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Synergistic induction of mitotic pyroptosis and tumor remission by inhibiting proteasome and WEE family kinases

Signal Transduction and Targeted Therapy 2024年第8期9卷 3467-3482页

作者： Zhan-Li chen chen Xie Wei Zeng Rui-Qi Huang Jin-E yang Jin-Yu Liu ya-jing chen Shi-Mei Zhuang MOE Key Laboratory of Gene Function and Regulation Guangdong Province Key Laboratory of Pharmaceutical Functional GenesSchool of Life SciencesState Key Laboratory of Oncology in Southern ChinaSun Yat-sen UniversityGuangzhouPR China Key Laboratory of Liver Disease of Guangdong Province The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630PR China

Mitotic catastrophe(MC),which occurs under dysregulated mitosis,represents a fascinating tactic to specifically eradicate tumor *** pyroptosis can be a death form of MC remains ***-mediated protein degradation is crucial for ***(BTZ),which inhibits the 20S catalytic particle of proteasome,is approved to treat multiple myeloma and mantle cell lymphoma,but not solid tumors due to primary *** date,whether and how proteasome inhibitor affected the fates of cells in M-phase remains ***,we show that BTZ treatment,or silencing of PSMC5,a subunit of 19S regulatory particle of proteasome,causes G2-and M-phase arrest,multi-polar spindle formation,and consequent caspase-3/GSDME-mediated pyroptosis in M-phase(designated as mitotic pyroptosis).Further investigations reveal that inhibitor of WEE1/PKMYT1(PD0166285),but not inhibitor of ATR,CHK1 or CHK2,abrogates the BTZ-induced G2-phase arrest,thus exacerbates the BTZ-induced mitotic arrest and *** BTZ and PD0166285 treatment(named BP-Combo)selectively kills various types of solid tumor cells,and significantly lessens the IC50 of both BTZ and PD0166285 compared to BTZ or PD0166285 *** using various mouse models show that BP-Combo has much stronger inhibition on tumor growth and metastasis than BTZ or PD0166285 monotreatment,and no obvious toxicity is observed in BP-Combo-treated *** findings disclose the effect of proteasome inhibitors in inducing pyroptosis in M-phase,characterize pyroptosis as a new death form of mitotic catastrophe,and identify dual inhibition of proteasome and WEE family kinases as a promising anti-cancer strategy to selectively kill solid tumor cells.

关键词： proteasome inhibiting catastrophe

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Chain Dynamics Heterogeneity in Plasticized Poly(vinyl butyral)(PVB) as Elucidated by Solid-State NMR

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Chinese Journal of Polymer Science 2024年第1期42卷 113-124,I0010页

作者： jing Lv Xu chen Zi-Shuo Wu ya-Hui Li Wei chen National Synchrotron Radiation Laboratory Anhui Provincial Engineering Laboratory of Advanced Functional Polymer FilmCAS Key Laboratory of Soft Matter ChemistryUniversity of Scienceand Technology of ChinaHefei 230026China

The chain dynamics heterogeneity of the poly(vinyl butyral)(PVB) plasticized by triethylene glycol bis(2-ethylhexa noate)(TEG-EH) was investigated by various solid-state NMR *** plasticized PVB shows two domains in distinct molecular dynamics differences,namely,rigid and soft domains,where the latter is the plasticizer-rich *** time domain low field NMR was first used to investigate the dynamics heterogeneity of the plasticized PVB,and the results show the decreasing activated energy of components in the soft domain of plasticized PVB(E_a=20.2 kJ/mol) as compared with that of the pristine one(E_a=24.3 kJ/mol).Detailed dynamics heterogeneity was obtained by high-field NMR with site-specific *** quadrupole-echo ~2H-NMR was adopted to elucidate the dynamics heterogeneity of the vinyl alcohol(VA) units,where only the hydroxyl group of VA is *** ~1H-^(13)C WISE NMR spectra show that there is not much difference in the mobility of the VB unit in PVB with and without plasticizer,whereas the glass transition temperature differed by approximately 53℃.This is further supported by Torchia's T_1 relaxation *** origin of such an unusual phenomenon is attributed to the critical role of the remaining VA(~22%) in the soft domain,where the VA units locally aggregate through hydrogen ***,the existence of a mobility gradient in the VB unit has been ***,the mobility difference for VB with different stereo-geometry(meso or racemic conformation) is observed for the first *** indicates the importance of modulating the ratio of meso over racemic VB for controlling the macroscopic perfo rmance of PVB.

关键词： Poly(vinyl butyral) Dynamics heterogeneity Plasticizer Solid state NMR

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Direct synthesis of N_(2)-unprotected five-memberedcyclic guanidines by regioselective[3+2]annulation of aziridines and cyanamides

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Organic Chemistry Frontiers 2022年第6期9卷 1574-1579页

作者： Chuan-Chuan Wang Xin-Lu Wang Qing-Ling Zhang Juntao Liu Zhi-Wei M Zhi-jing Liu ya-jing chen School of Pharmaceutical Sciences Key Laboratory of Advanced Drug Preparation TechnologiesMinistry of Education of ChinaCo-Innovation Center of Henan Province for New Drug R&D and Preclinical SafetyZhengzhou University100 Science AvenueZhengzhou 450001HenanChina Faculty of Science Livestock Product Quality Inspection InstituteHenan University of Animal Husbandry and EconomyNo.146 Yingcai StreetZhengzhou 450044HenanChina

A novel and efficient[3+2]annulation of 2-substituted aziridines and N-tosyl cyanamides via a dominoregioselective ring-opening/5-exo-dig cyclization procedure has been developed,allowing the directpreparation of N_(2)-unprotected five-membered cyclic guanidines in good to excellent yields under mildconditions without metals and strong ***,the highly biologically interesting urea analoguescould also be conveniently obtained via hydrolysis of the produced guanidines.

关键词： membered protected guanidine

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Quantitative proteomic analysis for high-throughput screening of differential glycoproteins in hepatocellular carcinoma serum

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Cancer Biology & Medicine 2015年第3期12卷 246-254页

作者： Hua-Jun Gao ya-jing chen Duo Zuo Ming-Ming Xiao Ying Li Hua Guo Ning Zhang Rui-Bing chen Research Center of Basic Medical Sciences & School of Medical Laboratory Tianjin Medical University Laboratory of Cancer Cell Biology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin Key Laboratory of Cancer Prevention and Therapy

Objective： Hepatocellular carcinoma （HCC） is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. This study employed a quantitative proteomic strategy to analyze the differential expression of serum glycoproteins between HCC and normal control serum samples. Methods： Lectin affinity chromatography （LAC） was used to enrich glycoproteins from the serum samples. Quantitative mass spectrometric analysis combined with stable isotope dimethyl labeling and 2D liquid chromatography （LC） separations were performed to examine the differential levels of the detected proteins between HCC and control serum samples. Western blot was used to analyze the differential expression levels of the three serum proteins. Results： A total of 2,280 protein groups were identified in the serum samples from HCC patients by using the 2D LC-MS/MS method. Up to 36 proteins were up-regulated in the HCC serum, whereas 19 proteins were down-regulated. Three differential glycoproteins, namely, fibrinogen gamma chain （FGG）, FOS-like antigen 2 （FOSL2）, and a-l, 6-mannosylglycoprotein 6-^-N-acetylglucosaminyltransferase B （MGATSB） were validated by Western blot. All these three proteins were up-regulated in the HCC serum samples. Conclusion： A quantitative glycoproteomic method was established and proven useful to determine potential novel biomarkers for HCC.

关键词： Glycoprotein hepatocellular carcinoma (HCC) mass spectrometry proteomics serum

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Integrated interconnected porous and lamellar structures realized fast ion/electron conductivity in high-performance lithium-sulfur batteries

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Chinese Chemical Letters 2024年第6期35卷 161-167页

作者： ya Song Mingxia Zhou Zhu chen Huali Nie Jiao-jing Shao Guangmin Zhou School of Materials and Metallurgy Guizhou UniversityGuiyang 550025China Medical College of Guizhou University Guiyang 550025China College of Biological Science and Medical Engineering Donghua UniversityShanghai 201620China Shenzhen Geim Graphene Center Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen 518055China

The practical application of high-energy-density lithium-sulfur(Li-S)batteries have been highly praised for energy storage devices,while are largely hindered by the“shuttling effect”.Herein,core-shell carbon spheres composed of interlinked porous core and lamellar shell were designed to restrain the polysulfide *** microporous structure with pore size of around 1 nm effectively trap lithium ***,the interconnected porous core shortens the ion transfer distance and the lamellar carbon shell endows the carbon spheres with fast electron conduction,finally facilitating polysulfide conversion ***,the Li-S batteries with the carbon spheres as the interlayer show high discharge specific capacity of 1002 m Ah/g at 2 C with 574 m Ah/g remaining after 600 cycles,and high areal capacity of 5.48 m Ah/cm^(2) with sulfur loading of 4.67 mg/cm^(2) at 0.1 *** corresponding pouch cells also exhibit stable cycling stability with an initial discharge specific capacity of 1082 m Ah/g at 0.1 C.

关键词： Interlayer Shuttle effect Strong adsorption Porous carbon spheres Lithium-sulfur batteries

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Enhanced Crystallization of Poly(butylene adipate-co-terephthalate)by a Self-assembly Nucleating Agent

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Chinese Journal of Polymer Science 2024年第5期42卷 663-674,I0010页

作者： cheng Zhou Kun chen Zi-Heng Zhang Meng-Fan jing Chun-Tai Liu Chang-Yu Shen ya-Ming Wang State Key Laboratory of Structural Analysis Optimization and CAE Software for Industrial EquipmentNational Engineering Research Center for Advanced Polymer Processing TechnologyZhengzhou UniversityZhengzhou450002China

Poly(butylene adipate-co-terephthalate)(PBAT)is a promising biodegradable flexible polymer but suffers from slow crystallization rate,making it less attractive for some applications like the injection-molded products in comparison with low-density polyethylene(LDPE).This work aimed to accelerate the crystallization of PBAT by adding a self-assembly nucleating agent octamethylenedicarboxylic dibenzoylhydrazide(OMBH).PBAT/OMBH composites with various OMBH contents(0 wt%,0.5 wt%,0.7 wt%,1 wt%,2 wt%,3 wt%and 5 wt%)were prepared through *** effect of OMBH on the crystallization behavior,morphologies and mechanical properties of PBAT was *** highest nucleation efficiency value of 59.6%was achieved for PBAT with 0.7 wt%OMBH,much higher than that of 22.7%for PBAT with 0.7 wt%*** force microscopy results showed that OMBH formed fine fibers and induced the formation of transcrystalline layers of *** transform infrared spectroscopy(FTIR)combined with two-dimensional correlation spectra suggested that the intermolecular dipole-dipole N—H…O=C interactions but not hydrogen bond between OMBH and PBAT promoted the crystallization of PBAT in the initial period of *** presence of OMBH did not change the crystal form of PBAT but had positive contribution in enhancing its crystallinity and mechanical *** work is essential for preparing PBAT with high crystallization rate,enhancing its potential applications in injection-molded products.

关键词： Poly(butylene adipate-co-terephthalate) Biodegradable Self-assembly nucleating agent Crystallization

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Gravitational wave fluxes on generic orbits in near-extreme Kerr spacetime:Higher spin and large eccentricity

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Science China(Physics,Mechanics & Astronomy) 2024年第11期67卷 16-28页

作者： Changkai chen Jiliang jing Department of Physics Key Laboratory of Low Dimensional Quantum Structures and Quantum Control of Ministry of EducationSynergetic Innovation Center for Quantum Effects and ApplicationsHunan Normal UniversityChangsha 410081China

To accurately obtain the waveform template of gravitational waves, substantial computational resources and extremely high precision are often required. In a previous study, we employed the confluent Heun function to obtain an exact solution to the Teukolsky equation. This approach allowed us to efficiently and accurately calculate the gravitational wave flux for a particle in circular orbits around a Schwarzschild black hole. Building on this method, we now extend its application to calculate the asymptotic gravitational wave fluxes from a particle in generic orbits around a near-extreme Kerr black hole. Our extended method proves particularly effective in handling computational challenges associated with large eccentricities(e = 0.9), higher spins(a = 0.999), higher harmonic modes, and strong-field regions. The results we obtained significantly outperform those derived from the numerical integration method based on the Mano-Suzuki-Takasugi method.

关键词： gravitational wave fluxes exact solution Teukolsky equation near-extreme Kerr black hole

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Kerr black hole shadows cast by extraordinary light rays with Weyl corrections

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Science China(Physics,Mechanics & Astronomy) 2024年第5期67卷 18-26页

作者： Songbai chen Jiliang jing Department of Physics Institute of Interdisciplinary StudiesKey Laboratory of Low Dimensional Quantum Structures and Quantum Control of Ministry of EducationSynergetic Innovation Center for Quantum Effects and ApplicationsHunan Normal UniversityChangsha 410081China Center for Gravitation and Cosmology College of Physical Science and TechnologyYangzhou UniversityYangzhou 225009China

We investigate the equation of motion for photons with Weyl corrections in a Kerr black hole spacetime in a small coupling *** results show that Weyl corrections yield phenomena of *** light rays propagating in the spacetime are separated into the ordinary rays and the extraordinary rays,and the propagation of the latter depends on the *** probe the effects of Weyl corrections on the Kerr black hole shadows casted by the extraordinary rays and find that such corrections result in a weak stretching or squeezing in the vertical direction for the black hole ***,we also study the change of the length of the Near-Horizon Extremal Kerr line(NHEK line)with Weyl *** features could help us to understand the electrodynamics with Weyl corrections from black hole shadows.

关键词： correction light stretching

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Carbon cathode with heteroatom doping and ultrahigh surface area enabling enhanced capacitive behavior for potassium-ion hybrid capacitors

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Rare Metals 2024年第5期43卷 2136-2149页

作者： yan Xiong ya-Fei Zhang Chun-Liu Zhu Lei yang Huan-Yu Liang jing Shi jing-Wei chen Wei-QianTian Shuai Liu Zhi Li jing-Yi Wu Huan-Lei Wang School of Materials Science and Engineering Ocean University of ChinaQingdao 266100China Department of Chemical and Materials Engineering University of AlbertaEdmontonAB T6G 2V4Canada

Potassium-ion hybrid capacitors(PIHCs)are widely regarded as highly promising energy storage devices,due to their exceptional energy density,impressive power density,and abundant potassium ***,restricted by the inherent capacitive storage mechanism,the carbon cathodes possess a much lower specific capacity than battery-type ***,designing high-performance carbon cathodes is extremely urgent for the development of ***,N,O codoped porous carbon(NOPC)was fabricated through the NaCl hard template method and combined KOH/melamine chemical activation technique,displaying the characteristics of abundant N/O content(4.7 at%/16.9 at%),ultrahigh specific surface area(3092 m^(2)g^(-1))and hierarchical pore *** designed NOPC cathode delivers a high specific capacity(164.4 mAh.g^(-1)at 0.05 A.g^(-1))and superior cyclability(95.1%retention ratio at 2 A·g^(-1)over 2500 cycles).Notably,the adjustable ratio of micropores to mesopores facilitates the achievement of the optimal bal-ance between capacity and rate ***,the pseudocapacitance can be further augmented through the incorporation of N/O functional *** expected,the graphite//NOPC based PIHC possesses a high energy density of 113 Wh·kg-at 747 W·kg^(-1)and excellent capacity retention of 84.4% fter 400 cycles at 1.0 A·g^(-1).This work introduces a novel strategy for designing carbon cathodes that enhances the electrochemical performance of PIHCs.

关键词： Template method N/O co-doping High specific surface area Carbon cathode Potassium-ion capacitors

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An active learning workflow for predicting hydrogen atom adsorption energies on binary oxides based on local electronic transfer features

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Green Energy & Environment 2024年第10期9卷 1489-1496页

作者： Wenhao jing Zihao Jiao Mengmeng Song ya Liu Liejin Guo International Research Center for Renewable Energy State Key Laboratory of Multiphase Flow in Power Engineering Xi'an Jiaotong University Department of Energy and Power Engineering Shandong University of Technology

Machine learning combined with density functional theory（DFT） enables rapid exploration of catalyst descriptors space such as adsorption energy, facilitating rapid and effective catalyst screening. However, there is still a lack of models for predicting adsorption energies on oxides,due to the complexity of elemental species and the ambiguous coordination environment. This work proposes an active learning workflow（Le NN） founded on local electronic transfer features（e） and the principle of coordinate rotation invariance. By accurately characterizing the electron transfer to adsorption site atoms and their surrounding geometric structures, Le NN mitigates abrupt feature changes due to different element types and clarifies coordination environments. As a result, it enables the prediction of *H adsorption energy on binary oxide surfaces with a mean absolute error（MAE） below 0.18 e V. Moreover, we incorporate local coverage（θl） and leverage neutral network ensemble to establish an active learning workflow, attaining a prediction MAE below 0.2 e V for 5419 multi-*H adsorption structures. These findings validate the universality and capability of the proposed features in predicting *H adsorption energy on binary oxide surfaces.

关键词： Machine learning Adsorption energy Binary oxide Electron transfer Active learning

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