62 results on '"L. Huo"'
Search Results
2. Flexible DNA Nanoclaws Offer Multivalent and Powerful Spatial Pattern-Recognition for Tumor Cells.
- Author
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Chen K, Mao M, Huo L, Wang G, Pu Z, and Zhang Y
- Subjects
- Humans, Cell Line, Tumor, Nanostructures chemistry, Neoplastic Cells, Circulating pathology, Neoplastic Cells, Circulating metabolism, Aptamers, Nucleotide chemistry, Epithelial Cell Adhesion Molecule metabolism, Receptor, ErbB-2 metabolism, DNA chemistry
- Abstract
Multivalent receptor-ligand interactions (RLIs) exhibit excellent affinity for binding when targeting cell membrane receptors with low expression. However, existing strategies only allow for limited control of the valency and spacing of ligands for a certain receptor, lacking recognition patterns for multiple interested receptors with complex spatial distributions. Here, we developed flexible DNA nanoclaws with multivalent aptamers to achieve powerful cell recognition by controlling the spacing of aptamers to match the spatial patterns of receptors. The DNA nanoclaw with spacing-controllable binding sites was constructed via hybrid chain reaction (HCR), enabling dual targeting of HER2 and EpCAM molecules. The results demonstrate that the binding affinity of multivalent DNA nanoclaws to tumor cells is enhanced. We speculate that the flexible structure may conform better to irregularly shaped membrane surfaces, increasing the probability of intermolecular contact. The capture efficiency of circulating tumor cells successfully verified the high affinity and selectivity of this spatial pattern. This strategy will further promote the potential application of DNA frameworks in future disease diagnosis and treatment.
- Published
- 2024
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3. Efficacy and Mechanism of Antibiotic Resistance Gene Degradation and Cell Membrane Damage during Ultraviolet Advanced Oxidation Processes.
- Author
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Wang J, Huo L, Bian K, He H, Dodd MC, Pinto AJ, and Huang CH
- Abstract
Combinations of UV with oxidants can initiate advanced oxidation processes (AOPs) and enhance bacterial inactivation. However, the effectiveness and mechanisms of UV-AOPs in damaging nucleic acids (e.g., antibiotic resistance genes (ARGs)) and cell integrity represent a knowledge gap. This study comprehensively compared ARG degradation and cell membrane damage under three different UV-AOPs. The extracellular ARG (eARG) removal efficiency followed the order of UV/chlorine > UV/H
2 O2 > UV/peracetic acid (PAA). Hydroxyl radical (• OH) and reactive chlorine species (RCS) largely contributed to eARG removal, while organic radicals made a minor contribution. For intracellular ARGs (iARGs), UV/H2 O2 did not remove better than UV alone due to the scavenging of• OH by cell components, whereas UV/PAA provided a modest synergism, likely due to diffusion of PAA into cells and intracellular• OH generation. Comparatively, UV/chlorine achieved significant synergistic iARG removal, suggesting the critical role of the RCS in resisting cellular scavenging and inactivating ARGs. Additionally, flow cytometry analysis demonstrated that membrane damage was mainly attributed to chlorine oxidation, while the impacts of radicals, H2 O2 , and PAA were negligible. These results provide mechanistic insights into bacterial inactivation and fate of ARGs during UV-AOPs, and shed light on the suitability of quantitative polymerase chain reaction (qPCR) and flow cytometry in assessing disinfection performance., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)- Published
- 2024
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4. Divergent Synthesis of Scabrolide A and Havellockate via an exo - exo - endo Radical Cascade.
- Author
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Peng C, Guo Q, Xu GX, Huo L, Wu W, Chen TY, Hong X, and Hu P
- Abstract
Here we report a concise and divergent synthesis of scabrolide A and havellockate, representative members of polycyclic marine natural product furano(nor)cembranoids. The synthesis features a highly efficient exo - exo - endo radical cascade. Through the generation of two rings, three C-C bonds, and three contiguous stereocenters in one step, this remarkable transformation not only assembles the bowl-shaped, common 6-5-5 fused ring system from simple building blocks but also precisely installs the functionalities at desired positions and sets the stage for further divergent preparation of both target molecules. Further studies reveal that the robust and unusual 6- endo radical addition in the cascade is likely facilitated by the rigidity of the substrate.
- Published
- 2024
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5. Piezoelectric Polarization and Sulfur Vacancy Enhanced Photocatalytic Hydrogen Evolution Performance of Bi 2 S 3 /ZnSn(OH) 6 Piezo-photocatalyst.
- Author
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Li N, Zhu B, Huang L, Huo L, Dong Q, and Ma J
- Abstract
The combination of piezoelectric catalysis and photocatalysis could effectively enhance the carrier separation efficiency and further improve the hydrogen production activity. However, piezoelectric polarization always suffers from a low polarization strength, which severely restricts its actual applications. In this study, we successfully synthesized a novel sulfur vacancy-rich Bi
2 S3 /ZnSn (OH)6 (BS-12/ZSH) piezo-photocatalyst for hydrogen evolution through water splitting. Notably, the piezo-photocatalytic hydrogen generation rate of the 8% BS-12/ZSH catalyst (336.21 μmol/g/h) was superior to that of pristine ZSH (29.71 μmol/g/h) and BS-12 (21.66 μmol/g/h). In addition, the hydrogen generation for 8% BS-12/ZSH (336.21 μmol/g/h) under ultrasonic coupling illumination was significantly higher than that under single illumination (52.09 μmol/g/h) and ultrasound (121.90 μmol/g/h), owing to the cooperative interaction of the sulfur vacancy and piezoelectric field. Various characterization analyses confirmed that (1) the introduction of sulfur vacancies in BS-12 provided more active sites, (2) BS-12 with sulfur vacancies acted as a co-catalyst to accelerate the hydrogen production rate, and (3) the piezoelectric field eliminated the electrostatic shielding and offered an additional driving force, which effectively promoted the separation of electron-hole pairs. This research clearly reveals the synergistic effect between piezocatalysis and photocatalysis as well as offers a promising sight for the rational design of high-efficiency piezo-photocatalysts.- Published
- 2024
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6. Computer-Aided Semi-Rational Design to Enhance the Activity of l-Sorbosone Dehydrogenase from Gluconobacter oxidans WSH-004.
- Author
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Li D, Wang X, Huo L, Zeng W, Li J, and Zhou J
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- Gluconobacter enzymology, Gluconobacter genetics, Gluconobacter metabolism, Sugar Acids metabolism, Sugar Acids chemistry, Fermentation, Protein Engineering, Metabolic Engineering, Carbohydrate Dehydrogenases metabolism, Carbohydrate Dehydrogenases genetics, Carbohydrate Dehydrogenases chemistry, Kinetics, Bacterial Proteins genetics, Bacterial Proteins metabolism, Bacterial Proteins chemistry
- Abstract
The titer of the microbial fermentation products can be increased by enzyme engineering. l-Sorbosone dehydrogenase (SNDH) is a key enzyme in the production of 2-keto-l-gulonic acid (2-KLG), which is the precursor of vitamin C. Enhancing the activity of SNDH may have a positive impact on 2-KLG production. In this study, a computer-aided semirational design of SNDH was conducted. Based on the analysis of SNDH's substrate pocket and multiple sequence alignment, three modification strategies were established: (1) expanding the entrance of SNDH's substrate pocket, (2) engineering the residues within the substrate pocket, and (3) enhancing the electron transfer of SNDH. Finally, mutants S453A, L460V, and E471D were obtained, whose specific activity was increased by 20, 100, and 10%, respectively. In addition, the ability of Gluconobacter oxidans WSH-004 to synthesize 2-KLG was improved by eliminating H
2 O2 . This study provides mutant enzymes and metabolic engineering strategies for the microbial-fermentation-based production of 2-KLG.- Published
- 2024
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7. Magnetic Field-Optimized Paramagnetic Nanoprobe for T 2 / T 1 Switchable Histopathological-Level MRI.
- Author
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Huo L, Zeng J, Wang Z, Sun X, Guo Y, Cao Z, Zhu S, Tan M, Li M, Chen X, and Zhao Z
- Subjects
- Animals, Mice, Humans, Magnetic Fields, Glutathione chemistry, Oxides chemistry, Cell Line, Tumor, Glioma diagnostic imaging, Glioma pathology, Particle Size, Magnetite Nanoparticles chemistry, Magnetic Resonance Imaging, Manganese Compounds chemistry, Manganese Compounds pharmacology, Contrast Media chemistry
- Abstract
Traditional magnetic resonance imaging (MRI) contrast agents (CAs) are a type of "always on" system that accelerates proton relaxation regardless of their enrichment region. This "always on" feature leads to a decrease in signal differences between lesions and normal tissues, hampering their applications in accurate and early diagnosis. Herein, we report a strategy to fabricate glutathione (GSH)-responsive one-dimensional (1-D) manganese oxide nanoparticles (MONPs) with improved T
2 relaxivities and achieve effective T2 / T1 switchable MRI imaging of tumors. Compared to traditional contrast agents with high saturation magnetization to enhance T2 relaxivities, 1-D MONPs with weak Ms effectively increase the inhomogeneity of the local magnetic field and exhibit obvious T2 contrast. The inhomogeneity of the local magnetic field of 1-D MONPs is highly dependent on their number of primary particles and surface roughness according to Landau-Lifshitz-Gilbert simulations and thus eventually determines their T2 relaxivities. Furthermore, the GSH responsiveness ensures 1-D MONPs with sensitive switching from the T2 to T1 mode in vitro and subcutaneous tumors to clearly delineate the boundary of glioma and metastasis margins, achieving precise histopathological-level MRI. This study provides a strategy to improve T2 relaxivity of magnetic nanoparticles and construct switchable MRI CAs, offering high tumor-to-normal tissue contrast signal for early and accurate diagnosis.- Published
- 2024
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8. A Formal Synthesis of (±)-Arborisidine.
- Author
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Huo L, Yang Y, Gao X, Chen W, She X, and Cao XP
- Abstract
Herein, we report a formal synthesis of (±)-arborisidine via the creation of Jiao's intermediate with the critical caged structure. Starting from tryptamine, a Pictet-Spengler cyclization forged the piperidine ring, a Pd-catalyzed indole allylation and ring-closing metathesis protocol afforded a bridged aza-bicyclo[3.3.1]nonane moiety, and an intramolecular N-alkylation closed the final pyrrolidine ring. This study provides a new approach to the unique caged framework of arborisidine and relevant alkaloids.
- Published
- 2024
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9. Synergy of Active Sites and Charge Transfer in Branched WO 3 /W 18 O 49 Heterostructures for Enhanced NO 2 Sensing.
- Author
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Zheng Q, Wang T, Zhang G, Zhang X, Huang C, Cheng X, Huo L, Cui X, and Xu Y
- Subjects
- Humans, Catalytic Domain, Environmental Monitoring, Nitrogen Dioxide, Dielectric Spectroscopy
- Abstract
Achieving reliable detection of trace levels of NO
2 gas is essential for environmental monitoring and protection of human health protection. Herein, a thin-film gas sensor based on branched WO3 /W18 O49 heterostructures was fabricated. The optimized WO3 /W18 O49 sensor exhibited outstanding NO2 sensing properties with an ultrahigh response value (1038) and low detection limit (10 ppb) at 50 °C. Such excellent sensing performance could be ascribed to the synergistic effect of accelerated charge transfer and increased active sites, which is confirmed by electrochemical impedance spectroscopy and temperature-programmed desorption characterization. The sensor exhibited an excellent detection ability to NO2 under different air quality conditions. This work provides an effective strategy for constructing WO3 /W18 O49 heterostructures for developing NO2 gas sensors with an excellent sensing performance.- Published
- 2024
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10. Discovery of (4-Pyrazolyl)-2-aminopyrimidines as Potent and Selective Inhibitors of Cyclin-Dependent Kinase 2.
- Author
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Hummel JR, Xiao KJ, Yang JC, Epling LB, Mukai K, Ye Q, Xu M, Qian D, Huo L, Weber M, Roman V, Lo Y, Drake K, Stump K, Covington M, Kapilashrami K, Zhang G, Ye M, Diamond S, Yeleswaram S, Macarron R, Deller MC, Wee S, Kim S, Wang X, Wu L, and Yao W
- Subjects
- Animals, Humans, Mice, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase 4 metabolism, Phosphorylation, Pyrimidines pharmacology, Pyrazoles chemistry, Pyrazoles metabolism, Pyrazoles pharmacology, Cyclin-Dependent Kinases, Neoplasms
- Abstract
CDK2 is a critical regulator of the cell cycle. For a variety of human cancers, the dysregulation of CDK2/cyclin E1 can lead to tumor growth and proliferation. Historically, early efforts to develop CDK2 inhibitors with clinical applications proved unsuccessful due to challenges in achieving selectivity over off-target CDK isoforms with associated toxicity. In this report, we describe the discovery of (4-pyrazolyl)-2-aminopyrimidines as a potent class of CDK2 inhibitors that display selectivity over CDKs 1, 4, 6, 7, and 9. SAR studies led to the identification of compound 17 , a kinase selective and highly potent CDK2 inhibitor (IC
50 = 0.29 nM). The evaluation of 17 in CCNE1 -amplified mouse models shows the pharmacodynamic inhibition of CDK2, measured by reduced Rb phosphorylation, and antitumor activity.- Published
- 2024
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11. Genome Mining of Myxopeptins Reveals a Class of Lanthipeptide-Derived Linear Dehydroamino Acid-Containing Peptides from Myxococcus sp. MCy9171.
- Author
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Wang H, Han Y, Wang X, Jia Y, Zhang Y, Müller R, and Huo L
- Subjects
- Escherichia coli metabolism, Peptides chemistry, Protein Processing, Post-Translational, Myxococcus metabolism, Hydro-Lyases genetics, Bacterial Proteins genetics
- Abstract
Myxobacteria exhibit a substantial capacity to produce bioactive natural products. The biosynthetic potential of ribosomally synthesized and post-translationally modified peptides (RiPPs) from myxobacteria remains largely underexplored. In our study, we identified a novel lanthipeptide-like biosynthetic pathway, mcy from Myxococcus sp. MCy9171, which was reconstituted in E. coli and in vitro proteolysis. Structural elucidation demonstrated that a series of dehydroamino acids were installed by an orphan McyB dehydratase onto the five McyA core peptides, named myxopeptins. Interestingly, compared with the canonical biosynthetic machinery of class I lanthipeptides, neither Cys residues existed in the diverse core regions, nor any LanC cyclase homologue was encoded in the mcy pathway. Thus, we propose myxopeptins as members of a new subclass of RiPPs, named lanthipeptide-derived linear dehydroamino acid-containing peptides (LDPs), which contain dehydrated amino acids as the class-defining post-translational modifications. Furthermore, sequence similarity network (SSN) analysis revealed the wide distribution of the biosynthetic potential of LDPs in various microbial phyla, implying a co-evolutionary scenario between the precursor peptide and class I lanthipeptide biosynthetic enzymes.
- Published
- 2023
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12. Discovery and Characterization of a Myxobacterial Lanthipeptide with Unique Biosynthetic Features and Anti-inflammatory Activity.
- Author
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Wang X, Chen X, Wang ZJ, Zhuang M, Zhong L, Fu C, Garcia R, Müller R, Zhang Y, Yan J, Wu D, and Huo L
- Subjects
- Peptides chemistry, Protein Processing, Post-Translational, Myxococcales
- Abstract
The genomes of myxobacteria harbor a variety of biosynthetic gene clusters encoding numerous secondary metabolites, including ribosomally synthesized and post-translationally modified peptides (RiPPs) with diverse chemical structures and biological activities. However, the biosynthetic potential of RiPPs from myxobacteria remains barely explored. Herein, we report a novel myxobacteria lanthipeptide myxococin identified from Myxococcus fulvus . Myxococins represent the first example of lanthipeptides, of which the characteristic multiple thioether rings are installed by employing a Class II lanthipeptide synthetase MfuM and a Class I lanthipeptide cyclase MfuC in a cascaded way. Unprecedentedly, we biochemically characterized the first M61 family aminopeptidase MfuP involved in RiPP biosynthesis, demonstrating that MfuP showed the activity of an endopeptidase activity. MfuP is leader-independent but strictly selective for the multibridge structure of myxococin A and responsible for unwrapping two rings via amide bond hydrolysis, yielding myxococin B. Furthermore, the X-ray crystal structure of MfuP and structural analysis, including active-site mutations, are reported. Finally, myxococins are evaluated to exhibit anti-inflammatory activity in lipopolysaccharide-induced macrophages without detectable cytotoxicity.
- Published
- 2023
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13. Deciphering the Biosynthesis of Novel Class I Lanthipeptides from Marine Pseudoalteromonas Reveals a Dehydratase PsfB with Dethiolation Activity.
- Author
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Wang X, Wang Z, Dong Z, Yan Y, Zhang Y, and Huo L
- Subjects
- Phylogeny, Peptides chemistry, Hydro-Lyases genetics, Bacteriocins metabolism, Pseudoalteromonas genetics
- Abstract
Lanthipeptides are a representative class of RiPPs that possess characteristic lanthionine and/or methyllanthionine thioether cross-links. The biosynthetic potentials of marine-derived lanthipeptides remain largely unexplored. In this study, we characterized three novel lanthipeptides pseudorosin A-C by heterologous expression of a class I lanthipeptide biosynthetic gene cluster from marine Pseudoalteromonas flavipulchra S16. Interestingly, pseudorosin C contains a large loop spanning 18 amino acid residues, which is rare in lanthipeptides. Unexpectedly, the dehydratase PsfB could catalyze the dethiolation of specific Cys residues in all three core peptides, thereby generating dehydroalanines in the absence of LanC cyclase. To the best of our knowledge, we identified the first member of the LanB dehydratase family to perform glutamylation and subsequent elimination on Cys thiol groups, which likely represents a new bypass for class I lanthipeptide biosynthesis. Furthermore, we employed mutagenesis to determine the important motif of the core peptide for dethiolation activity. Moreover, sequence analysis revealed that PsfB exhibited a distinct phylogenetic distance from the characterized LanBs from Gram-positive bacteria. Our findings, therefore, pave the way for further genome mining of lanthipeptides, novel post-translational modification enzymes from marine Gram-negative bacteria, and bioengineering applications.
- Published
- 2023
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14. Site- and Stereoselective Synthesis of Alkenyl Chlorides by Dual Functionalization of Internal Alkynes via Photoredox/Nickel Catalysis.
- Author
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Huo L, Li X, Zhao Y, Li L, and Chu L
- Abstract
Herein, we report a redox-neutral and atom-economical protocol to synthesize valuable alkenyl chlorides from unactivated internal alkynes and abundant organochlorides via photoredox and nickel catalysis. This protocol enables the site- and stereoselective addition of organochlorides to alkynes via chlorine photoelimination-initiated sequential hydrochlorination/remote C-H functionalization. The protocol is compatible with a wide range of medicinally relevant heteroaryl, aryl, acid, and alkyl chlorides for efficiently producing γ-functionalized alkenyl chlorides, exhibiting excellent regioselectivities and stereoselectivities. Late-stage modifications and synthetic manipulations of the products and preliminary mechanistic studies are also presented.
- Published
- 2023
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15. Engineered Biosynthesis of Complex Disorazol Polyketides in a Streamlined Burkholderia thailandensis .
- Author
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Wang ZJ, Liu X, Zhou H, Liu Y, Tu Q, Huo L, Yan F, Müller R, Zhang Y, and Xu X
- Subjects
- Polyketide Synthases genetics, Polyketide Synthases metabolism, Humans, Structure-Activity Relationship, Burkholderia, Polyketides metabolism
- Abstract
Engineering the biosynthetic pathways of complex natural products is a significant approach to obtain derivatives with improved properties. Here, we constructed a streamlined engineered biosynthesis system of myxobacterium-derived complex polyketide disorazol in a heterologous host, Burkholderia thailandensis E264. Inactivation of dehydratase domains in the disorazol biosynthetic pathway led to the production of two hydroxylated derivatives. Module deletion allowed the generation of an unnatural derivative with a truncated macrolactone ring, and the ACP-KS linker was the optimal fusion region for module deletion in this trans -AT polyketide synthase. These disorazol derivatives showed different activities against human cancer cell lines ranging from the nanomolar to micromolar level, suggesting the primary structure-activity relationship. The PKS engineering enables structural derivatization of disorazol, facilitating the in-depth engineered biosynthesis of polyketides.
- Published
- 2023
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16. Asymmetric Wettability Mediated Patterning of Single Crystalline Nematic Liquid Crystal and P-N Heterojunction Toward a Broadband Photodetector.
- Author
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Yue Y, Yang J, Zheng B, Huo L, Dong H, Wang J, and Jiang L
- Abstract
The well aligned and precise patterning of liquid crystals (LCs) are considered as two key challenges for large-scale and high-efficiency integrated optoelectronic devices. However, owing to the uncontrollable liquid flow and dewetting process in the conventional techniques, most of the reported research is mainly focused on simple sematic LCs, which are composed of terthiophenes or benzothieno[3, 2-b][1] benzothiophene backbone; only a few works are carried out on the complicated LCs. Herein, an efficient strategy was introduced to control the liquid flow and alignment of LCs and realized precise and high-quality patterning of A-π-D-π-A BTR, based on the asymmetric wettability interface. Through this strategy, the large-area and well-aligned BTR microwires array was fabricated, which exhibited highly ordered molecular packing and improved charge transport performance. Furthermore, the integration of BTR and PC
71 BM was achieved to manufacture uniform P-N heterojunction arrays, which still possessed highly ordered alignment of BTR. On the basis of these aligned heterojunction arrays, the high-performance photodetector exhibited an excellent responsivity of 27.56 A W-1 and a specific detectivity of 2.07 × 1012 Jones. This research not only provides an efficient strategy for the fabrication of aligned micropatterns of LCs but also gives a novel insight for the fabrication of high-quality micropatterns of the P-N heterojunction toward integrated optoelectronics.- Published
- 2023
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17. Gradual Recovery of Building Plumbing-Associated Microbial Communities after Extended Periods of Altered Water Demand during the COVID-19 Pandemic.
- Author
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Vosloo S, Huo L, Chauhan U, Cotto I, Gincley B, Vilardi KJ, Yoon B, Bian K, Gabrielli M, Pieper KJ, Stubbins A, and Pinto AJ
- Subjects
- Humans, Sanitary Engineering, Water Supply, RNA, Ribosomal, 16S genetics, Pandemics, Water Quality, Water Microbiology, Drinking Water microbiology, COVID-19, Microbiota
- Abstract
COVID-19 pandemic-related building restrictions heightened drinking water microbiological safety concerns post-reopening due to the unprecedented nature of commercial building closures. Starting with phased reopening (i.e., June 2020), we sampled drinking water for 6 months from three commercial buildings with reduced water usage and four occupied residential households. Samples were analyzed using flow cytometry and full-length 16S rRNA gene sequencing along with comprehensive water chemistry characterization. Prolonged building closures resulted in 10-fold higher microbial cell counts in the commercial buildings [(2.95 ± 3.67) × 10
5 cells mL-1 ] than in residential households [(1.11 ± 0.58) × 104 cells mL-1 ] with majority intact cells. While flushing reduced cell counts and increased disinfection residuals, microbial communities in commercial buildings remained distinct from those in residential households on the basis of flow cytometric fingerprinting [Bray-Curtis dissimilarity ( dBC ) = 0.33 ± 0.07] and 16S rRNA gene sequencing ( dBC = 0.72 ± 0.20). An increase in water demand post-reopening resulted in gradual convergence in microbial communities in water samples collected from commercial buildings and residential households. Overall, we find that the gradual recovery of water demand played a key role in the recovery of building plumbing-associated microbial communities as compared to short-term flushing after extended periods of reduced water demand.- Published
- 2023
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18. Scalable Total Syntheses of (±)-Catellatolactams A and B.
- Author
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Yang H, Zhang Y, Chen W, Shi H, Huo L, Li J, Li H, Xie X, and She X
- Abstract
The first total syntheses of (±)-catellatolactams A and B, two novel ansamacrolactams, are described in 5 and 8 steps, respectively. The strategy relies on an amidation reaction to couple the acylated Meldrum's acid and an aryl amine, a regioselective C-H insertion to construct the γ-lactam moiety, and an RCM reaction to forge the macrocycles with E -olefin. This concise and scalable synthesis provided over 200 mg of the target molecules.
- Published
- 2023
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19. Identification of N- and C-3-Modified Laudanosoline Derivatives as Novel Influenza PA N Endonuclease Inhibitors.
- Author
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Liao Y, Ye Y, Liu M, Liu Z, Wang J, Li B, Huo L, Zhuang Y, Chen L, Chen J, Gao Y, Ning X, Li S, Liu S, and Song G
- Subjects
- Animals, Mice, Humans, Antiviral Agents pharmacology, Antiviral Agents metabolism, Endonucleases, Influenza, Human, Orthomyxoviridae, Tetrahydroisoquinolines pharmacology
- Abstract
Influenza PA
N inhibitors are of particular importance in current efforts to develop a new generation of antiviral drugs due to the growing emergence of highly pathogenic influenza viruses and the resistance to existing antiviral inhibitors. Herein, we design and synthesize a set of 1,3-cis- N -substituted-1,2,3,4-tetrahydroisoquinoline derivatives to enhance their potency by further exploiting the pockets 3 and 4 in the PAN endonuclease based on the hit d,l-laudanosoline. Particularly, the lead compound 35 exhibited potent and broad anti-influenza virus effects with EC50 values ranging from 0.43 to 1.12 μM in vitro and good inhibitory activity in a mouse model. Mechanistic studies demonstrated that 35 could bind tightly to the PAN endonuclease of RNA-dependent RNA polymerase, thus blocking the viral replication to exert antiviral activity. Overall, our study might establish the importance of 1,2,3,4-tetrahydroisoquinoline-6,7-diol-based derivatives for the development of novel PAN inhibitors of influenza viruses.- Published
- 2023
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20. Recent Advances in Discovery, Bioengineering, and Bioactivity-Evaluation of Ribosomally Synthesized and Post-translationally Modified Peptides.
- Author
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Zhong G, Wang ZJ, Yan F, Zhang Y, and Huo L
- Abstract
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are of increasing interest in natural products as well as drug discovery. This empowers not only the unique chemical structures and topologies in natural products but also the excellent bioactivities such as antibacteria, antifungi, antiviruses, and so on. Advances in genomics, bioinformatics, and chemical analytics have promoted the exponential increase of RiPPs as well as the evaluation of biological activities thereof. Furthermore, benefiting from their relatively simple and conserved biosynthetic logic, RiPPs are prone to be engineered to obtain diverse analogues that exhibit distinct physiological activities and are difficult to synthesize. This Review aims to systematically address the variety of biological activities and/or the mode of mechanisms of novel RiPPs discovered in the past decade, albeit the characteristics of selective structures and biosynthetic mechanisms are briefly covered as well. Almost one-half of the cases are involved in anti-Gram-positive bacteria. Meanwhile, an increasing number of RiPPs related to anti-Gram-negative bacteria, antitumor, antivirus, etc., are also discussed in detail. Last but not least, we sum up some disciplines of the RiPPs' biological activities to guide genome mining as well as drug discovery and optimization in the future., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)
- Published
- 2022
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21. Uncovering a Subtype of Microviridins via the Biosynthesis Study of FR901451.
- Author
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Wang T, Wang X, Zhao H, Huo L, and Fu C
- Subjects
- Pancreatic Elastase, Esters, Amides, Adenosine Triphosphate metabolism, Protein Processing, Post-Translational, Ligases metabolism, Multigene Family
- Abstract
Microviridins are a class of ribosomally synthesized and post-translationally modified peptides originally discovered from cyanobacteria, featured by intramolecular ω-ester and ω-amide bonds catalyzed by two ATP-grasp ligases. In this study, 104 biosynthetic gene clusters of microviridins from Bacteroidetes were bioinformatically analyzed, which unveiled unique features of precursor peptides. The analysis of core peptides revealed a microviridin-like biosynthetic gene cluster from Chitinophagia japonensis DSM13484 consisting of two potential precursors ChiA1 and ChiA2. Unexpectedly, the core peptide sequence of ChiA1 is consistent with the backbone of the elastase-inhibiting peptide FR901451, while ChiA2 is likely to be a precursor of an unknown product. However, an unusual C-terminal follower cleavage compared to the previously known microviridin pathways was observed and found to be dispensable for other modifications. To confirm the biosynthetic origin of FR901451, ATP-grasp ligases ChiC and ChiB were biochemically characterized to be responsible for the intramolecular ester and amide bond formation, respectively. In vitro reconstitution of the pathway showed the three-fold dehydrations of ChiA1 while unusual four-fold dehydrations were observed for ChiA2. Furthermore, in vivo gene coexpression facilitated the production of chitinoviridin A1 (FR901451) and two novel microviridin-class compounds chitinoviridin A2A and chitinoviridin A2B, with an extra macrolactone ring. All of these peptides showed potent inhibitory effects against elastase and chymotrypsin independently.
- Published
- 2022
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22. Ultrathin Fe-ReS 2 Nanosheets as Electrocatalysts for Accelerating Sulfur Reduction in Li-S Batteries.
- Author
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Tang J, Jin C, Huo L, Du S, Xu X, Yan Y, Jiang K, Shang L, Zhang J, Li Y, Hu Z, and Chu J
- Abstract
Lithium-sulfur batteries are promising next-generation energy storage systems with high theoretical specific capacity. Despite extensive research efforts, it is still challenging to rationally design electrocatalysts with fast kinetics and effective adsorption of polysulfides. Herein, Fe-doped ReS
2 (Fe-ReS2 ) ultrathin nanosheets are prepared as an electrocatalyst to trap the intermediates and accelerate the sulfur reduction reaction kinetics. Density functional theory calculations combined with activation energies in the multistep sulfur reduction reaction reveal that the Fe-ReS2 considerably reduces the activation energy and optimizes the optimum adsorption strength of polysulfides and catalytic activity. The Fe-ReS2 /S exhibits a highly reversible discharge capacity of 882.3 mA h g-1 at 1 C. For 500 cycles, the capacity fade rate is 0.013% per cycle. Moreover, in situ Raman spectroscopy measurements further confirmed that both sulfur reduction and oxidation processes were significantly enhanced by Fe-ReS2 .- Published
- 2022
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23. Discovery of 5,7-Dihydro-6 H -pyrrolo[2,3- d ]pyrimidin-6-ones as Highly Selective CDK2 Inhibitors.
- Author
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Sokolsky A, Winterton S, Kennedy K, Drake K, Stump K, Huo L, Lo Y, Ye M, Covington M, Diamond S, Yang YO, Kim S, Yeleswaram S, Wu L, and Yao W
- Abstract
A series of exceptionally selective CDK2 inhibitors are described. Starting from an HTS hit, we successfully scaffold hopped to a 5,7-dihydro-6 H -pyrrolo[2,3- d ]pyrimidin-6-one core structure, which imparted a promising initial selectivity within the CDK family. Extensive further SAR identified additional factors that drove selectivity to above 200× for CDKs 1/4/6/7/9. General kinome selectivity was also greatly improved. Finally, use of in vivo metabolite identification allowed us to pinpoint sulfonamide dealkylation as the primary metabolite, which was ameliorated through the deuterium effect., Competing Interests: The authors declare the following competing financial interest(s): All authors are current or former employees of Incyte Corporation., (© 2022 American Chemical Society.)
- Published
- 2022
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24. De Novo Diastereoselective Synthesis of 1-Hydroxyl Allogibberic Methyl Ester en Route to Diverse Bioactive Molecules.
- Author
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Chen J, Yang Y, Wu C, Huo L, Xie X, Li H, and She X
- Subjects
- Cyclization, Esters, Lewis Acids
- Abstract
The first de novo synthesis of 1-hydroxyl allogibberic methyl ester, en route to pharbinilic acid and other bioactive molecules, is accomplished in diastereoselective manner. Key reactions of the synthesis include a Pd-catalyzed Suzuki-Miyaura cross-coupling reaction, a Lewis acid-catalyzed reductive Prins cyclization reaction, and a SmI
2 -mediated transannular pinacol coupling reaction. The synthesis provides a new avenue to access diverse relevant bioactive molecules.- Published
- 2022
- Full Text
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25. 86Y-Labeled Albumin-Binding Fibroblast Activation Protein Inhibitor for Late-Time-Point Cancer Diagnosis.
- Author
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Ding J, Xu M, Chen J, Zhang P, Huo L, Kong Z, and Liu Z
- Subjects
- Albumins metabolism, Fibroblasts metabolism, Gallium Radioisotopes metabolism, Humans, Membrane Proteins metabolism, Positron Emission Tomography Computed Tomography, Tissue Distribution, Carrier Proteins metabolism, Neoplasms drug therapy, Neoplasms metabolism
- Abstract
Fibroblast activation protein inhibitor (FAPI) is a novel quinoline-based radiopharmaceutical that has theranostic potential, yet the limited tumor retention hinders late-time diagnosis and radionuclide treatment. This study synthesized four albumin-binding FAPIs (TE-FAPI-01 to 04) and evaluated their in vitro stability, binding affinity, in vivo biodistribution, and tumor uptake with
68 Ga,86 Y, and177 Lu labeling, aiming to select the best molecule that has favorable pharmacokinetics to extend the blood circulation and tumor uptake in FAP-expressing tumors. All TE-FAPIs were stable in saline and plasma and displayed high FAP-binding affinity, with IC50 values ranging from 3.96 to 34.9 nmol/L. The capabilities of TE-FAPIs to be retained in circulation were higher than that of FAPI-04, and TE-FAPI-04 displayed minimum physiological uptake in major organs compared with other molecules. TE-FAPI-03 and TE-FAPI-04 exhibited persistent tumor accumulation, with tumor radioactivity 24 h after administration of 2.84 ± 1.19%ID/g and 3.86 ± 1.15%ID/g for177 Lu-TE-FAPI-03 and177 Lu-TE-FAPI-04, respectively, both of which outperformed177 Lu-FAPI-04 (0.34 ± 0.07%ID/g). TE-FAPI-04 was recognized as the albumin-binding FAPI with the most favorable pharmacokinetics and imaging performance. The enhanced circulation half-life and tumor uptake of TE-FAPI-04 aided the theranostics of malignant tumors and warrant further clinical investigations.- Published
- 2022
- Full Text
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26. Graphene Nanosheets as Lubricant Additives: Effects of Nature and Size on Lubricating Performance.
- Author
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Huo L, Guo J, Hu H, Zhang K, Zhou H, and Liu P
- Abstract
Graphene has been widely investigated as an additive in lubricating oils to enhance their tribological performance. Here, the effects of the nature and size of the graphene nanosheets on the tribological performance were investigated with the hydrogenated hydroxyl-terminated polybutadiene dioctoate (O-HHTPB-O) as a model base oil after alkylation of the graphene oxide (GO) of different sizes with 1-dodecylamine (DA) and reduction. The 1-dodecylamine-modified graphene oxide (DA-GO) showed better dispersibility in the O-HHTPB-O base oil and subsequently better tribological performance than the reduced one (DA-rGO) for both the larger graphene oxide nanosheets (GO
L ) and the smaller graphene oxide nanosheets (GOS ). The DA-GOS exhibited better wear-reduction performance than the DA-GOL , owing to its smaller size and higher polarity. Although the DA-GOL could be ground during the friction, the friction and wear in the original period affected the complete period lubricating performance.- Published
- 2022
- Full Text
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27. Discovery and Characterization of Marinsedin, a New Class II Lanthipeptide Derived from Marine Bacterium Marinicella sediminis F2 T .
- Author
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Han Y, Wang X, Zhang Y, and Huo L
- Subjects
- Amino Acids, Bacteria metabolism, Gammaproteobacteria, HeLa Cells, Humans, Sulfides chemistry, Sulfides pharmacology, Bacteriocins chemistry, Peptides chemistry
- Abstract
Microbial natural products provide a large number of drug leads. It is believed that abundant unexploited marine microorganisms also exhibit great potential for discovering compounds with novel chemical scaffolds and bioactivities. Lanthipeptides are a group of ribosomally synthesized and post-translationally modified peptides exhibiting a variety of biological functionalities. They are characterized by the presence of the thioether-containing bis-amino acids lanthionine and methyllanthionine. However, marine-derived lanthipeptides remain underexplored. Here we identified, heterologously expressed, and structurally characterized the unprecedented class II lanthipeptide marinsedin from the rare marine bacterium Marinicella sediminis F2
T . Marinsedin consists of 19 amino acids and contains a rare 2-oxobutyryl group blocking the N-terminus of the peptide chain and two overlapping intramolecular thioether rings including an unusual 12-membered macro-thioether ring. Furthermore, we also evaluated the biological activity of marinsedin, demonstrating that it exhibits moderate cytotoxicity against HeLa cells and weak cytotoxicity against HCT-116 cell lines.- Published
- 2022
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28. Phthalate Esters Released from Plastics Promote Biofilm Formation and Chlorine Resistance.
- Author
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Wang H, Yu P, Schwarz C, Zhang B, Huo L, Shi B, and Alvarez PJJ
- Subjects
- Biofilms, China, Chlorine pharmacology, Dibutyl Phthalate, Esters, Plastics, Diethylhexyl Phthalate, Phthalic Acids pharmacology
- Abstract
Phthalate esters (PAEs) are commonly released from plastic pipes in some water distribution systems. Here, we show that exposure to a low concentration (1-10 μg/L) of three PAEs (dimethyl phthalate (DMP), di-n-hexyl phthalate (DnHP), and di-(2-ethylhexyl) phthalate (DEHP)) promotes Pseudomonas biofilm formation and resistance to free chlorine. At PAE concentrations ranging from 1 to 5 μg/L, genes coding for quorum sensing, extracellular polymeric substances excretion, and oxidative stress resistance were upregulated by 2.7- to 16.8-fold, 2.1- to 18.9-fold, and 1.6- to 9.9-fold, respectively. Accordingly, more biofilm matrix was produced and the polysaccharide and eDNA contents increased by 30.3-82.3 and 10.3-39.3%, respectively, relative to the unexposed controls. Confocal laser scanning microscopy showed that PAE exposure stimulated biofilm densification (volumetric fraction increased from 27.1 to 38.0-50.6%), which would hinder disinfectant diffusion. Biofilm densification was verified by atomic force microscopy, which measured an increase of elastic modulus by 2.0- to 3.2-fold. PAE exposure also stimulated the antioxidative system, with cell-normalized superoxide dismutase, catalase, and glutathione activities increasing by 1.8- to 3.0-fold, 1.0- to 2.0-fold, and 1.2- to 1.6-fold, respectively. This likely protected cells against oxidative damage by chlorine. Overall, we demonstrate that biofilm exposure to environmentally relevant levels of PAEs can upregulate molecular processes and physiologic changes that promote biofilm densification and antioxidative system expression, which enhance biofilm resistance to disinfectants.
- Published
- 2022
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29. An All-Hydrophobic Fluid Diode for Continuous and Reduced-Wastage Water Transport.
- Author
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Huang G, Jin Y, Huo L, Yuan S, Zhao R, Zhao J, Li Z, and Li Y
- Abstract
Directional water transport that occurs in natural insects and plants is important to both organisms and advanced science and technology. Despite the many studies conducted to facilitate directional liquid transport by constructing double-layered hydrophilic/hydrophobic materials, it remains difficult to achieve continuous water transport and reduce liquid wastage due to the hydrophilic regions. Herein, a directional water transport fabric (DWTF) was fabricated using a simple single-side coating method based on entirely hydrophobic materials. With coating thicknesses of 13-29 μm, the fabric could guide the continuous water motion from the coated to the uncoated side and can be utilized as a "liquid diode". In addition, the DWTF exhibited a water wastage reduction during the transport process, benefiting from the intrinsic hydrophobic properties of the material. Moreover, a plausible mechanism of water transport is proposed to explain the water droplet transfer in the bilayered hydrophobic materials. Consequently, the resulting DWTF exhibited an excellent accumulative one-way transport capability (AOTC) of 965.7% and a desirable overall moisture management capability (OMMC) of 0.92. This work provides an avenue for fabricating smart fluid delivery materials to various applications such as flexible microfluidics, wound dressing, oil-water separation processes, and engineered desiccant materials.
- Published
- 2021
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30. Herbivore-Induced ( Z )-3-Hexen-1-ol is an Airborne Signal That Promotes Direct and Indirect Defenses in Tea ( Camellia sinensis ) under Light.
- Author
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Liao Y, Tan H, Jian G, Zhou X, Huo L, Jia Y, Zeng L, and Yang Z
- Subjects
- Herbivory, Hexanols, Tea, Camellia sinensis, Volatile Organic Compounds
- Abstract
Tea ( Camellia sinensis ) is the most popular nonalcoholic beverage worldwide. During cultivation, tea plants are susceptible to herbivores and pathogens, which can seriously affect tea yield and quality. A previous report showed that ( Z )-3-hexenol is a potentially efficient defensive substance. However, the molecular mechanism mediating ( Z )-3-hexenol signaling in tea plants and the resulting effects on plant defenses remain uncharacterized. To clarify the signaling mechanisms in which ( Z )-3-hexenol and light are involved, the gene transcription and metabolite levels were assessed, respectively. This study demonstrated that tea plants rapidly and continuously release ( Z )-3-hexen-1-ol in response to an insect infestation. ( Z )-3-Hexen-1-ol absorbed by adjacent healthy plants would be converted into three insect defensive compounds: ( Z )-3-hexenyl-glucoside, ( Z )-3-hexenyl-primeveroside, and ( Z )-3-hexenyl-vicianoside identified with laboratory-synthesized standards. Moreover, ( Z )-3-hexen-1-ol also activates the synthesis of jasmonic acid to enhance the insect resistance of tea plants. Additionally, a continuous light treatment induces the accumulation of ( Z )-3-hexenyl-glycosides. Hence, ( Z )-3-hexenol serves as a light-regulated signaling molecule that activates the systemic defenses of adjacent plants. Our study reveals the molecular mechanisms by which biotic and abiotic factors synergistically regulate the signaling functions of herbivore-induced plant volatiles in plants, providing valuable information for future comprehensive analyses of the systemic defense mechanisms in plants.
- Published
- 2021
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31. Novel Two-Dimensional WO 3 /Bi 2 W 2 O 9 Nanocomposites for Rapid H 2 S Detection at Low Temperatures.
- Author
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Zhang Y, Zhang X, Guo C, Xu Y, Cheng X, Zhang F, Major Z, and Huo L
- Abstract
Compared with single-component metal oxides, multicomponent metal oxides show good gas sensing performance in the field of gas sensing, but they still need to be further improved in terms of rapid response. In this paper, a two-dimensional flaky WO
3 /Bi2 W2 O9 composite material with a thickness of about 32.3 nm was synthesized by a simple solvothermal method. The composite has good sensing performance and selectivity toward H2 S. When the operating temperature is as low as 92 °C, the response to 100 ppm H2 S reaches 84.18, and the response time is 2 s, which is extremely fast due to the open system of the two-dimensional nanosheet. A combination of gas chromatography-mass spectrometry (GC-MS) and X-ray photoelectron spectroscopy (XPS) is used to analyze the changes of H2 S and the surface chemistry of WO3 /Bi2 W2 O9 composite materials; the sensing mechanism of H2 S was studied by a Kelvin probe and UV diffuse reflection. Compared with the pure phase WO3 and Bi2 W2 O9 , good gas sensing properties of the WO3 /Bi2 W2 O9 composite may be due to its unique heterostructure. This is the first application of WO3 /Bi2 W2 O9 in the field of gas sensing and is of great significance for the rapid detection of H2 S at low temperatures for multicomponent metal oxides.- Published
- 2020
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32. The Biomimetic Total Syntheses of the Antiplasmodial Tomentosones A and B.
- Author
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Zhang X, Dong C, Wu G, Huo L, Yuan Y, Hu Y, Liu H, and Tan H
- Subjects
- Antimalarials chemistry, Biomimetics, Molecular Structure, Phloroglucinol chemistry, Stereoisomerism, Antimalarials chemical synthesis, Phloroglucinol chemical synthesis
- Abstract
The first biomimetic total syntheses of natural phloroglucinols tomentosones A and B and their analogues have been accomplished. The synthetic strategy primarily referred to the potential biosynthetic precursors and their possible sequence of segments assembly by chemological evolution of the structural entities and enabled rapid access of the titled compounds in a practical fashion.
- Published
- 2020
- Full Text
- View/download PDF
33. Flexible and Superhydrophobic Composites with Dual Polymer Nanofiber and Carbon Nanofiber Network for High-Performance Chemical Vapor Sensing and Oil/Water Separation.
- Author
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Zhang S, Huang X, Wang D, Xiao W, Huo L, Zhao M, Wang L, and Gao J
- Abstract
Polymer nanofiber composites with superhydrophobicity are promising for the chemical vapor sensing or oil/water separation, but it remains challenging to develop superhydrophobic, anticorrosive, and durable nanofiber composites that can achieve both the organic solvent vapor detection and oil (organic solvent)/water separation with high separation flux and excellent recyclability. Here, a flexible, stretchable, and superhydrophobic/superoleophilic nanofiber composite membrane with excellent photothermal conversion performance is fabricated by decorating carbon nanofibers (CNFs) with a hollow structure onto the polyurethane nanofibers and subsequent polydimethylsiloxane (PDMS) modification. The combination of CNFs and PDMS greatly improves the membrane's tensile strength and Young's modulus without sacrificing its stretchability. The dual polymer nanofiber and CNF network are beneficial to the chemical vapor or liquid diffusion into the membrane and thus can be used for high-performance chemical vapor sensing and oil/water separation. The nanofiber composite is responsive to different organic vapors with a low detection limit and good selectivity. Also, the material can achieve fast oil/water separation with the oil (dichloromethane) permeate flux as high as 6577.3 L m
-2 h-1 . In addition, the separation flux and efficiency remain stable during the 30 separated oil/water separation tests, exhibiting excellent recyclability.- Published
- 2020
- Full Text
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34. Enantioselective Three-Component Fluoroalkylarylation of Unactivated Olefins through Nickel-Catalyzed Cross-Electrophile Coupling.
- Author
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Tu HY, Wang F, Huo L, Li Y, Zhu S, Zhao X, Li H, Qing FL, and Chu L
- Abstract
A nickel-catalyzed, enantioselective, three-component fluoroalkylarylation of unactivated alkenes with aryl halides and perfluoroalkyl iodides has been described. This cross-electrophile coupling protocol utilizes a chiral nickel/BiOx system as well as a pendant chelating group to facilitate the challenging three-component, asymmetric difunctionalization of unactivated alkenes, providing direct access to valuable chiral β-fluoroalkyl arylalkanes with high efficiency and excellent enantioselectivity. The mild conditions allow for a broad substrate scope as well as good functional group toleration.
- Published
- 2020
- Full Text
- View/download PDF
35. A-Site Cation-Ordering Layered Perovskite EuBa 0.5 Sr 0.5 Co 2- x Fe x O 5+δ as Highly Active and Durable Electrocatalysts for Oxygen Evolution Reaction.
- Author
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Wang X, Dou Y, Xie Y, Wang J, Xia T, Huo L, and Zhao H
- Abstract
The developments of high-performance and tolerant catalysts may enable more sustainable energy in the future, especially toward water oxidation. Herein, we report A-site cation-ordering layered perovskite EuBa
0.5 Sr0.5 Co2- x Fex O5+δ (EBSCF x ) ( x = 0.2-0.6) electrocatalysts. When evaluated for oxygen evolution reaction (OER) in alkaline media, EuBa0.5 Sr0.5 Co1.6 Fe0.4 O5+δ (EBSCF0.4) exhibits the best catalytic activity among all of these catalysts, as evidenced by the lowest overpotential of 420 mV at a current density of 10 mA cm-2 . Notably, the catalytic activity of EBSCF0.4 is better than that of commercial IrO2 at the overpotential >460 mV. Furthermore, the EBSCF0.4-20RuO2 (involving 20 wt % RuO2 ) composite catalyst is developed and gives an overpotential as low as 390 mV at 50 mA cm-2 , which is even superior to commercial RuO2 . For overall water splitting, an electrolysis voltage of merely 1.47 V is achieved at 10 mA cm-2 in an electrolyzer employing EBSCF0.4-20RuO2 as bifunctional catalysts, with exceptional durability for 24 h. Such a performance outperforms state-of-the-art IrO2 ∥Pt/C and RuO2 ∥Pt/C couples. According to density functional theory (DFT) calculations, the unique catalytic properties of EBSCF0.4 may benefit from highly active Fe sites with octahedral coordination, and the synergistic effects of Fe and Ru sites in the composite catalyst accelerate the electrochemical water oxidation., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)- Published
- 2020
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36. Genome Mining and Biosynthesis of Primary Amine-Acylated Desferrioxamines in a Marine Gliding Bacterium.
- Author
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Wang ZJ, Zhou H, Zhong G, Huo L, Tang YJ, Zhang Y, and Bian X
- Subjects
- Acylation, Bacteroidetes chemistry, Bacteroidetes genetics, Deferoxamine chemistry, Deferoxamine isolation & purification, Genome, Bacterial genetics, Molecular Structure, Stereoisomerism, Bacteroidetes metabolism, Deferoxamine metabolism
- Abstract
Genome mining of Fulvivirga sp. W222 revealed a desferrioxamine-like biosynthetic gene cluster containing an unknown gene fulF that is conserved in many Bacteroidetes species. A series of primary amine-acylated desferrioxamine G
1 analogues, fulvivirgamides, were identified, and fulvivirgamides A2 , B2 , B3 , and B4 ( 1 - 4 ) were purified and characterized. The function of FulF, which is a novel acyltransferase for the acylation of the primary amine of Desferrioxamine G1 , was verified by heterologous expression and feeding experiments.- Published
- 2020
- Full Text
- View/download PDF
37. Biomimetic Total Syntheses of Sanctis A-B with Structure Revision.
- Author
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Huo L, Dong C, Wang M, Lu X, Zhang W, Yang B, Yuan Y, Qiu S, Liu H, and Tan H
- Subjects
- Biomimetic Materials chemistry, Cycloaddition Reaction, Heterocyclic Compounds, 4 or More Rings chemistry, Molecular Structure, Stereoisomerism, Biomimetic Materials chemical synthesis, Heterocyclic Compounds, 4 or More Rings chemical synthesis
- Abstract
The first concise total syntheses of sanctis A and B were reported, and it enabled revision of the structure of sanctis B through single-crystal X-ray diffraction. The established synthetic approach mainly mimics a biosynthetic olefin isomerization/hemiacetalization/dehydration/[3 + 3]-type cycloaddition cascade sequence, offering a viable synthetic methodology to efficiently access sanctis A-B and their analogues.
- Published
- 2020
- Full Text
- View/download PDF
38. Enhanced Gas-Sensing Properties for Trimethylamine at Low Temperature Based on MoO 3 /Bi 2 Mo 3 O 12 Hollow Microspheres.
- Author
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Zhang F, Dong X, Cheng X, Xu Y, Zhang X, and Huo L
- Abstract
Most reported trimethylamine (TMA) sensors have to operate at high temperature, which will consume energy highly. To detect TMA at low temperature, it is necessary to modify the existing materials or develop new materials. In this paper, the sensor based on MoO
3 /Bi2 Mo3 O12 hollow microspheres can work at low operating temperature of 170 °C, which were prepared via a simple solvothermal route. The phase and morphology of the product were characterized by an X-ray diffraction meter, a scanning electron microscope and a transmission electron microscope. The surface chemistry of the MoO3 /Bi2 Mo3 O12 sensor was studied with an X-ray photoelectron spectroscope to investigate the TMA sensing mechanism. The MoO3 /Bi2 Mo3 O12 sensor ( S = 25.8) had a higher response to 50 ppm TMA than those of MoO3 hollow spheres ( S = 10.8) and Bi2 Mo3 O12 sensors ( S = 4.8) at 170 °C. In contrast to the pure MoO3 and Bi2 Mo3 O12 sensors, the MoO3 /Bi2 Mo3 O12 sensor exhibited an obviously enhanced gas-sensing property for TMA, which might be due to the heterostructure formed between MoO3 and Bi2 Mo3 O12 and the hollow morphology. It is the first time for MoO3 /Bi2 Mo3 O12 to apply in gas sensors, which might take an important step in the application of MoO3 /Bi2 Mo3 O12 or Bi2 Mo3 O12 in the field of gas sensing.- Published
- 2019
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39. Structural Evolution of Phosphorus Species on Graphene with a Stabilized Electrochemical Interface.
- Author
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Bi Z, Huo L, Kong Q, Li F, Chen J, Ahmad A, Wei X, Xie L, and Chen CM
- Abstract
Phosphorus doping is an effective approach to tailor the surface chemistry of carbon materials. In this work, two-dimensional graphene, as a simplified model for all sp
2 hybrid carbon allotropes, is employed to explore the surface chemistry of P-doped carbon materials. Thermally reduced graphene oxide, with abundant residual oxygen functionalities, is doped by phosphorus heteroatoms through H3 PO4 activation, followed by passivation in an inert atmosphere. The structural evolution of the phosphorus species in the carbon lattice during the thermal treatment is systematically studied by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and Raman spectroscopy with the assistance of first-principles calculations. The C3 -P═O configuration is identified as the most stable structure in the graphene lattice and plays a key role in stabilizing the electrochemical interface between the electrode and electrolyte. These features enable an electrode based on P-doped graphene to exhibit an enlarged potential window of 1.5 V in an aqueous electrolyte, a remarkable improved cycling stability, and an ultralow leak current. Therefore, this contribution provides insights for designing phosphorus-doped carbon materials toward electrocatalysis, energy-related applications, and so forth.- Published
- 2019
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40. High Efficiency Non-fullerene Organic Tandem Photovoltaics Based on Ternary Blend Subcells.
- Author
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Huang W, Chang SY, Cheng P, Meng D, Zhu B, Nuryyeva S, Zhu C, Huo L, Wang Z, Wang M, and Yang Y
- Abstract
The application of tandem structure that integrates multiple subcells into one device is a promising way to realize high efficiency organic solar cells. However, current-matching among different subcells remains as the main challenge for organic tandem photovoltaics. Here, we provide a facile approach to achieve a good current matching via engineering the chemical composition of non-fullerene ternary blend subcells. For the front subcell, a ternary blend of PDBT-T1:TPH-Se:ITIC is selected due to its good thermal stability. The amorphous nature of TPH-Se can sufficiently suppress the unfavorable phase separation of blends during the heat treatment, enabling a sintering in the fabrication of high quality interconnecting layer. A double-junction tandem device is fabricated with a rear subcell consisting of PBDB-T:ITIC. After the optimization of the chemical composition of the front subcell, the power conversion efficiency (PCE) of double-junction tandem device increased from 10.6% using PDBT-T1:TPH-Se binary front subcell to 11.5% using PDBT-T1:TPH-Se:ITIC (1:0.9:0.1) ternary front subcell due to better current matching. In order to further enhance the light absorption in the near-infrared region, a third junction PBDTTT-EFT:IEICO-4F is introduced. The champion cell of triple-junction non-fullerene tandem solar cell achieves a PCE of 13.0% with a high open circuit voltage of 2.52 V.
- Published
- 2018
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41. A Bioinspired Cascade Sequence Enables Facile Assembly of Methanodibenzo[b,f][1,5]dioxocin Flavonoid Scaffold.
- Author
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Liu H, Wang Y, Guo X, Huo L, Xu Z, Zhang W, Qiu S, Yang B, and Tan H
- Abstract
A remarkable bioinspired EDDA-mediated method for the selective construction of biologically interesting and highly strained bridged methanodibenzo[b,f][1,5]dioxocin flavonoid scaffold was uncovered by starting from a variety of readily available acylphloroglucinol and 2-hydroxycinnamaldehyde substrates. This method merges a fascinating olefin isomerization/hemiacetallization/dehydration/[3 + 3]-type cycloaddition cascade reaction driven by an in situ generated chromenylium intermediate and provides a convenient and viable synthetic strategy for the efficient access of such flavonoid analogues.
- Published
- 2018
- Full Text
- View/download PDF
42. Biomimetic-Inspired Syntheses of Myrtucommuacetalone and Myrtucommulone J.
- Author
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Liu H, Huo L, Yang B, Yuan Y, Zhang W, Xu Z, Qiu S, and Tan H
- Abstract
Driven by bioinspiration and appreciation of their structures, the first biomimetic total syntheses with structural revision of the acylphloroglucinols myrtucommulone J and myrtucommuacetalone, two biologically meaningful natural products, were achieved through a biosynthetic hemiacetalization/dehydration/[3 + 3]-type cycloaddition domino sequence with high step efficiency. These syntheses result in a corrected structure for myrtucommulone J.
- Published
- 2017
- Full Text
- View/download PDF
43. Hierarchical NiO Cube/Nitrogen-Doped Reduced Graphene Oxide Composite with Enhanced H 2 S Sensing Properties at Low Temperature.
- Author
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Yang M, Zhang X, Cheng X, Xu Y, Gao S, Zhao H, and Huo L
- Abstract
A novel hierarchical NiO cube (hc-NiO)/nitrogen-doped reduced graphene oxide (N-rGO) composite is synthesized via a facile hydrothermal method and a postcalcination treatment without any templates and surfactants added. The NiO cubes assembled by abundant nanoparticles in situ grow on the surface of N-rGO layers. The combination of hc-NiO and N-rGO results in enhanced sensing properties with the contributions of the N-rGO providing high specific surface area and more efficient active sites for the adsorption of H
2 S molecules and the hierarchically structured NiO cubes providing high sensitivity and distinctive selectivity to H2 S gas. At the optimal operating temperature of 92 °C, the hc-NiO/N-rGO composite based sensor shows not only high response to H2 S in a range of 0.1-100 ppm but also excellent selectivity for H2 S against the other seven gases. The gaseous product, produced from the contact of H2 S with the hc-NiO/N-rGO composite at 92 °C, is measured by GC-MS technique. The change of the surface composition and the chemical state of the hc-NiO/N-rGO composite before and after exposure to H2 S are investigated by XPS. The possible sensing mechanism of the hc-NiO/N-rGO composite is similar to that of semiconductor oxides. The H2 S molecules that absorbed on the sensor surface transform to SO2 by reacting with the adsorbed oxygen anions. Meanwhile, the electrons restricted by the surface-adsorbed oxygen return to the bulk and neutralize the holes, producing a change in resistance.- Published
- 2017
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44. Rational Re-Engineering of the O-Dealkylation of 7-Alkoxycoumarin Derivatives by Cytochromes P450 2B from the Desert Woodrat Neotoma lepida.
- Author
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Huo L, Liu J, Dearing MD, Szklarz GD, Halpert JR, and Wilderman PR
- Subjects
- Alkylation, Animals, Cytochrome P-450 Enzyme System chemistry, Cytochrome P-450 Enzyme System genetics, Cytochrome P-450 Enzyme System isolation & purification, Mutagenesis, Site-Directed, Sigmodontinae, Coumarins metabolism, Cytochrome P-450 Enzyme System metabolism
- Abstract
On the basis of recent functional and structural characterization of cytochromes P450 2B from the desert woodrat (Neotoma lepida), the 7-alkoxycoumarin and 7-alkoxy-4-(trifluoromethyl)coumarin O-dealkylation profiles of CYP2B35 and CYP2B37 were re-engineered. Point mutants interchanging residues at seven positions in the enzyme active sites were created and purified from an Escherichia coli expression system. In screens for O-dealkylation activity, wild-type CYP2B35 metabolized long-chain 7-alkoxycoumarins but not 7-alkoxy-4-(trifluoromethyl)coumarins or short-chain 7-alkoxycoumarins. Wild-type CYP2B37 metabolized short-chain substrates from both series of compounds. CYP2B35 A367V showed maximal activity with 7-butoxycoumarin as opposed to 7-heptoxycoumarin in the parental enzyme, and CYP2B35 A363I/A367V produced an activity profile like that generated by CYP2B37. CYP2B35 A363I/A367V/I477F showed 7-ethoxycoumarin and 7-ethoxy-4-(trifluoromethyl)coumarin O-dealkylation rates similar to those of CYP2B37 and higher than those of the double mutant. A CYP2B35 septuple mutant retained a CYP2B37-like activity profile. In contrast, the CYP2B37 septuple mutant produced very low rates of O-dealkylation of all substrates. As mutating residue 108 in either enzyme was detrimental, this change was removed from both septuple mutants. Remarkably, the CYP2B35 sextuple mutant produced an activity profile that was a hybrid of that of CYP2B35 and CYP2B37, whereas the CYP2B37 sextuple mutant had almost no O-dealkylation activity. Docking of 7-substituted coumarin derivatives into a model of the CYP2B35 sextuple mutant based on a previous crystal structure of the 4-(4-chlorophenyl)imidazole wild-type complex revealed how the mutant can exhibit activities of both CYP2B35 and CYP2B37.
- Published
- 2017
- Full Text
- View/download PDF
45. Platinum-Catalyzed Double Acylation of 2-(Aryloxy)pyridines via Direct C-H Activation.
- Author
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McAteer DC, Javed E, Huo L, and Huo S
- Abstract
A unique, platinum-catalyzed, direct C-H acylation of 2-(aryloxy)pyridines with acyl chlorides is discovered. The reaction requires neither an oxidant nor other additives. When both ortho positions of the aryl group are accessible, the double acylation occurs readily to produce the diacylated products. Aliphatic, aromatic, and α,β-unsaturated acyl groups can all be introduced. The acylation reaction may proceed through an analogous aromatic electrophilic substitution triggered by the nucleophilic attack of the platinum at the acyl chloride.
- Published
- 2017
- Full Text
- View/download PDF
46. Au-Loaded Hierarchical MoO 3 Hollow Spheres with Enhanced Gas-Sensing Performance for the Detection of BTX (Benzene, Toluene, And Xylene) And the Sensing Mechanism.
- Author
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Sui L, Zhang X, Cheng X, Wang P, Xu Y, Gao S, Zhao H, and Huo L
- Abstract
Monodisperse, hierarchical α-MoO
3 hollow spheres were fabricated using a facile template-free solvothermal method combined with subsequent calcination. Various quantities of Au nanoparticles (NPs) were deposited on the α-MoO3 hollow spheres to construct hybrid nanomaterials for chemical gas sensors and their BTX sensing properties were investigated. The 2.04 wt % Au-loaded α-MoO3 sensor can detect BTX effectively at 250 °C, especially, its responses to 100 ppm toluene and xylene are 17.5 and 22.1, respectively, which are 4.6 and 3.9 times higher than those of pure α-MoO3 hollow spheres at 290 °C. Besides, Au loading decreased the response times to toluene and xylene from 19 and 6 s to 1.6 and 2 s, respectively, lowered the working temperature from 290 to 250 °C as compared with those of pure α-MoO3 . The surface status of Au/α-MoO3 hollow spheres before and after contacting with toluene at 250 °C was analyzed through XPS technique. Possible oxidization product of toluene was confirmed by GC for the first time. The gas-sensing mechanism of the Au/α-MoO3 was speculated as the oxidation of toluene to water and carbon dioxide by chemisorbed oxygen and lattice oxygen. The possible reason related with improved gas-sensing properties of the Au-functionalized α-MoO3 was discussed.- Published
- 2017
- Full Text
- View/download PDF
47. Synthesis and Bioactivity of Diastereomers of the Virulence Lanthipeptide Cytolysin.
- Author
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Mukherjee S, Huo L, Thibodeaux GN, and van der Donk WA
- Subjects
- Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents chemistry, Dose-Response Relationship, Drug, Lactococcus lactis pathogenicity, Microbial Sensitivity Tests, Molecular Conformation, Perforin chemical synthesis, Perforin chemistry, Stereoisomerism, Structure-Activity Relationship, Virulence drug effects, Anti-Bacterial Agents pharmacology, Lactococcus lactis drug effects, Perforin pharmacology
- Abstract
Cytolysin, a two-component lanthipeptide comprising cytolysin S (CylL
S ″) and cytolysin L (CylLL ″), is the only family member to exhibit lytic activity against mammalian cells in addition to synergistic antimicrobial activity. A subset of the thioether cross-links of CylLS ″ and CylLL ″ have ll stereochemistry instead of the canonical dl stereochemistry in all previously characterized lanthipeptides. The synthesis of a CylLS ″ variant with dl stereochemistry is reported. Its antimicrobial activity was found to be decreased, but not its lytic activity against red blood cells. Hence, the unusual ll stereochemistry is not responsible for the lytic activity., Competing Interests: Notes The authors declare no competing financial interest.- Published
- 2016
- Full Text
- View/download PDF
48. Three-Bladed Rylene Propellers with Three-Dimensional Network Assembly for Organic Electronics.
- Author
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Meng D, Fu H, Xiao C, Meng X, Winands T, Ma W, Wei W, Fan B, Huo L, Doltsinis NL, Li Y, Sun Y, and Wang Z
- Abstract
Two kinds of conjugated C3-symmetric perylene dyes, namely, triperylene hexaimides (TPH) and selenium-annulated triperylene hexaimides (TPH-Se), are efficiently synthesized. Both TPH and TPH-Se have broad and strong absorption in the region 300-600 nm together with suitable LUMO levels of about -3.8 eV. Single-crystal X-ray diffraction studies show that TPH displays an extremely twisted three-bladed propeller configuration and a unique 3D network assembly in which three PBI subunits in one TPH molecule have strong π-π intermolecular interactions with PBI subunits in neighboring molecules. The integration of selenophene to TPH endows TPH-Se with a more distorted propeller configuration and a more compact 3D network assembly due to the Se···O interactions. A single-crystal transistor confirms that both TPH and TPH-Se possess good electron-transport ability. TPH and TPH-Se acceptor-based solar cells show high power conversion efficiency of 8.28% and 9.28%, respectively, which mainly results from the combined properties of broad and strong absorption ability, appropriate LUMO level, desirable aggregation, high electron mobility, and good film morphology with the polymer donor.
- Published
- 2016
- Full Text
- View/download PDF
49. A General Method for Constructing Two-Dimensional Layered Mesoporous Mono- and Binary-Transition-Metal Nitride/Graphene as an Ultra-Efficient Support to Enhance Its Catalytic Activity and Durability for Electrocatalytic Application.
- Author
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Liu B, Huo L, Si R, Liu J, and Zhang J
- Abstract
We constructed a series of two-dimensional (2D) layered mesoporous mono- and binary-transition-metal nitride/graphene nanocomposites (TMN/G, TM = Ti, Cr, W, Mo, TiCr, TiW, and TiMo) via an efficient and versatile nanocasting strategy for the first time. The 2D layered mesoporous TMN/G is constituted of small TMN nanoparticles composited with graphene nanosheets and has a large surface area with high porosity. Through decoration with well-dispersed Pt nanoparticles, 2D layered mesoporous Pt/TMN/G catalysts can be obtained that display excellent catalytic activity and stability for methanol electro-oxidation reactions (MOR) and oxygen reduction reactions (ORR) in both acidic and alkaline media. The 2D layered mesoporous binary-Pt/TMN/G catalysts possess catalytic activity superior to that of mono-Pt/TMN/G, graphene free Pt/TMN, Pt/G, and Pt/C catalysts. Encouragingly, the 2D layered mesoporous Pt/Ti0.5Cr0.5N/G catalyst exhibits the best electrocatalytic performance for both MOR and ORR. The outstanding electrocatalytic performance of the Pt/Ti0.5Cr0.5N/G catalyst is rooted in its large surface area, high porosity, strong interaction among Pt, Ti0.5Cr0.5N, and graphene, an excellent electron transfer property facilitated by N-doped graphene, and the small size of Pt and Ti0.5Cr0.5N nanocrystals. The outstanding catalytic performance provides the 2D layered mesoporous Pt/Ti0.5Cr0.5N/G catalyst with a wide range of application prospects in direct methanol fuel cells in both acidic and alkaline media. The synthetic method may be available for constructing other 2D layered mesoporous metal nitrides, carbides, and phosphides.
- Published
- 2016
- Full Text
- View/download PDF
50. Universal Strategy to Fabricate a Two-Dimensional Layered Mesoporous Mo2C Electrocatalyst Hybridized on Graphene Sheets with High Activity and Durability for Hydrogen Generation.
- Author
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Huo L, Liu B, Zhang G, and Zhang J
- Abstract
A universal strategy was developed for fabrication of a highly active and durable precious-metal-free mesoporous Mo2C/graphene (m-Mo2C/G) electrocatalyst with a two-dimensional layered structural feature via a nanocasting method using glucose as a carbon source and an in-stiu assembled mesoporous KIT-6/graphene (KIT-6/G) as a template. The m-Mo2C/G catalyst exhibits high catalytic activity and excellent durability for hydrogen evolution reaction (HER) over a wide pH range, which displays a small onset potential of 8 mV, owerpotential (η10) for driving a cathodic current density of 10 mA·cm(-2) of 135 mV, a Tafel slope of 58 mV·dec(-1), and an exchange current density of 6.31 × 10(-2) mA·cm(-2) in acidic media and an onset potential of of 41 mV, η10 of 128 mV, Tafel slope of 56 mV·dec(-1), and an exchange current density of 4.09 × 10(-2) mA·cm(-2) in alkaline media, respectively. Furthermore, such an m-Mo2C/G electrocatalyst also gives about 100% Faradaic yield and shows excellent durability during 3000 cycles of a long-term test, and the catalytic current remains stable over 20 h at fixed overpotentials, making it a great potential application prospect for energy issues.
- Published
- 2016
- Full Text
- View/download PDF
Catalog
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