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Precise diagnostic approaches have great potential in cancer intervention and prognosis. Although diverse DNA nanoprobes have been reported for tumor diagnosis, precise tumor imaging in vivo still ...

Enlightened from our previous work of structural simplification of quinine and innovative application of natural products against phytopathogenic fungi, lead structure 2,8-bis(trifluoromethyl)-4-quinolinol (3) was selected to be a candidate and its diversified design, synthesis, and antifungal evaluation were carried out. All of the synthesized compounds Aa1-Db1 were evaluated for their antifungal activity against four agriculturally important fungi, Botrytis cinerea, Fusarium graminearum, Rhizoctonia solani, and Sclerotinia sclerotiorum. Results showed that compounds Ac3, Ac4, Ac7, Ac9, Ac12, Bb1, Bb10, Bb11, Bb13, Cb1. and Cb3 exhibited a good antifungal effect, especially Ac12 had the most potent activity with EC50 values of 0.52 and 0.50 μg/mL against S. sclerotiorum and B. cinerea, respectively, which were more potent than those of the lead compound 3 (1.72 and 1.89 μg/mL) and commercial fungicides azoxystrobin (both >30 μg/mL) and 8-hydroxyquinoline (2.12 and 5.28 μg/mL). Moreover, compound Ac12 displayed excellent in vivo antifungal activity, which was comparable in activity to the commercial fungicide boscalid. The preliminary mechanism revealed that compound Ac12 might cause an abnormal morphology of cell membranes, an increase in membrane permeability, and release of cellular contents. These results indicated that compound Ac12 displayed superior in vitro and in vivo fungicidal activities and could be a potential fungicidal candidate against plant fungal diseases.

Chemical proteomics is widely used for the global investigation of protein activity and binding of small molecule ligands. Covalent probe binding and inhibition are assessed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to gain molecular information on targeted proteins and probe-modified sites. The identification of amino acid sites modified by large complex probes, however, is particularly challenging because of the increased size, hydrophobicity, and charge state of peptides derived from modified proteins. These studies are important for direct evaluation of proteome-wide selectivity of inhibitor scaffolds used to develop targeted covalent inhibitors. Here, we disclose reverse-phase chromatography and MS dissociation conditions tailored for binding site identification using a clickable covalent kinase inhibitor containing a sulfonyl-triazole reactive group (KY-26). We applied this LC-MS/MS strategy to identify tyrosine and lysine sites modified by KY-26 in functional sites of kinases and other ATP-/NAD-binding proteins (>65 in total) in live cells. Our studies revealed key bioanalytical conditions to guide future chemical proteomic workflows for direct target site identification of complex irreversible probes and inhibitors.

Inspired by natural 2-quinolinecarboxylic acid derivatives, a series of quinoline compounds containing acylhydrazine, acylhydrazone, sulfonylhydrazine, oxadiazole, thiadiazole, or triazole moieties were synthesized and evaluated for their fungicidal activity. Most of these compounds exhibited excellent fungicidal activity in vitro. Significantly, compound 2e displayed the superior in vitro antifungal activity against Sclerotinia sclerotiorum, Rhizoctonia solani, Botrytis cinerea, and Fusarium graminearum with the EC50 values of 0.39, 0.46, 0.19, and 0.18 μg/mL, respectively, and were more potent than those of carbendazim (EC50, 0.68, 0.14, >100, and 0.65 μg/mL, respectively). Moreover, compound 2e could inhibit spore germination of F. graminearum. Preliminary mechanistic studies showed that compound 2e could cause abnormal morphology of cell walls and vacuoles, loss of mitochondrion, increases in membrane permeability, and release of cellular contents. These results indicate that compound 2e displayed superior fungicidal activities and could be a potential fungicidal candidate against plant fungal diseases.

The interfacial electronic and geometric effects behind the size effect are crucial in determining the catalytic performance of supported metal catalysts, whereas they remain still unknown for most of important heterogeneous catalytic reactions such as water-gas shift reaction (WGSR). In this work, we report a profound size effect in five Pt/CeO2 catalysts among Pt single atoms, sub-nanoclusters (ca. 0.8 nm) and nanoparticles (3.8–9.3 nm) for the WGSR. The catalyst with about 3.8 nm Pt nanoparticles had the highest activity, superior to the other four Pt/CeO2 catalysts. Ptδ+-OV-Ce3+ species served as the interfacial active sites, wherein the carboxyl pathway seemed more preferred than the formate route, and favored high activity. Such high activity and pathway preference are due to both of the electronic and geometric effects. On the one hand, the electronic metal-support interaction (EMSI) modulated by the metal deposit size tunes the activation of the CO adsorbed on Pt sites. On the other hand, the abundant interfacial oxygen vacancies for the geometric effect of providing the active sites to activate and dissociate H2O.

In this work, copper hexacyanocobaltate was electro-deposited at amino-graphene-coated indium-tin-oxide glass to form multifunctional heterogeneous catalyst (CuCoG/ITO), which was confirmed by field emission scanning microscope, infrared spectra, X-ray diffraction, and electro-chemistry techniques. A novel heterogeneous photo-electro-Fenton-like system was established using CuCoG/ITO as an air-diffusion electrode, in which hydrogen peroxide (H2O2) and hydroxyl radical (•OH) could be simultaneously generated by air O2 reduction. The productive rate of •OH could reached to 70.5 μmol h-1 at - 0.8 V with 300 W visible light irradiation at pH 7.0, 0.1 M PBS. Levofloxacin could be quickly degraded at CuCoG/ITO during heterogeneous photo-electro-Fenton process in neutral media with a first-order kinetic constant of 0.49 h-1.

Thus far, all the stable singlet carbenes consist of a center carbon atom, and electron donor or withdrawing substituents with heteroatoms, such as, N, P, O, and S. Herein, carbene was generated by the lithium–bromine exchange reaction and used to functionalize C60. The reaction mechanisms, including the lithium–bromine exchange and carbene addition reactions, were studied in detail with ab initio density functional theory. The interaction between LiBr and the carbon atom was first characterized as a mainly ionic interaction, combined with the coordinate interaction and hyperconjugation. Then, a novel stable singlet fullerene carbene without the heteroatom, was primitively generated via lithium–bromine exchange and carbene addition reactions; it exhibited a remarkable stability with high singlet–triplet energy gap and HOMO–LUMO energy gap. This computational survey indicates that fullerene carbene will be a potential ligand in the coordinated compounds, and is useful for further functionalization and applications of fullerenes. Furthermore, theoretical results show that the lithium–bromine exchange reaction would be a powerful and feasible tool to functionalize the double bonds in some aliphatic and aromatic olefins, including anthracene, benzene, propylene, ethylene, 1-butene, propanal, and 3-pentanone. Based on the carbene reaction mechanisms and nature of corresponding bonds in their products, two indexes, bond length and the hybridization state of atoms, were suggested to distinguish the carbene addition and insertion to the double bond.

Density functional theory (DFT) and a periodic slab model were used to study the geometric structure, electronic structure and dehydrogenation mechanism of ammonia adsorption on the MoN(0001) surface. The surface energy calculation results indicated that MoN(0001) terminated by N was the most stable surface. The NH3 molecule was preferably adsorbed at the top position through its lone pair electrons, while the most stable adsorption sites of NH2 and H were triple hcp sites, and NH and N were adsorbed at triple fcc sites. The results of transition state calculations showed that the decomposition reaction of ammonia mainly takes place through a step-by-step dehydrogenation mechanism of N2H4, and the compound desorption reaction of nitrogen was the rate limiting step of the whole reaction. The results of electronic structure calculations showed that the N2H4 molecule was adsorbed on the surface through the mixture of the 2Pz orbital of N and the 4dz2 orbital of Mo. With the progress of dehydrogenation, the charge transfer phenomenon became more and more obvious. It could be predicted that the charge transfer between the adsorbate and substrate played an important role in the catalytic process of accelerating the dehydrogenation of NH3.

Sulfur electrophiles constitute an important class of covalent small molecules that have found widespread applications in synthetic chemistry and chemical biology. Various electrophilic scaffolds, including sulfonyl fluorides and arylfluorosulfates as recent examples, have been applied for protein bioconjugation to probe ligand sites amenable for chemical proteomics and drug discovery. In this review, we describe the development of sulfonyl-triazoles as a new class of electrophiles for sulfur–triazole exchange (SuTEx) chemistry. SuTEx achieves covalent reaction with protein sites through irreversible modification of a residue with an adduct group (AG) upon departure of a leaving group (LG). A principal differentiator of SuTEx from other chemotypes is the selection of a triazole heterocycle as the LG, which introduces additional capabilities for tuning the sulfur electrophile. We describe the opportunities afforded by modifications to the LG and AG alone or in tandem to facilitate nucleophilic substitution reactions at the SO2 center in cell lysates and live cells. As a result of these features, SuTEx serves as an efficient platform for developing chemical probes with tunable bioactivity to study novel nucleophilic sites on established and poorly annotated protein targets. Here, we highlight a suite of biological applications for the SuTEx electrophile and discuss future goals for this enabling covalent chemistry.

Carbon materials based on different hybridization of carbon atoms have drawn great attention because of their unique configurations and physical and chemical properties. Here, a previously unknown 2D carbon allotrope named L-2Gy, graphene-like carbon matryoshka graphynes (Gy) with two alkynyls (C[triple bond, length as m-dash]C) inserted into the three-fold carbon atoms of graphene, has been constructed with considerable thermal, dynamical, and mechanical stability by using ab initio density functional theory. With the increasing number of alkynyls between the three-fold carbon atoms of graphene, the stability of Gy will seriously decrease. L-2Gy has a fascinating chemical bond environment consisting of sp- and sp2-hybridized carbon atoms, and delocalized π electrons derived from the 27 three-center two-electron π bonds. This particular electronic structure plays a vital role in chemically stabilizing L-2Gy. The electronic band structure reveals the semi-metallic features of L-2Gy mainly contributed by the px/z orbitals of carbon atoms. Furthermore, compared with the acknowledged catalysts for the hydrogen evolution reaction (HER), L-2Gy, as a 2D carbon allotrope, shows excellent catalytic activity for the HER.

The present study aimed to establish an animal model of the osteofascial compartment syndrome (OFCS) in hind legs of rabbits, and to repair an early nerve injury using the self-polymerized peptide nanofiber material that was laced with nerve growth factors (NGFs). An animal model of the compartment syndrome was established using the tourniquet method. The intrafascial pressure of rabbit legs at different time points was measured after successful modeling. Western blotting was used to assess the proliferation of nerve cells after injury. After incision and decompression, the repair group was implanted with the self-polymerized peptide nanofiber material in combination with NGFs at the nerve injury sites for repair of the injured nerves. Rabbit hind leg nerve specimens were collected from experimental rabbits (control group), rabbits 5 days after injury (unrepaired group), and rabbits 5 days after injury (repaired group), and hematoxylin-eosin (HE) staining analysis and immunofluorescence experiments were also performed. After loosening the tourniquet, the intra-fascial pressure peaked on the 1st day after injury and then gradually decreased. A western blot showed low expression of the proliferating cell nuclear antigens (PCNAs) in the control group, as it began to increase 4 h after injury, peaked 5 days after injury (P < 0.05), and then gradually decreased. Meanwhile, the tissue morphology of the repair group was better than that of the non-repair group. Fluorescence double labeling results showed that the proliferation of nerve cells in the repair group increased significantly, and S100 and DAPI co-labeling intensities increased significantly. The early application of the self-polymerizing peptide nanofiber material combined with NGF exhibited evident effects on the nerve injury treatment in the osteofascial compartment syndrome.

Phytopathogenic fungal infections have become a major threat to agricultural production, food security, and human health globally, and novel antifungal agents with simple chemical scaffolds and high efficiency are needed. In this study, we designed and synthesized 38 8-hydroxyquinoline metal complexes and evaluated their antifungal activities. The results showed that most of the tested compounds possessed remarkable in vitro antifungal activity. Especially, compound 1e exhibited the highest antifungal potency among all target compounds, with EC50 values of 0.0940, 0.125, 2.95, and 5.96 μg/mL, respectively, against Sclerotinia sclerotiorum, Botrytis cinerea, Fusarium graminearum, and Magnaporthe oryzae. Preliminary mechanistic studies had shown that compound 1e might cause mycelial abnormalities of S. sclerotiorum, cell membrane permeability changes, leakage of cell contents, and inhibition of sclerotia formation and germination. Moreover, the results of in vivo antifungal activity of compound 1e against S. sclerotiorum showed that 1e possessed higher curative effects than that of the positive control azoxystrobin. Therefore, compound 1e is expected to be a novel leading structure for the development of new antifungal agents.

Phenolic glycosides are the major secondary metabolites of plants, which exhibit multiple attractive biological and pharmacological activities. In this study, we developed a new and efficient metho...

Four-electron transfer from U to the fullerene cage commonly exists in U@C2n (2n < 82) so far, while four- and three-electron transfers, which depend on the cage isomers, simultaneously occur in U@...

Poisson’s ratio is one of the fundamental features of materials, reflecting the transverse strain response to the applied certain axial strain. The materials with a negative Poisson’s ratio, also known as auxetic materials, are rare in nature and attract lots of research interest because of their unusual mechanical behavior and extensive applications in mechanical nanodevices. Here, we proposed and studied a novel hyperbolic two-dimensional graphene-like structure (GLS) showing a negative Poisson’s ratio behavior by first-principles calculation. The thermodynamic, dynamic, lattice dynamic, and mechanical stabilities of the GLS were carefully studied. In addition, we also explored the electronic structure, mechanical characteristics, and optical-electronic characteristics. The GLS not only displays a negative Poisson’s ratio in certain directions but also shows low-gap semiconductor characteristics and superior electronic conductivity. It is a potential sunscreen material because of the outstanding reflection and absorption for ultraviolet and infrared light.

The microstructure and segregation of 7N01 aluminum alloy microalloyed with Er and Zr before and after homogenization process at 470 °C for 24 h have been investigated using transmission electron microscope (TEM), and scanning electron microscope (SEM) equipped with energy dispersive X-ray spectroscope (EDS) and transmission electron detecter (STEM). SEM images and EDS line scan results showed that there were dendritic segregation of Mg and Zn and micron-sized primary phases along dendrites in the as-cast alloy. The primary phases were mainly Al2Mg3Zn3 containing Al, Zn, Mg and Mn. And a small amount of primary phases were the particles containing Al, Zn, Mg, Mn, Cr and Er and the particles containing Al, Zn, Mg, Er, Mn, Fe and Cr. After homogenization at 470°C for 24 h, dendritic segregation of Mg and Zn was eliminated, Al2Mg3Zn3 and the particles containing Al, Zn, Mg and Mn were basically dissolved. The particles containing Al, Zn, Mg, Mn, Cr and Er and the particles containing Al, Zn, Mg, Er, Mn, Fe and Cr remained. Meanwhile, TEM and STEM images showed that a large number of secondary phases appeared after the homogenization, which were mainly distributed in the inter-dendrite area. EDS results showed that the block-shaped and rod-shaped phases with the width of 10-70 nm and length of 100-500 nm were the particles containing Al, Cr and Mn or Al, Mg, Cr and Mn, and the ellipsoid secondary phase with the size of 50-100 nm was MgZn2.

Tuning reactivity of sulfur electrophiles is key for advancing click chemistry and chemical probe discovery. To date, activation of the sulfur electrophile for protein modification has been ascribed principally to stabilization of a fluoride leaving group (LG) in covalent reactions of sulfonyl fluorides and arylfluorosulfates. We recently introduced sulfur-triazole exchange (SuTEx) chemistry to demonstrate the triazole as an effective LG for activating nucleophilic substitution reactions on tyrosine sites of proteins. Here, we probed tunability of SuTEx for fragment-based ligand discovery by modifying the adduct group (AG) and LG with functional groups of differing electron-donating and -withdrawing properties. We discovered the sulfur electrophile is highly sensitive to the position of modification (AG versus LG), which enabled both coarse and fine adjustments in solution and proteome activity. We applied these reactivity principles to identify a large fraction of tyrosine sites (~30%) on proteins (~44%) that can be liganded across >1500 probe-modified sites quantified by chemical proteomics. Our proteomic studies identified non-catalytic tyrosine- and phosphotyrosine-sites that can be liganded by SuTEx fragments, with site specificity, in lysates and live cells to disrupt protein function. Collectively, we describe SuTEx as a versatile covalent chemistry with broad applications for chemical proteomics and protein ligand discovery.

Multimetallic nanoframes (NFs) with large specific area and unsaturated coordination sites showed superior catalytic performance in electrochemical catalysis. Herein, we synthesized robust trimetallic PtRuCu NFs with high shape selectivity via preferential etching of Cu in PtRuCu nanoparticles (NPs) with nitrosonium tetrafluoroborate (BF4NO). As far as we know, this is the first time that BF4NO has been used as an etching reagent. PtRuCu NF/C exhibited superior mass activity and specific area activity over commercial Pt/C towards the methanol oxidation reaction (MOR) due to the large specific area, high-density low-coordinated sites of the frame nanostructures and the synergistic effect of the trimetallics. Moreover, PtRuCu NFs/C also showed higher catalytic activity than the similar NFs obtained with acetic acid (HAc) as the etching reagent. We attributed the better performance to the fact that BF4NO was not only an etching-agent but also a ligand exchange reagent that could remove the olamine ligands on the catalyst surface, thus releasing more catalytic sites to improve the catalytic performance.

The question of how a racemate can be selectively converted into a single enantiomer is a challenging and fundamental scientific issue of chemistry. Recently, an unprecedented catalytic enantioselective photochemical transformation that enables the deracemization of chiral allene 3-(3,3-dimethyl-1-buten-1-ylidene)-2-piperidinone (rac-1a, 1a/ent-1a = 50/50, 0% ee) and their analogues was realized via a light-driven process in the presence of photosensitizer thioxanthone 2 by Bach's group (A. Holzl-Hobmeier, A. Bauer, A. V. Silva, S. M. Huber, C. Bannwarth and T. Bach, Catalytic deracemization of chiral allenes by sensitized excitation with visible light, Nature, 2018, 564, 240–243). However, the deracemization mechanism has not been explored deeply either in experiment or in theory. In this work, the photosensitized deracemization mechanism was theoretically investigated by using a density functional theory (DFT) method. The calculation results show that, firstly, photosensitizer 2 (S0 state) is vertically excited to its S2 state under irradiation at the wavelength of λ = 420 nm. Then, a rapid internal conversion of S2 → S1 would occur near the crossing point during the relaxation of the S2 state. Consequently, the T1 state of photosensitizer 2 can be easily formed from its S1 state via an intersystem crossing. After that, a Dexter-type energy transfer from the T1 of photosensitizer 2 to the S0 state of ent-1a would take place, resulting in the S0 state of photosensitizer 2 and T1 of ent-1a. Finally, the T1 of ent-1a can cross the triplet potential surface and convert to a transition state between ent-1a and 1a of the ground state S0, and ultimately form 1a/ent-1a (50/50).

Efficient photocatalytic conversion of CO2 into energy-rich chemicals is of great significance for both environmental conservation and alleviating the energy crisis. However, convenient synthesis of low-cost, durable and eco-friendly photocatalysts with a novel morphology or structure for highly selective photocatalytic CO2 reduction remains a challenge. Herein, Co3O4 hierarchical nanosheets were synthesized by calcination of novel cobalt metal-organic framework (MOF) nanosheets prepared by a facile oil bath method. In such Co MOF nanosheets, 1,4-naphthalenedicarboxylic acid was chosen as the organic linker, rather than the commonly used 2-methylimidazole for ZIF-67. After thermal treatment in air, the obtained Co3O4 inherited the 2D morphology of its MOF template and evolved into hierarchical nanosheets which were composed of small nanoparticles. Benefiting from the large surface area, abundant mesoporous structure and good capability towards the separation and transfer of photo-generated charge carriers induced by less internal oxygen vacancies, the Co3O4 hierarchical nanosheets showed a CO generation rate of 39.70 μmol h-1 in visible-light photocatalytic CO2 reduction, which was superior to that of Co3O4 nanoparticles and commercial Co3O4. What's more, a CO selectivity of 77.3% was achieved, which is among the highest of cobalt-based spinel oxide photocatalysts for CO2 conversion.

Bone mesenchymal stem cells (BMSCs) are related to fracture healing. In this paper, we study the effect of Nerve growth factors (NGF) on osteogenic differentiation of BMSCs and related mechanisms. The results indicated that NGF has a dose-dependent promotion effect on osteogenic differentiation of BMSCs, ALP activity, and protein expression of OPN, Osterix, Runx2, COL1A1. Further investigation showed that NGF enhanced the expression of TGF-β and BMP9, and increased phosphorylation of Smad and p38 MAPK. Moreover, block of BMP and TGF-β pathway reduced the promoted effect of NGF on osteogenic differentiation. The data revealed that NGF increased osteogenic differentiation through increased phosphorylation of Smad and MAPK p38 by regulating TGF-β and BMP pathway in BMSCs. Thus, NGF may be used in bone growth and fracture healing by improving osteogenic differentiation of BMSCs.

C60 was profoundly revealed as being an excellent container for stabilizing unusual Ga(I). Differently sized fullerenes performed as flexible tools for tuning the oxidation states of gallium. A fluoridation strategy was proposed for the further stabilization of Ga@Ih(1812)-C60. This will facilitate exploiting more features and applications involving rarely used Ga(I ).

Thermodynamically stable La@C2v(24 107)-C78, La@D3h(24 109)-C78, La@C1(22 595)-C78, Ce@D3h(24 109)-C78, Sm@C2v(24 107)-C78, and Sm@D3h(24 109)-C78 based on density functional theory and statistical thermodynamic analysis are studied in theory. C1(22 595)-C78, violating the isolated pentagon rule, is a second novel isomer stabilized by encaging a La atom. In addition, three- and two-electron transfers occur in M@C78 (M = La and Ce) and Sm@C78, respectively. Although there are two electrons transferred from Sm to C78, these electrons transferred to the surface of C2v(24 107)-C78 are unpaired. Thus, the surface of the endohedral metallofullerene, Sm@C2v(24 107)-C78, firstly displays diradical characteristics. Notably, the spin states of the two electrons transferred from Sm to D3h(24 109)-C78 are different from those on C2v(24 107)-C78, leading to different spin ground states. Furthermore, the natural bond orders and bond critical point analyses on thermodynamically stable M@C78 (M = La, Ce, and Sm) reveal that the distance between the metal and carbon atom plays an important role in the covalent interaction between the inner metal atoms and C78. Because of the strong ionic interaction, the studies on the magnetic character of M@C78 (M = La, Ce, and Sm) show that Sm@C78 is a promising candidate for single-molecule magnets with high isotropic susceptibility. The infrared spectra were simulated to facilitate further experimental study on the stable M@C78 (M = La, Ce, and Sm). We believe that this work will provide good guidance and assistance for the further study of mono-metallofullerenes and coordination compounds in both experiment and theory.

Fullerenes are important zero-dimensional materials in photoelectric, antioxidant, pharmaceutical, and single-molecular-magnet fields, but the fullerene-formation mechanism has been elusive since t...

Covalent probes serve as valuable tools for global investigation of protein function and ligand binding capacity. Despite efforts to expand coverage of residues available for chemical proteomics (e.g. cysteine and lysine), a large fraction of the proteome remains inaccessible with current activity-based probes. Here, we introduce sulfur-triazole exchange (SuTEx) chemistry as a tunable platform for developing covalent probes with broad applications for chemical proteomics. We show modifications to the triazole leaving group can furnish sulfonyl probes with ~5-fold enhanced chemoselectivity for tyrosines over other nucleophilic amino acids to investigate, for the first time, more than 10,000 tyrosine sites in lysates and live cells. We discover that tyrosines with enhanced nucleophilicity are enriched in enzymatic, protein-protein interaction, and nucleotide recognition domains. We apply SuTEx as a chemical phosphoproteomics strategy to monitor activation of phosphotyrosine sites. Collectively, we describe SuTEx as a biocompatible chemistry for chemical biology investigations of the human proteome.

Prolonged cold ischemia (CI) is a risk factor for acute kidney injury (AKI) after kidney transplantation (KT). AKI is an abrupt and rapid reduction in renal function due to multi-factors, including inflammation, oxidative stress and apoptosis. V-set immunoglobulin-domain-containing 4 (VSIG4) is a B7 family-related protein and specifically expressed in resting tissue-resident macrophages to mediate various cellular events. In the study, we attempted to explore the effects of VSIG4 on CI/KT-induced AKI in a mouse model. Our results showed that VSIG4 expression was markedly down-regulated in serum of kidney transplant recipients with acute rejection, and in renal tissues of cold ischemia-reperfusion (IR)-operated mice with AKI, which was confirmed in murine macrophages stimulated by oxygen glucose deprivation/reoxygenation (OGD/R). We then found that exogenous VSIG4 markedly ameliorated histological changes in kidney of CI/KT mice by suppressing inflammation and apoptosis through restraining nuclear factor-κB (NF-κB) and Caspase-3 activation, respectively. Oxidative stress and reactive oxygen species (ROS) accumulation in renal tissues were also mitigated by exogenous VSIG4 in CI/KT mice through improving nuclear factor-erythroid 2 related factor 2 (Nrf2) nuclear expression. The inhibitory effects of VSIG4 on inflammation, ROS generation and cell death were confirmed in OGD/R-treated macrophages, which further ameliorated oxidative damage and apoptosis in podocytes. More in vivo and in vitro studies showed that CI/KT- and OGD/R-induced AKI was further accelerated by VSIG4 knockdown. Mechanistically, VSIG4 directly interacted with AKT, and AKT activation was necessary for VSIG4 to govern all these above mentioned cellular processes. Collectively, our findings demonstrated that VSIG4 could mitigate AKI in a CI/KT mouse model, and we identified VSIG4/AKT axis as a promising therapeutic target for the treatment of the disease.

Background/aim Docetaxel has been widely used in metastatic Castration-resistant Prostate Cancer (mCRPC) patients for decades. The purpose of the study was to evaluate the efficacy of docetaxel rechallenge in patients with mCRPC. Patients and methods We retrospectively compared patients who had received either first-line docetaxel and rechallenge after Androgen Receptor-axis Targeted therapies (ARAT), to those without rechallenge docetaxel. Multivariate cox-regression analysis was used to evaluate survival. Results Out of the 204 patients with mCRPC enrolled in the study, 24 patients received docetaxel rechallenge and 180 did not. The median overall survival was 50.11 months in the rechallenge group, as compared to 26.36 months in the non-rechallenge group (p of log rank=0.044). In the multivariate model, doxetaxel rechallenge was an independent risk factor for overall survival [hazard ratio (HR)=0.59, 95% confidence interval (CI)=0.32-0.99], together with the performance status score 2 (HR=2.46, 95%CI=1.32-4.58), hormone-sensitive state duration (HR=0.99, 95%CI=0.99-0.999), liver (HR=1.90, 95%CI=1.04-3.47) and brain metastases (HR=2.23, 95%CI=1.26-5.46). The advantage of rechallenge was addressed in the androgen receptor-axis-targeted (ARAT) non-responsive patients (HR=0.36, 95%CI=0.17-0.78). Adverse events were at 29.17% with Grade 3/4 neutropenia and at 20.83% with Grade 1/2 neutropenia in the docetaxel rechallenge group. Conclusion The docetaxel rechallenge improved survival in patients with mCRPC failure of first-line docetaxel and subsequent abiraterone acetate or enzalutamide. Independent predictive factors for overall survival included i) the performance status, ii) hormone-sensitive state duration, iii) liver and iv) brain metastases. Patients non-responsive to ARATs will benefit from docetaxel rechallenge with regards to overall survival.

Proinflammatory cytokine production following infection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is associated with poor clinical outcomes. Like SARS CoV-1, SARS CoV-2 enters host cells via its spike protein, which attaches to angiotensin-converting enzyme 2 (ACE2). As SARS CoV-1 spike protein is reported to induce cytokine production, we hypothesized that this pathway could be a shared mechanism underlying pathogenic immune responses. We herein compared the capabilities of Middle East Respiratory Syndrome (MERS), SARS CoV-1 and SARS CoV-2 spike proteins to induce cytokine expression in human peripheral blood mononuclear cells (PBMC). We observed that only specific commercial lots of SARS CoV-2 induce cytokine production. Surprisingly, recombinant SARS CoV-2 spike proteins from different vendors and batches exhibited different patterns of cytokine induction, and these activities were not inhibited by blockade of spike protein-ACE2 binding using either soluble ACE2 or neutralizing anti-S1 antibody. Moreover, commercial spike protein reagents contained varying levels of endotoxin, which correlated directly with their abilities to induce cytokine production. The lipopolysaccharide (LPS) inhibitor, polymyxin B, blocked this cytokine induction activity. In addition, SARS CoV-2 spike protein avidly bound soluble LPS in vitro, rendering it a cytokine inducer. These results not only suggest caution in monitoring the purity of SARS CoV-2 spike protein reagents, but they indicate the possibility that interactions of SARS CoV-2 spike protein with LPS from commensal bacteria in virally infected mucosal tissues could promote pathogenic inflammatory cytokine production.

Bimetal-S-O composites have been rarely researched in electrochemical reduction of CO2 . Now, an amorphous Ag-Bi-S-O decorated Bi0 catalyst derived from Ag0.95 BiS0.75 O3.1 nanorods by electrochemical pre-treatment was used for catalyzing eCO2 RR, which exhibited a formate FE of 94.3 % with a formate partial current density of 12.52 mA cm-2 at an overpotential of only 450 mV. This superior performance was attributed to the attached amorphous Ag-Bi-S-O substance. S could be retained in the amorphous region after electrochemical pre-treatment only in samples derived from metal-S-O composites, and it would greatly enhance the formate selectivity by accelerating the dissociation of H2 O. The existence of Ag would increase the current density, resulting in a higher local pH, which made the role of S in activating H2 O more significantly and suppressed H2 evolution more effectively, thus endowing the catalyst with a higher formate FE at low overpotentials.

The thermodynamic and dynamic stabilities of Sc3 X@C80 (X = C, N, and O) are explored via density functional theory combined with statistical thermodynamic analysis and ab initio molecular dynamics. It is the first time to comprehensively consider the effect of nonmetal atoms on trimetallic endohedral clusterfullerenes. Relative to Sc3 X@Ih (31924)-C80 (X = N and O) with general six-electron transfer, an intriguing electronic structure of unexplored Sc3 C@D5h (31923)-C80 with thermodynamic and dynamic stabilities is clearly disclosed. Natural bond orbitals and charge decomposition analysis simultaneously suggest that one unpaired electron appears on the cage for neutral Sc3 C@D5h (31923)-C80 , which could be prospectively stabilized by effective exohedral derivatization and ionization in the future. Moreover, isoelectronic endohedral clusterfullerenes, (Sc3 C@C80 )- , Sc3 N@C80 , and (Sc3 O@C80 )+ , are also uniquely taken into account. The geometries, electronic structures, reactivities, and reactive sites of isoelectronic species are examined, and it turns out that all the three isoelectronic species would rather electrophilic than nucleophilic reactions. © 2019 Wiley Periodicals, Inc.

Mixed-metal uranium-based endohedral clusterfullerenes, Sc2UX@C80 (X = C, N), which were recently reported in experiments, have been investigated considering heptagon-containing isomers by density functional theory calculations in conjunction with statistical thermodynamic analysis. The triplet Sc2UC@Ih(31924)-C80 and quartet Sc2UN@Ih(31924)-C80, named after the spiral number (31924), are found to be thermodynamically stable and satisfy aromaticity rules. Furthermore, the restricted movements of the Sc2UX (X = C, N) cluster in Ih(31924)-C80 have been demonstrated via ab initio molecular dynamics simulations. The six-electron transfer from the inner cluster to the cage results in the electronic structures (Sc2UX)6+@C806– (X = C, N), which were also confirmed by natural bond orbital analysis. On the basis of the frontier molecular orbitals, the oxidation states of uranium in Sc2UC@C80 and Sc2UN@C80 are +IV and +III, respectively, with residual electrons in 5f orbitals of U. The chemical bond between U and C...

Background/aim Abiraterone (AA) and enzalutamide (ENZ) were introduced in Taiwan since 2012 for the treatment of patients with post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). This study aims to retrospectively compare the efficacy of the two regimens. Materials and methods The study cohort consisted of 77 mCRPC patients previously treated with docetaxel and subsequently with AA (n=63, the AA group) or ENZ (n=13, the ENZ group), all treated in our hospital. Clinical parameters of the two groups were compared to determine differences between pre-treatment variables and treatment outcomes. Results Sixty-four patients received AA and 13 received ENZ, with a median 18.2 vs. 14.5 months follow-up (p=0.434). Prostate-specific antigen (PSA) response >50% was 31 (48.4%) in AA and 9 (69.2%) in ENZ (p=0.171), while PSA response >90% was 16 (25%) in AA and 5 (38.5%) in ENZ (p=0.32). The median progression-free survival (PFS) was 7.3 (95%CI=4.796-9.804) months in AA and 9.5 months (95%CI=5.743-13.257) in ENZ (p of log rank=0.766). The median overall survival (OS) from second-line hormone treatment was 30.2 months in AA group and 16.2 months in ENZ group (p of log rank=0.734). Neither the uni- nor the multi-variate COX-regression analysis distinguished any advantage of the two-drug regimen in terms of PFS or OS. Metastasis volume (HR=3.032, 95%CI=1.281-7.178, p=0.012) and nadir PSA (HR=1.000, 95%CI=1.000-1.001, p=0.010) were shown as independent risk factors for the survival of AA/ENZ-treated patients. Conclusion AA and ENZ had a similar efficacy in treating post-docetaxel mCRPC patients. Metastatic volume and nadir PSA were independent risk factors of these patients in predicting their disease-specific survival and overall survival.

Significance Strigolactone plays a vital role in plant growth and development, but its response genes remain to be identified. In this study, we found that cytokinin content is markedly increased in the strigolactone signaling mutant d53, and that OsCKX9, which encodes a cytokinin oxidase to catalyze the degradation of cytokinin, functions as a primary strigolactone-responsive gene to regulate rice tillering, plant height, and panicle size, likely via a secondary response gene, OsRR5, which encodes a cytokinin-inducible rice type-A response regulator, demonstrating that strigolactone regulates rice shoot architecture through enhanced cytokinin catabolism by modulating OsCKX9 expression., Strigolactones (SLs), a group of terpenoid lactones derived from carotenoids, are plant hormones that control numerous aspects of plant development. Although the framework of SL signaling that the repressor DWARF 53 (D53) could be SL-dependently degraded via the SL receptor D14 and F-box protein D3 has been established, the downstream response genes to SLs remain to be elucidated. Here we show that the cytokinin (CK) content is dramatically increased in shoot bases of the rice SL signaling mutant d53. By examining transcript levels of all the CK metabolism-related genes after treatment with SL analog GR24, we identified CYTOKININ OXIDASE/DEHYDROGENASE 9 (OsCKX9) as a primary response gene significantly up-regulated within 1 h of treatment in the wild type but not in d53. We also found that OsCKX9 functions as a cytosolic and nuclear dual-localized CK catabolic enzyme, and that the overexpression of OsCKX9 suppresses the browning of d53 calli. Both the CRISPR/Cas9-generated OsCKX9 mutants and OsCKX9-overexpressing transgenic plants showed significant increases in tiller number and decreases in plant height and panicle size, suggesting that the homeostasis of OsCKX9 plays a critical role in regulating rice shoot architecture. Moreover, we identified the CK-inducible rice type-A response regulator OsRR5 as the secondary SL-responsive gene, whose expression is significantly repressed after 4 h of GR24 treatment in the wild type but not in osckx9. These findings reveal a comprehensive plant hormone cross-talk in which SL can induce the expression of OsCKX9 to down-regulate CK content, which in turn triggers the response of downstream genes.

Sulfur (S) and Nitrogen (N) metabolisms in plants are interacted and it is known that S deficiency decrease N absorption and metabolism. In leguminous plants S deficiency also decreases N2 fixation by rhizobia in the nodules. Deep placement of a controlled-release N fertilizer is a good method to provide nitrogen to soybean without inhibiting N2 fixation; thus, it was hypothesized that this method is able to provide nitrogen effectively to sulfur-deficient soybean plants. In this study effects of deep placement of coated urea on S-N physicological interaction, growth and productivity in soybean plants were examined using pot experiments. Soybean plants were grown with sulfate concentrations of 30, 100, or 1000 μM, with or without deep placement of coated urea. Shoot weights at the developing stage were not affected by S deficiency. SPAD values of leaves during the flowering stage decreased with S deficiency and increased with the deep placement of coated urea. S deficiency decreased seed weight per plant at the harvesting stage, but this decrease was attenuated by the deep placement of coated urea. N and S content in shoots at the developing stage increased with the deep placement of coated urea, whereas in seeds, only the N content increased. N2 fixation activity based on the relative ureide-N content in xylem sap indicated that the deep placement of coated urea did not inhibit N2 fixation activity at the early flowering stage. Without deep placement of coated urea, the relative ureide-N content decreased under S deficiency at the seed filling stage. These results suggest that the deep placement of coated urea is an efficient method to supply N to support soybean yield under S deficiency. Abbreviations: Deep+: with deep placement of coated urea; Deep–: without deep placement of coated urea