1,507 results on '"Yufen Zhao"'
Search Results
102. Palladium-catalyzed C–P cross-coupling of allenic alcohols with H-phosphonates leading to 2-phosphinoyl-1,3-butadienes
- Author
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Pengxiang Xu, Junhong Chen, Wenyu Sun, Yuxing Gao, Yufen Zhao, Shanshan Hu, Sipei Li, and Runmin Zhao
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Allene ,Metals and Alloys ,Regioselectivity ,chemistry.chemical_element ,General Chemistry ,Combinatorial chemistry ,Catalysis ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Coupling (electronics) ,chemistry.chemical_compound ,chemistry ,Materials Chemistry ,Ceramics and Composites ,Palladium - Abstract
The first facile, efficient, atom-economical and regioselective palladium-catalyzed direct C–P cross-coupling of unprotected allenic alcohols with H-phosphonates for the one-pot synthesis of structurally diverse multisubstituted 2-phosphinoyl-1,3-butadienes was developed. This strategy would enrich the allene chemistry and afford new scaffolds to construct complex molecular skeletons.
- Published
- 2021
103. A Potential Biomarker Phosphate for Life Exploration on Mars Biomarker for Life
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Yufen ZHAO, Yan LIU, Biling HUANG, and Xinchang GAO
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Complementary and alternative medicine ,Pharmaceutical Science ,Pharmacology (medical) - Published
- 2021
104. Straightforward Synthesis of Succinimide-Fused Pyrrolizidines by A Three-Component Reaction of α-Diketone, Amino Acid, and Maleimide
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Hua Zhao, Jian Wei, Peng Shen, Yeting Guo, Hongbin Zhai, and Yufen Zhao
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chemistry.chemical_classification ,Diketone ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Azomethine ylide ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Catalysis ,Cycloaddition ,0104 chemical sciences ,Amino acid ,chemistry.chemical_compound ,Succinimide ,Yield (chemistry) ,Functional group ,Maleimide - Abstract
An efficient, one-pot, three-component [3+2] cycloaddition reaction of azomethine ylide obtained from α-dicarbonyl compounds (cyclic and acyclic diketone or keto ester) and amino acids with maleimides under catalyst-free conditions has been developed. This cascade protocol shows high efficiency and remarkable functional group tolerance, and the ubiquitous succinimide-fused pyrrolizidines with a highly compact and strained scaffold were obtained with high yield and excellent diastereoselectivity. Furthermore, this novel and atom-economical strategy could be performed on a gram scale with comparable reaction efficiency.
- Published
- 2020
105. Visible-Light-Induced Phosphorylation of Imidazo-Fused Heterocycles under Metal-Free Conditions
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Xiao-Yun Li, Tao Shi, Kai Sun, Yufen Zhao, Lingbo Qu, Xiaolan Chen, Bing Yu, and Fan Gao
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010405 organic chemistry ,Chemistry ,Organic Chemistry ,Compatibility (geochemistry) ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,Solvent ,chemistry.chemical_compound ,Metal free ,Phosphorylation ,Irradiation ,Phosphine ,Visible spectrum - Abstract
A metal-free and base-free procedure for the phosphorylation of imidazo[1,2-a]pyridines with phosphine oxides under the irradiation of visible light at room temperature in green solvent was reported, featuring mild and sustainable conditions, convenient operation, as well as good functional group compatibility.
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- 2020
106. A rapid selection strategy for umami peptide screening based on machine learning and molecular docking
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Chen Li, Ying Hua, Daodong Pan, Lulu Qi, Chaogeng Xiao, Yongzhao Xiong, Wenjing Lu, Yali Dang, Xinchang Gao, and Yufen Zhao
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Molecular Docking Simulation ,Machine Learning ,Sheep ,Taste ,Animals ,General Medicine ,Peptides ,Food Science ,Analytical Chemistry ,Receptors, G-Protein-Coupled - Abstract
Umami peptides have been the focus of umami studies in recent years because of their high nutritional value and flavor activity. However, the existing screening methods of umami peptides were cumbersome, complex, time-consuming and laborious, and it was difficult to achieve high-throughput screening. In this study, a novel umami peptide rapid screening model was designed and by using lamb bone aqueous extract as raw material, through the step-by-step screening of peptidomics, machine learning methods, and molecular docking technology. Results showed that six novel peptides about lamb bones were obtained, which verified the feasibility of the model and could be used for high-throughput screening of umami peptides. Results of molecular docking between umami peptide and T1R3 subunit revealed that the main interaction forces were hydrogen bonding and electrostatic interaction, and the key binding sites were GLU277 and SER146. It provides the basis for studying the binding mechanism of umami peptide.
- Published
- 2022
107. Transport, Stability, and In Vivo Hypoglycemic Effect of a Broccoli-Derived DPP-IV Inhibitory Peptide VPLVM
- Author
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Jingyan Pei, Zhu Liu, Daodong Pan, Yufen Zhao, Yali Dang, and Xinchang Gao
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Dipeptidyl-Peptidase IV Inhibitors ,Dipeptidyl Peptidase 4 ,Diabetes Mellitus ,Humans ,Hypoglycemic Agents ,General Chemistry ,Brassica ,Caco-2 Cells ,General Agricultural and Biological Sciences ,Peptides - Abstract
Diabetes is a major metabolic disease that requires long-term pharmacotherapy. Bioactive peptides have unique advantages such as higher potency, selectivity, and safety over small molecules and have achieved great success in the treatment of diabetes. We previously isolated a dipeptidyl peptidase-IV (DPP-IV) inhibitory peptide VPLVM with IC
- Published
- 2022
108. Discovery and validation of bladder cancer related excreted nucleosides biomarkers by dilution approach in cell culture supernatant and urine using UHPLC-MS/MS
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Qi Chang, Pinjin Chen, Jianjian Yin, Guisen Liang, Yuanheng Dai, Yudong Guan, Yongqiang Chen, Yufen Zhao, Yong-Jie Lu, Lirong Zhang, Dongkui Song, and Hang Yuan
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Urinary Bladder Neoplasms ,Tandem Mass Spectrometry ,Biophysics ,Biomarkers, Tumor ,Cell Culture Techniques ,Humans ,Nucleosides ,Biochemistry ,Chromatography, High Pressure Liquid ,Chromatography, Liquid ,Body Fluids - Abstract
The exploration of nucleoside changes in human biofluids has profound potential for cancer diagnosis. Herein, we developed a rapid methodology to quantify 17 nucleosides by UHPLC-MS/MS. Five pairs of isomers were successfully separated within 8 min. The ME was mostly eliminated by sample dilution folds of 1000 for urine and 40 for CCS. The optimized method was firstly applied to screen potential nucleoside biomarkers in CCS by comprising bladder cancer cell lines (5637 and T24) and normal human bladder cell line SV-HUC-1 together with student's t-test and OPLS-DA. Nucleosides with significant differences in the supernatant of urine samples were also uncovered comparing BCa with the non-tumor group, as well as a comparison of BCa recurrence group with the non-recurrence group. By intersecting the differential nucleosides in CCS and urine supernatant, and then further confirmed using validation sets, the combination of m
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- 2022
109. Development and application of a sensitive phosphonium-hydrazide oligosaccharide labelling reagent in capillary electrophoresis- electrospray ionization- mass spectrometry
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Qianru Ma, Wentao Wang, Xu Yang, Yunhong Chen, Yan Liu, Hongxu Chen, and Yufen Zhao
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Spectrometry, Mass, Electrospray Ionization ,Hydrazines ,Immunoglobulin G ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Organic Chemistry ,Electrophoresis, Capillary ,Oligosaccharides ,Indicators and Reagents ,General Medicine ,Biochemistry ,Analytical Chemistry - Abstract
Glycosylation is one of the most ubiquitous post-translational modifications (PTM) of proteins. Although the ionization efficiency of native glycans is fairly low, with the assistance of chemical derivation strategies, mass spectrometry (MS) has been extensively used in glycomics because of its high sensitivity, accuracy, and speed. In this study, a novel glycan labelling reagent, (4-hydrazidebutyl) triphenylphosphonium bromide (P
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- 2022
110. The Varied Frustrated Lewis Pair Reactivity of the Germylene Phosphaketene (CH{(CMe)(2,6‐ i Pr 2 C 6 H 3 N)} 2 )GePCO
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Yile Wu, Zhao Zhao, Ting Chen, Jingjie Tan, Zheng‐Wang Qu, Stefan Grimme, Yufen Zhao, and Douglas W. Stephan
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Organic Chemistry ,General Chemistry ,Catalysis - Published
- 2022
111. The chameleon-like nature of elusive cobalt-oxygen intermediates in C-H bond activation reactions
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Anran Zhou, Xuanyu Cao, Huanhuan Chen, Dongru Sun, Yufen Zhao, Wonwoo Nam, and Yong Wang
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Inorganic Chemistry - Abstract
C–H bond activation in which reaction rates are correlated with the pKa of C–H bonds proceeds via a PCET(PT) mechanism.
- Published
- 2022
112. Simultaneous analysis of amino acids based on discriminative
- Author
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Biling, Huang, Lihua, Xu, Zhao, Zhao, Ning, Wang, Yufen, Zhao, and Shaohua, Huang
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Magnetic Resonance Spectroscopy ,Humans ,Trypsin ,Amino Acid Sequence ,Amines ,Amino Acids ,Peptide Fragments - Abstract
The simultaneous analysis of amino acids (AAs) is crucial for human health, diagnosis and treatment of disease, and nutritional quality evaluation in foodstuffs. Here, we establish an easy and rapid method for the simultaneous analysis of AAs using a single reagent 2-(trifluoromethyl)benzaldehyde (oTFMBA) based on spectral-separation-enabled
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- 2022
113. Mars Exploration and Chirality of Celestial Minerals.
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Hui Zhang, Xinling Liu, Ziang Nan, Xuming Sha, Shilin Zhang, Shaohua Huang, Jihao Su, and Yufen Zhao
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MARTIAN exploration ,HISTORY of science ,CHIRALITY ,MINERALS ,MODERN society - Abstract
From the Earth to the Moon to Mars, human beings have never stopped exploring for treasures. From Iceland spar to quartz to amethysts, the optical phenomena presented by these sparkling and clear ores have inspired scientists to make persistent efforts to reveal "what is light" and "the origin of chirality" throughout the history of science. This has contributed to the advancement of science, technology, and modern society, and will continue to have an immeasurable impact on the future of science and technology. [ABSTRACT FROM AUTHOR]
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- 2023
- Full Text
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114. MiR-21-5p in macrophage-derived extracellular vesicles affects podocyte pyroptosis in diabetic nephropathy by regulating A20
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Mengxing Pan, Lina Wu, Na Jing, Yongping Song, Feng Guo, Yufen Zhao, Xiaojun Ma, Hao-Hao Zhang, Ao Shen, Guijun Qin, L Zhao, and Xiaoxu Ding
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Inflammasomes ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Cell Line ,Flow cytometry ,Podocyte ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Western blot ,Cell-Derived Microparticles ,Pyroptosis ,medicine ,Animals ,Macrophage ,Diabetic Nephropathies ,Tumor Necrosis Factor alpha-Induced Protein 3 ,chemistry.chemical_classification ,Gene knockdown ,Reactive oxygen species ,medicine.diagnostic_test ,Podocytes ,Macrophages ,Inflammasome ,Cell biology ,Disease Models, Animal ,MicroRNAs ,Glucose ,medicine.anatomical_structure ,Gene Expression Regulation ,chemistry ,Sweetening Agents ,030220 oncology & carcinogenesis ,medicine.drug - Abstract
Podocyte pyroptosis, characterized by inflammasome activation, plays an important role in inflammation-mediated diabetic nephropathy (DN). Our study aimed to investigate whether miR-21-5p in macrophage-derived extracellular vesicles (EVs) could affect podocyte injury in DN. EVs were extracted after the treatment of RAW 264.7 (mouse macrophage line) with high glucose (HG). The podocyte pyroptosis was determined using the flow cytometry and the western blot. After the knockdown of miR-21-5p in HG-induced RAW264.7 cells, we injected the extracted EVs into DN model mice. The level of miR-21-5p was higher in HG-stimulated macrophage-derived EVs than in normal glucose-cultured macrophage-derived EVs. The co-culture of EVs and podocytes promoted reactive oxygen species (ROS) production and activation of inflammatory in MPC5 cells (mouse podocyte line). However, restraint of miR-21-5p in EVs reduced ROS production and inhibit inflammasome activation in MPC5 cells, thereby reducing podocytes injury. Meanwhile, we found that miR-21-5p inhibited the A20 expression through binding with its 3′-untranslated regions in MPC5 cells. Further studies showed that A20 was also involved in the regulation of miR-21-5p of RAW 264.7-derived EVs on MPC5 injury. At the same time, it was also proved in the DN model mice that miR-21-5p in macrophage-derived EVs could regulate podocyte injury. MiR-21-5p in macrophage-derived EVs can regulate pyroptosis-mediated podocyte injury by A20 in DN.
- Published
- 2020
115. Organocatalytic Atroposelective Construction of Axially Chiral N-Aryl Benzimidazoles Involving Carbon–Carbon Bond Cleavage
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Zhenbang Lou, Ningning Man, Hua Fu, Haijun Yang, Yuming Li, and Yufen Zhao
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inorganic chemicals ,chemistry.chemical_classification ,010405 organic chemistry ,Chemistry ,organic chemicals ,Aryl ,Organic Chemistry ,Enantioselective synthesis ,010402 general chemistry ,Cleavage (embryo) ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Carbon–carbon bond ,Molecule ,heterocyclic compounds ,Physical and Theoretical Chemistry ,Axial symmetry - Abstract
Axially chiral compounds widely occur in natural products, biologically active molecules, ligands, and catalysts, and their efficient and enantioselective synthesis is highly desirable. Herein, we ...
- Published
- 2020
116. Imaging Hg2+-Induced Oxidative Stress by NIR Molecular Probe with 'Dual-Key-and-Lock' Strategy
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Di Zhang, Xiaojing Han, Yong Ye, Yufen Zhao, Jianfei Liu, Yongru Zhang, Xiaopeng Yang, and Jun Tang
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Chemistry ,010401 analytical chemistry ,technology, industry, and agriculture ,Glutathione ,equipment and supplies ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Fluorescence ,In vitro ,0104 chemical sciences ,Analytical Chemistry ,chemistry.chemical_compound ,Downregulation and upregulation ,In vivo ,Toxicity ,medicine ,Biophysics ,Molecular probe ,Oxidative stress - Abstract
Mercury (Hg) is considered an extremely toxic heavy metal which is extremely harmful to both the human body and environment. In addition, Hg2+-induced oxidative stress also exerts a crucial role to play in pathophysiological mechanisms of mercury toxicity. Thus, efficient and specific fluorescent probes for imaging Hg2+-induced oxidative stress are necessary. In the present study, we rationally design a novel Hg2+-activated and ICT-based NIR emission fluorescent probe NIR-HO for sequentially monitoring the ONOO- level with a "dual-key-and-lock" strategy. The probe NIR-HO showed rapid response and excellent specificity and sensitivity for the detection of Hg2+ and ONOO- in vitro. Cell imaging demonstrated that Hg2+-induced oxidative stress was involved in ONOO- upregulation. Also, GSH, NAC, and EDTA were employed as excellent detoxifying drugs against Hg2+-induced toxicity. Moreover, the probe NIR-HO was successfully used for imaging Hg2+ and ONOO- in vivo. In brief, NIR-HO provides a simple and powerful approach which can be used to image Hg2+-induced oxidative stress in the pathological environment.
- Published
- 2020
117. TfOH-Catalyzed Phosphinylation of 2,3-Allenols into γ-Ketophosphine Oxides
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Yufen Zhao, Xianhua Huang, Minning Wang, Pengxiang Xu, Yuxing Gao, Shanshan Hu, and Runmin Zhao
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010405 organic chemistry ,Organic Chemistry ,Bond formation ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis ,Metal ,chemistry.chemical_compound ,chemistry ,visual_art ,Functional group ,visual_art.visual_art_medium - Abstract
The first facile and efficient acid-catalyzed direct coupling of a wide range of unprotected 2,3-allenols with arylphosphine oxides was developed, offering a general, one-step approach for the synthesis of structurally diverse γ-ketophosphine oxides accompanied by concurrent C-P/C═O bond formation with remarkable functional group tolerance and complete atom-economy under metal- and additive-free conditions. Mechanistic studies showed that this transformation involved a rearrangement and a phospha-Michael reaction.
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- 2020
118. Synthesis of 2-phenoxyl-2-oxo-1,4,2-oxazaphosphinanes from a three component reaction
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Xiling Ding, Yufen Zhao, Wenzhu Bi, Zi-Jie Li, Xiaolan Chen, and Wen-Jie Zhang
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Inorganic Chemistry ,010405 organic chemistry ,Chemistry ,Computational chemistry ,Component (thermodynamics) ,Organic Chemistry ,Kabachnik–Fields reaction ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences - Abstract
A one-pot synthetic strategy was developed for the synthesis of heterocyclic 1,4,2-oxazaphosphinanes via a three component Kabachnik-Fields reaction of 2-aminophenol, diphenyl H-phosphonate and car...
- Published
- 2020
119. Copper-Catalyzed Remote C(sp3)–H Phosphorothiolation of Sulfonamides and Carboxamides in a Multicomponent Reaction
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Yufen Zhao, Yumeng Zhang, Chen Luo, Shanshan Shi, Shaohua Zhuo, Guo Tang, and Pengbo Zhang
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010405 organic chemistry ,Chemistry ,Organic Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Copper catalyzed ,Surface modification ,Organic chemistry ,Organic synthesis ,Physical and Theoretical Chemistry - Abstract
The catalytic C(sp3)–H functionalization is highly desirable yet challenging in organic synthesis. Incorporation of the SP(O)(OR)2 group through C(sp3)–H functionalization remains unexplored. We he...
- Published
- 2020
120. NMR-based investigation into protein phosphorylation
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Yufen Zhao, Biling Huang, Hongwei Yao, and Yan Liu
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inorganic chemicals ,Cell signaling ,Magnetic Resonance Spectroscopy ,Phosphatase ,macromolecular substances ,02 engineering and technology ,environment and public health ,Biochemistry ,03 medical and health sciences ,Cell Signaling Process ,Structural Biology ,Animals ,Humans ,Protein phosphorylation ,Phosphorylation ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Kinase ,Chemistry ,Proteins ,General Medicine ,Nuclear magnetic resonance spectroscopy ,021001 nanoscience & nanotechnology ,Cell biology ,enzymes and coenzymes (carbohydrates) ,Crosstalk (biology) ,Eukaryotic Cells ,bacteria ,0210 nano-technology ,Protein Processing, Post-Translational ,Signal Transduction - Abstract
Protein phosphorylation is a major switch mechanism for cell signaling process regulation within eukaryotic cells. Abnormal phosphorylation is either a cause or consequence of human diseases. It is imperative to comprehensively delve into the relationship between phosphorylation events and cell signaling transduction. NMR spectroscopy, a potent tool for monitoring protein phosphorylation events, is applicable for identifying the phospho-sites, quantifying the kinetic rate, discovering kinase/phosphatase inhibitors and delineating phosphorylation crosstalk with other post-translational modifications. Here, we decipher the recent progress in the investigation of eukaryotic protein O-phosphorylation by NMR spectroscopy. We focus specifically on the dynamic establishment of O-phosphorylation and its role in the cell signaling processes. Simultaneously, we positively propose a strategy for the investigation of acid-labile and "high-energy" N-phosphorylation by NMR spectroscopy. We expect that the strategy could enrich the investigation of protein N-phosphorylation.
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- 2020
121. Facile Synthesis of Novel Benzoylthiophene C-Nucleoside Analogues via Coupling of Sugar Alkynes, Aroyl Chlorides, and 1,4-Dithiane-2,5-diol
- Author
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Yang Luo, Fei Gao, Yufen Zhao, Fuyi Zhang, and Hong Liu
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chemistry.chemical_classification ,010405 organic chemistry ,organic chemicals ,Organic Chemistry ,Diol ,Alkyne ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Benzoyl chloride ,chemistry ,Thiophene ,Organic chemistry ,C nucleosides ,Sugar ,Dithiane - Abstract
Concise synthesis of novel benzoylthiophene C-nucleoside analogues has been achieved by the reaction of various terminal sugar alkynes with substituted benzoyl chlorides and 1,4-dithiane-2,5-diol, and subsequent dilute HCl-promoted dehydration in one pot. The sugar alkynes include pyranosides, furanosides, and acyclic sugar. The benzoyl chloride has various substituents. Twenty-eight examples are given. The desired products are obtained in 70–89% yields, and the mechanism has been clarified by isolation of the intermediate.
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- 2020
122. Bioorthogonal Ligation and Cleavage by Reactions of Chloroquinoxalines with ortho ‐Dithiophenols
- Author
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Yufen Zhao, Youshan Li, Hua Fu, Hongyun Li, Zhenbang Lou, and Haijun Yang
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010405 organic chemistry ,General Chemistry ,General Medicine ,010402 general chemistry ,Cleavage (embryo) ,01 natural sciences ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,Chemical kinetics ,chemistry.chemical_compound ,Quinoxaline ,Nucleophile ,chemistry ,Biotin ,Molecule ,Bioorthogonal chemistry ,Conjugate - Abstract
A bioorthogonal ligation and cleavage method via reactions of chloroquinoxalines (CQ) and ortho-dithiophenols (DT) is presented. Double nucleophilic substitutions of ortho-dithiophenols to chloroquinoxalines provide conjugates containing tetracyclic benzo[5,6][1,4]dithiino[2,3-b]quinoxaline with strong built-in fluorescence together with release of the other functional molecules. Three cleavable linkers were designed and successfully used in release of the molecules containing biotin from the protein conjugates. The CQ-DT bioorthogonal reactions can be applied for the bioorthogonal ligations, bioorthogonal cleavages, and trans-tagging of proteins, and show advantages of readily accessible unnatural orthogonal groups, appealing reaction kinetics (k2 ≈1.3 m-1 s-1 ), excellent biocompatibility of orthogonal groups, and high stability of conjugates. This complements previous bioorthogonal reactions and is a new route for protein-fishing applications and in-gel fluorescence analysis.
- Published
- 2020
123. An AIE probe for imaging mitochondrial SO2-induced stress and SO2 levels during heat stroke
- Author
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Yufen Zhao, Jianfei Liu, Di Zhang, Jinsa Li, Xiaojing Han, Jun Tang, Yong Ye, and Xiaopeng Yang
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010405 organic chemistry ,Chemistry ,Cell ,Metals and Alloys ,General Chemistry ,Mitochondrion ,010402 general chemistry ,medicine.disease_cause ,medicine.disease ,complex mixtures ,01 natural sciences ,Catalysis ,respiratory tract diseases ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Bursting ,medicine.anatomical_structure ,Induced stress ,Materials Chemistry ,Ceramics and Composites ,Biophysics ,medicine ,Stroke ,Oxidative stress - Abstract
A probe, MITO-TPE, was developed for imaging mitochondrial SO2 with good selectivity, high sensitivity, and a fast response time. Cell imaging indicated that SO2-induced oxidative stress may cause damage to cells through O2˙− bursting. MITO-TPE has here been used to image the misregulation of SO2 levels in mitochondria during heat stroke for the first time.
- Published
- 2020
124. Coupled electron and proton transfer in the piperidine drug metabolism pathway by the active species of cytochromes P450
- Author
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Zhiqiang Fu, Yufen Zhao, Yong Wang, Dongru Sun, Zexing Qu, Lili Yang, and Jiali Gao
- Subjects
Molecular Structure ,Chemistry ,Stereochemistry ,Imine ,Electrons ,Hydrogen atom ,Tautomer ,Homolysis ,Inorganic Chemistry ,chemistry.chemical_compound ,Cytochrome P-450 Enzyme System ,Piperidines ,Moiety ,Density functional theory ,Piperidine ,Protons ,Density Functional Theory ,Bond cleavage - Abstract
Ring contraction of piperidine drugs by cytochrome P450 enzymes (P450s) is among the most important drug metabolisms for human beings. However, the underlying mechanism remains elusive and controversial even after decades of experimental study. Kohn-Sham density functional theory (KS-DFT) combined with multistate density functional theory (MSDFT) was used to explore the chemical nature of ring contraction of 2,2',6,6'-tetramethylpiperidine (2,2',6,6'-TMPi) mediated by the active species, Compound I of P450s. Our calculated results demonstrate that ring contraction is initiated by N-H bond activation. MSDFT combined with KS-DFT methods revealed that the N-H bond activation involves an initial tightly coupled electron-proton pair, essentially of hydrogen atom transfer (HAT) character prior to the diabatic crossing point, after which the mechanism is dominated by the concerted electron proton transfer (CEPT) product formation. The nascent N-centered radical intermediate undergoes electron tautomerism via rate-limiting homolytic C-C bond cleavage (ca. 21 kcal mol-1) to form a ring-opened, carbon-centered radical imine intermediate. The following barrierless C-N bond formation concomitant with hydroxyl rebound from the Fe-OH moiety forms the ring-contracted pyrrolidine product. To the best of our knowledge, this is the first application of MSDFT in P450 chemistry, and also the first comprehensive theoretical report on the ring contraction mediated by P450, in which the revealed new mechanism will undoubtedly promote relative rational drug design.
- Published
- 2020
125. A bifunctional fluorescent sensor for CCCP-induced cancer cell apoptosis imaging
- Author
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Jun Tang, Yongru Zhang, Yufen Zhao, Xiaofei Zhu, Huawei Niu, and Yong Ye
- Subjects
Carbonyl Cyanide m-Chlorophenyl Hydrazone ,Apoptosis ,Inflammation ,complex mixtures ,Catalysis ,chemistry.chemical_compound ,Limit of Detection ,Materials Chemistry ,medicine ,Humans ,Sulfur Dioxide ,skin and connective tissue diseases ,Bifunctional ,Fluorescent Dyes ,Microscopy, Confocal ,Chemistry ,Metals and Alloys ,General Chemistry ,Hydrogen-Ion Concentration ,Fluorescence ,Carbonyl cyanide ,respiratory tract diseases ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Spectrometry, Fluorescence ,Cancer cell apoptosis ,Ceramics and Composites ,Biophysics ,sense organs ,medicine.symptom ,HeLa Cells - Abstract
The detailed mechanism and the extent of pH/SO2 changes during apoptosis remain unknown. The developed sensor NPCF for SO2 and pH dual detection illustrates that SO2 can reduce the inflammation caused by LPS and the acidification of the environment. The levels of SO2 and pH change during carbonyl cyanide m-chlorophenylhydrazone (CCCP)-induced apoptosis.
- Published
- 2020
126. Nondestructive capture, release, and detection of circulating tumor cells with cystamine-mediated folic acid decorated magnetic nanospheres
- Author
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Minning Wang, Yufen Zhao, Hengyi Xu, Huahuan Cai, Yaohui He, Fulai Li, and Yan Liu
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Detection limit ,Lysis ,Cystamine ,Biomedical Engineering ,Cell Separation ,General Chemistry ,General Medicine ,Neoplastic Cells, Circulating ,Proteomics ,Molecular biology ,Dithiothreitol ,In vitro ,chemistry.chemical_compound ,Folic Acid ,HEK293 Cells ,Circulating tumor cell ,chemistry ,Folate receptor ,Neoplasms ,Magnets ,Humans ,General Materials Science ,Nanospheres ,HeLa Cells - Abstract
Circulating tumor cell (CTC) detection and enumeration have been considered as a noninvasive biopsy method for the diagnosis, characterization, and monitoring of various types of cancers. However, CTCs are exceptionally rare, which makes CTC detection technologically challenging. In the past few decades, much effort has been focused on highly efficient CTC capture, while the activity of CTCs has often been ignored. Here, we develop an effective method for nondestructive CTC capture, release, and detection. Folic acid (FA), as a targeting molecule, is conjugated on magnetic nanospheres through a cleavable disulfide bond-containing linker (cystamine) and a polyethylene glycol (PEG2k) linker, forming MN@Cys@PEG2k-FA nanoprobes, which can bind with folate receptor (FR) positive CTCs specifically and efficiently, leading to the capture of CTCs with an external magnetic field. When approximately 150 and 10 model CTCs were spiked in 1 mL of lysis blood, 93.1 ± 2.9% and 80.0 ± 9.7% CTCs were recovered, respectively. In total, 81.3 ± 2.6% captured CTCs can be released from MN@Cys@PEG2k-FA magnetic nanospheres by treatment with dithiothreitol. The released CTCs are easily identified from blood cells for specific detection and enumeration combined with immunofluorescence staining with a limit of detection of 10 CTC mL-1 lysed blood. Moreover, the released cells remain healthy with high viability (98.6 ± 0.78%) and can be cultured in vitro without detectable changes in morphology or behavior compared with healthy untreated cells. The high viability of the released CTCs may provide the possibility for downstream proteomics research of CTCs; therefore, cultured CTCs were collected for proteomics. As a result, 3504 proteins were identified. In conclusion, the MN@Cys@PEG2k-FA magnetic nanospheres prepared in this study may be a promising tool for early-stage cancer diagnosis and provide the possibility for downstream analysis of CTCs.
- Published
- 2020
127. Direct synthesis of phosphorotrithioites and phosphorotrithioates from white phosphorus and thiols
- Author
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Yueqiao Wang, Xinlei Huangfu, Yufen Zhao, Guo Tang, Yinwei Cao, and Guozhang Lu
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chemistry.chemical_classification ,Green chemistry ,Base (chemistry) ,010405 organic chemistry ,White Phosphorus ,010402 general chemistry ,01 natural sciences ,Pollution ,0104 chemical sciences ,Solvent ,chemistry.chemical_compound ,chemistry ,Functional group ,Environmental Chemistry ,Organic chemistry ,Molecule - Abstract
White phosphorus (P4) is still the major commercial P-atom source for the production of organophosphorus compounds. Conventionally, C–S–P bonds were constructed from environmentally questionable P(O)X directly or indirectly. From the green chemistry point of view, formation of C–S–P bonds from inorganic molecule P4 in an easy-to-operate and atom-economical way is essential because it will avoid the hazardous chlorination process. Only five methods for the formation of C–S–P bonds from P4 have been developed over the past 70 years. Here, the first general and high-yielding synthesis of P(SR)3 and P(O)(SR)3 involving P4 and thiols is presented. With the use of KOH or K2CO3 as a base and DMSO–toluene as a solvent, both arythiols and alkylthiols are tolerant in this transformation. The reaction is characterized by a complete conversion of white phosphorus. This operationally simple and environmentally sound reaction shows a broad scope of substrates and good functional group tolerance. Moreover, this method can be easily adapted to large-scale preparation.
- Published
- 2020
128. A three-channel fluorescent probe to image mitochondrial stress
- Author
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Zipeng Li, Yufen Zhao, Yong Ye, Xiaofei Zhu, Huawei Niu, Jun Tang, and Yongru Zhang
- Subjects
Molecular Structure ,Channel (digital image) ,Chemistry ,Proton Magnetic Resonance Spectroscopy ,Metals and Alloys ,General Chemistry ,Fluorescence ,Mass Spectrometry ,Catalysis ,Mitochondria ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Stress (mechanics) ,Stress, Physiological ,MCF-7 Cells ,Materials Chemistry ,Ceramics and Composites ,Biophysics ,Humans ,Sulfur Dioxide ,Carbon-13 Magnetic Resonance Spectroscopy ,Fluorescent Dyes ,HeLa Cells - Abstract
Dual-recognition probes based on one reacting site inevitably encounter competition problems. Here, NPClA, a two-photon fluorescent probe based on a dual-site response for SO2/HOCl, was developed and applied in imaging mitochondrial stress.
- Published
- 2020
129. Novel flame retardant rigid spirocyclic biphosphate based copolymer gel electrolytes for sodium ion batteries with excellent high-temperature performance
- Author
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Jinyun Zheng, Xiangming Feng, Wenjie Li, Yufen Zhao, Weihua Chen, and Yiwan Yang
- Subjects
chemistry.chemical_classification ,Materials science ,Renewable Energy, Sustainability and the Environment ,02 engineering and technology ,General Chemistry ,Polymer ,Electrolyte ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Electrochemistry ,01 natural sciences ,Pentaerythritol ,0104 chemical sciences ,chemistry.chemical_compound ,Monomer ,chemistry ,Chemical engineering ,Ionic conductivity ,General Materials Science ,Thermal stability ,In situ polymerization ,0210 nano-technology - Abstract
Polymer electrolytes are recognized as the optimal solution to resolve the bottlenecks of liquid electrolytes such as safety hazards, decomposition and sodium dendrite problems. Herein, a novel multifunctional monomer which combines nonflammable spirocyclic pentaerythritol diphosphates and the easily polymerizable acrylates are designed and prepared, and the corresponding cross-linked gel copolymer electrolytes are synthesized by in situ polymerization with ethyl acrylate and trifluoroethyl methacrylate. The gel polymer electrolytes have good thermal stability, good interfacial compatibility, a high ionic conductivity of 3.26 × 10−3 S cm−1, a high ion transfer number of 0.604, and excellent electrochemical stability of up to 4.9 V (vs. Na+/Na), and thus could be used as possible less flammable electrolytes. The Na3V2(PO4)3 cells using gel polymer electrolytes deliver better long term cycle stability than the corresponding liquid electrolyte, which retain 81.4% and 69.5% capacity after 1600 cycles, respectively. Moreover, the gel polymer electrolyte based Na3V2(PO4)3 cell exhibits much higher capacity and superior cycle stability compared to the liquid cell when running at an elevated temperature of 60 °C. Furthermore, within the operating temperature, the gel polymer electrolyte cell has better reversibility of temperature adjustment. In addition, gel polymer electrolytes also exhibit good cycle performance with organic cathodes, holding great promise for the production of safer phosphate-containing cell systems.
- Published
- 2020
130. Synthesis of mixed phosphorotrithioates from white phosphorus
- Author
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Yinwei Cao, Yufen Zhao, Guozhang Lu, Xinlei Huangfu, Guo Tang, Peiyun Chen, and Yue Zhang
- Subjects
chemistry.chemical_classification ,Base (chemistry) ,White Phosphorus ,Chemistry ,Phosphorus ,Halide ,chemistry.chemical_element ,Alkylation ,Pollution ,Medicinal chemistry ,Solvent ,Environmental Chemistry ,Alkyl ,Bond cleavage - Abstract
The first general and high-yielding synthesis of mixed phosphorotrithioates (R1S)2P(O)SR2 involving white phosphorus, disulfides, and alkyl halides is presented, which provides the shortest and environmentally benign method to synthesize these compounds of practical importance. Only one method for the formation of (R1S)2P(O)SR2 from elemental phosphorus has been developed. Here, with the use of KOH as a base and DMSO–toluene as a solvent, various disulfides couple readily with white phosphorus to give O-potassium S,S-dialkylphosphorotrithioates (R1S)2P(S)OK in almost quantitative yields, which react with alkyl halides to form (R1S)2P(O)SR2 in high yields. The reaction is characterized by the complete conversion of white phosphorus. Moreover, this method can be easily adapted to large-scale preparation. Our mechanistic data suggest that the attack of RSK on S,S,S-trialkyl phosphorotrithioates and subsequent C–S bond cleavage, the Michaelis–Arbuzov-like dealkylation, are the key steps in the formation of (R1S)2P(S)OK.
- Published
- 2020
131. Metal-organic framework nanoparticles as a free radical scavenger improving the stability of epoxy under high dose gamma irradiation
- Author
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Shuai Wang, Leilei Song, Shengkai Liu, Xiaoyuan Pei, Yufen Zhao, Chunying Min, Ruiqi Shao, Tianshuai Ma, Yue Yin, Zhiwei Xu, and Chunhong Wang
- Subjects
Polymers and Plastics ,Mechanics of Materials ,Materials Chemistry ,Condensed Matter Physics - Published
- 2023
132. Determination of the Amino Acid Recruitment Order in Early Life by Genome-Wide Analysis of Amino Acid Usage Bias
- Author
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Mingxiao Zhao, Ruofan Ding, Yan Liu, Zhiliang Ji, and Yufen Zhao
- Subjects
Evolution, Molecular ,Base Composition ,LUCA ,pseudotime analysis ,genetic codon ,proteogenesis ,recruitment ,Amino Acids ,Codon ,Codon Usage ,Molecular Biology ,Biochemistry ,Genome-Wide Association Study - Abstract
The mechanisms shaping the amino acids recruitment pattern into the proteins in the early life history presently remains a huge mystery. In this study, we conducted genome-wide analyses of amino acids usage and genetic codons structure in 7270 species across three domains of life. The carried-out analyses evidenced ubiquitous usage bias of amino acids that were likely independent from codon usage bias. Taking advantage of codon usage bias, we performed pseudotime analysis to re-determine the chronological order of the species emergence, which inspired a new species relationship by tracing the imprint of codon usage evolution. Furthermore, the multidimensional data integration showed that the amino acids A, D, E, G, L, P, R, S, T and V might be the first recruited into the last universal common ancestry (LUCA) proteins. The data analysis also indicated that the remaining amino acids most probably were gradually incorporated into proteogenesis process in the course of two long-timescale parallel evolutionary routes: I→F→Y→C→M→W and K→N→Q→H. This study provides new insight into the origin of life, particularly in terms of the basic protein composition of early life. Our work provides crucial information that will help in a further understanding of protein structure and function in relation to their evolutionary history.
- Published
- 2021
133. Radical-induced denitration of
- Author
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Kangdong, Mo, Xiaocong, Zhou, Ju, Wu, and Yufen, Zhao
- Abstract
A robust dearomative denitration of nitroarene derivatives induced by a radical
- Published
- 2021
134. A bifunctional fluorescent probe based on PETICT for simultaneously recognizing Cys and H
- Author
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Huawei, Niu, Yuhan, Duan, Yuanyuan, Zhang, Xinting, Hua, Chuan, Xu, Zhaozhou, Li, Jinliang, Ma, Fangyuan, Qin, Yaping, Zhai, Yong, Ye, and Yufen, Zhao
- Subjects
Oxadiazoles ,Positron-Emission Tomography ,Humans ,Cysteine ,Glutathione ,Ethers ,Fluorescent Dyes - Abstract
Most reported probes that respond to Cysteine (Cys) and Hydrogen sulfide (H
- Published
- 2021
135. Technique development of high-throughput and high-sensitivity sample preparation and separation for proteomics
- Author
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Yufen Zhao, Minyang Zheng, Zhenbin Zhang, and Perry G. Wang
- Subjects
Proteomics ,Chromatography ,Materials science ,Clinical Biochemistry ,Separation (statistics) ,General Medicine ,Analytical Chemistry ,High-Throughput Screening Assays ,Specimen Handling ,Medical Laboratory Technology ,Separation method ,Technique development ,Humans ,Sample preparation ,Sensitivity (control systems) ,General Pharmacology, Toxicology and Pharmaceutics ,Throughput (business) - Abstract
Sample preparation and separation methods determine the sensitivity and the quantification accuracy of the proteomics analysis. This article covers a comprehensive review of the recent technique development of high-throughput and high-sensitivity sample preparation and separation methods in proteomics research.
- Published
- 2021
136. Gas‐phase fragmentation of protonated 3‐phenoxy imidazo[1,2‐a] pyridines using tandem mass spectrometry and computational chemistry
- Author
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Yufen Zhao, Hong Chen, Yuexiu Wang, Yanchun Guo, Shigai Li, and Shuxia Cao
- Subjects
Fragmentation (mass spectrometry) ,Computational chemistry ,Chemistry ,Protonation ,Tandem mass spectrometry ,Spectroscopy ,Gas phase - Abstract
Imidazo[1,2-a] pyridine is one of the pharmaceutically important scaffolds and has been widely studied due to its extensive biological activities. In this work, electrospray ionization tandem mass spectrometry (ESI-MS/MS) in positive mode was used to study the gas-phase fragmentation behavior of a series of 3-phenoxy imidazo[1,2-a] pyridines. Proposed fragmentation pathways were supported by ESI-MS/MS data and computational thermochemistry. Homolytic cleavage of the 3-phenoxy C-O bond was the characteristic fragmentation of 3-phenoxy imidazo [1,2-a] pyridines. The eliminations of the one substituted phenoxy radical and CO produced other diagnostic ions for 3-phenoxy imidazo [1,2-a] pyridines, which were useful to identify the 3-phenoxy group and imidazo [1,2-a] pyridine scaffold. The results contribute to the further understanding of the gas-phase fragmentation of 3-phenoxy imidazo [1,2-a] pyridines and the identification of other analogs using tandem mass spectrometry techniques.
- Published
- 2021
137. Micronized Palmitoylethanolamide Ameliorates Methionine- and Choline-Deficient Diet–Induced Nonalcoholic Steatohepatitis via Inhibiting Inflammation and Restoring Autophagy
- Author
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Yufen Zhao, Long Li, Huabin Ma, Jiaji Hu, Jie Yao, Hanglu Ying, Jin Wenhui, and Longhe Yang
- Subjects
Pharmacology ,autophagy ,Palmitoylethanolamide ,Autophagy ,nutritional and metabolic diseases ,food and beverages ,AMPK ,RM1-950 ,medicine.disease ,Neuroprotection ,chemistry.chemical_compound ,chemistry ,inflammation ,Fibrosis ,medicine ,oxidative stress ,Pharmacology (medical) ,Therapeutics. Pharmacology ,Liver function ,nonalcoholic steatohepatitis ,Steatosis ,Hepatic fibrosis ,palmitoylethanolamide ,Original Research - Abstract
Nonalcoholic steatohepatitis (NASH) has become one of the serious causes of chronic liver diseases, characterized by hepatic steatosis, hepatocellular injury, inflammation and fibrosis, and lack of efficient therapeutic agents. Palmitoylethanolamide (PEA) is an endogenous bioactive lipid with various pharmacological activities, including anti-inflammatory, analgesic, and neuroprotective effects. However, the effect of PEA on nonalcoholic steatohepatitis is still unknown. Our study aims to explore the potential protective role of PEA on NASH and to reveal the underlying mechanism. In this study, the C57BL/6 mice were used to establish the NASH model through methionine- and choline-deficient (MCD) diet feeding. Here, we found that PEA treatment significantly improved liver function, alleviated hepatic pathological changes, and attenuated the lipid accumulation and hepatic fibrosis in NASH mice induced by MCD diet feeding. Mechanistically, the anti-steatosis effect of PEA may be due to the suppressed expression of ACC1 and CD36, elevated expression of PPAR-α, and the phosphorylation levels of AMPK. In addition, hepatic oxidative stress was greatly inhibited in MCD-fed mice treated with PEA via enhancing the expression and activities of antioxidant enzymes, including GSH-px and SOD. Moreover, PEA exerted a clear anti-inflammatory effect though ameliorating the expression of inflammatory mediators and suppressing the NLRP3 inflammasome pathway activation. Furthermore, the impaired autophagy in MCD-induced mice was reactivated with PEA treatment. Taken together, our research suggested that PEA protects against NASH through the inhibition of inflammation and restoration of autophagy. Thus, PEA may represent an efficient therapeutic agent to treat NASH.
- Published
- 2021
138. Novel Broccoli-Derived Peptides Hydrolyzed by Trypsin with Dual-Angiotensin I-Converting Enzymes and Dipeptidyl Peptidase-IV-Inhibitory Activities
- Author
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Jingyan Pei, Daodong Pan, Zhu Liu, Tingyi Zhou, Yali Dang, Xinchang Gao, and Yufen Zhao
- Subjects
chemistry.chemical_classification ,Dipeptidyl-Peptidase IV Inhibitors ,Chemistry ,Angiotensin-Converting Enzyme Inhibitors ,General Chemistry ,Brassica ,Pharmacology ,medicine.disease ,Trypsin ,Hydrolysate ,Dipeptidyl peptidase ,Rats ,Mice ,Enzyme ,Oral administration ,Diabetes mellitus ,Renin–angiotensin system ,medicine ,Animals ,Angiotensin I ,General Agricultural and Biological Sciences ,Peptides ,IC50 ,medicine.drug - Abstract
Broccoli-derived peptides show beneficial metabolic effects, and it is necessary to examine their exact functional sequences. First, peptides from the trypsin hydrolysate of broccoli proteins were isolated and identified using column chromatography and quadrupole time-of-flight mass spectrometry. After that, their functions were verified by oral administration. The results identified two novel peptides as Leu-Pro-Gly-Val-Leu-Pro-Val-Ala (LPGVLPVA) and Tyr-Leu-Tyr-Ser-Pro-Ala-Tyr (YLYSPAY). LPGVLPVA exhibited an ACE IC50 value of 0.776 ± 0.03 μM and a DPP-IV IC50 value of 392 ± 24 μM; YLYSPAY showed an ACE IC50 value of 8.52 ± 0.63 μM and a DPP-IV IC50 value of 181 ± 4 μM. Administration of the peptides reduced the blood pressure of spontaneously hypertensive rats and reduced blood glucose levels in the oral glucose tolerance test in mice. The results indicated that LPGVLPVA and YLYSPAY could be potential nutritional candidates for hypertensive and diabetic people, especially for those with diabetes associated with hypertension.
- Published
- 2021
139. A bifunctional fluorescent probe based on 'AND logic' for the simultaneous recognition of H
- Author
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Huawei, Niu, Xintong, Mi, Xinting, Hua, Yuanyuan, Zhang, Yaping, Zhai, Fangyuan, Qin, Yong, Ye, and Yufen, Zhao
- Subjects
MCF-7 Cells ,Humans ,Nitrogen Oxides ,Fluorescent Dyes - Abstract
The reaction of NO and H
- Published
- 2021
140. One-pot synthesis and multiple MS/MS fragmentation studies of phospholysine peptides
- Author
-
Yufen Zhao, Songsen Fu, Xuelian Zhao, and Feng Ni
- Subjects
Phosphopeptides ,Chemistry ,Stereochemistry ,Lysine ,Organic Chemistry ,Chemistry Techniques, Synthetic ,Mass spectrometry ,Chemical synthesis ,Dissociation (chemistry) ,Analytical Chemistry ,NMR spectra database ,Electron-transfer dissociation ,Electron transfer ,Fragmentation (mass spectrometry) ,Tandem Mass Spectrometry ,Amino Acid Sequence ,Phosphorylation ,Spectroscopy ,Histidine - Abstract
RATIONALE Compared with phosphorylation of arginine and histidine, the study of phosphorylation of lysine lags far behind. The major challenges toward the current study of phosphorylation of lysine include synthesis and unambiguous phosphosite identification. This study provided a simple chemical synthesis method to construct phospholysine peptides (pLys peptides) and investigated their fragmentation under multiple activation types. METHODS Herein, we developed a synthetic method for pLys peptides in aqueous solution within one pot. Two peptides were lysine-phosphorylated using this method. The purified pLys peptides were first characterized using NMR, then were subjected to nano-liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) analysis under multiple fragmentation method including collision-induced dissociation (CID), higher energy collisional dissociation (HCD), electron transfer dissociation (ETD), electron transfer/higher energy collisional dissociation (EThcD), and ultraviolet photodissociation (UVPD) fragmentation to investigate the relevant diagnostic ions. RESULTS Two pLys peptides were synthesized with a moderate yield following an easily handled experimental protocol. NMR spectra showed the phosphorylation occurred on e-NH2 of lysine but not other groups. As for the fragmentation, in general, pLys immonium ions and phosphate-related neutral losses were ubiquitous among spectra derived from these activation types except for ETD. Using these ions as diagnostic ions, the misassigned phosphosites by algorithm could be recorrected. UVPD-generated spectra owned good sequence-coverage and abundant fragment ions, with pLys immonium ions and neutral losses of weak intensity. CONCLUSIONS A synthetic method was developed for pLys peptides in aqueous solution within one pot. The characteristic pLys immonium ions and phosphate-related neutral loss could serve as the diagnostic ions for unambiguous phosphosite identification of pLys peptides. In addition, UVPD was promising for the identification of pLys peptides.
- Published
- 2021
141. The efficacy and safety of dupilumab in Chinese patients with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled study
- Author
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J. Wang, X Yao, Y Guo, X. Zhu, X Gao, Y Ding, Marcella Ruddy, L Wu, N Amin, M Wang, Leda Mannent, John T. O'Malley, Xiaoming Liu, J Zhang, J Gu, Q Liu, L Bai, Yufen Zhao, L.‐f. Li, L Liu, T Ota, J. Luo, S. Geng, Wei Li, Z Song, C Zhang, N Dang, H Su, L Dong, Ashish Bansal, Qianjin Lu, and E. Laws
- Subjects
Adult ,Male ,medicine.medical_specialty ,China ,Placebo-controlled study ,Eczema ,Dermatology ,Placebo ,Antibodies, Monoclonal, Humanized ,Eczema Area and Severity Index ,Severity of Illness Index ,Dermatitis, Atopic ,Double-Blind Method ,Internal medicine ,Injection site reaction ,Clinical endpoint ,Medicine ,Humans ,Adverse effect ,business.industry ,Incidence (epidemiology) ,medicine.disease ,Dupilumab ,Treatment Outcome ,Female ,business - Abstract
BACKGROUND Dupilumab is an antibody against interleukin-4 receptor α, used in the treatment of atopic dermatitis (AD). OBJECTIVES To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate-to-severe AD. METHODS In this randomized, double-blind, placebo-controlled, parallel-group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0-1 and a reduction from baseline of ≥ 2 points at week 16. RESULTS Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37-32·65; P
- Published
- 2021
142. Pyroptosis of syncytia formed by fusion of SARS-CoV-2 spike and ACE2-expressing cells
- Author
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Jiahuai Han, Zhoujie Zhu, Huabin Ma, Peipei Zhang, Yufen Zhao, Huaipeng Lin, Long Li, Shanshan Wang, Jinling Wang, and Yanguo Li
- Subjects
Cell death ,Programmed cell death ,Coronavirus disease 2019 (COVID-19) ,viruses ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Cell ,Biochemistry ,Correspondence ,Genetics ,medicine ,Molecular Biology ,Syncytium ,QH573-671 ,Chemistry ,Pyroptosis ,virus diseases ,Cell Biology ,biochemical phenomena, metabolism, and nutrition ,In vitro ,Cell biology ,medicine.anatomical_structure ,Mechanisms of disease ,Lytic cycle ,Apoptosis ,Cytology ,hormones, hormone substitutes, and hormone antagonists - Abstract
SARS-Cov-2 infected cells fused with the ACE2-positive neighboring cells forming syncytia. However, the effect of syncytia in disease development is largely unknown. We established an in vitro cell-cell fusion system and used it to mimic the fusion of SARS-CoV-2 infected cells with ACE2-expressing cells to form syncytia. We found that Caspase-9 was activated after syncytia formation, and Caspase-3/7 was activated downstream of Caspase-9, but it triggered GSDME-dependent pyroptosis rather than apoptosis. What is more, single cell RNA-sequencing data showed that both ACE2 and GSDME were expression in alveolar type 2 cells in human lung. We propose that pyroptosis is the fate of syncytia formed by SARS-CoV-2 infected host cells and ACE2-positive cells, which indicated that lytic death of syncytia may contribute to the excessive inflammatory responses in severe COVID-19 patients.
- Published
- 2021
143. A novel in-situ strategy for enantiomeric discrimination and selective identification of multicomponent carboxylic acids in foods
- Author
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Biling Huang, Lihua Xu, Jianxi Ying, Yufen Zhao, and Shaohua Huang
- Subjects
Magnetic Resonance Spectroscopy ,Pharmaceutical Preparations ,Carboxylic Acids ,Environmental Chemistry ,Stereoisomerism ,Biochemistry ,Spectroscopy ,Acetic Acid ,Analytical Chemistry - Abstract
Chiral carboxylic acids are ubiquitous in nature and are of pivotal importance in practical applications in the field of food science and pharmaceuticals. Simultaneous enantiomeric analysis of carboxylic acids mixtures is a significant research goal. Herein, we demonstrate a new strategy involving the use of the highly selective chiral derivatizing agent (R)-2-amino-1,1,1-trifluoropropane ((R)-TFPA) for the enantiomeric discrimination and selective identification of carboxylic acids in mixtures, even structurally similar drugs. The key success of this sensing approach lies in the distinguishable
- Published
- 2022
144. Dual-site fluorescent sensor for tracking lysosomal ATP and H2S during liver injury
- Author
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Xiaopeng Yang, Peiyao Xie, Jianfei Liu, Xiaojing Han, Di Zhang, Yong Ye, and Yufen Zhao
- Subjects
General Chemical Engineering ,Environmental Chemistry ,General Chemistry ,Industrial and Manufacturing Engineering - Published
- 2022
145. Different phosphorylation and farnesylation patterns tune Rnd3-14-3-3 interaction in distinct mechanisms
- Author
-
Yufen Zhao, Yong-Xiang Chen, Xue-Meng Sun, Jing-Yun Su, and Jun Hu
- Subjects
0303 health sciences ,Cell signaling ,Rnd3 ,Dimer ,Cooperativity ,Lipid-anchored protein ,General Chemistry ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Chemistry ,Monomer ,chemistry ,Prenylation ,Biophysics ,Phosphorylation ,030304 developmental biology - Abstract
Protein posttranslational modifications (PTMs) are often involved in the mediation or inhibition of protein–protein interactions (PPIs) within many cellular signaling pathways. Uncovering the molecular mechanism of PTM-induced multivalent PPIs is vital to understand the regulatory factors to promote inhibitor development. Herein, Rnd3 peptides with different PTM patterns as the binding epitopes and 14-3-3ζ protein were used as models to elucidate the influences of phosphorylation and farnesylation on binding thermodynamics and kinetics and their molecular mechanism. The quantitative thermodynamic results indicate that phosphorylated residues S210 and S218 (pS210 and pS218) and farnesylated C241 (fC241) enhance Rnd3–14-3-3ζ interactions in the presence of the essential pS240. However, distinct PTM patterns greatly affect the binding process. Initial association of pS240 with the phosphate-binding pocket of one monomer of the 14-3-3ζ dimer triggers the binding of pS210 or pS218 to another monomer, whereas the binding of fC241 to the hydrophobic groove on one 14-3-3ζ monomer induces the subsequent binding of pS240 to the adjacent pocket on the same monomer. Based on the experimental and molecular simulation results, we estimate that pS210/pS218 and pS240 mediate the multivalent interaction through an additive mechanism, whereas fC241 and pS240 follow an induced fit mechanism, in which the cooperativity of these two adjacent PTMs is reflected by the index ε described in our established thermodynamic binding model. Besides, these proposed binding models have been further used for describing the interaction between 14-3-3ζ and other substrates containing adjacent phosphorylation and lipidation groups, indicating their potential in general applications. These mechanistic insights are significant for understanding the regulatory factors and the design of PPI modulators., Different protein posttranslational modifications (PTMs) patterns affect the binding thermodynamics and kinetics and their molecular mechanism of multivalent protein–protein interaction (PPIs).
- Published
- 2021
146. Application of aromatic amide-derived atropisomers as chiral solvating agents for discrimination of optically active mandelic acid derivatives in
- Author
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Xiaojing, Zheng, Tingfeng, Tang, Li, Li, Li-Wen, Xu, Shaohua, Huang, and Yufen, Zhao
- Abstract
Non-biaryl atropisomers and their stereochemistry have attracted much attentions in the past years. However, application of the non-biaryl atropisomers as chiral solvating agents is yet to be explored. In this work, four aromatic amide-derived atropisomeric phosphine ligands (hosts) were used as chiral solvating agents to recognize various mandelic acid derivatives (guests) in
- Published
- 2021
147. Effects of Comonomers on the Performance of Stable Phosphonate-Based Gel Terpolymer Electrolytes for Sodium-Ion Batteries with Ultralong Cycling Stability
- Author
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Yufen Zhao, Weihua Chen, Xiangming Feng, Jinyun Zheng, Wenjie Li, and Sun Yanke
- Subjects
chemistry.chemical_classification ,Materials science ,Radical polymerization ,Ionic bonding ,Sodium-ion battery ,02 engineering and technology ,Polymer ,Electrolyte ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Electrochemistry ,01 natural sciences ,Arrhenius plot ,0104 chemical sciences ,chemistry ,Chemical engineering ,General Materials Science ,Thermal stability ,0210 nano-technology - Abstract
Gel polymer electrolyte (GPE) is one of the most promising alternatives to solve the bottlenecks of nonaqueous liquid electrolytes such as decomposition, safety hazards, and growth of dendrites. In this work, three novel methyl phosphonate-based crosslinking gel terpolymer electrolytes with different comonomers are designed and prepared by in situ radical polymerization. The gel polymer electrolytes have excellent thermal stability, wide electrochemical windows (≥4.9 V), and high ionic conductivities (±3 mS cm-1), and may be used as less-flammable electrolytes for sodium-ion batteries. 31P NMR spectra, Arrhenius plot, and density functional theory (DFT) calculations confirm that multifunctional phosphonate structural units promote the dissociation of NaClO4 and help to transport the sodium ions freely in the polymer framework. X-ray photoelectron spectroscopy (XPS) results show that the gel polymer electrolytes have the capability of inhibiting liquid electrolyte decomposition and the formation of the stable solid electrolyte interphase (SEI) film. The Na3V2(PO4)3/GPE/Na cells exhibit better ultralong cycling stability and enhanced temperature performance than those of liquid cells. Strikingly, GPE1 has the best comprehensive electrochemical performance, especially the rate performance and long-term cycling stability with a capacity retention ratio of 82.6% after 3500 cycles, which indicates that different comonomers have obvious effects on the performance. Therefore, the full cell of SnS2/GPE1/Na3V2(PO4)3 is evaluated and delivers good cycling stability of 500 cycles, holding a great prospect for the design and production of phosphorus-containing electrolytes for safer sodium-ion batteries.
- Published
- 2021
148. Author response for 'Application of Aromatic Amide‐Derived Atropisomers as Chiral Solvating Agents for Discrimination of Optically Active Mandelic Acid Derivatives in 1 H NMR Spectroscopy'
- Author
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Shaohua Huang, Xiaojing Zheng, Tingfeng Tang, Li Li, Li-Wen Xu, and Yufen Zhao
- Subjects
chemistry.chemical_compound ,Atropisomer ,chemistry ,Stereochemistry ,Amide ,Proton NMR ,Optically active ,Mandelic acid ,Spectroscopy - Published
- 2021
149. 8a, a New Acridine Antiproliferative and Pro-Apoptotic Agent Targeting HDAC1/DNMT1
- Author
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Huabin Ma, Yufen Zhao, Haoxiang Qiu, Ning Wang, Ze Wang, Tao Wang, Yifan Gu, Bin Zhang, Qiting Zhang, Ziyan Wang, and Xinyuan Chen
- Subjects
anti-proliferative ,DNA (Cytosine-5-)-Methyltransferase 1 ,QH301-705.5 ,Antineoplastic Agents ,Histone Deacetylase 1 ,DNA methyltransferase ,Catalysis ,Article ,Inorganic Chemistry ,acridine ,Cell Line, Tumor ,Neoplasms ,Humans ,Epigenetics ,Physical and Theoretical Chemistry ,Biology (General) ,Molecular Biology ,QD1-999 ,Spectroscopy ,Cell Proliferation ,biology ,Chemistry ,Organic Chemistry ,DNMT1 ,apoptosis ,General Medicine ,U937 Cells ,HDAC1 ,Computer Science Applications ,Cell biology ,Gene Expression Regulation, Neoplastic ,Histone Deacetylase Inhibitors ,Molecular Docking Simulation ,Histone ,Acetylation ,DNA methylation ,embryonic structures ,biology.protein ,Histone deacetylase ,K562 Cells ,Epigenetic therapy ,epigenetic ,HeLa Cells - Abstract
Epigenetic therapy using histone deacetylase (HDAC) inhibitors has become an attractive project in new drug development. However, DNA methylation and histone acetylation are important epigenetic ways to regulate the occurrence and development of leukemia. Given previous studies, N-(2-aminophenyl)benzamide acridine (8a), as a histone deacetylase 1 (HDAC1) inhibitor, induces apoptosis and shows significant anti-proliferative activity against histiocytic lymphoma U937 cells. HDAC1 plays a role in the nucleus, which we confirmed by finding that 8a entered the nucleus. Subsequently, we verified that 8a mainly passes through the endogenous (mitochondrial) pathway to induce cell apoptosis. From the protein interaction data, we found that 8a also affected the expression of DNA methyltransferase 1 (DNMT1). Therefore, an experiment was performed to assess the binding of 8a to DNMT1 at the molecular and cellular levels. We found that the binding strength of 8a to DNMT1 enhanced in a dose-dependent manner. Additionally, 8a inhibits the expression of DNMT1 mRNA and its protein. These findings suggested that the anti-proliferative and pro-apoptotic activities of 8a against leukemia cells were achieved by targeting HDAC1 and DNMT1.
- Published
- 2021
150. Palladium‐Catalyzed Domino Heck/Phosphorylation towards 3,3‐Disubstituted Phosphinonyloxindoles
- Author
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Yufen Zhao, Zi'ang Wu, Xinlei Huangfu, Guo Tang, and Guozhang Lu
- Subjects
Chemistry ,Heck reaction ,Phosphorus ,Phosphorylation ,chemistry.chemical_element ,General Chemistry ,Medicinal chemistry ,Domino ,Catalysis ,Palladium - Published
- 2019
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