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Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

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World Journal of Stem Cells 2024年第4期16卷 444-458页

作者： Cheng-Jin Ai ling-juan Chen li-Xuan Guo Ya-Ping Wang Zi-Yi Zhao Department of Laboratory Medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Department of Ophthalmology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Central Laboratory Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Traditional Chinese Medicine Regulating Metabolic Diseases Key Laboratory of Sichuan Province Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

关键词： Leukemia stem cells Gossypol acetic acid Reactive oxygen species Mitochondrial dysfunction Interleukin 6/janus kinase 1/signal transducer and activator of transcription 3 signaling

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Ratiometric fluorescence probe for accurate detection of Concanavalin A by coupling fluorescent microsphere with boric acid functionalized carbon dots

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Chinese Chemical Letters 2024年第2期35卷 460-463页

作者： Mingyue Xie juan Chen Yufei Wang Bojun liu Rong-Bin Song Hong-Min Meng Zhaohui li College of Chemistry Institute of Analytical Chemistry for Life ScienceHenan Joint International Research Laboratory of Green Construction of Functional Molecules and their Bioanalytical ApplicationsZhengzhou UniversityZhengzhou 450001China Zhengzhou Key Laboratory of Forensic Science and Technology Railway Police CollegeZhengzhou 450053China School of Ecology and Environment Zhengzhou UniversityZhengzhou 450001China

Accurate and sensitive strategies for Concanavalin A(Con A)sensing are conducive to the better cognition of various important biological and physiological processes.Here,by designing dextran-functionalized fluorescent microspheres(DxFMs)and boric acid-modified carbon dots(BCDs)as recognition unit and built-in signal reference respectively,a ratiometric fluorescent detection platform was proposed for Con A detection with high reliability.In this protocol,the BCDs/DxFMs precipitation was formed due to the covalent interactions between cis-diol of DxFMs and boronic acid groups of BCDs,thus only fluorescence of BCDs could be detected in the supernatant.When Con A was presented,it could bind to DxFMs through its carbohydrate recognition ability and suppress the subsequent assembly between DxFMs and BCDs,leading to the simultaneous capture of DxFMs and BCDs fluorescence in the supernatant.Since the BCDs content was superfluous,their fluorescence intensities were basically constant in all cases.Based on the unchanged BCDs fluorescence signal and target-dependent DxFMs fluorescence signal in supernatant,the ratiometric detection of Con A was realized.Under optimized conditions,this ratiometric fluorescent platform displayed a linear detection range from 0.125μg/mL to 12.5μg/mL with a detection limit of 0.089μg/mL.Moreover,satisfied analytical outcomes for Con A detection in serum samples were obtained,manifesting huge application potential of this ratiometric fluorescent platform in clinical diagnosis.

关键词： Concanavalin A Fluorescent microspheres Carbon dots Ratiometric fluorescent assay Reliability

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Effects of ulinastatin combined with dexmedetomidine on cognitive dysfunction and emergence agitation in elderly patients who underwent total hip arthroplasty

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World Journal of Psychiatry 2024年第1期14卷 26-35页

作者： Qi-Fan Huo li-juan Zhu Jian-Wei Guo Yan-An Jiang Jing Zhao Department of Anesthesiology Shaanxi Provincial People’s HospitalXi’an 710068Shaanxi ProvinceChina

BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture increases.Hip fracture is a common type of fracture in older people.Total hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint function.AIM To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent THA.METHODS A total of 397 patients who underwent THA from February 2019 to August 2022.We conducted a three-year retrospective cohort study in Shaanxi Provincial People’s Hospital.Comprehensive demographic data were obtained from the electronic medical record system.We collected preoperative,intraoperative,and postoperative data.One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group.One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group.One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin group.The patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were evaluated.RESULTS There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(Plinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all Plinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of the alertness/sedation score and Ramsay score of t

关键词： Ulinastatin Dexmedetomidine Postoperative cognitive dysfunction Inflammatory cytokines Total hip arthroplasty

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Textured Asymmetric Membrane Electrode Assemblies of Piezoelectric Phosphorene and Ti_(3)C_(2)T_(x)MXene Heterostructures for Enhanced Electrochemical Stability and Kinetics in liBs

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Nano-Micro Letters 2024年第4期16卷 394-414页

作者： Yihui li juan Xie Ruofei Wang Shugang Min Zewen Xu Yangjian Ding Pengcheng Su Xingmin Zhang liyu Wei Jing‑Feng li Zhaoqiang Chu Jingyu Sun Cheng Huang Volta and DiPole Materials Labs College of EnergySoochow Institute for Energy and Materials InnovationS(SIEMIS)Key Laboratory of Advanced Carbon Materials and Wearable Energy Technologies of Jiangsu ProvinceKey Laboratory of Core Technology of High Specific Energy Battery and Key Materials for Petroleum and Chemical IndustrySoochow UniversitySuzhou 215006People’s Republic of China School of Materials Science and Engineering Jiangsu UniversityZhenjiang 212013People’s Republic of China College of Underwater Acoustic Engineering Harbin Engineering UniversityHarbin 150001People’s Republic of China Shanghai Synchrotron Radiation Facility Shanghai Advanced Research InstituteShanghai Institute of Applied PhysicsChinese Academy of SciencesShanghai 201204People’s Republic of China State Key Laboratory of New Ceramics and Fine Processing School of Materials Science and EngineeringTsinghua UniversityBeijing 100084People’s Republic of China High Density Materials Technology Center for Flexible Hybrid Electronics Suzhou Institute of Electronic Functional Materials TechnologySuzhou Industrial Technology Research InstituteSuzhou 215151People’s Republic of China Institute of Advanced Materials and Institute of Membrane Science and Technology Jiangsu National Synergistic Innovation Center for Advanced MaterialsSuzhou Laboratory and Nanjing Tech UniversityNanjing 211816People’s Republic of China

Black phosphorus with a superior theoretical capacity(2596 mAh g^(-1))and high conductivity is regarded as one of the powerful candidates for lithium-ion battery(liB)anode materials,whereas the severe volume expansion and sluggish kinetics still impede its applications in liBs.By contrast,the exfoliated two-dimensional phosphorene owns negligible volume variation,and its intrinsic piezoelectricity is considered to be beneficial to the li-ion transfer kinetics,while its positive influence has not been discussed yet.Herein,a phosphorene/MXene heterostructure-textured nanopiezocomposite is proposed with even phosphorene distribution and enhanced piezo-electrochemical coupling as an applicable free-standing asymmetric membrane electrode beyond the skin effect for enhanced li-ion storage.The experimental and simulation analysis reveals that the embedded phosphorene nanosheets not only provide abundant active sites for li-ions,but also endow the nanocomposite with favorable piezoelectricity,thus promoting the li-ion transfer kinetics by generating the piezoelectric field serving as an extra accelerator.By waltzing with the MXene framework,the optimized electrode exhibits enhanced kinetics and stability,achieving stable cycling performances for 1,000 cycles at 2 A g^(-1),and delivering a high reversible capacity of 524 m Ah g^(-1)at-20℃,indicating the positive influence of the structural merits of self-assembled nanopiezocomposites on promoting stability and kinetics.

关键词： Phosphorene Nanopiezocomposite Piezo-electrochemical coupling Membrane electrode assembly lithium-ion storage

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Effects of depth-and composition-dependent thermal conductivity and the compositional viscosity ratio on the long-term evolution of large thermochemical piles of primordial material in the lower mantle of the Earth:Insights from 2-D numerical modeling

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Science China Earth Sciences 2023年第8期66卷 1865-1876页

作者： Yang li Zhigang ZHANG Juan Li Zhidong SHI liang ZHAO State Key Laboratory of lithospheric Evolution Institute of Geology and GeophysicsChinese Academy of SciencesBeijing 100029China Key Laboratory of Earth and Planetary Physics Institute of Geology and GeophysicsChinese Academy of SciencesBeijing 100029China College of Earth and Planetary Science University of Chinese Academy of SciencesBeijing 100049China Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) Zhuhai 519080China

Thermal conductivity plays an important role in the thermochemical evolution of Earth’s mantle.Recent mineral physics studies suggest that the thermal conductivity of the mantle varies with pressure and composition,and this may play an important role in the evolution of the Earth’s mantle.Meanwhile,the rheology of the deep mantle is also supposed to be composition-dependent.However,the dynamic influences of these factors remain not well understood.In this study,we performed numerical experiments of thermochemical mantle convection in 2-D spherical annulus geometry to systematically investigate the effects of depth-and composition-dependent thermal conductivity and the compositional viscosity ratio on the long-term evolution of the large thermochemical structure of primordial material in Earth’s mantle.Our results show that increasing the depth-dependent thermal conductivity leads to a larger core-mantle boundary(CMB)heat flow and allows the formation of more stable large thermochemical piles(e.g.,Large Low Shear Velocity Provinces,LLSVPs);while decreasing the composition-dependent thermal conductivity would slightly destabilize the primordial thermochemical piles,increase the altitude of these piles and the temperature differences between the piles and the ambient mantle.If the primordial mantle material is compositionally more viscous(e.g.,20 times than that of the ambient mantle),the long-term stability of the thermochemical piles of primordial material decreases,and this destabilizing effect will be enhanced by decreasing the composition-dependent thermal conductivity.As a result,the thermochemical piles would be unstable in the core-mantle boundary region.Therefore,our study indicates that the combined effects of depth-and composition-dependent thermal conductivity and compositional viscosity ratio are pronounced to the thermochemical evolution of the mantle.

关键词： Mantle convection Thermal conductivity Core-mantle boundary heat flow Primordial mantle material LLSVPs

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Early Triassic Volcanic Rocks in the Western Yarlung Zangbo Suture Zone:Implications for the Opening of the Neo-Tethys Ocean

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Acta Geologica Sinica(English Edition) 2024年第2期98卷 324-336页

作者： HE juan li Yalin HOU Yunling ZHOU Aorigele WEI Yushuai CHEN Xi DAI Jingen School of Civil Engineering and Architecture West Yunnan University of Applied SciencesDaliYunnan 671006China School of Earth Sciences and Resources China University of Geosciences(Beijing)Beijing 100080China West Yunnan University of Applied Sciences DaliYunnan 671006China MLR Key Laboratory of Metallogeny and Mineral Assessment Institute of Mineral ResourcesChinese Academy of Geological SciencesBeijing 100080China

In this study,zircon U-Pb dating of volcanic rocks from the Zhongba ophiolite of the Yarlung Zangbo Suture Zone(YZSZ)in southern Xizang(Tibet)yielded an age of 247±3 Ma.According to whole rock geochemical and Sr-NdPb isotopic data,the Early Triassic samples could be divided into two groups:Group 1 with P-MORB affinity,showing initial^(87)Sr/^(86)Sr ratios of 0.70253–0.70602,ε_(Nd)(t)values of 4.2–5.3,(^(206)Pb/^(204)Pb)_(t)ratios of 16.353–18.222,(^(207)Pb/^(204)Pb)_(t)ratios of 15.454–15.564,and(^(208)Pb/^(204)Pb)_(t)ratios of 35.665–38.136;Group 2 with OIB affinity,showing initial^(87)Sr/^(86)Sr ratios of 0.70249–0.70513,ε_(Nd)(t)values of 4.4–4.9,(^(206)Pb/^(204)Pb)_(t)ratios of 17.140–18.328,(^(207)Pb/^(204)Pb)_(t)ratios of 15.491–15.575,and(^(208)Pb/^(204)Pb)_(t)ratios of 36.051–38.247.Group 2 rocks formed by partial melting of the mantle source enriched by a former plume,and assimilated continental crustal material during melt ascension.The formation of Group 1 rocks corresponds to the mixing of OIB melts,with the same components as Group 2 and N-MORBs.The Zhongba Early Triassic rocks belong to the continental margin type ophiolite and formed in the continental–oceanic transition zone during the initial opening of the Neo-Tethys in southern Xizang(Tibet).

关键词： rift Early Triassic magmatism Yarlung Zangbo Suture Zone Neo-Tethys Southern Xizang Tibet

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Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1230-1243页

作者： Jun Zhou Jiaqi liu Bingjing Wang Nan li Juan Liu Yanmei Han Xuetao Cao Institute of Immunology Zhejiang University School of MedicineHangzhou 310058China National Key Laboratory of Immunity and Inflammation Institute of ImmunologyNaval Medical UniversityShanghai 200433China Department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100005China Institute of Immunology College of Life SciencesNankai UniversityTianjin 300071China

Memory CD8+T cell generation is crucial for pathogen elimination and effective vaccination against infection.The cellular and molecular circuitry that underlies the generation of memory CD8+T cells remains elusive.Eosinophils can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune defense.Here we report that eosinophils are required for the generation of memory CD8+T cells by inhibiting CD8+T cell apoptosis.Eosinophil-deficient mice display significantly impaired memory CD8+T cell response and weakened resistance against listeria monocytogenes(L.m.)infection.Mechanistically,eosinophils secrete interleukin-4(IL-4)to inhibit JNK/Caspase-3 dependent apoptosis of CD8+T cells upon L.m.infection in vitro.Furthermore,active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+T cell apoptosis during early stage of L.m.infection in vivo.Adoptive transfer of wild-type(WT)eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+T cell memory responses.Together,our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+T cell memory and enhances immune defense against L.m.infection.Our study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

关键词： impaired immunity spleen

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Langasite-based SAW high-temperature vibration sensor with temperature decoupling

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Science China Technological Sciences 2024年第6期67卷 1946-1956页

作者： ZHANG juan CHENG WenHua WANG Hao ZHANG Lei li XiangRong MA HongShuai PANG JunQi TAN Qiulin State Key Laboratory of Dynamic Measurement Technology North University of China Department of Mechanical Engineering Taiyuan Institute of Technology

Monitoring high-temperature vibrations is critical in aerospace engineering, industrial manufacturing, and energy production,where harsh conditions necessitate robust vibration sensors for detecting anomalous signals. However, the accuracy of such sensors is often compromised by crosstalk between temperature and vibration signals. This study introduces a high-temperature vibration sensor based on langasite(LGS) surface acoustic wave(SAW) technology, designed to withstand temperatures up to500°C. The sensor demonstrates high sensitivity, ranging from 12.54 kHz/g at 25°C to 15.63 k Hz/g at 500°C. A comprehensive mechanical and electrical coupling model for the SAW vibration sensor was developed by integrating theoretical equations with numerical simulations to optimize the sensor’s performance. Additionally, a novel decoupling algorithm for temperature and vibration was established, achieving thermomechanical decoupling with precise vibration parameters. Experimental results indicated a maximum relative deviation of 4.67% for the algorithm. In conclusion, the proposed LGS SAW vibration sensor emerges as a promising solution for the accurate detection of multiple parameters in high-temperature vibration monitoring.

关键词： high temperature langasite (LGS) surface acoustic wave (SAW) piezoelectric vibration sensor temperature decoupling

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Meiotic transcriptional reprogramming mediated by cell-cell communications in humans and mice revealed by scATACseq and scRNA-seq

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Zoological Research 2024年第3期45卷 601-616页

作者： Hai-Quan Wang Xiao-Long Wu Jing Zhang Si-Ting Wang Yong-juan Sang Kang li Chao-Fan Yang Fei Sun Chao-Jun li State Key Laboratory of Reproductive Medicine and Offspring Health Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Medical School Nanjing UniversityNanjingJiangsu 210093China Zhejiang University School of Medicine HangzhouZhejiang 310016China Department of Urology and Andrology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouZhejiang 310000China Model Animal Research Center of Medical School Nanjing UniversityNanjingNanjingJiangsu 210093China liangzhu Laboratory Zhejiang UniversityHangzhouZhejiang 311121China

Meiosis is a highly complex process significantly influenced by transcriptional regulation.However,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are limited.Here,we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes.This event,conserved in mice,involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset.Furthermore,we identified 282 transcriptional regulators(TRs)that underwent activation or deactivation subsequent to this process.Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes,while secreted ENHO signals may alter metabolic patterns in these cells.Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia(NOA).This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.

关键词： Single-cell RNA-seq Single-cell ATAC-seq Spermatogenesis Meiosis Transcriptional reprogramming Cell-cell communication

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Energy saving design of the machining unit of hobbing machine tool with integrated optimization

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Frontiers of Mechanical Engineering 2022年第3期17卷 209-227页

作者： Yan LV Congbo li Jixiang HE Wei li Xinyu li Juan Li State Key Laboratory of Mechanical Transmission College of Mechanical and Vehicle EngineeringChongqing UniversityChongqing400044China Department of Process Technology Sichuan Aerospace Fenghuo Servo Control Technology CorporationChengdu611130China State Key Laboratory of Digital Manufacturing Equipment and Technology Huazhong University of Science and TechnologyWuhan430074China

The machining unit of hobbing machine tool accounts for a large portion of the energy consumption during the operating phase.The optimization design is a practical means of energy saving and can reduce energy consumption essentially.However,this issue has rarely been discussed in depth in previous research.A comprehensive function of energy consumption of the machining unit is built to address this problem.Surrogate models are established by using effective fitting methods.An integrated optimization model for reducing tool displacement and energy consumption is developed on the basis of the energy consumption function and surrogate models,and the parameters of the motor and structure are considered simultaneously.Results show that the energy consumption and tool displacement of the machining unit are reduced,indicating that energy saving is achieved and the machining accuracy is guaranteed.The influence of optimization variables on the objectives is analyzed to inform the design.

关键词： energy saving design energy consumption machining unit integrated optimization machine tool

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