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A proteomic landscape of pharmacologic perturbations for functional relevance

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Journal of Pharmaceutical Analysis 2024年第1期14卷 128-139页

作者： Zhiwei liu Shangwen Jiang Bingbing Hao Shuyu Xie Yingluo liu Yuqi Huang heng Xu Cheng Luo Min Huang Minjia Tan jun-Yu Xu State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing210023China Zhongshan Institute for Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshanGuangdong528400China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing210023China

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

关键词： Proteomics Drug Perturbation Drug target Drug combination

A Novel Design of a Pre-separation Panel Structure to Protect Against the Impact of an Explosion in an Aircraft Plenum Chamber

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Acta Mechanica Solida Sinica 2024年第1期37卷 166-180页

作者： Zongxing liu Xiang Yang jun liu School of Aeronautics Northwestern Polytechnical UniversityXi'an 710072China COMAC Shanghai Aircraft Design and Research Institute Shanghai 201210China

To reduce the damage of the pressurizing panel structure of a fuselage caused by an explosion at the“least risk bomb location”in an aircraft structure,a new pre-separation panel structure was designed to resist blast loading.First,the dynamic strain response and morphology of impact damage of the new pre-separation panel were measured in an impact damage test.Second,the commercial software LS-DYNA was used to calculate the propagation of the blast shock wave,and the results were compared with empirical equations to verify the rationality of the numerical calculation method.Finally,the fluid–structure coupling method was used to calculate the damage process of the pre-separation panel structure under the impact of an explosion wave and an impact block.The calculated results were in good agreement with the test results,which showed the rationality of the calculation method and the model.The residual strength of the damaged pre-separation panel was significantly higher than that of the original damaged panel.The results show that the new pre-separation panel structure is reasonable and has certain significance for guiding the design of plenum chambers with strong resistance to implosion for aircraft fuselages.

关键词： Pre-separation panel structure Explosive response Residual strength Aircraft plenum chamber Least risk bomb location

Establishing Modular Cell-Free Expression System for the Biosynthesis of Bicyclomycin from a Chemically Synthesized Cyclodipeptide

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Chinese Journal of Chemistry 2024年第4期42卷 384-390页

作者： Yi-Pei liu Yu-heng Zhao Wen-Qi Zhang Lian Wu Linjuan Huang Gong-Li Tang jun-Bin He Shaanxi Natural Carbohydrate Resource Engineering Research Center College of Food Science and TechnologyNorthwest UniversityXi'anShaanxi710069 China State Key Laboratory of Chemical Biology Shanghai Institute of Organic ChemistryUniversity of Chinese Academy of Sciences(CAS)CASShanghai200032 China School of Chemistry and Materials Science Hangzhou Institute for Advanced StudyUniversity of CAS1 Sub-lane XiangshanHangzhouZhejiang310024 China

Cell-free expression systems have emerged as a versatile and powerful platform for metabolic engineering,biosynthesis and synthetic biology studies.Nevertheless,successful examples of the synthesis of complex natural products using this system are still limited.Bicyclomycin,a structurally unique and complex diketopiperazine alkaloid,is a clinically promising antibiotic that selectively inhibits the transcription termination factor Rho.Here,we established a modular cell-free expression system with cascade catalysis for the biosynthesis of bicyclomycin from a chemically synthesized cyclodipeptide.The six cell-free expressed biosynthetic enzymes,including five iron-andα-ketoglutarate-dependent dioxygenases and one cytochrome P450 monooxygenase,were active in converting their substrates to the corresponding products.The co-expressed enzymes in the cell-free module were able to complete the related partial pathway.In vitro biosynthesis of bicyclomycin was also achieved by reconstituting the entire biosynthetic pathways(i.e.,six enzymes)using the modular cell-free expression system.This study demonstrates that the modular cell-free expression system can be used as a robust and promising platformforthe biosynthesis of complex antibiotics.

关键词： Natural products Bicyclomycin Biosynthesis Iron-andα-ketoglutarate-dependent dioxygenases Cytochrome P450 monooxygenase Cell-freeprotein synthesis Enzyme catalysis

Algorithm of automatic identification of diabetic retinopathy foci based on ultra-widefield scanning laser ophthalmoscopy

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 610-615页

作者： Jie Wang Su-Zhen Wang Xiao-Lin Qin Meng Chen heng-Ming Zhang Xin liu Meng-jun Xiang Jian-Bin Hu Hai-Yu Huang Chang-jun Lan Aier Eye Hospital(East of Chengdu) Chengdu 610051Sichuan ProvinceChina Department of Ophthalmology Chengdu First People’s HospitalChengdu 610095Sichuan ProvinceChina School of Computer and Artificial Intelligence Southwest Jiaotong UniversityChengdu 610097Sichuan ProvinceChina Chengdu Aier Eye Hospital Chengdu 610041Sichuan ProvinceChina

AIM:To propose an algorithm for automatic detection of diabetic retinopathy(DR)lesions based on ultra-widefield scanning laser ophthalmoscopy(SLO).METHODS:The algorithm utilized the FasterRCNN(Faster Regions with CNN features)+ResNet50(Residua Network 50)+FPN(Feature Pyramid Networks)method for detecting hemorrhagic spots,cotton wool spots,exudates,and microaneurysms in DR ultra-widefield SLO.Subimage segmentation combined with a deeper residual network FasterRCNN+ResNet50 was employed for feature extraction to enhance intelligent learning rate.Feature fusion was carried out by the feature pyramid network FPN,which significantly improved lesion detection rates in SLO fundus images.RESULTS:By analyzing 1076 ultra-widefield SLO images provided by our hospital,with a resolution of 2600×2048 dpi,the accuracy rates for hemorrhagic spots,cotton wool spots,exudates,and microaneurysms were found to be 87.23%,83.57%,86.75%,and 54.94%,respectively.CONCLUSION:The proposed algorithm demonstrates intelligent detection of DR lesions in ultra-widefield SLO,providing significant advantages over traditional fundus color imaging intelligent diagnosis algorithms.

关键词： diabetic retinopathy ultra-widefield scanning laser ophthalmoscopy intelligent diagnosis system

Environmental factors controlling soil warming and wetting during 2000-2020 in permafrost and non-permafrost regions across the Qinghai-Tibet Plateau

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Advances in Climate Change Research 2024年第2期15卷 285-296页

作者： Guo-An YIN Jing LUO Fu-jun NIU Ming-Hao liu Ze-Yong GAO Tian-Chun DONG Wei-heng NI State Key Laboratory of Frozen Soil Engineering Northwest Institute of Eco-Environment and ResourcesChinese Academy of SciencesLanzhou 730000China China Railway Qinghai-Tibet Group Co. Ltd.Xining 810000China University of Chinese Academy of Sciences Beijing 100049China

The Qinghai-Tibet Plateau(QTP)has experienced rapid environmental changes,including climate warming and wetting,since the 1980s.These environmental changes significantly impact the shallow soil hydrothermal conditions,which have key roles in land-atmosphere feedback and ecosystem functions.However,the spatial variations and responses of soil hydrothermal conditions to environmental changes over the QTP with permafrost(PF)and seasonal frost(SF)remain unclear.In this study,we investigated the spatial variations in soil temperature(ST)and soil moisture(SM)changes over the QTP from 2000 to 2020 using 99 in-situ sites with observations at 4 depths(i.e.10,40,100 and 200 cm).The main environmental controlling factors were further identified using a calibrated statistical model.Results showed that significant(p<0.05)soil warming occurred at multiple soil layers during 2000-2020 with a wide variation(i.e.0.033-0.039℃ per year on average),whereas the warming rates at PF sites were two times greater than those at SF sites.In addition,the soil wetting rate was high over the SF region,whereas the soil wetting rate was low over the PF region.Aside from air temperature,changes in thawing degree days and solar radiation(Srad)contributed most to soil warming in the PF region,whereas changes in rainfall,Srad and evaporation(EVA)have been identified as the key factors in the SF region.As for soil wetting,changes in snowfall,freezing degree days and vegetation have noticeable nonlinear effects over the PF region,whereas changes in EVA,Srad and rainfall highlighted distinct linear and nonlinear effects in the SF region.These findings enhance our understanding of the hydrothermal impacts of future environmental changes over the QTP.

关键词： Warming amd wetting Soil hydrothermal change Factor Permafrost Seasonal frost

A novel small-signal equivalent circuit model for GaN HEMTs incorporating a dual-field-plate

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Journal of Semiconductors 2024年第5期45卷 61-68页

作者： Jinye Wang jun liu Zhenxin Zhao School of Integrated Circuit Science and Engineering Hangzhou Dianzi UniversityHangzhou 310018China

An accurate and novel small-signal equivalent circuit model for GaN high-electron-mobility transistors(HEMTs)is proposed,which considers a dual-field-plate(FP)made up of a gate-FP and a source-FP.The equivalent circuit of the overall model is composed of parasitic elements,intrinsic transistors,gate-FP,and source-FP networks.The equivalent circuit of the gate-FP is identical to that of the intrinsic transistor.In order to simplify the complexity of the model,a series combination of a resistor and a capacitor is employed to represent the source-FP.The analytical extraction procedure of the model parameters is presented based on the proposed equivalent circuit.The verification is carried out on a 4×250μm GaN HEMT device with a gate-FP and a source-FP in a 0.45μm technology.Compared with the classic model,the proposed novel small-signal model shows closer agreement with measured S-parameters in the range of 1.0 to 18.0 GHz.

关键词： small-signal model dual field-plate(FP) GaN high-electron-mobility transistors(HEMT) parameter extraction

Room-temperature phonon-coupled single-photon emission in hexagonal boron nitride

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Science China(Physics,Mechanics & Astronomy) 2024年第5期67卷 109-114页

作者： Jia-Min Lai Qing-Hai Tan Feilong Song Haonan Chang Yanpei Lv Xue-Lu liu Jinghua Teng Weibo Gao Ping-heng Tan jun Zhang State Key Laboratory of Superlattices and Microstructures Institute of SemiconductorsChinese Academy of SciencesBeijing100083China Key Laboratory of Magnetic Molecules and Magnetic Information Materials of Ministry of Education&Research Institute of Materials Science Shanxi Normal UniversityTaiyuan 030000China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China Division of Physics and Applied Physics School of Physical and Mathematical SciencesNanyang Technological UniversitySingapore 637371Singapore Institute of Materials Research and Engineering(IMRE) Agency for ScienceTechnology and Research(A*STAR)Singapore 138634Singapore

Photon-lattice(phonon)coupling is fundamental to light-matter interaction,particularly when it reaches the quantum limit of the phonon-coupled single-photon emission,which holds great potential for quantum manipulation and quantum information transduction.Here,we report single defect state-phonon coupling in hexagonal boron nitride(h BN)at room temperature.An ultrabroad spectrum of single-photon emissions can be achieved by selecting the excitation energies.Using photoluminescence excitation spectroscopy,we observe single-phonon-assisted resonance-enhanced single-photon emission,along with multiple phonon replicas that herald the creation of phonon Fock state.We also develop a transition model to gain insight into the physical process behind the single defect state-phonon coupling.Our work sets the stage for manipulating electron-phonon coupling state with single quantum-level precision at room temperature.

关键词： temperature phonon hexagonal

Jaffe-Campanacci syndrome resulted in amputation: A case report

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World Journal of Clinical Cases 2024年第10期12卷 1785-1792页

作者： jun Jiang Min liu Department of Pediatric Surgery West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina

BACKGROUND Jaffe-Campanacci syndrome(JCS)is a very rare syndrome.The treatment of JCS is more conservative,and most authors recommend that no surgery should be done in asymptomatic patients.The conventional concept holds that the natural course of non-ossifying fibromas(NOFs)grows with the development of bones,and the osteolytic region gradually stops expanding and self-healing through bone ossifying around the lesion and ossification within the lesion.But in this case,the bone lesions were potentially biologically aggressive,which led to severe limb deformities and pain.CASE SUMMARY We present the case of a 5-year-old girl with JCS presenting with not only NOF sand café-au-lait macules,but also showed features not mentioned before,severe limb pain,and at last resulted in amputation.She was admitted to our hospital after presenting with claudication and mild pain over her right thigh,which worsened when stretching or being touched.Skin examination revealed multiple café-au-lait macules on the neck,arm,axilla,and torso,including the nipples and perineum.Radiographs revealed multiple lytic lesions in the proximal part of the right humerus,distal part of the right clavicle,proximal and distal parts of the right femur,and proximal parts of the right tibia and fibula.Curettage and biopsy were performed on the distal part of the right femur.At the age of 7,the girl was re-admitted to our hospital for a pathological fracture in the middle in the right femur and underwent Intralesional excision,internal fixation,bone grafting,and spica casting.At the age of 10,the girl came to our hospital again for severe pain of the right leg.Amputation from the middle level of the right femur was performed.We present the case of a 5-year-old girl with JCS presenting with not only NOFs and café-au-lait macules,but also showed features not mentioned before,severe limb pain,and at last resulted in amputation.She was admitted to our hospital after presenting with claudication and mild pain over her right thigh,which worsened when stretchi

关键词： Jaffe-Campanacci syndrome Multiple non-ossifying fibromas Café-au-lait macule Amputation Case report

Full waveform inversion based on hybrid gradient

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Petroleum Science 2024年第3期21卷 1660-1670页

作者： Chuang Xie Zhi-Liang Qin Jian-Hua Wang Peng Song heng-Guang Shen Sheng-Qi Yu Ben-jun Ma Xue-Qin liu Qingdao Innovation and Development Base Harbin Engineering University Qingdao Innovation and Development Center Harbin Engineering University CNOOC Research Institute Co. Ltd. College of Marine Geoscience Ocean University of China Weihai Sunfull Geophysical Exploration Equipment Co. Ltd.

The low-wavenumber components in the gradient of full waveform inversion(FWI) play a vital role in the stability of the inversion. However, when FWI is implemented in some high frequencies and current models are not far away from the real velocity model, an excessive number of low-wavenumber components in the gradient will also reduce the convergence rate and inversion accuracy. To solve this problem, this paper firstly derives a formula of scattering angle weighted gradient in FWI, then proposes a hybrid gradient. The hybrid gradient combines the conventional gradient of FWI with the scattering angle weighted gradient in each inversion frequency band based on an empirical formula derived herein.Using weighted hybrid mode, we can retain some low-wavenumber components in the initial lowfrequency inversion to ensure the stability of the inversion, and use more high-wavenumber components in the high-frequency inversion to improve the convergence rate. The results of synthetic data experiment demonstrate that compared to the conventional FWI, the FWI based on the proposed hybrid gradient can effectively reduce the low-wavenumber components in the gradient under the premise of ensuring inversion stability. It also greatly enhances the convergence rate and inversion accuracy,especially in the deep part of the model. And the field marine seismic data experiment also illustrates that the FWI based on hybrid gradient(HGFWI) has good stability and adaptability.

关键词： Full waveform inversion Hybrid gradient Scattering angle weighted Low-wavenumber component