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Dual Diomarkers Triggered Prodrugs for Precise Treatment of Melanoma:Design,Synthesis and Activities

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Chemical Research in Chinese Universities 2022年第4期38卷 949-956页

作者： RUAN Yawen huang Peiling YAN Jiangyu LI Guorui HUANG Jing State Key Laboratory of Chemo/Biosensing and Chemometrics School of Biomedical SciencesHunan UniversityChangsha410082P.R.China

Targeted prodrug strategy,which utilizes the endogenous biomarkers in cancer cells as activators to release the active drug,has been well established either in the fundamental research or the clinical treatment.However,many prodrugs suffer from safety concern due to“off-target activation”.Dual or multiple biomarkers triggered prodrug may provide an effective strategy to overcoming the“off-target effect”.Melanoma cells have both high levels of reactive oxygen species(ROS)and tyrosinase(TYR),which makes them significantly different from other tumor cells and normal cells.Here we reported a series of quinazolinone-aryl boronic acid/ester-based prodrugs,which can be activated by the cascade of ROS and TYR and selectively kill melanoma cells.The structure-activity relationship(SAR)analysis revealed that mitochondria-targeting property was vital for their cytotoxicity and the dual activated effector played a significant role in their selectivity towards melanoma cells.Among these candidates,compound 4b showed the highest toxicity to B16,leading to an imbalance of the redox system in melanoma cells,causing mitochondrial DNA damage,and then promoting melanoma cells death.

关键词： Targeted prodrug Melanoma Cell death Cascade activation

Carbene chemistry for unnatural biosynthesis

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Science China(Life Sciences) 2024年第1期67卷 204-207页

作者： jing huang Jay D.Keasling Department of Chemical and Biomolecular Engineering University of CaliforniaBerkeley 94720USA Joint BioEnergy Institute Lawrence Berkeley National LaboratoryEmeryville 94608USA Biological Systems and Engineering Division Lawrence Berkeley National LaboratoryBerkeley 94720USA Novo Nordisk Foundation Center for Biosustainability Technical University of DenmarkKongens Lyngby 2800Denmark Department of Bioengineering University of CaliforniaBerkeley 94720USA Synthetic Biochemistry Center Institute for Synthetic BiologyShenzhen Institutes for Advanced TechnologiesShenzhen 518055China

Previously,chemists working in synthesis were jealous of biologists since the enzymes found in nature usually exhibited great catalytic properties(e.g.,high catalytic efficiency,excellent selectivity such as substrate selectivity,regioselectivity and stereoselectivity).However,biological systems lack many counterparts of reactions widely used in chemical synthesis.

关键词： synthesis selectivity catalytic

Breast cancer immunology and immunotherapy:targeting the programmed cell death protein-1/programmed cell death protein ligand-1

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Chinese Medical Journal 2020年第7期133卷 853-862页

作者： jing Zhao Jian huang Department of Medical Oncology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province HangzhouZhejiang 310009China Department of Breast Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China

Historically,breast cancer has been regarded as an immunogenic"cold"tumor.However,the discovery of immune checkpoint inhibitors has made immunotherapy becoming an emerging new treatment modality for breast cancer.This review discusses the immune system,immune features of breast cancer,and the programmed cell death protein-1/programmed cell death protein ligand-1(PD-1/PD-L1)inhibitors used in the treatment of breast cancer.High T lymphocyte infiltration and mutation burden were observed in triple-negative breast cancer and human epidermal growth factor receptor 2 positive breast cancer.Increasing breast cancer immunogenicity and modulating the tumor microenvironment has been reported to improve the therapeutic efficacy of immunotherapy.Recent clinical trials involving PD-1/PD-L1 inhibitors monotherapy in breast cancer has revealed little efficacy,which highlights the need to develop combinations of PD-1/PD-L1 inhibitors with chemotherapy,molecularly targeted therapies,and other immunotherapies to maximize the clinical efficacy.Collectively,the immunotherapy might be a promising therapeutic strategy for breast cancer and several clinical trials are still on-going.

关键词： Breast cancer Immune microenvironment Immunotherapy Programmed cell death protein ligand-1 inhibitors Programmed cell death protein-1 inhibitors

Dirac Cohomology and Character Lifting

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Acta Mathematica Sinica,English Series 2021年第4期37卷 525-537页

作者： jing Song huang Department of Mathematics Hong Kong University of Science and TechnologyClear Water BayKowloonHong Kong SARP.R.China

The endoscopic transfer factor is expressed as difference of characters for the even and odd parts of the spin modules,or Dirac index of the trivial representation.The lifting of tempered characters in terms of index ... 详细信息

关键词： Dirac cohomology Dirac series cubic Dirac operators endoscopic transfer character lifting

Neoadjuvant Immunotherapy for Head and Neck Squamous Cell Carcinoma:Expecting Its Application in Temporal Bone Squamous Cell Carcinoma

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Current Medical Science 2023年第2期43卷 213-222页

作者： Meng-wen SHI jing huang Yu SUN Department of Otorhinolaryngology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Cancer Center Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China

Temporal bone malignant tumors are characterized by atypical clinical symptoms,and easy recurrence and metastasis.They account for 0.2%of head and neck tumors,and the most common pathological type is squamous cell carcinoma.Patients with squamous cell carcinoma of the temporal bone are often at advanced stages when diagnosed,and lose the chance for surgery.Neoadjuvant immunotherapy has recently been approved as the first-line treatment for refractory recurrent/metastatic squamous cell carcinoma of the head and neck.However,it remains to be determined whether neoadjuvant immunotherapy can be used as the first-line treatment for temporal bone squamous cell carcinoma to reduce the tumor stage before surgery,or as a palliative treatment for patients with unresectable advanced stage carcinoma.The present study reviews the development of immunotherapy and its clinical application in head and neck squamous cell carcinoma,summarizes the treatment of temporal bone squamous cell carcinoma,and prospects the neoadjuvant immunotherapy as the first-line treatment for temporal bone squamous cell carcinoma.

关键词： neoadjuvant immunotherapy programmed cell death-1 head and neck squamous cell carcinoma temporal bone squamous cell carcinoma

Commentary on “A population of stem cells with strong regenerative potential discovered in deer antlers ”

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Chinese Journal of Natural Medicines 2023年第6期21卷 401-402页

作者： LIU jing SHAO Li huang Weihua Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangsha 410008China Institute of Clinical Pharmacology Hunan Key Laboratory of PharmacogeneticsCentral South UniversityChangsha 410078China Department of Pharmacognosy School of PharmacyHunan University of Chinese MedicineChangsha 410128China

In this groundbreaking study,Qin et al.identified,characterized,and isolated a previously unknown population of stem cells responsible for the regenerative potential in deer antlers[1].The researchers identified these cells as antler blastema progenitor cells(ABPCs),originating from paired related homeobox 1(PRRX1)+mesenchymal cells in the antler blastemal.The authors convincingly demonstrated that these ABPCs are a shared stem cell type among mammalian appendages,opening up new avenues for bone tissue repair and regeneration.

关键词： potential breaking

Surface available gravitational potential energy in the world oceans

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Acta Oceanologica Sinica 2022年第4期41卷 40-56页

作者： Ruixin huang Bo Qiu Zhiyou jing State Key Laboratory of Tropical Oceanography South China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China Woods Hole Oceanographic Institution Woods HoleMA 02543USA Department of Oceanography University of Hawaii at ManoaHonoluluHI 96822USA

Satellite altimetry observations,including the upcoming Surface Water and Ocean Topography mission,provide snapshots of the global sea surface high anomaly field.The common practice in analyzing these surface elevation data is to convert them into surface velocity based on the geostrophic approximation.With increasing horizontal resolution in satellite observations,sea surface elevation data will contain many dynamical signals other than the geostrophic velocity.A new physical quantity,the available surface potential energy,is conceptually introduced in this study defined as the density multiplied by half of the squared deviation from the local mean reference surface elevation.This gravitational potential energy is an intrinsic property of the sea surface height field and it is an important component of ocean circulation energetics,especially near the sea surface.In connection with other energetic terms,this new variable may help us better understand the dynamics of oceanic circulation,in particular the processes in connection with the free surface data collected through satellite altimetry.The preliminary application of this concept to the numerically generated monthly mean Global Ocean Data Assimilation System data and Archiving,Validation,and Interpretation of Satellite Oceanographic altimeter data shows that the available surface potential energy is potentially linked to other dynamic variables,such as the total kinetic energy,eddy kinetic energy and available potential energy.

关键词： satellite altimetry surface available potential energy eddy kinetic energy

Design optimization of a hexapod vibration isolation system for electro-optical payload

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Chinese Journal of Aeronautics 2024年第2期37卷 330-342页

作者： jing LI Weipeng LI Xiaoyan ZHANG Hai huang School of Astronautics Beihang UniversityBeijing 100191China

The electro-optical payloads on mobile platforms generally suffer undesirable vibrations generated by maneuvers and turbulence.These vibrations are in six degrees of freedom and cause line-of-sight jitters,resulting in image blurring and loss of tracking accuracy.In this paper,a Hexapod Vibration Isolation System(HVIS)is proposed and optimized to solve this problem.The optimization aims to centralize and minimize the natural frequencies of HVIS,for expanding the vibration isolation bandwidth and improving the vibration isolation in the higher frequency band.Considering that the design space for HVIS is limited and interfered with the frames of the mobile platform,a non-collision algorithm is proposed and applied in the optimization to obtain the feasible optimal design.The optimization result shows that the natural frequency bandwidth has been reduced by 42.9%,and the maximum natural frequency is reduced by 30.2%.The prototypes of initial and optimal designs are manufactured and tested.Both simulated and experimental results demonstrate the validity of the optimization,and the optimal design provides a maximum of 15 dB more isolation in rotation direction than the initial design.

关键词： Electro-optical payload Vibrations Isolation system Hexapod Optimization Non-collision design

Defects Recognition of Train Wheelset Tread Based on Improved Spiking Neural Network

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Chinese Journal of Electronics 2023年第5期32卷 941-954页

作者： ZHANG Changfan huang Congcong HE jing College of Railway Transportation Hunan University of Technology

Surface defect recognition of train wheel-set is crucial for the safe operation of the train wheel system. However, due to the diversity and complexity of such defects, it is difficult for existing algorithms to make rapid and accurate recognitions. To solve this problem, an improved spiking neural network(SNN) based defect recognition method for train wheelset tread is proposed.Specifically, a hybrid convolutional encoding module is first designed to conduct image-to-spike conversion and to create multi-scale sparse representations of the features.Second, a residual spiking convolutional neural network is implemented to extract spiking features optimally, and a multi-scale structure is adopted to enhance the SNN’s ability to handle details. A channel attention module is then incorporated to re-calibrate the weights of four-dimensional spiking feature maps. Finally, effective spiking features are obtained according to the recognition decisions which are made. The experimental results showed that the proposed method improved the accuracy of defect recognition. The recognition time of a single image is only 0.0195 s on average. The overall performance of the proposed method is noticeably superior to current mainstream algorithms.

关键词： Defects recognition Spiking neural network Spike train encoding Dilated convolution Channel attention module Wheelset tread