPARγ Activity Under Disturbed Flow in Mice.

BACKGROUND: Numerous genome-wide association studies revealed that SNPs (single nucleotide polymorphisms) at the PHACTR1 (phosphatase and actin regulator 1) locus strongly correlate with coronary artery disease. However, the biological function of PHACTR1 remains poorly understood. Here, we identified the proatherosclerotic effect of endothelial PHACTR1, contrary to macrophage PHACTR1. METHODS: We generated global (Phactr1-/-) and endothelial cell (EC)-specific (Phactr1ECKO) Phactr1 KO (knockout) mice and crossed these mice with apolipoprotein E-deficient (Apoe-/-) mice. Atherosclerosis was induced by feeding the high-fat/high-cholesterol diet for 12 weeks or partially ligating carotid arteries combined with a 2-week high-fat/high-cholesterol diet. PHACTR1 localization was identified by immunostaining of overexpressed PHACTR1 in human umbilical vein ECs exposed to different types of flow. The molecular function of endothelial PHACTR1 was explored by RNA sequencing using EC-enriched mRNA from global or EC-specific Phactr1 KO mice. Endothelial activation was evaluated in human umbilical vein ECs transfected with siRNA targeting PHACTR1 and in Phactr1ECKO mice after partial carotid ligation. RESULTS: Global or EC-specific Phactr1 deficiency significantly inhibited atherosclerosis in regions of disturbed flow. PHACTR1 was enriched in ECs and located in the nucleus of disturbed flow areas but shuttled to cytoplasm under laminar flow in vitro. RNA sequencing showed that endothelial Phactr1 depletion affected vascular function, and PPARγ (peroxisome proliferator-activated receptor gamma) was the top transcription factor regulating differentially expressed genes. PHACTR1 functioned as a PPARγ transcriptional corepressor by binding to PPARγ through the corepressor motifs. PPARγ activation protects against atherosclerosis by inhibiting endothelial activation. Consistently, PHACTR1 deficiency remarkably reduced endothelial activation induced by disturbed flow in vivo and in vitro. PPARγ antagonist GW9662 abolished the protective effects of Phactr1 KO on EC activation and atherosclerosis in vivo. CONCLUSIONS: Our results identified endothelial PHACTR1 as a novel PPARγ corepressor to promote atherosclerosis in disturbed flow regions. Endothelial PHACTR1 is a potential therapeutic target for atherosclerosis treatment.

Ruthenium-catalysed decarboxylative unsymmetric dual ortho-/meta-C-H bond functionalization of arenecarboxylic acids.

Here, we describe a ruthenium-catalysed decarboxylative unsymmetric ortho-C-H azaarylation/meta-C-H alkylation via a traceless directing group relay strategy. The installation of a 2-pyridyl functionality via carboxyl directed ortho-C-H activation is critical to promote decarboxylation and enable meta-C-H bond alkylation to streamline the synthesis of 4-azaaryl-benzo-fused five-membered heterocycles. This protocol is characterized by high regio- and chemoselectivity, broad substrate scopes, and good functional group tolerance under redox-neutral conditions.

Copper-Coordinated Cellulose Fibers for Electric Devices with Motion Sensitivity and Flame Retardance.

Nanocomposite conductive fibers are of great significance in applications of wearable devices, smart textiles, and flexible electronics. Integration of conductive nanomaterials into flexible bio-based fibers with multifunctionality remains challenging due to interface failure, poor flexibility, and inflammability. Although having broader applications in textiles, regenerated cellulose fibers (RCFs) cannot meet the requirements of wearable electronics owing to their intrinsic insulation. In this study, we constructed conductive RCFs fabricated by coordinating copper ions with cellulose and reducing them into stable Cu nanoparticles coated on their surface. The Cu sheath offered excellent electrical conductivity (4.6 × 105 S m-1), electromagnetic interference shielding, and enhanced flame retardance. Inspired by plant tendrils, the conductive RCF was wrapped around an elastic rod to develop wearable sensors for human health and motion monitoring. The resultant fibers not only form stable conductive nanocomposites on the fiber surface by chemical bonds but also exhibit a huge potential for wearable devices, smart sensors, and flame-retardant circuits.

Immature neutrophil is associated with coronary plaque vulnerability based on optical coherence tomography analysis.

INTRODUCTION: High neutrophil to lymphocyte ratio is considered to predict poor prognosis of acute coronary syndrome (ACS). However, the association of neutrophil subpopulation with plaque vulnerability and the incidence of ACS remains unknown. METHODS AND RESULTS: Blood samples from 48 patients with unstable angina (UA), 31 with ST-segment elevation myocardial infarction (STEMI) and 33 healthy controls were collected at admission. The morphology of coronary plaques in 48 UA patients were further evaluated by optical coherence tomography (OCT). According to maturation stages of neutrophils and the expression of CD10 and CD101, circulating neutrophils could be divided into pre-neutrophils (CD101-CD10-), immature neutrophils (CD101+CD10-) and mature neutrophils (CD101+CD10+). While the number of pre-neutrophil was quite low in blood and comparable among three groups, the absolute counts and percentage of CD10- immature neutrophils were higher in peripheral bloods of UA and STEMI patients compared with those in healthy controls. The concentration of plasma myeloperoxidase was positively associated with the percentage of CD10- immature neutrophils. Furthermore, UA patients with thin-cap fibroatheroma (TCFA) observed by OCT had a higher proportion and larger number of immature neutrophils as compared to those without TCFA. The percentage of immature neutrophils also closely correlated with plaque rupture and the feature of vulnerable plaque, including thinner fibrous cap and larger lipid core, but did not associate with percent lumen stenosis. CONCLUSION: Our findings emphasize that the abnormally increased level of CD10- immature neutrophils may sever as a promising marker of the incidence of ACS and plaque vulnerability.

Transportable, Endurable, and Recoverable Liquid Metal Powders with Mechanical Sintering Conductivity for Flexible Electronics and Electromagnetic Interference Shielding.

Liquid metals (LMs, e.g., EGaIn) promise a vast potential in accelerating the development of flexible electronics, smart robots, and wearable and biomedical devices. Although a variety of emerging processing methods are reported, they suffer several risks (e.g., leakage, weak adhesion, and low colloidal and chemical stability) because of their excellent fluidity, high surface tension, and rapid oxidation. Herein, liquid metal powders (LMPs) are fabricated based on a versatile method by vigorously stirring EGaIn with nonmetallic or organic particles through interfacial interactions. During the mixing process, EGaIn microdroplets are wrapped with a nonmetallic or an organic shell by electrostatic adsorption, and a more sticky oxide layer is constantly generated and then broken owing to the shearing friction. These transportable powders exhibit superior stability under extreme conditions (e.g., water and high temperature), being capable of recovering electrical conductivity and strong adhesion on different substrates upon mechanical sintering. A flexible, robust, and conductive coating can be constructed via swabbing with an integrated Joule heating effect and excellent electromagnetic interference shielding performances, and it is applicable in flexible wearable electronics, microcircuits, and wireless power transmission systems.

Direct Synthesis of Adipic Esters and Adiponitrile via Photoassisted Cobalt-Catalyzed Alkene Hydrodimerization.

The direct hydrodimerization of acrylates and acrylonitrile offers a general streamlined access to industrially important intermediates to nylon 6,6. However, a practical catalytic method for this process has thus far underdeveloped owing to the challenges in regioselectivity and environmental compatibility of applied reagents. Here, we report a cobalt-catalyzed tail-to-tail hydrodimerization of activated alkenes driven by a visible-light photoredox catalysis at ambient temperature, which is applicable to both adipates and adiponitrile synthesis from potentially renewable feedstocks. This protocol utilizes half equivalent of hantzsch ester as a recyclable two-electron and two-proton donor with the assistance of catalytic amount of base as a proton shuttle, and has been shown to be highly regioselective and efficient for hydrodimerizing various activated alkenes to 1,4-difunctionalized butane derivatives.

Flow and Heat Transfer Performances of Liquid Metal Based Microchannel Heat Sinks under High Temperature Conditions.

Developments in applications such as rocket nozzles, miniature nuclear reactors and solar thermal generation pose high-density heat dissipation challenges. In these applications, a large amount heat must be removed in a limited space under high temperature. In order to handle this kind of cooling problem, this paper proposes liquid metal-based microchannel heat sinks. Using a numerical method, the flow and heat transfer performances of liquid metal-based heat sinks with different working fluid types, diverse microchannel cross-section shapes and various inlet velocities were studied. By solving the 3-D steady and conjugate heat transfer model, we found that among all the investigated cases, lithium and circle were the most appropriate choices for the working fluid and microchannel cross-section shape, respectively. Moreover, inlet velocity had a great influence on the flow and heat transfer performances. From 1 m/s to 9 m/s, the pressure drop increased as much as 65 times, and the heat transfer coefficient was enhanced by about 74.35%.

Reduced Notch1 Cleavage Promotes the Development of Pulmonary Hypertension.

Clinical trials of Dll4 (Delta-like 4) neutralizing antibodies (Dll4nAbs) in cancer patients are ongoing. Surprisingly, pulmonary hypertension (PH) occurs in 14% to 18% of patients treated with Dll4nAbs, but the mechanisms have not been studied. Here, PH progression was measured in mice treated with Dll4nAbs. We detected Notch signaling in lung tissues and analyzed pulmonary vascular permeability and inflammation. Notch target gene array was performed on adult human pulmonary microvascular endothelial cells (ECs) after inhibiting Notch cleavage. Similar mechanisms were studied in PH mouse models and pulmonary arterial hypertension patients. The rescue effects of constitutively activated Notch1 in vivo were also measured. We observed that Dll4nAbs induced PH in mice as indicated by significantly increased right ventricular systolic pressure, as well as pulmonary vascular and right ventricular remodeling. Mechanistically, Dll4nAbs inhibited Notch1 cleavage and subsequently impaired lung endothelial barrier function and increased immune cell infiltration in vessel walls. In vitro, Notch targeted genes' expression related to cell growth and inflammation was decreased in human pulmonary microvascular ECs after the Notch1 inactivation. In lungs of PH mouse models and pulmonary arterial hypertension patients, Notch1 cleavage was inhibited. Consistently, EC cell-cell junction was leaky, and immune cell infiltration increased in PH mouse models. Overexpression activated Notch1-attenuated progression of PH in mice. In conclusion, Dll4nAbs led to PH development in mice by impaired EC barrier function and increased immune cell infiltration through inhibition of Notch1 cleavage in lung ECs. Reduced Notch1 cleavage in lung ECs could be an underlying mechanism of PH pathogenesis.

A novel peptide inhibitor of Dll4-Notch1 signalling and its pro-angiogenic functions.

BACKGROUND AND PURPOSE: The Dll4-Notch1 signalling pathway plays an important role in sprouting angiogenesis, vascular remodelling and arterial or venous specificity. Genetic or pharmacological inhibition of Dll4-Notch1 signalling leads to excessive sprouting angiogenesis. However, transcriptional inhibitors of Dll4-Notch1 signalling have not been described. EXPERIMENTAL APPROACH: We designed a new peptide targeting Notch signalling, referred to as TAT-ANK, and assessed its effects on angiogenesis. In vitro, tube formation and fibrin gel bead assay were carried out, using human umbilical vein endothelial cells (HUVECs). In vivo, Matrigel plug angiogenesis assay, a developmental retinal model and tumour models in mice were used. The mechanisms underlying TAT-ANK activity were investigated by immunochemistry, western blotting, immunoprecipitation, RT-qPCR and luciferase reporter assays. KEY RESULTS: The amino acid residues 179-191 in the G-protein-coupled receptor-kinase-interacting protein-1 (GIT1-ankyrin domain) are crucial for GIT1 binding to the Notch transcription repressor, RBP-J. We designed the peptide TAT-ANK, based on residues 179-191 in GIT1. TAT-ANK significantly inhibited Dll4 expression and Notch 1 activation in HUVECs by competing with activated Notch1 to bind to RBP-J. The analyses of biological functions showed that TAT-ANK promoted angiogenesis in vitro and in vivo by inhibiting Dll4-Notch1 signalling. CONCLUSIONS AND IMPLICATIONS: We synthesized and investigated the biological actions of TAT-ANK peptide, a new inhibitor of Notch signalling. This peptide will be of significant interest to research on Dll4-Notch1 signalling and to clinicians carrying out clinical trials using Notch signalling inhibitors. Furthermore, our findings will have important conceptual and therapeutic implications for angiogenesis-related diseases.

Safety and Efficacy of Therapeutic Erythrocytapheresis Treatment in Chronic Mountain Sickness Patients in Shigatse, Tibet, China.

BACKGROUND Therapeutic erythrocytapheresis (TEA) is a medical technology that separates erythrocytes from whole blood and has been used in various hematological conditions. However, reports on the use of TEA to treat chronic mountain sickness (CMS) are lacking. The aim of the present study was to evaluate the efficacy, safety, and use of TEA in treatment of CMS. MATERIAL AND METHODS A total of 32 patients living in the Shigatse area of Tibet (altitude 4000 m) who had CMS were treated with TEA. Clinical data, CMS score, Borg dyspnea score, 6-min walking test score, and NYHA classification values were collected prior to and after TEA therapy. RESULTS TEA treatment significantly increased SpO2 (93.8±2.6 vs. 80.5±5.8%, P<0.001) and decreased red blood cell (5.77±0.70 vs. 7.48±0.67×10¹²/L, P<0.001), hematocrit (53.8±5.6 vs. 69.2±4.8%, P<0.001) and hemoglobin (178±16 vs. 236±14 g/L, P<0.001). Significantly lower systolic and diastolic blood pressure were also noted (P<0.001). Echocardiography showed higher left ventricle diameter (4.6±0.4 vs. 4.4±0.5 cm, P<0.01). TEA markedly decreased CMS scores (0.45±0.85 vs. 7.58±2.31, P<0.001), Borg dyspnea scale scores (0.48±0.73 vs. 0.88±0.81, P<0.001), and NYHA classification scores (P<0.05). Additionally, there was marked improvement in the 6-min walking test scores (578.5±83.1 vs. 550.4±79.0 m, P<0.001). The procedure was well tolerated, with no complications. CONCLUSIONS Our novel approach of treating CMS patients with TEA safely and effectively reduced erythrocytosis, which remains a fundamental challenge in CMS patients.

Liquid Metal Initiator of Ring-Opening Polymerization: Self-Capsulation into Thermal/Photomoldable Powder for Multifunctional Composites.

Liquid metal nanodroplets not only share similar metallic properties and nanoscale effect with solid metal nanoparticles, but also possess the additional uniqueness in nonvolatile fluidity and ambient sintering ability into continuous conductors. In most cases, liquid metal nanodroplets are encapsulated into ultrathin and fragile shells of oxides and amphiphile monolayers, and may be hindered from incorporating homogeneously into various composites through conventional processing methods. In this study, ring-opening polymerization is found to be initiated by sonicating the liquid metal EGaIn in fluidic lactones. By this in situ polymerization, EGaIn nanodroplets are encapsulated into polylactone shells with tunable thickness, which can further be dried into a solid powder. Besides high chemical stability and dispersibility in organic solvents, the powder of the EGaIn capsules combines the exceptional properties of the EGaIn droplets (e.g., photothermal effect) and the polylactone shells (e.g., biocompatibility, biodegradability, and compatibility with different polymer matrixes), being capable of being introduced into thermoplastic composites through liquid casting and thermal- or photomolding for the notch-insensitive tearing property, sintering-induced electric conductivity, and photothermal effect. Thus, the EGaIn initiator of ring-opening polymerization may start a pathway to produce stable andthermal/photomoldable powders of EGaIn capsules and their multifunctionalcomposites, applicable in biomedicines, soft electronics, and smart robots.

Quaternized Silk Nanofibrils for Electricity Generation from Moisture and Ion Rectification.

Protein nanostructures in living organisms have attracted intense interests in biology and material science owing to their intriguing abilities to harness ion transportation for matter/signal transduction and bioelectricity generation. Silk nanofibrils, serving as the fundamental building blocks for silk, not only have the advantages of natural abundance, low cost, biocompatibility, sustainability, and degradability but also play a key role in mechanical toughness and biological functions of silk fibers. Herein, cationic silk nanofibrils (SilkNFs), with an ultrathin thickness of ∼4 nm and a high aspect ratio up to 500, were successfully exfoliated from natural cocoon fibers via quaternization followed by mechanical homogenization. Being positively charged in a wide pH range of 2-12, these cationic SilkNFs could combine with different types of negatively charged biological nanofibrils to produce asymmetric ionic membranes and aerogels that have the ability to tune ion translocation. The asymmetric ionic aerogels could create an electric potential as high as 120 mV in humid ambient air, whereas asymmetric ionic membranes could be used in ionic rectification with a rectification ratio of 5.2. Therefore, this green exfoliation of cationic SilkNFs may provide a biological platform of nanomaterials for applications as diverse as ion electronics, renewable energy, and sustainable nanotechnology.

Pyrazole-Isoindoline-1,3-dione Hybrid: A Promising Scaffold for 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.

The discovery of 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) inhibitors has been an active area of research due to their great potential as herbicides for weed control. Starting from the binding mode of known inhibitors of HPPD, a series of HPPD inhibitors with new molecular scaffolds were designed and synthesized by hybridizing 2-benzoylethen-1-ol and isoindoline-1,3-dione fragments. The results of the in vitro tests indicated that the newly synthesized compounds showed good HPPD inhibitory activity with IC50 values against the recombinant Arabidopsis thaliana HPPD (AtHPPD) ranging from 0.0039 µM to over 1 µM. Most promisingly, compound 4ae, 2-benzyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4- carbonyl)isoindoline-1,3-dione, showed the highest AtHPPD inhibitory activity with a Ki value of 3.92 nM, making it approximately 10 times more potent than pyrasulfotole (Ki = 44 nM) and slightly more potent than mesotrione (Ki = 4.56 nM). In addition, the cocrystal structure of the AtHPPD-4ae complex was successfully resolved at a resolution of 1.8 Å. The X-ray diffraction analysis indicated that the two carbonyl groups of 2-benzoylethen-1-ol formed a bidentate chelating interaction with the metal ion, while the isoindoline-1,3-dione moiety formed pronounced π-π stacking interactions with Phe381 and Phe424. Moreover, water-mediated hydrogen bonding interactions were observed between Asn282 and the nitrogen atoms of the pyrazole ring of 4ae. The above results showed that the pyrazole-isoindoline-1,3-dione hybrid is a promising scaffold for developing HPPD inhibitors.

Evaporation-induced sintering of liquid metal droplets with biological nanofibrils for flexible conductivity and responsive actuation.

Liquid metal (LM) droplets show the superiority in coalescing into integral liquid conductors applicable in flexible and deformable electronics. However, the large surface tension, oxide shells and poor compatibility with most other materials may prevent spontaneous coalescence of LM droplets and/or hybridisation into composites, unless external interventions (e.g., shear and laser) are applied. Here, we show that biological nanofibrils (NFs; including cellulose, silk fibroin and amyloid) enable evaporation-induced sintering of LM droplets under ambient conditions into conductive coating on diverse substrates and free-standing films. The resultants possess an insulating NFs-rich layer and a conductive LM-rich layer, offering flexibility, high reflectivity, stretchable conductivity, electromagnetic shielding, degradability and rapid actuating behaviours. Thus this sintering approach not only extends fundamental knowledge about sintering LM droplets, but also starts a new scenario of producing flexible coating and free-standing composites with flexibility, conductivity, sustainability and degradability, and applicable in microcircuits, wearable electronics and soft robotics.