Endothelial RSPO3 mediates pulmonary endothelial regeneration by LGR4-dependent activation of ß-catenin and ILK signaling pathways after inflammatory vascular injury.

Endothelial repair is essential for restoring tissue fluid homeostasis following lung injury. R-spondin3 (RSPO3), a secreted protein mainly produced by endothelial cells (ECs), has shown its protective effect on endothelium. However, the specific mechanisms remain unknown. To explore whether and how RSPO3 regulates endothelial regeneration after inflammatory vascular injury, the role of RSPO3 in sepsis-induced pulmonary endothelial injury was investigated in EC-specific RSPO3 knockdown, inducible EC-specific RSPO3 deletion mice, EC-specific RSPO3 overexpression mice, systemic RSPO3-administration mice, in isolated mouse lung vascular endothelial cells (MLVECs), and in plasma from septic patients. Here we show that plasma RSPO3 levels are decreased in septic patients and correlated with endothelial injury markers and PaO2/FiO2 index. Both pulmonary EC-specific knockdown of RSPO3 and inducible EC-specific RSPO3 deletion inhibit pulmonary ECs proliferation and exacerbate ECs injury, whereas intra-pulmonary EC-specific RSPO3 overexpression promotes endothelial recovery and attenuates ECs injury during endotoxemia. We show that RSPO3 mediates pulmonary endothelial regeneration by a LGR4-dependent manner. Except for ß-catenin, integrin-linked kinase (ILK)/Akt is also identified as a novel downstream effector of RSPO3/LGR4 signaling. These results conclude that EC-derived RSPO3 mediates pulmonary endothelial regeneration by LGR4-dependent activation of ß-catenin and ILK signaling pathways after inflammatory vascular injury.

Increased R-spondin 3 contributes to aerobic exercise-induced protection against renal vascular endothelial hyperpermeability and acute kidney injury.

AIM: Exercise training exerts protective effects against sepsis-associated multiple organ dysfunction. This study aimed to investigate whether aerobic exercise protected against sepsis-associated acute kidney injury (AKI) via modulating R-spondin 3 (RSPO3) expression. METHODS: To investigate the effects of aerobic exercise on lipopolysaccharide (LPS)-induced AKI, LPS (20 mg/kg) was intraperitoneally injected after six weeks of treadmill training. To investigate the role of RSPO3 in LPS-induced AKI, wild-type (WT) or inducible endothelial cell-specific RSPO3 knockout (RSPO3EC-/- ) mice were intraperitoneally injected with 12 mg/kg LPS. RSPO3 was intraperitoneally injected 30 min before LPS treatment. RESULTS: Aerobic exercise-trained mice were more resistant to LPS-induced body weight loss and hypothermia and had a significant higher survival rate than sedentary mice exposed to LPS. Exercise training restored the LPS-induced decreases in serum and renal RSPO3 levels. Exercise or RSPO3 attenuated, whereas inducible endothelial cell-specific RSPO3 knockout exacerbated LPS-induced renal glycocalyx loss, endothelial hyperpermeability, inflammation, and AKI. Bioinformatics analysis results revealed significant increases in the expression of matrix metalloproteinases (MMPs) in kidney tissues of mice exposed to sepsis or endotoxaemia, which was validated in renal tissue from LPS-exposed mice and LPS-treated human microvascular endothelial cells (HMVECs). Both RSPO3 and MMPs inhibitor restored LPS-induced downregulation of tight junction protein, adherens junction protein, and glycocalyx components, thus ameliorating LPS-induced endothelial leakage. Exercise or RSPO3 reversed LPS-induced upregulation of MMPs in renal tissues. CONCLUSION: Increased renal expression of RSPO3 contributes to aerobic exercise-induced protection against LPS-induced renal endothelial hyperpermeability and AKI by suppressing MMPs-mediated disruption of glycocalyx and tight and adherens junctions.

Synthesis of Diarylselenides through Rh-Catalyzed Direct Diarylation of Elemental Selenium with Benzamides.

Diarylselenides are a representative class of molecules in organoselenium compounds. We herein report a Rh-catalyzed direct diarylation of selenium with benzamide derivatives. The use of elemental selenium as the Se source is intriguing in terms of atom economy, cost, stability, and handling. A series of diarylselenides with amide moieties were readily accessible through directed C-H activation. The intermediacy of electrophilic Se(IV) species was indicated by control experiments.

LncRNA DLEU1 facilitates the progression of oral squamous cell carcinoma by miR-126-5p/GAB1 axis.

Oral squamous cell carcinoma (OSCC) is one of the most frequent malignancies found in head and neck cancers. Dysregulation of lncRNAs has been proposed to be related to the development of OSCC. Here, we investigated the function and probable mechanisms of lncRNA DLEU1 in OSCC. OSCC cell lines and human oral keratinocytes (HOKs) were cultured, while SCC-25 and CAL-27 cells were transfected with the corresponding plasmids. Reverse transcription quantitative PCR (RT-qPCR) and western blot were carried out to measure the RNA and protein levels. Cell proliferation, migration and invasion were evaluated using MTT assays, wound healing and Transwell assays. The StarBase database predicted the interactions between DLEU1 and miR-126-5p, as well as miR-126-5p and GAB1, which were further validated using a dual-luciferase reporter assay. Our results indicated that DLEU1 and GAB1 were upregulated, while miR-126-5p was downregulated in OSCC cells. Silencing DLEU1 reduced OSCC cell proliferation, migration, and invasion, while DLEU1 overexpression had the opposite effects. DLEU1 mediated biological effects in OSCC through binding to miR-126-5p, which directly targeted GAB1. miR-126-5p knockdown rescued the inhibitory function of DLEU1 depletion on proliferation, migration and invasion. Meanwhile, the miR-126-5p mimic exerted suppressive functions in the progression of OSCC, which were neutralized after GAB1 overexpression. In summary, lncRNA DLEU1 targets the miR-126-5p/GAB1 axis to aggravate OSCC progression, providing a novel target for treating OSCC.

Visualizing Assembly Dynamics of All-Liquid 3D Architectures.

To better exploit all-liquid 3D architectures, it is essential to understand dynamic processes that occur during printing one liquid in a second immiscible liquid. Here, the interfacial assembly and transition of 5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (H6 TPPS) over time provides an opportunity to monitor the interfacial behavior of nanoparticle surfactants (NPSs) during all-liquid printing. The formation of J-aggregates of H4 TPPS2- at the interface and the interfacial conversion of the J-aggregates of H4 TPPS2- to H-aggregates of H2 TPPS4- is demonstrated by interfacial rheology and in situ atomic force microscopy. Equally important are the chromogenic changes that are characteristic of the state of aggregation, where J-aggregates are green in color and H-aggregates are red in color. In all-liquid 3D printed structures, the conversion in the aggregate state with time is reflected in a spatially varying change in the color, providing a simple, direct means of assessing the aggregation state of the molecules and the mechanical properties of the assemblies, linking a macroscopic observable (color) to mechanical properties.

Synthesis of Benzoisoselenazolones via Rh(III)-Catalyzed Direct Annulative Selenation by Using Elemental Selenium.

Isoselenazolone derivatives have attracted significant research interest because of their potent therapeutic activities and indispensable applications in organic synthesis. Efficient construction of functionalized isoselenazolone scaffolds is still challenging, and thus new synthetic approaches with improved operational simplicity have been of particular interest. In this manuscript, we introduce a rhodium-catalyzed direct selenium annulation by using stable and tractable elemental selenium. A series of benzamides as well as acrylamides were successfully coupled with selenium under mild reaction conditions, and the obtained isoselenazolones could be pivotal synthetic precursors for several organoselenium compounds. Based on the designed control experiments and X-ray absorption spectroscopy measurements, we propose an unprecedented selenation mechanism involving a highly electrophilic Se(IV) species as the reactive selenium donor. The reaction mechanism was further verified by a computational study.

Visualizing Interfacial Jamming Using an Aggregation-Induced-Emission Molecular Reporter.

With the interfacial jamming of nanoparticles (NPs), a load-bearing network of NPs forms as the areal density of NPs increases, converting the assembly from a liquid-like into a solid-like assembly. Unlike vitrification, the lineal packing of the NPs in the network is denser, while the remaining NPs can remain in a liquid-like state. It is a challenge to determine the point at which the assemblies jam, since both jamming and vitrification lead to a solid-like behavior of the assemblies. Herein, we show a real-time fluorescence imaging method to probe the evolution of the interfacial dynamics of NP surfactants at the water/oil interface using aggregation-induced emission (AIE) as a reporter for the transition of the assemblies into the jammed state. The AIEgens show typical fluorescence behavior at densities at which they can move and rotate. However, when aggregation of these fluorophores occurs, the smaller intermolecular separation distance arrests rotation, and a significant enhancement in the fluorescence intensity occurs.

Surfactant-Induced Interfacial Aggregation of Porphyrins for Structuring Color-Tunable Liquids.

Locking nonequilibrium shapes of liquids into targeted architectures by interfacial jamming of nanoparticles is an emerging area in material science. 5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (H6 TPPS) shows three different aggregation states that present an absorption imaging platform to monitor the assembly and jamming of supramolecular polymer surfactants (SPSs) at the liquid/liquid interface. The interfacial interconversion of H6 TPPS, specifically H4 TPPS2- dissolved in water, from J- to an H-aggregation was induced by strong electrostatic interactions with amine-terminated polystyrene dissolved in toluene at the water/toluene interface. This resulted in color-tunable liquids due to interfacial jamming of the SPSs formed between H4 TPPS2- and amine-terminated polystyrene. However, the formed SPSs cannot lock in nonequilibrium shapes of liquids. In addition, a self-wrinkling behavior was observed when amphiphilic triblock copolymers of PS-block-poly(2-vinylpyridine)-block-poly(ethylene oxide) were used to interact with H4 TPPS2- . Subsequently, the SPSs formed can lock in nonequilibrium shapes of liquids.

Conductive Thin Films over Large Areas by Supramolecular Self-Assembly.

We report a "one-step" method for preparing conductive thin films with cylindrical microdomains oriented normal to the surface over large areas using the supramolecular assembly of poly(styrene-block-4-vinylpyridine) (PS19-b-P4VP5) and 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine (HOTPP). HOTPP interacts with the P4VP block by hydrogen bonding between the hydroxyl group of HOTPP and pyridine ring of PS19-b-P4VP5, forming cylindrical P4VP(HOTPP) domains having an average diameter of ∼17 nm in a PS matrix. Dynamic light scattering, contact angle, and in situ grazing incidence small-angle X-ray scattering measurements show a morphological transition from spherical micelles in solution to cylindrical microdomains oriented normal to the substrate surface during the drying process. From the dependence of current on voltage, an average current of ∼4.0 nA is found to pass through a single microdomain, pointing to a promising route for organic semiconductor device applications.

Highly Diastereoselective Synthesis of Polycyclic Indolines through Formal [4+2] Propargylic Cycloaddition of Indoles with Ethynyl Benzoxazinanones.

A formal [4+2] propargylic annulation of indoles and pyrrole with ethynyl benzoxazinanones was described. This protocol provides a concise synthesis of tetrahydro-5H-indolo[2,3-b]quinolines and tetrahydro-3H-pyrrolo[3,2-b]quinoline, the core structures of alkaloid frameworks, featuring excellent yields, high diastereoselectivity, mild conditions and wide substrate scope.

Enantioselective Synthesis of 4-Allyl Tetrahydroquinolines via Copper(I) Hydride-Catalyzed Hydroallylation of 1,2-Dihydroquinolines.

CuCl/(R,R)-Ph-BPE-catalyzed asymmetric hydroallylation of 1,2-dihydroquinolines, prepared from readily available quinolines, was developed. The optically active tetrahydroquinolines (THQs) bearing an allylic functionality at position 4 were obtained in good yields and excellent enantioselectivity. The introduced allylic groups are amenable to diverse transformations, thus offering chances to rapidly expand the THQ libraries.

Chiral phosphoric acid-catalyzed asymmetric dearomatization reactions.

We summarize in this review the recent development of chiral phosphoric acid (CPA)-catalyzed asymmetric dearomatization reactions. A wide array of electron-rich arenes (indoles, phenols, naphthols, benzothiophenes, benzofurans, etc.) and electron-poor arenes (pyridines, quinolines, isoquinolines, etc.) has been proved reactive towards various reaction partners in the presence of a CPA catalyst, enabling asymmetric dearomatization reactions that lead to structurally-diverse polycyclic molecules. The reactions are grouped according to the roles of the arenes in the reactions (as nucleophiles or electrophiles) and the types of reaction partners. This review closes with a personal perspective on the dynamic research area of asymmetric dearomatization reactions by CPAs.

Environmentally Robust Memristor Enabled by Lead-Free Double Perovskite for High-Performance Information Storage.

Memristors are emerging as a rising star of new computing and information storage techniques. However, the practical applications are severely challenged by their instability toward harsh conditions, including high moisture, high temperatures, fire, ionizing irradiation, and mechanical bending. In this work, for the first time, lead-free double perovskite Cs2 AgBiBr6 is utilized for environmentally robust memristors, enabling highly efficient information storage. The memory performance of the typical indium-tin-oxide/Cs2 AgBiBr6 /Au sandwich-like memristors is retained after 1000 switching cycles, 105 s of reading, and 104 times of mechanical bending, comparable to other halide perovskite memristors. Most importantly, the memristive behavior remains robust in harsh environments, including humidity up to 80%, temperatures as high as 453 K, an alcohol burner flame for 10 s, and 60 Co γ-ray irradiation for a dosage of 5 × 105 rad (SI), which is not achieved by any other memristors and commercial flash memory techniques. The realization of an environmentally robust memristor from Cs2 AgBiBr6 with a high memory performance will inspire further development of robust electronics using lead-free double perovskites.

Independent Memcapacitive Switching Triggered by Bromide Ion Migration for Quaternary Information Storage.

Memcapacitors are emerging as an attractive candidate for high-density information storage due to their multilevel and adjustable capacitances and long-term retention without a power supply. However, knowledge of their memcapacitive mechanism remains unclear and accounts for the limited implementation of memcapacitors for multilevel memory technologies. Here, repeatable and reproducible quaternary memories fabricated from hybrid perovskite (CH3 NH3 SnBr3 ) memcapacitors are reported. The device can be modulated to at least four capacitive states ranging from 0 to 169 pF with retention for 104 s. Impressively, an effective device yield approaching 100% for quaternary memory switching is achieved by a batch of devices; each state has a sufficiently narrow distribution that can be distinguished from the others and is superior to most multilevel memories that have a low device yield as well as an overlapping distribution of states. The memcapacitive switching stems from the modulated p-i-n junction capacitance triggered by Br- migration, as demonstrated by in situ element mapping, X-ray photoelectron spectra, and frequency-dependent capacitance measurements; this mechanism is different from the widely reported memristive switching involving filamentary conduction. The results provide a new way to produce high-density information storage through memcapacitors.

Stabilizing Liquids Using Interfacial Supramolecular Polymerization.

The strong electrostatic interactions at the oil-water interface between a small molecule, 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin, H6 TPPS, dissolved in water, and an amine terminated hydrophobic polymer dissolved in oil are shown to produce a supramolecular polymer surfactant (SPS) of H6 TPPS at the interface with a binding energy that is sufficiently strong to allow an intermolecular aggregation of the supramolecular polymers. SPSs at the oil-water interface are confirmed by in situ real-space atomic force microcopy imaging. The assemblies of these aggregates can jam at the interface, opening a novel route to kinetically trap the liquids in non-equilibrium shapes. The elastic film, comprised of SPSs, wrinkles upon compression, providing a strategy to stabilize liquids in non-equilibrium shapes.

Enantioselective Synthesis of 4-Aminotetrahydroquinolines via 1,2-Reductive Dearomatization of Quinolines and Copper(I) Hydride-Catalyzed Asymmetric Hydroamination.

A 1,2-reductive dearomatization of quinolines and copper(II) acetate monohydrate/( R, R)-Ph-BPE/P( p-tolyl)3-catalyzed enantioselective hydroamination sequence was developed, affording diverse 4-amino-1,2,3,4-tetrahydroquinolines with high levels of enantioselectivity in either a stepwise or one-pot fashion. Pleasingly, internal cis-cyclic alkenes, which are challenging substrates in copper hydride-catalyzed enantioselective hydroamination reactions, were transformed efficiently under mild conditions.

Detection of NO2 Down to One ppb Using Ion-in-Conjugation-Inspired Polymer.

Nitrogen dioxide (NO2 ) emission has severe impact on human health and the ecological environment and effective monitoring of NO2 requires the detection limit (limit of detection) of several parts-per-billion (ppb). All organic semiconductor-based NO2 sensors fail to reach such a level. In this work, using an ion-in-conjugation inspired-polymer (poly(3,3'-diaminobenzidine-squarine, noted as PDBS) as the sensory material, NO2 can be detected as low as 1 ppb, which is the lowest among all reported organic NO2 sensors. In addition, the sensor has high sensitivity, good reversibility, and long-time stability with a period longer than 120 d. Theoretical calculations reveal that PDBS offers unreacted amine and zwitterionic groups, which can offer both the H-bonding and ion-dipole interaction to NO2 . The moderate binding energies (≈0.6 eV) offer high sensitivity, selectivity as well as good reversibility. The results demonstrate that the ion-in-conjugation can be employed to greatly improve sensitivity and selectivity in organic gas sensors by inducing both H-bonding and ion-dipole attraction.

Copper-Catalyzed Ring Opening of Benzofurans and an Enantioselective Hydroamination Cascade.

A copper(II) acetate/(R)-DTBM-SEGPHOS-catalyzed ring opening of benzofurans and enantioselective hydroamination cascade with dimethoxymethylsilane (DMMS) and hydroxylamine esters is described. Starting from readily available substituted benzofurans, a series of chiral N,N-dibenzylaminophenols, which are of high interest in pharmaceutical chemistry, were obtained with excellent enantioselectivities (up to 66 % yield, 94 % ee).

Mussel-Inspired Polydopamine Coating for Flexible Ternary Resistive Memory.

In recent years, numerous organic molecules and polymers carrying various functional groups were synthesized and used in fabrication of wearable electronic devices. Compared to previous materials that suffer from poisonousness, stiffness and complex film fabrication, we circumvent above matters by taking advantage of mussel-inspired polydopamine as our active material to realize resistive random access memories (RRAMs). Polydopamine thin films were grown on indium tin oxide glass catalyzed by Cu2 SO4 /H2 O2 and characterized by Fourier infrared spectroscopy (FT-IR), UV/Vis spectroscopy and scanning electron microscopy. The Al/Polydopamine film/ITO devices possess ternary memory behavior with good ternary device yield with two threshold voltages around 1.50 V and 3.50 V, long data retention over 104  s of continuous reading or 104 pulse reading. The two resistance switchings are attributed to defects functioning as charge traps and the formation of conductive filaments. A flexible device based on Al/polydopamine film/ITO/polyethylene terephthalate retains its ternary memory behavior after being bent with a bending radius of 1.54 cm and bending cycles up to 5000, demonstrating good compatibility and flexibility of polydopamine.

The Effect of Random and Block Copolymerization with Pendent Carbozole Donors and Naphthalimide Acceptors on Multilevel Memory Performance.

Polymeric materials have been widely used in the fabrication of data-storage devices, owing to their unique advantages and defined conduction mechanisms. To date, the most-functional polymers that have been reported for memory devices were synthesized through random copolymerization, whilst there have been no reports regarding the memory effect of block polymers. Herein, we synthesized a random copolymer (PMCz8 -co-PMBNa2 ) and its corresponding block copolymer (PMCz8 -b-PMBNa2 ) to study the effect of the method of polymerization on the memory properties of the corresponding devices. Interestingly, both devices (ITO/PMCz8 -co-PMBNa2 /Al and ITO/PMCz8 -b-PMBNa2 /Al) exhibited ternary memory performance, with threshold voltages of -1.7 V/-3.3 V and -2.7 V/-3.8 V, respectively. However, based on comprehensive measurements, the memory properties of PMCz8 -co-PMBNa2 and PMCz8 -b-PMBNa2 were found to be owing to the operation of different conduction mechanisms, which resulted from different molecular stacking in the film state. Therefore, we expect that this work will be helpful for improving our understanding of the conduction mechanisms in polymer-based data-storage devices.