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Detecting H 2 S in oxygen-deficient conditions is vital for identifying leaks in SF 6 -insulated electrical equipment. Current infrared-based detection methods are expensive and sensitive to environmental conditions, highlighting the necessity for cost-effective and stable gas sensors. Existing gas sensors based on semiconducting metal oxides (SMOXs) are limited by redox reactions with oxygen and require high operating temperatures. Here, we introduce a room-temperature (RT) H 2 S sensor for oxygen-deficient environments using the intrinsic conducting two-dimensional (2D) metal-organic framework (MOF), Co 1.8 Ni 1.2 (hexaiminotriphenylene) 2 [Co 1.8 Ni 1.2 (HITP) 2 ], overcoming the limitations of SMOX gas sensors. Remarkably, Co 1.8 Ni 1.2 (HITP) 2 sensors exhibit exceptional selectivity for H 2 S with negligible cross-responses and a sensitivity drift of less than 4.13% in an SF 6 atmosphere over 60 days. The Co 1.8 Ni 1.2 (HITP) 2 gas sensor shows significant promise for real-time and stable monitoring of H 2 S gas in oxygen-deficient environments.

Fuel cell gas sensors have emerged as promising advanced sensing devices owing to their advantageous features of low power consumption and cost-effectiveness. However, commercially available Pt/C electrodes pose significant challenges in terms of stability and accurate detection of low concentrations of target gases. Here, we introduce an efficient Cu-Pt/CrN-based fuel cell gas sensor, designed specifically for the ultrasensitive detection of hydrogen sulfide (H 2 S) at room temperature. Compared to the commercial Pt/C sensor, the Cu-Pt/CrN sensor exhibits excellent sensitivity (0.26 μA/ppm), with an increase in the selectivity by a factor of 2.5, and demonstrates good stability over a 2 month period. The enhanced sensing performance can be attributed to the modulation of the electronic arrangement of Pt by Cu, resulting in an augmentation of H 2 S adsorption. The Cu-Pt/CrN fuel cell gas sensor provides an opportunity for detecting parts per billion-level H 2 S in various applications.

Cost and durability have become crucial hurdles for the commercialization of proton exchange membrane fuel cells (PEMFCs). Although a continuous reduction of Pt loading within the cathode catalyst layers (CCLs) can lead to cost savings, it also increases the oxygen transport resistance, which is further compounded by key material degradation. Hence, a further understanding of the mechanism of significant performance loss due to oxygen transport limitations at the triple phase boundaries (TPBs) during the degradation process is critical to the development of low Pt loading PEMFCs. The present study systematically investigates the impact of carbon corrosion in CCLs on the performance and oxygen transport process of low Pt loading PEMFCs through accelerated stress tests (ASTs) that simulate start-up/shutdown cycling. A decline in peak power density from 484.3 to 251.6 mW cm -2 after 1500 AST cycles demonstrates an apparent performance loss, especially at high current densities. The bulk and local oxygen transport resistances ( r bulk and R local ) of the pristine cell and after 200, 600, 1000, and 1500 AST cycles are quantified by combining the limiting current method with a dual-layer CCL design. The results show that r bulk increased from 1527 to 1679 s cm -2 , R local increased from 0.38 to 0.99 s cm -1 , and the local oxygen transport resistance with the normalized Pt surface area ( r local ) exhibited an increase from 18.5 to 32.0 s cm -1 , indicating a crucial impact on the structure collapse and changes in the chemical properties of the carbon supports in the CCLs. Further, the interaction between the ionomer and carbon supports during the carbon corrosion process is deeply studied via electrochemical quartz crystal microbalance and molecular dynamics simulations. It is concluded that the oxygen-containing functional groups on the carbon surface could impede the adsorption of ionomers on carbon supports by creating an excessively water-rich layer, which in turn aggravates the formation of ionomer agglomerations within the CCLs. This process ultimately leads to the destruction of the TPBs and hinders the transport of oxygen through the ionomer.

Owing to the decomposition issue of Mg 3 N 2 , many Mg-containing ternary nitrides were prepared by the hybrid arc evaporation/sputtering technique, which has the advantages including access to the unstable phases, high film purity, good density, and uniform film formation but the drawbacks of cost and long production cycle for the required targets. In the present study, we demonstrate that rocksalt-type Ti 1- x Mg x N, previously prepared exclusively by the thin-film methods, can be obtained as a disordered cubic phase by the conventional bulk synthesis method through a facile one-step reaction. Employing a combination of experimental measurements and theoretical calculations, we discover that the crystal structure and the physical properties of the as-synthesized Ti 1- x Mg x N solid solution can be tuned by the Mg content; a metal-to-semiconductor transition and also suppression of the superconducting phase transition are observed when the Mg and Ti content ratio increases to close to 1. Theoretical calculations indicate that the lattice distortions in the disordered Ti 1- x Mg x N induced by the different ionic sizes of Mg and Ti increase with the Mg content and the disordered cubic rocksalt structures become unstable. The ordered rocksalt-derived structures are more stable than the disordered rocksalt structures on composition x = 0.5. Furthermore, electronic structure calculations provide an insight into the low resistance behavior and transport property evolution of Ti 1- x Mg x N from the aspects of Ti 3+ content, the cation distribution, or nitrogen defects. The results highlight the feasibility of the simple bulk route for the successful synthesis of Mg-containing ternary nitrides and the heterovalent ion substitution on modulating the properties of nitrides.

It is crucial to clarify the permeation behavior of O 2 through the ionomer film for enhancing local O 2 transport in cathodes of fuel cells. However, all existing studies mainly deal with pure O 2 rather than air. Herein, the permeation behavior of the O 2 /N 2 mixture through the ionomer film has been well explored in view of molecular bond length variations by molecular dynamics simulations. The bond lengths for O 2 and N 2 are shortened under a low hydration level when permeating through a dense layer with small free voids while no obvious change occurs at higher hydration. In the bulk ionomer region, O 2 molecules residing in water domains are energetically unstable because the bond lengths deviate far from the equilibrium length; thus, O 2 diffuses through the interfacial or hydrophobic regions. N 2 molecules show similar properties with O 2 . This study provides a novel perspective on the permeation behavior of O 2 and N 2 through the ionomer film, which definitely benefits enhancing local O 2 transport.

Enediyne natural products, including neocarzinostatin and calicheamicin γ 1 , are used in the form of a copolymer or antibody-drug conjugate to treat hepatomas and leukemia. Tiancimycin (TNM) A is a novel anthraquinone-fused enediyne that can rapidly and completely kill tumor cells. Herein, we encapsulated TNM A in liposomes (Lip-TNM A) and cyclic arginine-glycine-aspartate (cRGD)-functionalized liposomes (cRGD-Lip-TNM A) and demonstrated its antitumor activity using mouse xenografts. Because TNM A causes rapid DNA damage, cell cycle arrest, and apoptosis, these nanoparticles exhibited potent cytotoxicity against multiple tumor cells for 8 h. In B16-F10 and KPL-4 xenografts, both nanoparticles showed superior potency over doxorubicin and trastuzumab. However, cRGD-Lip-TNM A reduced the tumor weight more significantly than Lip-TNM A in B16-F10 xenografts, in which the α v β 3 -integrin receptors are significantly overexpressed in this melanoma. Lip-TNM A was slightly more active than cRGD-Lip-TNM A against KPL-4 xenografts, which probably reflected the difference of their in vivo fate in this mouse model. In a highly metastatic 4T1 tumor model, cRGD-Lip-TNM A reduced tumor metastasis induced by losartan, a tumor microenvironment-remodeling agent. These findings suggest that targeted delivery of enediynes with unique modes of action may enable more effective translation of anticancer nanomedicines.

Deep eutectic solvents (DESs) have attracted extensive research for their potential applications as leaching solvent to recycle valuable metal elements from spent lithium ion batteries (LIBs). Despite various advantages like being economical and green, the full potential of conventional binary DES has not yet been harnessed because of the kinetics during leaching. Herein, we consider the fundamental rate-determining-step (RDS) in conventional binary DES and attempt to design ternary DES, within which the chemical reaction kinetics and diffusion kinetics can be regulated to maximize the overall leaching rate. As a proof of concept, we show that the ternary choline chloride/succinic acid/ethylene glycol (ChCl/SA/EG) type ternary DES can completely dissolve LCO powder at 140 °C in 16 h. By systematically studying the leaching process at various conditions, the energy barrier during leaching can be calculated to be 11.77 kJ/mol. Furthermore, we demonstrate that the extraction of the cobalt ions from the leaching solution can be directly achieved by adding oxalic ions without neutralizing the solution. The precipitate can be used to regenerate LCO with high purity. The recycled materials show comparable electrochemical performance with commercial LCO. Our design strategy of ternary DES with regulated RDS is expected to have both scientific and technological significance in the field of hydrometallurgical recycling of LIBs., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Comparative analyses of four anthraquinone-fused enediyne biosynthetic gene clusters (BGCs) identified YpmL as a cytochrome P450 enzyme unique to the yangpumicin (YPM) BGC. In vitro characterization of YpmL established it as a hydroxylase, catalyzing C-6 hydroxylation in YPM A biosynthesis. In vivo application of YpmL enabled engineered production of four new tiancimycin analogues ( 14 - 17 ). Evaluation of their cytotoxicity against selected human cancer cell lines shed new insights into the enediyne structure-activity relationship.

A novel multifunctional Janus magnetic micromotor was designed and constructed by using MIL-100(Fe)@TiO 2 @Fe 3 O 4 multicore-shells modified with horseradish peroxidase (HRP) as a smart active platform to realize detection and degradation of hydroquinone (HQ). The obtained micromotor showed a unique three-dimensional (3D) hierarchical architecture with highly exposed active sites and could autonomously move at a speed of 140 ± 7.0 μm·s -1 by O 2 bubbles generated from the catalytic decomposition of H 2 O 2 fuel. Benefiting from the combination of active self-propulsive motion, high peroxidase-like activity, tuned heterojunctions with matching band structures, and a 3D hierarchical structure, an effective platform involving dynamically sensitive detection and quick removal of HQ from water was established by using the multifunctional HRP-integrated MIL-100(Fe)@TiO 2 @Fe 3 O 4 Janus micromotor. The proposed multifunctional Janus magnetic micromotor had advantages of simple and feasible fabrication, sensitive detection and effective photo-Fenton degradation of HQ in a wide pH range of 4-7, and magnetic recycling, revealing potential for environmental remediation applications.

Catalytically powered micro/nanobots (MNBs) can perform active movement by harnessing energy from in situ chemical reactions and show tremendous potential in biomedical applications. However, the development of imageable MNBs that are driven by bioavailable fuels and possess multiple therapeutic functions remains challenging. To resolve such issues, we herein propose enzyme (urease) powered liquid metal (LM) nanobots that are naturally of multiple therapeutic functions and imaging signals. The main body of the nanobot is composed of a biocompatible LM nanoparticle encapsulated by polydopamine (PDA). Urease enzyme needed for the powering and desired drug molecules, e . g ., cefixime trihydrate antibiotic, are grafted on external surfaces of the PDA shell. Such a chemical composition endows the nanobots with dual-mode ultrasonic (US) and photoacoustic (PA) imaging signals and favorable photothermal effect. These LM nanobots exhibit positive chemotaxis and therefore can be collectively guided along a concentration gradient of urea for targeted transportation. When exposed to NIR light, the LM nanobots would deform and complete the function change from active drug carriers to photothermal reagents, to achieve synergetic antibacterial treatment by both photothermal and chemotherapeutic effects. The US and PA properties of the LM nanoparticle can be used to not only track and monitor the active movement of the nanobots in a microfluidic vessel model but also visualize their dynamics in the bladder of a living mouse in vivo . To conclude, the LM nanobots demonstrated herein represent a proof-of-concept therapeutic nanosystem with multiple biomedical functionalities, providing a feasible tool for preclinical studies and clinical trials of MNB-based imaging-guided therapy.

Tiancimycin (TNM) A belongs to the anthraquinone-fused subfamily of enediyne natural products, and selected enediynes have been translated into clinical drugs. Previously, inactivation of tnmL in Streptomyces sp. CB03234 resulted in the accumulation of TNM B and TNM E, supporting the functional assignment of TnmL as a cytochrome P450 hydroxylase that catalyzes A-ring modification in TNM A biosynthesis. Herein, we report in vitro characterization of TnmL, revealing that (i) TnmL catalyzes two successive hydroxylations of TNM E, resulting in sequential production of TNM F and TNM C, (ii) TnmL shows a strict substrate preference, with the C-26 side chain playing a critical role in substrate binding, and (iii) TnmL demethylates the C-7 OCH 3 group of TNM G, affording TNM F, thereby channeling the shunt product TNM G back into TNM A biosynthesis and representing a rare proofreading logic for natural product biosynthesis. These findings shed new insights into anthraquinone-fused enediyne biosynthesis.

Micro/nanorobots have been extensively explored as a tetherless small-scale robotic biodevice to perform minimally invasive interventions in hard-to-reach regions. Despite the emergence of versatile micro/nanorobots in recent years, matched in vivo development remains challenging, limited by unsatisfactory integration of core functions. Herein, we report a polydopamine (PDA)-coated magnetic microswimmer consisting of a magnetized Spirulina (MSP) matrix and PDA surface. Apart from the properties of the existing MSP ( e.g. , robust propulsion, natural fluorescence, tailored biodegradation, and selective cytotoxicity), the introduced PDA coating enhances the photoacoustic (PA) signal and photothermal effect of the MSP, thus making PA image tracking and photothermal therapy possible. Meanwhile, the PDA's innate fluorescence quenching and diverse surface reactivity allows an off-on fluorescence diagnosis with fluorescence probes ( e.g. , coumarin 7). As a proof of concept, real-time image tracking (by PA imaging) and desired theranostic capabilities of PDA-MSP microswimmer swarms are demonstrated for the treatment of pathogenic bacterial infection. Our study suggests a feasible antibacterial microrobot for in vivo development and a facile yet versatile functionalization strategy of micro/nanorobots.

C-1027 is a chromoprotein enediyne antitumor antibiotic, consisting of the CagA apoprotein and the C-1027 chromophore. The C-1027 chromophore features a nine-membered enediyne core appended with three peripheral moieties, including an ( S)-3-chloro-5-hydroxy-β-tyrosine. In a convergent biosynthesis of the C-1027 chromophore, the ( S)-3-chloro-5-hydroxy-β-tyrosine moiety is appended to the enediyne core by the free-standing condensation enzyme SgcC5. Unlike canonical condensation domains from the modular nonribosomal peptide synthetases that catalyze amide-bond formation, SgcC5 catalyzes ester-bond formation, as demonstrated in vitro, between SgcC2-tethered ( S)-3-chloro-5-hydroxy-β-tyrosine and ( R)-1-phenyl-1,2-ethanediol, a mimic of the enediyne core as an acceptor substrate. Here, we report that (i) genes encoding SgcC5 homologues are widespread among both experimentally confirmed and bioinformatically predicted enediyne biosynthetic gene clusters, forming a new clade of condensation enzymes, (ii) SgcC5 shares a similar overall structure with the canonical condensation domains but forms a homodimer in solution, the active site of which is located in a cavity rather than a tunnel typically seen in condensation domains, and (iii) the catalytic histidine of SgcC5 activates the 2-hydroxyl group, while a hydrogen-bond network in SgcC5 prefers the R-enantiomer of the acceptor substrate, accounting for the regio- and stereospecific ester-bond formation between SgcC2-tethered ( S)-3-chloro-5-hydroxy-β-tyrosine and ( R)-1-phenyl-1,2-ethanediol upon acid-base catalysis. These findings expand the catalytic repertoire and reveal new insights into the structure and mechanism of condensation enzymes.

Remarkable progress has been made in reducing the cathodic Pt loading of PEMFCs; however, a huge performance loss appears at high current densities, indicating the existence of a large oxygen transport resistance associated with the ultralow Pt loading catalyst layer. To reduce the Pt loading without sacrificing cell performance, it is essential to illuminate the oxygen transport mechanism in the catalyst layer. Toward this goal, an experimental approach to measure the oxygen transport resistance in catalyst layers is proposed and realized for the first time in this study. The measuring approach involves a dual-layer catalyst layer design, which consists of a dummy catalyst layer and a practical catalyst layer, followed by changing the thickness of dummy layer to respectively quantify the local and bulk resistances via limiting current measurements combined with linear extrapolation. The experimental results clearly reveal that the local resistance dominates the total resistance in the catalyst layer.

A new anthraquinone-fused enediyne, yangpumicin A (YPM A, 1), along with four Bergman cyclization congeners (YPM B-E, 2-5), was isolated from Micromonospora yangpuensis DSM 45577 after mining enediyne biosynthetic gene clusters from public actinobacterial genome databases and prioritizing the hits by an enediyne genome neighborhood network analysis for discovery. YPM A is potent against a broad spectrum of human cancer cell lines. The discovery of 1 provides new opportunities for the functionalization of enediynes to develop new conjugation chemistries for antibody-drug conjugates.

In this work, a hollow LiNi 1/3 Co 1/3 Mn 1/3 O 2 (H-NCM) nanosphere cathode with excellent electrochemical performance is developed for lithium-ion batteries. Preparation of the H-NCM nanospheres involves the sacrificial template method, in which carbon nanospheres work as the template and polyvinylpyrrolidone works as an additive. Structural and morphological analyses show that the as-prepared H-NCM nanospheres are highly uniform with diameters of approximately 50 nm and wall thicknesses of 10 nm. Electrochemical tests demonstrate that the H-NCM cathode not only manifests outstanding rate performance in the potential window of 2.5-4.5 V with high reversible specific capacities of 205.6, 194.9, 177.8, 165.9, 151.7, 126.0, and 115.3 mA h g -1 at 0.1, 0.2, 0.5, 1, 2, 5, and 10 C, respectively, but also delivers excellent stability with a capacity retention of 60.1% at 10 C after 2000 cycles. The superior electrochemical performance of the H-NCM cathode can be put down to the distinctive hollow interior structure with thin nanostructured walls, which can synergistically benefit the significantly enhanced rate capability and cycling stability., Competing Interests: The authors declare no competing financial interest.

Cellular adhesion is regulated by the dynamic ligation process of surface receptors, such as integrin, to adhesive motifs, such as Arg-Gly-Asp (RGD). Remote control of adhesive ligand presentation using external stimuli is an appealing strategy for the temporal regulation of cell-implant interactions in vivo and was recently demonstrated using photochemical reaction. However, the limited tissue penetration of light potentially hampers the widespread applications of this method in vivo. Here, we present a strategy for modulating the nanoscale oscillations of an integrin ligand simply and solely by adjusting the frequency of an oscillating magnetic field to regulate the adhesion and differentiation of stem cells. A superparamagnetic iron oxide nanoparticle (SPION) was conjugated with the RGD ligand and anchored to a glass substrate by a long flexible poly(ethylene glycol) linker to allow the oscillatory motion of the ligand to be magnetically tuned. In situ magnetic scanning transmission electron microscopy and atomic force microscopy imaging confirmed the nanoscale motion of the substrate-tethered RGD-grafted SPION. Our findings show that ligand oscillations under a low oscillation frequency (0.1 Hz) of the magnetic field promoted integrin-ligand binding and the formation and maturation of focal adhesions and therefore the substrate adhesion of stem cells, while ligands oscillating under high frequency (2 Hz) inhibited integrin ligation and stem cell adhesion, both in vitro and in vivo. Temporal switching of the multimodal ligand oscillations between low- and high-frequency modes reversibly regulated stem cell adhesion. The ligand oscillations further induced the stem cell differentiation and mechanosensing in the same frequency-dependent manner. Our study demonstrates a noninvasive, penetrative, and tunable approach to regulate cellular responses to biomaterials in vivo. Our work not only provides additional insight into the design considerations of biomaterials to control cellular adhesion in vivo but also offers a platform to elucidate the fundamental understanding of the dynamic integrin-ligand binding that regulates the adhesion, differentiation, and mechanotransduction of stem cells.

The lack of therapies for neurodegenerative diseases arises from our incomplete understanding of their underlying cellular toxicities and the limited number of predictive model systems. It is critical that we develop approaches to identify novel targets and lead compounds. Here, a phenotypic screen of yeast proteinopathy models identified dihydropyrimidine-thiones (DHPM-thiones) that selectively rescued the toxicity caused by β-amyloid (Aβ), the peptide implicated in Alzheimer's disease. Rescue of Aβ toxicity by DHPM-thiones occurred through a metal-dependent mechanism of action. The bioactivity was distinct, however, from that of the 8-hydroxyquinoline clioquinol (CQ). These structurally dissimilar compounds strongly synergized at concentrations otherwise not competent to reduce toxicity. Cotreatment ameliorated Aβ toxicity by reducing Aβ levels and restoring functional vesicle trafficking. Notably, these low doses significantly reduced deleterious off-target effects caused by CQ on mitochondria at higher concentrations. Both single and combinatorial treatments also reduced death of neurons expressing Aβ in a nematode, indicating that DHPM-thiones target a conserved protective mechanism. Furthermore, this conserved activity suggests that expression of the Aβ peptide causes similar cellular pathologies from yeast to neurons. Our identification of a new cytoprotective scaffold that requires metal-binding underscores the critical role of metal phenomenology in mediating Aβ toxicity. Additionally, our findings demonstrate the valuable potential of synergistic compounds to enhance on-target activities, while mitigating deleterious off-target effects. The identification and prosecution of synergistic compounds could prove useful for developing AD therapeutics where combination therapies may be required to antagonize diverse pathologies.

Lithium ion batteries (LIBs) are promising candidates for energy storage, with the development of novel anode materials. We report the fabrication of Fe 3 O 4 nanoparticles/graphene foam via electrostatic assembly and directly utilize it as a binder-free anode for LIBs. Owing to the integrated effect of the well-dispersed Fe 3 O 4 nanoparticles and the conductive graphene foam network, such composite exhibited remarkable electrochemical performances. It delivered a large reversible specific capacity reaching to ∼1198 mAh g -1 at a current density of 100 mA g -1 , a good rate capacity, and an excellent cyclic stability over 400 cycles. This work demonstrated a facile methodology to design and construct high-performance anode materials for LIBs.

A spatial-resolved analysis method for profiling of gibberellins (GAs) in a single leaf was developed on the basis of microscale sample preparation and precolumn derivatization coupled with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The proposed microscale sample preparation was based on modified matrix solid-phase dispersion (MSPD) method, in which the plant sample (<1 mg) and C18 sorbent were ground together in one microcentrifuge tube, and then extraction solvent was added followed by centrifugation. In this protocol, the grinding, extraction, and purification were performed in one microcentrifuge tube without any sample transfer step, resulting in an obvious decrease in sample loss. Moreover, a new derivatization reagent, 3-bromopropyltrimethylammonium bromide (BPTAB), was used to further enhance the signal intensities of GAs on MS by 3-4 orders of magnitude, which was much higher than the reported derivatization reagents for GAs such as bromocholine bromide and 3-bromoactonyltrimethylammonium bromide. The present method showed high sensitivity (minimum detectable amount (MDA) of 10.1-72.3 amol for eight GAs) and low sample consumption (down to 0.30 mg FW). Under the optimized conditions, the distribution of GA 19 in a single Arabidopsis thaliana leaf was profiled with a spatial resolution of 2 × 2 mm 2 .

Cells sense and respond to the surrounding microenvironment through binding of membranous integrin to ligands such as the Arg-Gly-Asp (RGD) peptide. Previous studies show that the RGD tether properties on substrate influence cell adhesion and spreading, but few studies have reported strategies to control the tether mobility of RGD on substrate via a physical and noncontact approach. Herein, we demonstrate a novel strategy to tune the tether mobility of RGD on substrate via magnetic force. We conjugate a monolayer of RGD-bearing magnetic nanoparticles (MNPs) on a glass substrate via the flexible and coiled poly(ethylene glycol) linker of large molecular weight (PEG, average MW: 2000), and this increases the RGD tether mobility, which can be significantly reduced by applying magnetic attraction on MNPs. Our data show that high RGD tether mobility delays the early adhesion and spreading of human mesenchymal stem cells (hMSCs), leading to compromised osteogenic differentiation at later stage. In contrast, hMSCs cultured on substrate with restricted RGD tether mobility, achieved either via a shorter PEG linker (MW: 200) or magnetic force, show significantly better adhesion, spreading, and osteogenic differentiation. The control utilizing RGD-bearing nonmagnetic nanoparticles shows no such enhancing effect of magnetic field on cellular events, further supporting our conjecture of magnetic tuning of RGD tether mobility. We hypothesize that high tether mobility of RGD entails additional time and effort by the cells to fully develop traction force and mechanical feedback, thereby delaying the maturation of FAs and activation of subsequent mechanotransduction signaling. Our staining results of vinculin, a critical component of FAs, and Yes-associated protein (YAP), an important mechanosensitive transcriptional factor, support our hypothesis. We believe that our work not only sheds light on the impact of dynamic presentation of cell adhesive ligands on cellular behaviors, which should be taken into consideration for designing novel biomaterials, but also formulate an effective noncontact strategy that enables further investigation on the mechanobiological mechanisms underlying such cellular responses.

C-1027 is a chromoprotein enediyne antitumor antibiotic produced by Streptomyces globisporus. In the last step of biosynthesis of the (S)-3-chloro-5-hydroxy-β-tyrosine moiety of the C-1027 enediyne chromophore, SgcE6 and SgcC compose a two-component monooxygenase that hydroxylates the C-5 position of (S)-3-chloro-β-tyrosine. This two-component monooxygenase is remarkable for two reasons. (i) SgcE6 specifically reacts with FAD and NADH, and (ii) SgcC is active with only the peptidyl carrier protein (PCP)-tethered substrate. To address the molecular details of substrate specificity, we determined the crystal structures of SgcE6 and SgcC at 1.66 and 2.63 Å resolution, respectively. SgcE6 shares a similar β-barrel fold with the class I HpaC-like flavin reductases. A flexible loop near the active site of SgcE6 plays a role in FAD binding, likely by providing sufficient space to accommodate the AMP moiety of FAD, when compared to that of FMN-utilizing homologues. SgcC shows structural similarity to a few other known FADH2-dependent monooxygenases and sheds light on some biochemically but not structurally characterized homologues. The crystal structures reported here provide insights into substrate specificity, and comparison with homologues provides a catalytic mechanism of the two-component, FADH2-dependent monooxygenase (SgcE6 and SgcC) that catalyzes the hydroxylation of a PCP-tethered substrate.

Ten eudesmanolides (1-10) including five new ones (1-4 and 6) were isolated from the whole plant of Wedelia trilobata (L.) Hitchc., a notoriously invasive weed in South China. As main constituents of W. trilobata, eight of these eudesmanolides were tested for their antitobacco mosaic virus (TMV) activities by the conventional half-leaf and leaf-disk method along with Western blot analysis. All of the tested compounds, at 10 μg/mL, showed strong antiviral activities in the pretreated tobacco plants with inhibition rates ranging from 46.7% to 76.5%, significantly higher than that of the positive control, ningnanmycin (13.5%). Their potential of inducing systemic acquired resistance (SAR) was also evaluated, and compounds 1 and 8 showed excellent induction activities. Furthermore, it was found that different concentrations of compound 1 promoted phenylalanine ammonia-lyase (PAL) activity in tobacco plants. To our knowledge, this is the first report that eudesmanolides could induce resistance in tobacco plants against the viral pathogen TMV.