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褪黑素缓解白消安损伤小鼠睾丸的机理研究

畜牧兽医学报 2024年第6期55卷 2486-2497页

作者：吴开慧张留光汪超许师源刘松奇原开敏王栋庞云渭中国农业科学院北京畜牧兽医研究所北京100193 海口玛丽医院生殖科海口570203 吉林农业大学动物科学技术学院长春130118

旨在揭示褪黑素(melatonin, MT)缓解白消安损伤睾丸的机理,提高白消安制备精原干细胞移植受体的效率,并探究其对白消安毒害雄性生精机能的治疗作用。本研究以6~7周ICR雄鼠为模型动物,分为对照组,白消安处理组和白消安+褪黑素处理组,每组... 详细信息

旨在揭示褪黑素(melatonin, MT)缓解白消安损伤睾丸的机理,提高白消安制备精原干细胞移植受体的效率,并探究其对白消安毒害雄性生精机能的治疗作用。本研究以6~7周ICR雄鼠为模型动物,分为对照组,白消安处理组和白消安+褪黑素处理组,每组8个重复,于注射后第7天取样。通过ELISA检测睾丸组织的炎性细胞因子水平,并对睾丸和附睾进行HE染色。此外,免疫组化或免疫荧光检测血睾屏障(blood-testis barrier, BTB)相关蛋白的表达情况,以分析MT对BTB影响。结果表明,小鼠经白消安注射后,联合MT处理,观察到MT显著缓解了睾丸重和睾体率下降的趋势,并减缓了精子数量下降的速度;睾丸组织HE染色和炎性细胞因子检测发现,MT显著减缓了核转录因子κB(nuclear transportation factorκB,NF-κB)、p-NF-κB、白介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-ɑ(tumor necrosis factor-ɑ,TNF-α)及髓过氧化物酶(myeloperoxidase, MPO)水平的上升趋势,从而减少了组织中炎性细胞浸润;免疫组化或免疫荧光检测发现,MT缓解了白消安处理导致的BTB组成蛋白(Occludin、connexin-43、N-cadherin)和细胞骨架蛋白(F-actin和Vimentin)含量的下降。综上,MT通过下调睾丸组织中炎性细胞因子水平,缓解白消安诱发的小鼠睾丸炎症反应;并通过减缓BTB相关蛋白含量的下降,缓解白消安对BTB和支持细胞的损伤,进而缓解小鼠生精机能的损伤。

关键词：褪黑素白消安睾丸炎血睾屏障细胞骨架

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Abrogation of Hn RNP L enhances anti-PD-1 therapy efficacy via diminishing PD-L1 and promoting CD8^(+) T cell-mediated ferroptosis in castration-resistant prostate cancer

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Acta Pharmaceutica Sinica B 2022年第2期12卷 692-707页

作者： Xumin Zhou Libin Zou Hangyu Liao Junqi Luo Taowei Yang Jun wu Wenbin Chen kaihui wu Shengren Cen Daojun Lv Fangpeng Shu Yu Yang Chun Li Bingkun Li Xiangming Mao Department of Urology Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China Second Department of Hepatobiliary Surgery Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China Nursing Department Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Department of Urology Minimally Invasive Surgery Centerthe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Urology Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510623China Department of Urology Peking University Shenzhen HospitalShenzhen 518036China

Owing to incurable castration-resistant prostate cancer(CRPC)ultimately developing after treating with androgen deprivation therapy(ADT),it is vital to devise new therapeutic strategies to treat *** that target programmed cell death protein 1(PD-1)and programmed death ligand-1(PD-L1)have been approved for human cancers with clinical ***,many patients,especially prostate cancer,fail to respond to anti-PD-1/PD-L1 treatment,so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting *** the present study,analyzing the data from our prostate cancer tissue microarray,we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L(Hn RNP L).Hence,we further investigated the potential role of Hn RNP L on the PD-L1 expression,the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in ***,Hn RNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo,on the contrary,Hn RNP L overexpression led to the opposite effect in CRPC *** addition,consistent with the previous study,we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death,and Hn RNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC ***,Hn RNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8^(+)T cells and synergized with anti-PD-1 therapy in CRPC *** study provided biological evidence that Hn RNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.

关键词： HnRNP L PD-L1 YY1 Ferroptosis Immune escape Immune checkpoint blockade Anti-PD-1 therapy Castration-resistant prostate cancer

A Novel Pre-control Method of Vehicle Dynamics Stability Based on Critical Stable Velocity during Transient Steering Maneuvering

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Chinese Journal of Mechanical Engineering 2016年第3期29卷 475-485页

作者： CHEN Jie SONG Jian LI Liang RAN Xu JIA Gang wu kaihui State Key Laboratory of Automotive Safety and Energy Tsinghua University

The current research of direct yaw moment control（DYC） system focus on the design of target yaw moment and the distribution of wheel brake force. The differential braking intervention can effectively improve the lateral stability of the vehicle, however, the effect of DYC can be improved a step further by applying the control of vehicle longitudinal velocity. In this paper, the relationship between the vehicle longitudinal velocity and lateral stability is studied, and the simulation results show that a decrease of 5 km/h of longitudinal velocity at a particular situation can bring 100° increasing of stable steering upper limit. A critical stable velocity considering the effect of steering and yaw rate measurement is defined to evaluate the risk of losing steer-ability or stability. A novel velocity pre-control method is proposed by using a hierarchical pre-control logic and is integrated with the traditional DYC system. The control algorithm is verified through a hardware in-the-loop simulation system. Double lane change（DLC） test results on both high friction coefficient（μ） and low μ roads show that by using the pre-control method, the steering effort in DLC test can be reduced by 38% and 51% and the peak value of brake pressure control can be reduced by 20% and 12% respectively on high μ and low μ roads, the lateral stability is also improved. This research proposes a novel DYC system with lighter control effort and better control effect.

关键词： vehicle dynamics direct yaw moment control critical stable velocity pre-control

The Magnaporthe oryzae effector Avr-PikD suppresses rice immunity by inhibiting an LSD1-like transcriptional activator

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The Crop Journal 2024年第2期12卷 482-492页

作者： Jiayuan Guo Yiling wu Jianqiang Huang kaihui Yu Meilian Chen Yijuan Han Zhenhui Zhong Guodong Lu Yonghe Hong Zonghua Wang Xiaofeng Chen Fujian Universities Engineering Research Center of Marine Biology and Drugs Fuzhou Institute of OceanographyCollege of Geography and OceanographyMinjiang UniversityFuzhou 350108FujianChina Rice Research Institute Fujian Academy of Agricultural SciencesFuzhou 350018FujianChina Ministerial and Provincial Joint Innovation Center for Safety Production of Cross-Strait Crops Minjiang UniversityFuzhou 350108FujianChina State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops College of Plant ProtectionFujian Agriculture and Forestry UniversityFuzhou 350002FujianChina

Avirulence effectors(Avrs),encoded by plant pathogens,can be recognized by plants harboring the corresponding resistance proteins,thereby initiating effector-triggered immunity(ETI).In susceptible plants,however,Avrs can function as effectors,facilitating infection via effector-triggered susceptibility(ETS).Mechanisms of Avr-mediated ETS remain largely *** we report that the Magnaporthe oryzae effector Avr-PikD enters rice cells via the canonical cytoplasmic secretion pathway and suppresses rice basal ***-PikD interacts with an LSD1-like transcriptional activator AKIP30 of rice,and AKIP30 is also a positive regulator of rice immunity,whereas Avr-PikD impedes its nuclear localization and suppresses its transcriptional *** summary,*** delivers Avr-PikD into rice cells to facilitate ETS by inhibiting AKIP30-mediated transcriptional regulation of immune response against ***.

关键词： Magnaporthe oryzae Avirulence effector Avr-PikD Effector-triggered susceptibility Rice immunity Transcriptional activator

Algorithm for Calculating Torque Base in Vehicle Traction Control System

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Chinese Journal of Mechanical Engineering 2012年第6期25卷 1130-1137页

作者： LI Hongzhi LI Liang SONG Jian wu kaihui QIAO Yanjuan LIU Xingchun XIA Yongguang State Key Laboratory of Automotive Safety and Energy Tsinghua University Beijing 100084 China Chang'an Automotive Engineering General Research Institute Chongqing 400023 China

Existing research on the traction control system（TCS） mainly focuses on control methods, such as the PID control, fuzzy logic control, etc, aiming at achieving an ideal slip rate of the drive wheel over long control periods. The initial output of the TCS （referred to as the torque base in this paper）, which has a great impact on the driving performance of the vehicle in early cycles, remains to be investigated. In order to improve the control performance of the TCS in the first several cycles, an algorithm is proposed to determine the torque base. First, torque bases are calculated by two different methods, one based on states judgment and the other based on the vehicle dynamics. The confidence level of the torque base calculated based on the vehicle dynamics is also obtained. The final torque base is then determined based on the two torque bases and the confidence level. Hardware-in-the-loop（HIL） simulation and vehicle tests emulating sudden start on low friction roads have been conducted to verify the proposed algorithm. The control performance of a PID-controlled TCS with and without the proposed torque base algorithm is compared, showing that the proposed algorithm improves the performance of the TCS over the first several cycles and enhances about 5% vehicle speed by contrast. The proposed research provides a more proper initial value for TCS control, and improves the performance of the first several control cycles of the TCS.

关键词： traction control system torque base torque control initial value

Pyrimethamine upregulates BNIP3 to interfere SNARE-mediated autophagosome-lysosomal fusion in hepatocellular carcinoma

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Journal of Pharmaceutical Analysis 2024年第2期14卷 211-224页

作者： Jingjing Wang Qi Su Kun Chen Qing wu Jiayan Ren Wenjuan Tang Yu Hu Zeren Zhu Cheng Cheng kaihui Tu Huaizhen He Yanmin Zhang School of Pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an710061China

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

关键词： Pyrimethamine BNIP3 SNARE Autophagosome-lysosome fusion Hepatocellular carcinoma Sorafenib

Effect of the electro-acupuncture on senile plaques and its formation in APPD/PS1D double transgenic mice

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Genes & Diseases 2019年第3期6卷 282-289页

作者： Qinghua Yang Shujuan Zhu Jin Xu Chenglin Tang kaihui wu Yanjun wu Yiying Wang Huajun Sheng Institute of Neuroscience Chongqing Medical UniversityChongqingChina College of Traditional Chinese Medicine Chongqing Medical UniversityChongqingChina

Alzheimer’s disease(AD)is a progressive neurodegenerative disease and its incidence will increase with age and is *** senile plaques(SPs)are one of three main pathological features in AD patients,which are formed by amyloid b-protein(Ab)overaccumulation.b-amyloid precursor protein(APP),b-site APP cleavage(BACE1),and insulin degrading enzyme(IDE)proteins participate in the process of Ab production and *** present,the pathogenesis of AD is not yet clear and the current treatment methods can only relief the related symptoms of *** electro-acupuncture(EA)is a traditional Chinese medicine treatment combined the acupuncture and electrical stimulation and the treatment effect can also be controlled by transform the electrical ***,in this experiment,we carried out behavioral test,immunohistochemistry(IHC),and Western Blot(WB)after different period treatments to the model mice by electro-acupuncturing“Baihui”and“Shenshu”acupoints in APPt/PS1t double transgenic *** was found that the EA therapy can improve the ability of learning,memory and spatial exploration,and reduce the deposition of SPs in brain of AD model mice,and reduce the expressions of APP and BACE1,increase the expression of IDE *** results prompt that EA can effectively alleviate the pathological process of *** speculate that EA may play a comprehensive role in preventing the development of AD,considering the previous data.

关键词： Alzheimer’s disease Amyloid b-protein Electro-acupuncture Senile plaques Transgenic mice

Towards growth of pure AB-stacked bilayer graphene single crystals

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Nano Research 2024年第5期17卷 4616-4621页

作者： Xiaowen Zhang Tao Zhou Yunlong Ren Zuo Feng Ruixi Qiao Qinghe Wang Bin Wang Jinxia Bai Muhong wu Zhilie Tang Xu Zhou kaihui Liu Xiaozhi Xu Guangdong Basic Research Center of Excellence for Structure and Fundamental Interactions of Matter Guangdong Provincial Key Laboratory of Quantum Engineering and Quantum MaterialsSchool of PhysicsSouth China Normal UniversityGuangzhou 510006China Guangdong-Hong Kong Joint Laboratory of Quantum Matter School of PhysicsSouth China Normal UniversityGuangzhou 510006China Physical Science and Engineering Division King Abdullah University of Science and TechnologyThuwal 23955–6900Saudi Arabia State Key Laboratory for Mesoscopic Physics Frontiers Science Center for Nano-optoelectronicsSchool of PhysicsPeking UniversityBeijing 100871China Institute for Frontier Science Nanjing University of Aeronautics and AstronauticsNanjing 210094China International Centre for Quantum Materials Collaborative Innovation Centre of Quantum MatterPeking UniversityBeijing 100871China Songshan Lake Materials Laboratory Institute of PhysicsChinese Academy of SciencesDongguan 523808China

Given its intriguing band structure and unique tunable bandgap,AB-stacked bilayer graphene has great potentials in the applications of high-end electronics,optoelectronics and *** epitaxial growth of AB-stacked single-crystal bilayer graphene films requires a strict AB-stacked lattice,identical orientations and seamless stitching of bilayer graphene ***,the particles inevitably present on the metal surface that produced during high temperature growth would induce random orientations,twisted stacking islands,and uncontrollable multilayers,which is a great challenge to ***,we propose a heat-resisting-box assisted strategy to produce nearly pure AB-stacked bilayer graphene single-crystal films on Cu/Ni(111)*** our technique,the particles on the Cu/Ni(111)surface are effectively eliminated,which greatly minimizes the occurrence of randomly twisted islands and uncontrollable *** as-grown AB-stacked bilayer graphene films show>99%alignment and>99%AB stacking *** work provides a promising method towards the growth of pure AB-stacked bilayer graphene single crystals and would accelerate its device applications.

关键词： bilayer graphene AB stacking uniform growth heat-resisting box

Preparation and Characterization of Fe^(3+)-doped Nanometer TiO_2 Photocatalysts

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Journal of wuhan University of Technology(Materials Science) 2006年第3期21卷 57-60页

作者：刘君武 College of Materials Science and Engineering Hefei University of TechnologyHefei 230009China

Fe^3＋ -doped nanometer TiO2 photocatalysts were prepared by sol-gel technique. TiO2 powders with different Fe^3＋ / Ti^4 ＋ molar ratios ranging from 0. 05% to 25% were synthesized by calcinating the gels in the temperature range of 200-600 ℃ . The effects of the content of iron ions and calcination temperature on the physical properties of the powders and their photocatalytic activities were examined by the photodecorapositon of methyl orange in sunlight. The results show that Fe dopant can decrease the temperature of nanatase-ratile transformation. The ideal photocatalytic property was achieved when the sample with an Fe^3＋ / Ti^4＋ ratio of 20 at% was calcined at about 300 ℃ for an hour, which is superior to that of commercial Degussa P-25. The optimum microstructure of the Fe-doped TiO2 for a high photocatalytic activity in sunlight is consisted of nanatase and ratile.

关键词： titania Fe^3 + - doping sunlight methyl orange photocatalytic degradation