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Screening of Common Traditional Chinese Drugs for Reversing Multidrug Resistance of KBV200 In Vitro 被引量:1
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作者 张庆林 赵精华 +5 位作者 曹菊荣 宋京 毕建进 王小娜 龚萍 吴祖泽 《Journal of Chinese Pharmaceutical Sciences》 CAS 2002年第3期64-67,共4页
The ethanolic extracts of 100 common traditional Chinese drugs, which are widely used in many prescriptions in treatment of cancer in China, were screened for MDR of KBV200 cell line in vitro with MTT method. The ... The ethanolic extracts of 100 common traditional Chinese drugs, which are widely used in many prescriptions in treatment of cancer in China, were screened for MDR of KBV200 cell line in vitro with MTT method. The result showed 9 extracts having MDR reversal activity. They were the extracts of Fructus Lagenariae Sicerariae, Radix Glycyrrhizae, Poria, Herba Andrographitis, Radix Sophorae Tonkinensis, Caulis Mahoniae, Folium Artemisiae Argyi, Rhizoma Curcumae, Fructus Cnidii. Other 5 extracts showed cytotoxic on KBV200 cell line. $$$$ 展开更多
关键词 Traditional Chinese drugs reversing MDR SCREENING In vitro
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Screening of Common Traditional Chinese Drugs for Reversing Multidrug Resistance of KBV200 In Vitro 被引量:4
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作者 张庆林 赵精华 +5 位作者 曹菊荣 宋京 毕建进 王小娜 龚萍 吴祖泽 《Journal of Chinese Pharmaceutical Sciences》 CAS 2002年第3期64-67,共页
The ethanolic extracts of 100 common traditional Chinese drugs, which are widely used in many prescriptions in treatment of cancer in China, were screened for MDR of KBV200 cell line in vitro with MTT method. The ... The ethanolic extracts of 100 common traditional Chinese drugs, which are widely used in many prescriptions in treatment of cancer in China, were screened for MDR of KBV200 cell line in vitro with MTT method. The result showed 9 extracts having MDR reversal activity. They were the extracts of Fructus Lagenariae Sicerariae, Radix Glycyrrhizae, Poria, Herba Andrographitis, Radix Sophorae Tonkinensis, Caulis Mahoniae, Folium Artemisiae Argyi, Rhizoma Curcumae, Fructus Cnidii. Other 5 extracts showed cytotoxic on KBV200 cell line. $$$$ 展开更多
关键词 Traditional Chinese drugs reversing MDR SCREENING In vitro
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Reversing design methodology of investment casting die profile based on ProCAST 被引量:11
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作者 Dou Yangqing Bu Kun +1 位作者 Dou Yangliu Dong Yiwei 《China Foundry》 SCIE CAS 2010年第2期132-137,共6页
Turbine blade is one of the critical components of aircraft engine.The performance of the engine depends on the shape and dimensions of components,but superalloy blade material cannot be easily machined.Although inves... Turbine blade is one of the critical components of aircraft engine.The performance of the engine depends on the shape and dimensions of components,but superalloy blade material cannot be easily machined.Although investment casting is an ideal process for such net-shape components,it requires an accurate determination of the casting-die profile.In this paper,a reversing design methodology for investment casting die using ProCAST is proposed.By combining the methods of simplifying grid files and quick sorting,the efficiency of sorting and matching can be largely improved.Further,the mould/die cavity anti-deformation system can be easily built.With ProCAST,the optimized die profile for investment casting can be established. 展开更多
关键词 investment casting reversing design methodology node matching numerical simulation PROCAST
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Hydraulic calculation and dynamic analysis of columnar reversing gate 被引量:3
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作者 You-an HU Meng WANG Miao-miao WANG Ge SONG Wen-xuan NIU Ting XU 《Water Science and Engineering》 EI CAS 2011年第3期294-304,共11页
According to the hydraulic calculation principles of the orifice outflow, the discharge capacity of the columnar reversing gate under the partial opening condition was calculated and checked. Using ANSYS, a large fini... According to the hydraulic calculation principles of the orifice outflow, the discharge capacity of the columnar reversing gate under the partial opening condition was calculated and checked. Using ANSYS, a large finite element analysis software, the discharge process was simulated. The distribution rule of the velocities in the gate chamber and downstream channel was obtained. An FEM model of the columnar reversing gate was built, and the natural vibration properties of the gate were analyzed. Based on the Westergaard added mass method, the added mass caused by the fluid-structure coupling motion was taken into account, and the effects of the coupling interaction were discussed. The results show that the size of the small gates meets the demand for discharge capacity, the current in the gate chamber is quite turbulent, the trunnion and arms are obviously impacted by flow, and the effects of water on vibration characteristics are remarkable. The study provides a reference for the design and calculation of gates of the same type. 展开更多
关键词 columnar reversing gate hydraulic calculation structural dynamic analysis finite element analysis
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The status of Chinese medicine in reversing multi-drug resistance of hepatocellular carcinoma 被引量:3
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作者 Shengli Yang Yunxia Wang Xiaoli Pan Zhifan Xiong 《The Chinese-German Journal of Clinical Oncology》 CAS 2011年第9期541-546,共6页
Multi-drug resistance(MDR) is a major obstacle in the chemotherapy of hepatocellular carcinoma.Comparing with western reversal agents,traditional Chinese medicine have advantages of low cost,hypotoxicity,wide safety r... Multi-drug resistance(MDR) is a major obstacle in the chemotherapy of hepatocellular carcinoma.Comparing with western reversal agents,traditional Chinese medicine have advantages of low cost,hypotoxicity,wide safety range,broad-spectrum and multi-targets,etc.Therefore,traditional Chinese medicine may be expected to open up a new path to reverse MDR of liver cancer.Studies about applying traditional Chinese medicine to reverse MDR in hepatocellular carcinoma are outlined below. 展开更多
关键词 Chinese medicine multi-drug resistance reversing hepatocellular carcinoma
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Reversing multiple age-related pathologies by controlling the senescence-associated secretory phenotype of stem cells 被引量:1
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作者 Daisuke Hisamatsu Hayato Naka-Kaneda 《Neural Regeneration Research》 SCIE CAS CSCD 2016年第11期1746-1747,共2页
Regenerative medicine by cell transplantation is a novel therapy for treating end-stage organ failure and tissue damage. Cell-based therapy based on the transplantation of neural stem/progenitor cells (NSPCs) repres... Regenerative medicine by cell transplantation is a novel therapy for treating end-stage organ failure and tissue damage. Cell-based therapy based on the transplantation of neural stem/progenitor cells (NSPCs) represents an attractive strategy for the treatment of neurodegenerative diseases, but obtaining large numbers of these cells is difficult and their differentiation potential is strictly restricted in a spatiotemporally-regulated manner during central nervous system (CNS) development. Therefore, embryonic stem cells and induced pluripotent stem cells represent an attractive alternative for cell-transplantation therapy in regenerative medicine. 展开更多
关键词 cell stem reversing multiple age-related pathologies by controlling the senescence-associated secretory phenotype of stem cells MSCs SASP
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Dynamic Performance Research on Reversing Valve of Hydraulic Breaker 被引量:1
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作者 Guoping Yang Yubao Chen Bo Chen 《World Journal of Mechanics》 2012年第6期288-296,共9页
The structure and operational principle on a new type reversing valve of hydraulic breaker are introduced. The nonlinear mathematic model and simulation model of the new type reversing valve are built. The dynamic sim... The structure and operational principle on a new type reversing valve of hydraulic breaker are introduced. The nonlinear mathematic model and simulation model of the new type reversing valve are built. The dynamic simulation research of the new type reversing valve is conducted. The effects of the system parameters on the working performance are researched systematically and deeply. The regular understanding on the motion of the reversing valve is obtained, which provides theoretical basis for the innovation and manufacturing of a new generation of hydraulic breaker reversing valve. 展开更多
关键词 HYDRAULIC BREAKER reversing VALVE DYNAMIC Performance NONLINEAR Mathematic Model COMPUTER Simulation
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Research on Car Reversing Warning System based on CAN Bus 被引量:1
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作者 Qi Wei Zhang Xiuru 《International Journal of Technology Management》 2014年第8期119-121,共3页
The paper study the software and hardware principles of ultrasonic ranging reversing radar, design the vehicle reversing radar based on intelligent node of CAN bus, realize data communication and resource sharing with... The paper study the software and hardware principles of ultrasonic ranging reversing radar, design the vehicle reversing radar based on intelligent node of CAN bus, realize data communication and resource sharing with other intelligent nodes of the reversing radar. The experimental results show that, the design can achieve the expected technical indicators design, measurement precision and the reliability is high, which has certain guiding significance in the design of the car reversing radar, has wide application prospect and practical significance in the function of the extended CAN bus communication messages design and automotive CAN network. 展开更多
关键词 Ultrasonic ranging reversing radar single chip microcomputer CAN bus
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Mechanisms of remaining oil formation by water flooding and enhanced oil recovery by reversing water injection in fractured-vuggy reservoirs
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作者 WANG Jing QI Xiangsheng +4 位作者 LIU Huiqing YANG Min LI Xiaobo LIU Hongguang ZHANG Tuozheng 《Petroleum Exploration and Development》 CSCD 2022年第5期1110-1125,共16页
To get a deeper understanding on the formation mechanisms and distribution laws of remaining oil during water flooding, and enhanced oil recovery(EOR) mechanisms by reversing water injection after water flooding, 3D v... To get a deeper understanding on the formation mechanisms and distribution laws of remaining oil during water flooding, and enhanced oil recovery(EOR) mechanisms by reversing water injection after water flooding, 3D visualization models of fractured-vuggy reservoir were constructed based on the elements and configuration of fractures and vugs, and typical fracture-vug structures by using advanced CT scanning and 3D printing technologies. Then, water flooding and reversing water injection experiments were conducted. The formation mechanisms of remaining oil during water flooding include inadequate injection-production well control, gravity difference between oil and water, interference between different flow channels, isolation by low connectivity channel, weak hydrodynamic force at the far end. Under the above effects, 7 kinds of remaining oil may come about, imperfect well-control oil, blind side oil, attic oil at the reservoir top, by-pass residual oil under gravity, by-pass residual oil in secondary channel, isolated oil in low connectivity channel, and remaining oil at far and weakly connected end. Some remaining oil can be recovered by reversing water injection after water flooding, but its EOR is related to the remaining oil type, fracture-cavity structure and reversing injection-production structure. Five of the above seven kinds of remaining oil can be produced by six EOR mechanisms of reversing water injection: gravity displacement, opening new flow channel, rising the outflow point, hydrodynamic force enhancement, vertically equilibrium displacement, and synergistic effect of hydrodynamic force and gravity. 展开更多
关键词 fractured-vuggy reservoir water flooding remaining oil reversing water injection stimulation mechanism enhanced oil recovery 3D printing
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Logical Design and Control of Network in Local Mine Air-Reversing System
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作者 李建民 王省身 《Journal of China University of Mining and Technology》 2001年第1期33-38,共6页
This paper sets up a mathematical model of switching network and switching function by utilizing graph theory to describe the logical function of different paths.The function varies with open and closed states of air ... This paper sets up a mathematical model of switching network and switching function by utilizing graph theory to describe the logical function of different paths.The function varies with open and closed states of air doors in a complex mine air sub network, and the computer program for solving the switching function of complex networks are offered. It gives the method for discriminating a reversible branch in a complex network by means of the switching function, and the method of counter inverted logical control of airflow inversion by means of open and short circuit conversion of key branches. The research has solved the problem of the stablization of air flow for normal ventination and reversing ventination in a diagonal network. 展开更多
关键词 mine ventination air reversing graph theory local mine air network
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Empirical six-dimensional framework for slowing and reversing ageing using modern science and ancient wisdom
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作者 Asoka Nimal Jinadasa 《Life Research》 2019年第3期106-112,共7页
There are numerous published theories that cover the different biological processes relating to ageing. No one seems to have integrated such complex and seemingly unrelated information into a holistic framework that e... There are numerous published theories that cover the different biological processes relating to ageing. No one seems to have integrated such complex and seemingly unrelated information into a holistic framework that explains in simple terms the key aspects of ageing and provides a set of daily practices for staying young and healthy. An atiempt is made here to select a 6-dimensional framework symbolized by heart, mind, passion, focus, body and health, and correlate it to the mental, emotional, physical and health aspects of ageing. Based on grounded theory, this paper empirically correlates 30 practical methods that can be used to develop all six dimensions, with 18 key factors that were found to infl uence ageing: Neurogenesis;Epigenetic reprogramming;Removing dying cells;Mitochondria resuscitation;Calorie restriction;Plant-based diet;Regular physical activity;Chi Kung (Qigong);Overcoming anxiety, depression and stress;Positive mind-set;Some worrying;Vitamins and minerals;L-Theanine;Omega-3 and healthy fats;Coenzyme Q-10;Pyrroloquinoline quinone;Nitric oxide;Choline. In this study, 26 references were used to establish that all 18 of these seemingly unrelated key anti-ageing factors can be developed using 30 daily practices derived from the 6-dimensional framework. These simple daily prac-tices can help people of all ages to stay young and healthy, and help older people who are living alone to self-improve their quality of life without needing anyone to look atier them. Since many anti-ageing drugs seem to be ineffective, this study provides a holistic new research direction for using modern science and ancient human energy practices combined with wholesome nutrition to slow ageing and age-related illnesses. 展开更多
关键词 Slowing ageing reversing ageing AGE-RELATED illnesses Prolonging YOUTH Improving health Alzheimer's
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Reversing Desertification
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《ChinAfrica》 2019年第6期2-2,共1页
Deserts usually impress people with the image of vast desolated sand area with no water or plants. But in China, it is no longer the case, as some parts of its vast deserts have become grassland, forest and even wetla... Deserts usually impress people with the image of vast desolated sand area with no water or plants. But in China, it is no longer the case, as some parts of its vast deserts have become grassland, forest and even wetland. In the Kubuqi Desert in north China's Inner Mongolia Autonomous Region, and the Babusha Desert and Mu Us Desert in northwest China's Gansu and Shaanxi provinces, just to name a few, efforts in different forms have been made to stop the deserts from expanding, and reclaim the land from the deserts, involving people from all walks of life, such as individuals, businesses and social organizations. 展开更多
关键词 reversing DESERTIFICATION PEOPLE
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Reversing Horizons Artist Reflections of the Hong Kong Handover 10^(th) Anniversary
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《大美术》 2007年第7期159-160,共2页
■With great ceremony and amidst a torrential downpour on the 1st July, 1997,Hong Kong ceased to be a British colony and was handed back to China. Since the 1842 British occupation of Hong
关键词 ANNIVERSARY reversing Horizons Artist Reflections of the Hong Kong Handover 10 th
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Reversing effects of interferon α on drug resistance of bone marrow cells in leukemia
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作者 张勇 张一军 +1 位作者 夏顺中 周成康 《Journal of Medical Colleges of PLA(China)》 CAS 1999年第4期286-288,共3页
Objective:To investigate the reversing effects of interferon a (IFN-a) on drug resistance of bone marrow cells in leukemia and its possible mechanism. Methods: Before and after the bone marrow cells extracted from50 c... Objective:To investigate the reversing effects of interferon a (IFN-a) on drug resistance of bone marrow cells in leukemia and its possible mechanism. Methods: Before and after the bone marrow cells extracted from50 cases of acute leukemia and 2 of chronic leukemia (BP) were incubated in the media with the addition of IFN-α,MDR1 mRNA expression and concentration of daunorubicin (DNR) in the cells were determined respectively withSAG-ISH and respectrofluorimetry. Results: Twenty-four (64. 2% ) our of all the 52 cases presented MDR1 mRNA expression. There was significant difference in the concentration of DNR between MDR1-positive and MDR1-negative cases before and after incubation. In all the 52 cases, no significant difference was found between the concentration of DNR before the incubation and that after the incubation. Conclusion: IFN-a can increase the concentration of DNR in the bone marrow cells in leukemia. No occurrence of MDR reversal is on the level of MDRl buton other levels. 展开更多
关键词 LEUKEMIA INTERFERON α REVERSAL DRUG RESISTANCE
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EDSM-Based Binary Protocol State Machine Reversing
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作者 Shen Wang Fanghui Sun +3 位作者 Hongli Zhang Dongyang Zhan Shuang Li Jun Wang 《Computers, Materials & Continua》 SCIE EI 2021年第12期3711-3725,共15页
Internet communication protocols define the behavior rules of network components when they communicate with each other.With the continuous development of network technologies,many private or unknown network protocols ... Internet communication protocols define the behavior rules of network components when they communicate with each other.With the continuous development of network technologies,many private or unknown network protocols are emerging in endlessly various network environments.Herein,relevant protocol specifications become difficult or unavailable to translate in many situations such as network security management and intrusion detection.Although protocol reverse engineering is being investigated in recent years to perform reverse analysis on the specifications of unknown protocols,most existing methods have proven to be time-consuming with limited efficiency,especially when applied on unknown protocol state machines.This paper proposes a state merging algorithm based on EDSM(Evidence-Driven State Merging)to infer the transition rules of unknown protocols in form of state machines with high efficiency.Compared with another classical state machine inferring method based on Exbar algorithm,the experiment results demonstrate that our proposed method could run faster,especially when dealing with massive training data sets.In addition,this method can also make the state machines have higher similarities with the reference state machines constructed from public specifications. 展开更多
关键词 Network security protocol state machine EDSM algorithm protocol reverse engineering protocol analyzing
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Clinical study of Cangbai Shiduqing Granul in reversing drug resistance of ureaplasma urealyticum
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作者 Zhang Yingchun Li Yuanwen +5 位作者 Li Wei Zhou Zhiqiang Zhao Yajing WU Meichao Shi Jingwen Cai Lingling 《World Journal of Integrated Traditional and Western Medicine》 2017年第2期5-8,共4页
Ureaplasma Urealyticum(UU) can not only cause a wide range of nongonococcalinfectionsto urogenital tract,but also lead to infertility,sterility,intrauterinefetal infection,abortion or other bad consequences.For males,... Ureaplasma Urealyticum(UU) can not only cause a wide range of nongonococcalinfectionsto urogenital tract,but also lead to infertility,sterility,intrauterinefetal infection,abortion or other bad consequences.For males,UU may cause prostatitis,epididymitis and other diseases.With great harm to the human health,UU infection has been taken as one of the most important STDs in China for prevention and cure.However,the drug resistance of UU is increasingly stronger with the widespread use of antibiotics.Many nongonococcal patients with mycoplasma infection often fail to be cured after a long time of treatment,and drug sensitive tests find that,multidrug resistance brings physical and mental pains to patients all the time.Luckily,integrated Chinese traditional and western medicine greatly improves the cure rate,though the mechanism is not clear.There have been many studies on the reversion action and mechanism of TCM on the antibiotic resistance of bacteria,but studies on the reversion to UU drug resistance are deficient.Here we chose some voluntary patients with multidrug resistance as the research objects,who received treatment in my hospital in recent 3 years.They were given the oral administration of self-prescribed Cangbai Shiduqing Granule.Then,Cangbai Shiduqing Granule's reversion effect on UU drug resistance,namely,the sensitivity transformation situation of drug-resistant antibiotics,was observed.And the observation results are presented in the paper. 展开更多
关键词 Ureaplasmaurealyticum(uu) Drug resistance REVERSION ANTIBIOTICS
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Reversing free-electron transfer of sulfide cocatalyst for exceptional photocatalytic H_(2)evolution 被引量:1
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作者 Yanfeng Zhang Zhenyi Zhang 《Journal of Materials Science & Technology》 SCIE EI CAS CSCD 2024年第4期147-149,共3页
Recently,Yu and co-workers deeply explore the potential impact of free electron transfer between co-catalysts and photocatalyst carriers on H_(2)evolution efficiency of active sites over MoS_(2+x).They pro-pose an ele... Recently,Yu and co-workers deeply explore the potential impact of free electron transfer between co-catalysts and photocatalyst carriers on H_(2)evolution efficiency of active sites over MoS_(2+x).They pro-pose an electron-reversal tactics to evade the unexpected electron transfer and synchronously regulate the above transfer in a beneficial orientation for weakening hydrogen adsorption on S sites.Herein,this highlight not only discusses and summarizes the essences of electron reversal and the optimized H ad-sorption/desorption mechanism,but also emphasizes the significance of femtosecond transient absorp-tion spectroscopy(fs-TAS)and in-situ irradiated X-ray photoelectron spectroscopy(ISI-XPS)for revealing charge transfer dynamics and processes.We anticipate that this highlight can disseminate a new per-spective on the roles of photocatalyst carriers in improving cocatalytic H_(2)-production kinetics. 展开更多
关键词 Photocatalysis COCATALYST Electron reversal Antibonding-orbital occupancy S–H bonds
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Optimizing the drying parameters of a fixed bed with reversing ventilation for peanut using computer simulation 被引量:2
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作者 Jianchun Yan Huanxiong Xie +2 位作者 Hai Wei Huichang Wu Zhaoyan You 《International Journal of Agricultural and Biological Engineering》 SCIE EI CAS 2021年第5期255-266,共12页
To obtain the optimal operation parameters of fixed-bed reversing ventilation drying of peanuts,a set of partial differential equations indicating the heat and mass transfer relationships between the peanut pods and a... To obtain the optimal operation parameters of fixed-bed reversing ventilation drying of peanuts,a set of partial differential equations indicating the heat and mass transfer relationships between the peanut pods and air during drying was proposed.Then,a series of discretized models were established for simulation,and the time consumed,unevenness,and energy consumption for batch drying were calculated.The results showed that reversing ventilation and segmented drying was helpful to these issues for high drying ability.The optimal operation parameters were determined by uniform design experimentation of mathematical simulation.The result showed that when the moisture content(wet basis)was above 22%,a ventilation velocity of 0.46 m/s was optimal;when the moisture content was between 8%and 22%,a ventilation velocity of 0.20 m/s was optimal.Using the optimal parameters,the computer simulating result was compared with the experimental results.The correlation coefficients between the simulating and the experimental values for the temperature and moisture content were all above 0.98 and the quality of dried peanuts was close to that of natural sun-dried ones,which indicates that the optimization results of the drying parameters are highly reliable. 展开更多
关键词 PEANUT fix bed drying reversing ventilation SIMULATION OPTIMIZATION
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Bioinspired Passive Tactile Sensors Enabled by Reversible Polarization of Conjugated Polymers
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作者 Feng He Sitong Chen +3 位作者 Ruili Zhou Hanyu Diao Yangyang Han Xiaodong Wu 《Nano-Micro Letters》 SCIE EI CAS 2025年第1期361-377,共17页
Tactile perception plays a vital role for the human body and is also highly desired for smart prosthesis and advanced robots.Compared to active sensing devices,passive piezoelectric and triboelectric tactile sensors c... Tactile perception plays a vital role for the human body and is also highly desired for smart prosthesis and advanced robots.Compared to active sensing devices,passive piezoelectric and triboelectric tactile sensors consume less power,but lack the capability to resolve static stimuli.Here,we address this issue by utilizing the unique polarization chemistry of conjugated polymers for the first time and propose a new type of bioinspired,passive,and bio-friendly tactile sensors for resolving both static and dynamic stimuli.Specifically,to emulate the polarization process of natural sensory cells,conjugated polymers(including poly(3,4-ethylenedioxythiophen e):poly(styrenesulfonate),polyaniline,or polypyrrole)are controllably polarized into two opposite states to create artificial potential differences.The controllable and reversible polarization process of the conjugated polymers is fully in situ characterized.Then,a micro-structured ionic electrolyte is employed to imitate the natural ion channels and to encode external touch stimulations into the variation in potential difference outputs.Compared with the currently existing tactile sensing devices,the developed tactile sensors feature distinct characteristics including fully organic composition,high sensitivity(up to 773 mV N^(−1)),ultralow power consumption(nW),as well as superior bio-friendliness.As demonstrations,both single point tactile perception(surface texture perception and material property perception)and two-dimensional tactile recognitions(shape or profile perception)with high accuracy are successfully realized using self-defined machine learning algorithms.This tactile sensing concept innovation based on the polarization chemistry of conjugated polymers opens up a new path to create robotic tactile sensors and prosthetic electronic skins. 展开更多
关键词 Passive tactile sensors Reversible polarization of conjugated polymers Tactile perception Machine learning algorithm Object recognition
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BIBR1532 inhibits proliferation and metastasis of esophageal squamous cancer cells by inducing telomere dysregulation
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作者 Qin Wang Qing-Rong Li +7 位作者 Lei Xu Zi-Chun Yuan Xiao Liu Mao-Ju Tang Man Luo Xiao-Wu Zhong Qiang Ma Xiao-Lan Guo 《World Journal of Gastrointestinal Oncology》 SCIE 2025年第1期214-225,共12页
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a malignant tumor with high morbidity and mortality,and easy to develop resistance to chemotherapeutic agents.Telomeres are DNA-protein complexes located at the te... BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a malignant tumor with high morbidity and mortality,and easy to develop resistance to chemotherapeutic agents.Telomeres are DNA-protein complexes located at the termini of chro-mosomes in eukaryotic cells,which are unreplaceable in maintaining the stability and integrity of genome.Telomerase,an RNA-dependent DNA polymerase,play vital role in telomere length maintain,targeting telomerase is a promising therapeutic strategy for cancer.KYSE150 and KYSE410 cells were cultured and exposed to various concentrations of BIBR1532.Cell viability was assessed at 48 hours and 72 hours to determine the IC50 values.The effects of BIBR1532 on ESCC cell proliferation,migration,and cellular senescence were evaluated using the cell counting kit-8 assay,plate colony formation assay,scratch assay,transwell assay,andβ-galactosidase staining,respectively.Western blotting was performed to detect the expression of RESULTS The IC50 values for KYSE150 and KYSE410 cells after 48 hours of BIBR1532 exposure were 48.53μM and 39.59μM,respectively.These values decreased to 37.22μM and 22.71μM,respectively,following a longer exposure of 72 hours.BIBR1532 exhibited dose-dependent effects on KYSE150 and KYSE410 cells,including decreased hTERT expression,inhibition of proliferation and metastasis,and induction of cellular senescence.Mechanistically,BIBR1532 upregulated the expression of the DDR protein,γ-H2AX,and activated the ataxia telangiectasia and Rad3-related protein(ATR)/check point kinase 1(CHK-1)and ataxia-telangiectasia mutated gene(ATM)/CHK2 pathways.BIBR1532 downregulated the expression of telomere-binding proteins,including telomeric-repeat binding factor 1(TRF1),TRF2,protection of telomeres 1,and TIN2-interacting protein 1.In a nude mouse xenograft model,BIBR1532 significantly suppressed tumor growth,reduced hTERT expression,and increasedγ-H2AX protein levels.Hematoxylin and eosin staining of various organs,including the heart,liver,spleen,lungs,and kidneys,revealed no apparent adverse effects.CONCLUSION BIBR1532 exerts anti-cancer effects on ESCC by inducing DDR through the ATR/CHK1 and ATM/CHK2 pathways and downregulating the expression of telomere-binding proteins. 展开更多
关键词 Esophageal squamous cell carcinoma BIBR1532 Human telomerase reverse transcriptase DNA damage response Telomere-binding proteins
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