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Construction of a mutant of Actinoplanes sp. N902-109 that produces a new rapamycin analog

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Chinese Journal of Natural Medicines 2018年第3期16卷 210-218页

作者： huang he GAO Ping ZHAO Qi HU Hai-Feng Shanghai Institute of Pharmaceutical Industry Shanghai 201203 China Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200032 China

In the present study, we introduced point mutations into Ac_rap A which encodes a polyketide synthase responsible for rapamycin biosynthesis in Actinoplanes sp. N902-109, in order to construct a mutant with an inactivated enoylreductase(ER) domain, which was able to synthesize a new rapamycin analog. Based on the homologous recombination induced by double-strand breaks in chromosome mediated by endonuclease I-SceI, the site-directed mutation in the first ER domain of Ac_rapA was introduced using non-replicating plasmid pL YERIA combined with an I-SceI expression plasmid. Three amino acid residues of the active center, Ala-Gly-Gly, were converted to Ala-Ser-Pro. The broth of the mutant strain SIPI-027 was analyzed by HPLC and a new peak with the similar UV spectrum to that of rapamycin was found. The sample of the new peak was prepared by solvent extraction, column chromatography, and crystallization methods. The structure of new compound, named as SIPI-rapxin, was elucidated by determining and analyzing its MS and NMR spectra and its biological activity was assessed using mixed lymphocyte reaction(MLR). An ER domain–deficient mutant of Actinoplanes sp. N902-109, named as SIPI-027, was constructed, which produced a novel rapamycin analog SIPI-rapxin and its structure was elucidated to be 35, 36-didehydro-27-O-demethylrapamycin. The biological activity of SIPI-rapxin was better than that of rapamycin. In conclusion, inactivation of the first ER domain of rap A, one of the modular polyketide synthase responsible for macro-lactone synthesis of rapamycin, gave rise to a mutant capable of producing a novel rapamycin analog, 35, 36-didehydro-27-O-demethylrapamycin, demonstrating that the enoylreductase domain was responsible for the reduction of the double bond between C-35 and C-36 during rapamycin synthesis.

关键词： Actinoplanes sp. N902-109 Rapamycin Structural analog Polyketide synthase Enoylreductase

SymTopo: An automatic tool for calculating topological properties of nonmagnetic crystalline materials

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Chinese Physics B 2019年第8期28卷 294-305页

作者： Yuqing he Yi Jiang Tiantian Zhang he huang Chen Fang Zhong Jin Computer Network Information Center Chinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Beijing National Laboratory for Condensed Matter Physics and Institute of PhysicsChinese Academy of SciencesBeijing 100190China Center of Scientific Computing Applications & Research Chinese Academy of SciencesBeijing 100190China

Topological materials have novel properties both in their bulk and boundaries,thereby attracting a wide interest in the theoretical and experimental *** recent development of the topological quantum chemistry and symmetrybased indicator theory in this field has significantly simplified the procedure for determining the topological properties of nonmagnetic crystalline ***,a large number of new topological materials have been found by scanning large crystal *** study provides details on the algorithm used in the Catalogue of Topological Electronic ***,based on the algorithm,we develop an automatic package named SymTopo,which calculates the symmetry representations of any given nonmagnetic crystalline material and predicts its topological *** package may facilitate the discovery of more topological materials in the future.

关键词： topological insulators topological semimetals topological invariants high-throughput research mode

An Analogue of Beurling's Theorem for the Jacobi Transform

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Acta Mathematica Sinica,English Series 2009年第1期25卷 85-94页

作者： Ji Zheng huang he Ping LIU Jian Ming LIU LMAM School of Mathematical Sciences Peking University Beijing lO0871 P. R. China

In this paper, we prove Beurling＇s theorem for the Jacobi transform, from which we derive some other versions of uncertainty principles.

关键词： Jacobi transform uncertainty principle Beurling's theorem Abel transform

Remnants of the amalgamation of the east and west Cathaysia blocks revealed by a short-period dense nodal array

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Geoscience Frontiers 2023年第1期14卷 207-214页

作者： he huang Xuzhang Shen Jian Xu Rui Gao Wentian Wang Qiming Zhou Qiangqiang huang Guangdong Provincial Key Laboratory of Geodynamics and Geohazards School of Earth Sciences and EngineeringSun Yat-Sen UniversityGuangzhou 510275China Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) Zhuhai 519082China

The Cathaysia block located at the southeast South China block(SCB)is considered formed by the amalgamation of the east and west Cathaysia blocks along the Gaoyao-Huilai and Zhenghe-Dapu deep faults(here referred as GHF and ZDF,respectively).Although the extension of the ZDF to the northeast,which represents the amalgamation of the two sub-blocks has been confirmed,the development of the GHF to the southwest remains to be *** better constrain the detailed deep structure beneath the southwest Cathaysia,which hold great significance for revealing the evolution of the SCB,a linear seismic array with 331 nodal geophones was deployed across the Sanshui basin(SSB).Combining with the regional 10 permanent stations(PA),we obtained two profiles with teleseismic P-wave receiver function *** most obvious feature in our results is the ascending Moho towards the coastal area,which is consistent with the passive margin continental and extensional tectonic *** stacking profile from the dense nodal array(DNA)shows that the Moho is offset beneath the transition zone of the Nanling orogeny and *** deduce that this offset may be casued by the deep extension of the GHF,which represents the remnants of the amalgamation of the Cathaysia *** the other evidences,we infer that the widespread and early erupted felsic magmas in the SSB may have resulted from lithospheric materials that were squeezed out to the *** relative higher Bouguer gravity and heat flow support the consolidation of magmas and the residual warm state in the shallow crustal scale beneath the *** sporadic basaltic magmas in the middle SSB may have a close relation to deep extension of the GHF,which serves as a channel for upwelling hot materials.

关键词： Dense short-period nodal array Teleseismic receiver function Cathaysia block Offset Moho High V_(p)/V_(s)ratio

Synthesis, Structure and Photophysical Properties of a Dinuclear Copper (Ⅰ) Complex Based on Phosphinopyridine and Diphosphine Mixed-ligands

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Chinese Journal of Structural Chemistry 2021年第2期40卷 175-181,145页

作者： YU Wen-Si huang Chun-Hua huang Xi-he Institute of Optical Crystalline Materials College of ChemistryFuzhou UniversityFuzhou 350116China

Treatment of bis(diphenylphosphino)methane(dppm)and 2-(diphenylphosphanyl)pyridine(dpppy)with Cu(CH_(3)CN)_(4)BF_(4)afforded a dinuclear Cu(I)complex[Cu_(2)(dpppy)_(2)(dppm)(CH_(3)CN)](BF_(4))_(2)·3CH_(2)Cl_(2)(1).Complex 1 was structurally characterized by X-ray single-crystal analysis and its photophysical properties were studied in *** crystallizes in triclinic space group P1^(-)with a=13.0834(8),b=13.5568(8),c=21.8544(11)Å,α=76.090(5)°,β=80.803(5)°,γ=64.582(6)°,V=3391.3(3)Å^(3),Z=2,M_(r)=1507.42,D_(c)=1.476 g/cm^(3),F(000)=1532,GOOF=1.071,the final R=0.0700 for 9041 observed reflections with I>2σ(I)and wR=0.2063 for all *** complex contains a Cu_(2)-core structure surrounded by one dppm and two dpppy ligands in a head-to-head *** the crystalline phase,complex 1 exhibits bright bluish-green photoluminescence(λ_(max)=488 nm)with high quantum yield(ϕ=0.57)at room *** is still a relatively high emission quantum yield(ϕ=0.36)in doped PMMA thin film with 20 wt%dopant of complex *** emission peaks of 1 in dichloromethane solution and doped PMMA(20 wt%)thin films are 510 and 494 nm,respectively,showing a very slight bathochromic shift compared to that in crystalline *** phenomenon might be attributed to its rigid conformation that precludes the possible distortion of copper centers in the excited state.

关键词： copper(I)complex thermally activated delayed fluorescence crystalline structure

Rapid Shape Memory and p H-modulated Spontaneous Actuation of Dopamine Containing Hydrogels

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Chinese Journal of Polymer Science 2017年第10期35卷 1297-1306页

作者： Jie-xin Liao Jia-he huang 王涛 Wei-xiang Sun 童真 Research Institute of Materials Science South China University of Technology Guangzhou 510640 China State Key Laboratory of Luminescent Materials and Devices South China University of Technology Guangzhou 510640 China

The dopamine containing hydrogels with rapid responsive shape memory capability were synthesized by a one-pot method. The temporary shape of hydrogel was fixed within 20 s in Na OH solution by the tris-complex crosslinking of metalligand complex between Fe3＋ ions and catechol groups, while the permanent shape was recovered completely in HCl solution within 60 s upon the change from tris-complex to mono-complex. The hydrogel showed unique spontaneous actuation behavior. It could curl spontaneously without further external force deformation when immersed in Na OH solution again after the first shape recovery in HCl solution. This might be attributed to the competitive result of swelling and additional tris-complex crosslinking formation when immersed in Na OH solution. In addition, the hydrogels also had proper modulus, elongation ratio and tensile strength. Such hydrogel provides a new candidate material for designing soft actuators and robots modulated with spontaneous actuating.

关键词： DNA hydrogel duplex supramolecular cytosine assemble assembly motif intermolecular acrylamide

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

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Signal Transduction and Targeted Therapy 2021年第11期6卷 3230-3245页

作者： Xia Li Mi Shao Xiangjun Zeng Pengxu Qian he huang Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouPeople’s Republic of China Liangzhu Laboratory Zhejiang University Medical Center1369 West Wenyi RoadHangzhou311121People’s Republic of China Institute of hematology Zhejiang UniversityHangzhouZhejiangPeople’s Republic of China Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy HangzhouZhejiangPeople’s Republic of China Center of Stem Cell and Regenerative Medicine Zhejiang University School of MedicineHangzhouPeople’s Republic of China

Cytokine release syndrome(CRS)embodies a mixture of clinical manifestations,including elevated circulating cytokine levels,acute systemic inflammatory symptoms and secondary organ dysfunction,which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza,SARS-CoV and COVID-19,immunotherapy of tumor,after chimeric antigen receptor T(CAR-T)therapy,and in monogenic disorders and autoimmune ***,severe CRS is a very significant and life-threatening complication,which is clinically characterized by persistent high fever,hyperinflammation,and severe organ ***,CRS is a double-edged sword,which may be both helpful in controlling tumors/viruses/infections and harmful to the *** a high incidence and high levels of cytokines are features of CRS,the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain *** the present review,we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of *** that CRS is the major adverse event in human diseases and intervention therapy,our review delineates the characteristics,kinetics,signaling pathways,and potential mechanisms of CRS,which shows its clinical relevance for achieving both favorable efficacy and low toxicity.

关键词： cytokine release kinetics

Aureobasidium subglaciale F134 is a bifunctional whole-cell biocatalyst for Baeyer-Villiger oxidation or selective carbonyl reduction controllable by temperature

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Chinese Journal of Chemical Engineering 2020年第12期28卷 3044-3051页

作者： Liqun Shen Ran Cang Guang Yang Anqi Zeng he huang Zhigang Zhang School of Pharmaceutical Sciences Nanjing Tech UniversityNanjing 211816China State Key Laboratory of Materials-Oriented Chemical Engineering Nanjing Tech UniversityNanjing 211816China

The microbial production of either ester/lactones or enantio-enriched alcohols through Baeyer-Villiger oxidation or stereoselective reduction of ketones,respectively,is possible by using whole cells of *** F134 as a bifunctional *** chemoselective pattern of acetophenone biotransformation catalyzed by these cells can be regulated through reaction temperature,directing the reaction either towards oxidation or reduction *** Baeyer–Villiger oxidation activity of *** F134 whole cells is particularly dependent on reaction *** was transformed efficiently to phenol via the primary Baeyer–Villiger product phenyl acetate at 20℃ after 48 h with 100% *** contrast,at 35℃,enantio-enriched(S)-1-phenylethanol was obtained as the sole product with 64% conversion and 89% *** addition,*** F134 cells also catalyze the selective reduction of various structurally different aldehydes and ketones to alcohols with 40% to 100% yield,indicating broad substrate spectrum and good enantioselectivity in relevant *** study provides a bifunctional biocatalyst systemthat can be used in Baeyer–Villiger oxidation aswell as in asymmetric carbonyl reduction,setting the stage for future work concerning the identification and isolation of the respective enzymes.

关键词： Biocatalysis Whole cells Baeyer-Villiger oxidation Aureobasidium subglaciale Carbonyl reduction

Impacts of exercise interventions on different diseases and organ functions in mice

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Journal of Sport and health Science 2020年第1期9卷 53-73页

作者： Shanshan Guo Yiru huang Yan Zhang he huang Shangyu Hong Tiemin Liu School of Kinesiology Shanghai University of SportShanghai 20043&China State Key Laboratory of Genetic Engineering School of Life SciencesFudan UniversityShanghai 200032China Key Laboratory of Molecular Enzymology and Engineering of Ministry of Education College of Life ScienceJilin UniversityChangchun 130012China Department of Endocrinology and Metabolism State Key Laboratory of Genetic EngineeringSchool of Life SciencesZhongshan HospitalFudan UniversityShanghai 200032China

Background'. In recent years, much evidence has emerged to indicate that exercise can benefit people when performed properly. This reviewsummarizes the exercise interventions used in studies involving mice as they are related to special diseases or physiological status. To furtherunderstand the effects of exercise interventions in treating or preventing diseases, it is important to establish a template for exercise interventionsthat can be used in future exercise-related ***'. PubMed was used as the data resource for articles. To identify studies related to the effectiveness of exercise interventions for treatingvarious diseases and organ functions in mice, we used the following search language: (exercise [Title] OR training [Title] OR physical activity[Title]) AND (mice [title/abstract] OR mouse [title/abstract] OR mus [title/abstract]). To limit the range of search results, we included 2 filters:one that limited publication dates to "in 10 years,^ and one that sorted the results as "best match^^. Then we grouped the commonly used exercisemethods according to their similarities and differences. We then evaluated the effectiveness of the exercise interventions for their impact on diseasesand organ functions in 8 different ***'. A total of 331 articles were included in the analysis procedure. The articles were then segmented into 8 systems for which the exerciseinterventions were used in targeting and treating disorders: motor system (60 studies), metabolic system (45 studies), cardio-cerebral vascularsystem (58 studies), nervous system (74 studies), immune system (32 studies), respiratory system (7 studies), digestive system (1 study), and thesystem related to the development of cancer (54 studies). The methods of exercise interventions mainly involved the use of treadmills, voluntarywheel-running, forced wheel-running, swimming, and resistance training. It was found that regardless of the specific exercise method used, mostof them demonstrat

关键词： Diseases Exercise intervention Mice Organ functions