39 results on '"Zhou, Zhu"'
Search Results
2. Molecular genetics, therapeutics and RET inhibitor resistance for medullary thyroid carcinoma and future perspectives
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Ying Zhang, Wei-Hui Zheng, Shi-Hong Zhou, Jia-Lei Gu, Qing Yu, Yi-Zhou Zhu, Yu-Jie Yan, Zhi Zhu, and Jin-Biao Shang
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Medullary thyroid carcinoma (MTC) ,Rearrangement during transfection (RET) ,Tyrosine kinase inhibitors (TKIs) ,Targeted therapy ,Medicine ,Cytology ,QH573-671 - Abstract
Abstract Medullary thyroid carcinoma (MTC) is a rare type of thyroid malignancy that accounts for approximately 1–2% of all thyroid cancers (TCs). MTC include hereditary and sporadic cases, the former derived from a germline mutation of rearrangement during transfection (RET) proto-oncogene, whereas somatic RET mutations are frequently present in the latter. Surgery is the standard treatment for early stage MTC, and the 10-year survival rate of early MTC is over 80%. While for metastatic MTC, chemotherapy showing low response rate, and there was a lack of effective systemic therapies in the past. Due to the high risk (ca. 15–20%) of distant metastasis and limited systemic therapies, the 10-year survival rate of patients with advanced MTC was only 10–40% from the time of first metastasis. Over the past decade, targeted therapy for RET has developed rapidly, bringing hopes to patients with advanced and progressive MTC. Two multi-kinase inhibitors (MKIs) including Cabozantinib and Vandetanib have been shown to increase progression-free survival (PFS) for patients with metastatic MTC and have been approved as choices of first-line treatment. However, these MKIs have not prolonged overall survival (OS) and their utility is limited due to high rates of off-target toxicities. Recently, new generation TKIs, including Selpercatinib and Pralsetinib, have demonstrated highly selective efficacy against RET and more favorable side effect profiles, and gained approval as second-line treatment options. Despite the ongoing development of RET inhibitors, the management of advanced and progressive MTC remains challenging, drug resistance remains the main reason for treatment failure, and the mechanisms are still unclear. Besides, new promising therapeutic approaches, such as novel drug combinations and next generation RET inhibitors are under development. Herein, we overview the pathogenesis, molecular genetics and current management approaches of MTC, and focus on the recent advances of RET inhibitors, summarize the current situation and unmet needs of these RET inhibitors in MTC, and provide an overview of novel strategies for optimizing therapeutic effects.
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- 2024
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3. Biomechanical behaviour of tilted abutment after fixed partial denture restoration of CAD/CAM materials
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Tong Zhu, Jingyi Chen, Yichen Xu, Zhou Zhu, Jian Wang, Xibo Pei, Mingxin Qiao, Bin Cheng, Ruyi Li, and Qianbing Wan
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CAD/CAM ,Dental material ,Biomechanical behaviour ,Tilted abutment ,Dentistry ,RK1-715 - Abstract
Abstract Background Failure to restore missing teeth in time can easily lead to the mesial tilting of the distal abutment teeth. However, a fixed partial denture (FPD) can improve stress conduction and distribution and prevent periodontal injuries. In these more complex cases, it is necessary to consider various factors comprehensively to improve conventional treatment planning and achieve better results. Methods We selected a patient with a missing first molar and a mesial inclination of the second molar, leaving inadequate space or bone mass for implant denture restoration, necessitating an FPD for restoration. Three-dimensional finite element analysis (3D-FEA) combined with photoelastic analysis were used to explore how the inclination angle (0 ‒ 30°) and different dental restoration materials (zirconia, lithium disilicate, polymer-infiltrated ceramic network, and resin composite) affect the biomechanical behaviour of FPD‒abutments‒periodontal tissue complex. Results The stress was easily concentrated in the FPD connectors, enamel shoulder collar, periapical area, and root bifurcation. The stress on FPD and the periodontal ligament (PDL) of the second premolar increased with an increase in the elastic modulus of FPD, with an opposite trend in the abutments, the alveolar bone, and the PDL of the second molar. The stress on the FPD and alveolar bone increased with increased inclination angle of the distal abutment. The stress on two abutments and their PDL were positively correlated with the inclination angle in two stages; however, when the inclination angle > 12°, the second premolar and its PDL showed a negative correlation. Conclusions FPDs can be used for restoration within 24° of distal abutment inclination, but protecting the abutments ( 12° especially) must be taken seriously. For this purpose, an FPD material with higher strength is recommended.
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- 2024
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4. Predicting prognosis for epithelial ovarian cancer patients receiving bevacizumab treatment with CT-based deep learning
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Xiaoyu Huang, Yong Huang, Kexin Liu, Fenglin Zhang, Zhou Zhu, Kai Xu, and Ping Li
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Epithelial ovarian cancer (EOC) presents considerable difficulties in prognostication and treatment strategy development. Bevacizumab, an anti-angiogenic medication, has demonstrated potential in enhancing progression-free survival (PFS) in EOC patients. Nevertheless, the identification of individuals at elevated risk of disease progression following treatment remains a challenging task. This study was to develop and validate a deep learning (DL) model using retrospectively collected computed tomography (CT) plain scans of inoperable and recurrent EOC patients receiving bevacizumab treatment diagnosed between January 2013 and January 2024. A total of 525 patients from three different institutions were retrospectively included in the study and divided into training set (N = 400), internal test set (N = 97) and external test set (N = 28). The model’s performance was evaluated using Harrell’s C-index. Patients were categorized into high-risk and low-risk group based on a predetermined cutoff in the training set. Additionally, a multimodal model was evaluated, incorporating the risk score generated by the DL model and the pretreatment level of carbohydrate antigen 125 as input variables. The Net Reclassification Improvement (NRI) metric quantified the reclassification performance of our optimal model in comparison to the International Federation of Gynecology and Obstetrics (FIGO) staging model. The results indicated that DL model achieved a PFS predictive C-index of 0.73 in the internal test set and a C-index of 0.61 in the external test set, along with hazard ratios of 34.24 in the training set (95% CI: 21.7, 54.1; P
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- 2024
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5. The Effect of Nb on Microstructure and Properties of GH4169 Alloy Pipe
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Wang Shaobing, Sun Wenqiang, Wang Man, Zhou Zhu, Liu Zhengdong, Zhong Qiang
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gh4169 alloy pipe; nb content; grain size; tensile at room temperature; high temperature tensile at 200 ℃; precipitated phase ,Materials of engineering and construction. Mechanics of materials ,TA401-492 ,Technology - Abstract
With the manufacturing process by vacuum induction, electroslag remelting, vacuum self consumption, homogenization heat treatment, forging, hot extrusion, cold rolling, and heat treatment. we can get two types of GH4169 alloy pipes with Nb content of 4.90% and 5.30% respectively. The effect of Nb content on the microstructure and properties of GH4169 alloy pipes was studied while other components remained basically the same. The results show that under the same heat treatment process, with the increase of Nb element content, the Nb content becomes higher and the grain size becomes smaller; At 200 ℃ and room temperature with the tensile strength and yield strength both increase with the increasing of Nb content, And the content of precipitates in GH4169 alloy pipes also increases. Under different solid solution heat treatments and the same aging heat treatment process, the grain size of GH4169 alloy pipes is in the range of 4.0-7.0. The smaller the grain size, the higher the tensile strength and yield strength of the pipes; At the same grain size, the higher the Nb content, the higher the tensile strength and yield strength of the pipe.
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- 2024
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6. Thread-structural microneedles loaded with engineered exosomes for annulus fibrosus repair by regulating mitophagy recovery and extracellular matrix homeostasis
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Shaojun Hu, Meng Zhu, Hongyuan Xing, Yucheng Xue, Jun Li, Zhan Wang, Zhou Zhu, Miaojie Fang, Zilong Li, Jianbin Xu, Yong He, and Ning Zhang
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Intervertebral disc degeneration ,Microneedle ,Exosomes ,Annulus fibrosus ,Mitophagy ,Materials of engineering and construction. Mechanics of materials ,TA401-492 ,Biology (General) ,QH301-705.5 - Abstract
Low back pain is among the most grave public health concerns worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The destruction of annulus fibrosus (AF) is the primary cause of IVDD. A sustainable and stable treatment system for IVDD is lacking because of the special organizational structure and low nutrient supply of AF. We here found that IVDD results in the impaired mitochondrial function of AF tissue, and mitochondrial autophagy (mitophagy) plays a protective role in this process. We therefore reported a thread-structural microneedle (T-MN) matching the ring structure of AF. Based on the adsorption effect of laminin, our T-MN could load with bone marrow mesenchymal stem cell-derived exosomes to envelope the regulating mitophagy microRNA (miRNA 378), named as T-MN@EXO@miR−378. In general, we offered in situ locking in the defect site of AF to prevent nucleus pulposus leakage and promoted AF repair. The design of the thread structure was aimed at bionically matching the layered AF structure, thereby providing stronger adhesion. The T-MN@EXO@miR−378 effectively attached to AF and slowly released therapeutic engineered exosomes, and prevented IVDD progression by restoring mitophagy, promoting AF cell proliferation and migration, and inhibiting the pathological remodeling of the extracellular matrix. This functional system can be used as an excellent tool for sustained drug release and has a certain prospect in substituting the conventional treatment of IVDD.
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- 2024
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7. Effect of cross-platform gene-expression, computational methods on breast cancer subtyping in PALOMA-2 and PALLET studies
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Maggie Chon U Cheang, Mothaffar Rimawi, Stephen Johnston, Samuel A. Jacobs, Judith Bliss, Katherine Pogue-Geile, Lucy Kilburn, Zhou Zhu, Eugene F. Schuster, Hui Xiao, Lisa Swaim, Shibing Deng, Dongrui R. Lu, Eric Gauthier, Jennifer Tursi, Dennis J. Slamon, Hope S. Rugo, Richard S. Finn, and Yuan Liu
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Intrinsic breast cancer molecular subtyping (IBCMS) provides significant prognostic information for patients with breast cancer and helps determine treatment. This study compared IBCMS methods on various gene-expression platforms in PALOMA-2 and PALLET trials. PALOMA-2 tumor samples were profiled using EdgeSeq and nanostring and subtyped with AIMS, PAM50, and research-use-only (ruo)Prosigna. PALLET tumor biopsies were profiled using mRNA sequencing and subtyped with AIMS and PAM50. In PALOMA-2 (n = 222), a 54% agreement was observed between results from AIMS and gold-standard ruoProsigna, with AIMS assigning 67% basal-like to HER2-enriched. In PALLET (n = 224), a 69% agreement was observed between results from PAM50 and AIMS. Different IBCMS methods may lead to different results and could misguide treatment selection; hence, a standardized clinical PAM50 assay and computational approach should be used. Trial number: NCT01740427
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- 2024
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8. Data-Driven Prediction Method of Tactical Missile Aerodynamic Characteristics
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Zhou, Ling, Lin, Jiazhe, Zhou, Zhu, Wu, Pin, Fu, Mou, Tang, Tao, Liu, Hongyang, Angrisani, Leopoldo, Series Editor, Arteaga, Marco, Series Editor, Chakraborty, Samarjit, Series Editor, Chen, Shanben, Series Editor, Chen, Tan Kay, Series Editor, Dillmann, Rüdiger, Series Editor, Duan, Haibin, Series Editor, Ferrari, Gianluigi, Series Editor, Ferre, Manuel, Series Editor, Hirche, Sandra, Series Editor, Jabbari, Faryar, Series Editor, Jia, Limin, Series Editor, Kacprzyk, Janusz, Series Editor, Khamis, Alaa, Series Editor, Kroeger, Torsten, Series Editor, Li, Yong, Series Editor, Liang, Qilian, Series Editor, Martín, Ferran, Series Editor, Ming, Tan Cher, Series Editor, Minker, Wolfgang, Series Editor, Misra, Pradeep, Series Editor, Mukhopadhyay, Subhas, Series Editor, Ning, Cun-Zheng, Series Editor, Nishida, Toyoaki, Series Editor, Oneto, Luca, Series Editor, Panigrahi, Bijaya Ketan, Series Editor, Pascucci, Federica, Series Editor, Qin, Yong, Series Editor, Seng, Gan Woon, Series Editor, Speidel, Joachim, Series Editor, Veiga, Germano, Series Editor, Wu, Haitao, Series Editor, Zamboni, Walter, Series Editor, Tan, Kay Chen, Series Editor, and Fu, Song, editor
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- 2024
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9. Multi-organ involvement caused by Scedosporium apiospermum infection after near drowning: a case report and literature review
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Yao Yao, Qian Xu, Wenwen Liang, Suqiong Ji, Mohammadreza Kosari, Shabei Xu, Zhou Zhu, and Zhijuan Mao
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Scedosporium apiospermum ,Metagenomic next-generation sequencing ,Normal immune function ,Voriconazole ,Vision loss ,Multiple (brain) lesions ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Scedosporium apiospermum (S. apiospermum) is a rare fungal pathogen that causes disseminated infections. It rarely affects immunocompetent individuals and has a poor prognosis. Case presentation A 37-year-old woman presented with multiple lesions in the lungs, brain, and eyes, shortly after near drowning in a car accident. The primary symptoms were chest tightness, limb weakness, headache, and poor vision in the left eye. S. apiospermum infection was confirmed by metagenomic next-generation sequencing (mNGS) of intracranial abscess drainage fluid, although intracranial metastases were initially considered. After systemic treatment with voriconazole, her symptoms improved significantly; however, she lost vision in her left eye due to delayed diagnosis. Conclusion While S. apiospermum infection is rare, it should be considered even in immunocompetent patients. Prompt diagnosis and treatment are essential. Voriconazole may be an effective treatment option.
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- 2024
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10. Slope instability mechanism with differential rock mass structure along a fault: a mine landslide from Southwest China
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Tao Wei, GuoQing Chen, Zhou Zhu, Peng Tang, and Ming Yan
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Mining-induced rockslide ,Fault ,Failure mechanism ,Discrete element method ,Geophysics. Cosmic physics ,QC801-809 - Abstract
Abstract Mine slope stability and mining sustainability are related to the local geological structures, which could change the rock mass structure in deep mining. After 20 years mining in a mudstone mine, western China, the slope structure transforms from anti-dipping structure into a bedding structure by a recently discovered fault (F1), further inducing the two landslides (Landslide #I and Landslide #II). Landslide investigation suggested the residual deposits in Landslide #I first slid over 100 m and overburdened the rear of Landslide #II. The bedding rock with weak interlayers at footwall is separated from the anti-dipping rock at the hanging wall by F1. After excavation, a weak interlayer was exposed and softened by rainfall, resulting in the slip of footwall rock mass and further inducing large scale toppling deformation. The fragmented rock mass sliding along a weak interlayer triggers consequent deformation of adjacent slope, reducing safety reserve of the open mine. The discrete element analysis reveals that the bedding rock mass of footwall slid once the weak interlayer was exposed by mining. And retrogressive deformation transmitted to the hanging wall and induced bending and toppling deformation of anti-dipping rock mass. Mine feasibility assessment should recognize the potential deep geological structures as important in the future.
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- 2024
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11. Impact of calcium and magnesium concentration on irrigator clogging in drip fertigation using brackish water and humic acid fertilizer
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HE Xin, LIU Xinyu, ZHOU Long, ZHAO Xiao, LIU Peng, SU Yanping, ZHOU Zhu, and LI Wei
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brackish water ,calcium and magnesium ions ,clogged irrigators ,humic acid fertilizer ,Agriculture (General) ,S1-972 ,Irrigation engineering. Reclamation of wasteland. Drainage ,TC801-978 - Abstract
【Objective】 Drip fertigation is an irrigation technique increasingly used to simultaneously irrigate and fertilize crops grown in different environments. However, calcium and magnesium in the water could react chemically to precipitate, clogging the irrigator as a result. In this paper, we experimentally study the impact of calcium and magnesium concentration on irrigator clogging in drip fertigation using brackish water and humic acid fertilizer. 【Method】 In this experiment, four types of irrigators (FE1, FE2, FE3, FE4) with different rated flow rates (1.6, 1.1, 1.4, 1.75 L/h) were selected, in which three groups of brackish water treatments with calcium ion mass concentration, with ion mass concentrations of 100, 150 and 200 mg/L (G1, G2, G3), and three groups of brackish water treatments with magnesium ion mass concentration, with ion mass concentrations of 100, 150 and 200 mg/L (M1, M2, M3). In each treatment, fertigation using local groundwater was taken as the control (CK), we measured the average flow rate in the irrigator (Dra), clogging distribution in the irrigator, the dry mass of clogging materials (DW), and mineral fraction of the clogging materials in the irrigator. 【Result】 Compared to CK, fertigation using water with elaborated Ca2+ and Mg2+ concentration and humic acid fertilizer increased Dra by 21.58% to 56.75%, and DW by 67.14% to 270.09%, respectively, with the increase depending on dripping rate and Ca2+ and Mg2+ concentration. When Ca2+ and Mg2+concentration was the same, increasing dripping rate reduced DW by 4.77% to 27.26%, with the reduction depending on Ca2+ and Mg2+ concentration. 【Conclusion】 Increasing calcium and magnesium concentration in the fertigation water significantly increased irrigator clogging. When calcium and magnesium concentration was the same, an increase in magnesium concentration significantly reduced the mass of clogged materials due to the reduced carbonate. Thus, increasing magnesium ion can ameliorate irrigator clogging and reduce the risk of irrigator blockage.
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- 2024
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12. Effect of Heat Treatment Process on Mechanical Properties of High Chromium Low Activated Ferritic-martensitic Steel
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Sun Wenqiang , Zhou Zhu, Xu Amin , Wang Shaobing, Su Cheng , Shen Qiang
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ferritic-martensitic steel; yield strength, normalizing; tempering; m23c6; thermodynamic calculation ,Materials of engineering and construction. Mechanics of materials ,TA401-492 ,Technology - Abstract
Ferritic-martensitic steel is a kind of steel with excellent anti-radiation properties, which is one of superior candidate materials for structural components of the new generation of nuclear reactors with high radiation doses. The harsh service environment requires that ferritic-martensitic steel has good comprehensive mechanical properties, suitable grain size and few internal defects. In this paper, the effects of normalizing and tempering heat treatment on mechanical properties and microstructure evolution of new composition ferritic-martensitic steel were studied. At the same time, the ThermoCalc software is used to calculate the volume proportion of different phase states and compare it with the experimental results, it finds that the calculated results of the two-phase ratio change are highly consistent with the experimental results.After normalizing treatment, the tensile strength and yield strength of the material are mainly affected by the ratio of two phases. The results show high-martensitic steel treated with 1 080 ℃ normalizing + 670 ℃ tempering heat has a tensile strength of 903 MPa and yield strength of 732 MPa, showing the best comprehensive performance of the materials.
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- 2024
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13. De novo mutations promote inflammation in children with STAT3 gain-of-function syndrome by affecting IL-1β expression
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Chen, Ji-Yu, Li, Yan-Fang, Zhou, Zhu, Jiang, Xue-Mei, Bi, Xin, Yang, Mi-Feng, and Zhao, Bo
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- 2024
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14. Integrated Locking Compensation Mechanism between Suspended Track Beams and Turnout Beams
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Zhou ZHU
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suspended rail transit ,track beam ,locking and compensation mechanism ,Transportation engineering ,TA1001-1280 - Abstract
[Objective] To compensate for the preset turnout safety gap between track beam and switch beam of the mobile turnout in the suspended monorail transit system, ensure reliable locking when turnout is in place, and improve the safety and passenger comfort when train passing through turnout area, an integrated mechanism for locking and compensation is proposed, where the locking and compensating functions share a common power source, meeting the sequential requirements for locking before compensation after the turnout is in place. [Method] The current application status of suspended monorail turnouts and the main existing problems are introduced, and the application scenarios are analyzed. The design composition of the locking and compensation mechanism between the suspended track beam and the turnout beam is presented, along with an analysis of the motion working principle of the mechanism. [Result & Conclusion] The proposed locking and compensation mechanism has a compact overall external structure, meeting the installation space constraints between the suspended monorail mobile turnout beam and the track beam. Through the spatial layout design of the integrated linkage rod, the mechanism achieves reliable locking between beams, seam compensation between the turnout beam and the track beam, and fulfills the sequential requirements for locking before compensation.
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- 2024
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15. Rapid detection of endogenous impurities in walnuts using near-infrared hyperspectral imaging technology
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Wang, Dongdong, Zheng, Jian, Li, Linhui, Liang, Zile, Zheng, Yiyin, Huang, Shunying, Zheng, Xinyu, Zhou, Zhu, and Dai, Dan
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- 2024
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16. Structural and functional investigation on stem and peel polysaccharides from different varieties of pitaya
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Zheng, Chi-Chong, Li, Tong, Tang, Ya-Yuan, Lu, Tian, Wu, Meng-Ke, Sun, Jian, Man, Ruo-Jun, He, Xue-Mei, and Zhou, Zhu-Gui
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- 2024
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17. Changes of FGF23 and hearing in chronic renal failure and their correlation analysis
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Li, Jiaqing, Nie, Jingwen, Zhou, Zhu, Guo, Min, Yang, Qing, Yuan, Dunlu, Huang, Jingjing, Li, Ruomei, and Li, Qing
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- 2024
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18. SIVA-1 enhances acquired chemotherapeutic drug resistance of gastric cancer in vivo by regulating the ARF/MDM2/p53 pathway
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Xiao-Tong Wang, Lei Li, Zhou Zhu, Yu-Liang Huang, Huan-Huan Chen, Zheng-Yi Shi, Qiao-Ming Deng, Kun Wu, Long-Jie Xia, Wei Mai, Jian-Rong Yang, and Fan-Biao Kong
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SIVA-1 ,Drug resistance ,Gastric cancer ,ARF ,MDM2 ,p53 ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
SIVA-1 has been shown to affect apoptotic processes in various different cell lines, and SIVA-1 significantly contributes to the decreased responsiveness of cancer cells to some chemotherapy agents. However, whether SIVA-1 has potential application in gastric cancer remains unknown. Therefore, the objective of this investigation was to clarify the distinct function of SIVA-1 in chemotherapeutic drug resistance within a living murine model with gastric malignancy, and initially elucidate the underlying mechanisms. In an established multidrug-resistant gastric cancer xenograft mouse model, lentivirus, named Lv-SIVA-1, was injected into xenograft tumors, and increased the mRNA and protein expression of endogenous SIVA-1 in tumors. Immunohistochemical assays of xenograft tumor showed that SIVA-1 was significantly upregulated, and the protein expression levels of SIVA-1 were highly increased, as detected by Western blotting. In addition, we detected the role of SIVA-1 in cell proliferation and cell apoptosis in gastric cancer cells by TUNEL and found that SIVA-1 decreased tumor cell apoptosis and promoted tumor growth in vivo. Using a TMT assay between tumor tissues of experimental and control groups, differentially expressed proteins were examined and three potential biomarkers of multidrug resistance (ARF, MDM2, and p53) were screened. We further investigated the molecular mechanism by which SIVA-1 played an efficient role against chemotherapies and found that overexpressed SIVA-1 leads to increased ARF and MDM2 expression and suppressed expression of p53 in tumor tissue. In conclusion, SIVA-1 plays a significant role in the multidrug resistance of gastric tumors. In addition, overexpressed SIVA-1 positively regulates cell proliferation, adjusts cycle progression, and reduces the response to drug treatment for gastric cancer in an ARF/MDM2/p53-dependent manner. This novel research provides a basis for chemical management of gastric cancer through regulation of SIVA-1 expression.
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- 2024
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19. Author Correction: A mussel-inspired film for adhesion to wet buccal tissue and efficient buccal drug delivery
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Shanshan Hu, Xibo Pei, Lunliang Duan, Zhou Zhu, Yanhua Liu, Junyu Chen, Tao Chen, Ping Ji, Qianbing Wan, and Jian Wang
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Science - Published
- 2024
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20. p21 as a Predictor and Prognostic Indicator of Clinical Outcome in Rectal Cancer Patients
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Li Ching Ooi, Vincent Ho, Jing Zhou Zhu, Stephanie Lim, Liping Chung, Askar Abubakar, Tristan Rutland, Wei Chua, Weng Ng, Mark Lee, Matthew Morgan, Scott MacKenzie, and Cheok Soon Lee
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p21 ,rectal cancer (CRC) ,tissue microarrays ,radiotherapy ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The cell cycle plays a key and complex role in the development of human cancers. p21 is a potent cyclin-dependent kinase inhibitor (CDKI) involved in the promotion of cell cycle arrest and the regulation of cellular senescence. Altered p21 expression in rectal cancer cells may affect tumor cells’ behavior and resistance to neoadjuvant and adjuvant therapy. Our study aimed to ascertain the relationship between the differential expression of p21 in rectal cancer and patient survival outcomes. Using tissue microarrays, 266 rectal cancer specimens were immunohistochemically stained for p21. The expression patterns were scored separately in cancer cells retrieved from the center and the periphery of the tumor; compared with clinicopathological data, tumor regression grade (TRG), disease-free, and overall survival. Negative p21 expression in tumor periphery cells was significantly associated with longer overall survival upon the univariate (p = 0.001) and multivariable analysis (p = 0.003, HR = 2.068). Negative p21 expression in tumor periphery cells was also associated with longer disease-free survival in the multivariable analysis (p = 0.040, HR = 1.769). Longer overall survival times also correlated with lower tumor grades (p= 0.011), the absence of vascular and perineural invasion (p = 0.001; p < 0.005), the absence of metastases (p < 0.005), and adjuvant treatment (p = 0.009). p21 expression is a potential predictive and prognostic biomarker for clinical outcomes in rectal cancer patients. Negative p21 expression in tumor periphery cells demonstrated significant association with longer overall survival and disease-free survival. Larger prospective studies are warranted to investigate the ability of p21 to identify rectal cancer patients who will benefit from neoadjuvant and adjuvant therapy.
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- 2024
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21. Preclinical metabolism and metabolic drug–drug interaction profile of pedunculoside and rotundic acid.
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Wu, Liang, Dong, Linling, Zhou, Zhu, Wang, Xin, Lin, Yujie, Shi, Xuesong, Wang, Peijing, Xu, Suocheng, and Fang, Zhiyi
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LIVER microsomes ,DRUG metabolism ,DRUG interactions ,GLUCURONIDATION ,DRUG therapy - Abstract
Pedunculoside and rotundic acid, the most abundant components in plants of the genus Ilex L. (Aquifoliaceae), exhibit biological and pharmacological significance in the treatment of cardiovascular diseases. However, there have been few studies on their metabolism. This study performed a systematic metabolism study of pedunculoside and rotundic acid and evaluated their potential for herb–drug interaction. Pedunculoside or rotundic acid was incubated with human liver microsomes and recombinant human metabolic enzymes, and analyzed using LC‐Q‐TOF/MS and LC–MS/MS. Pedunculoside was found to be the most stable in human liver microsomes, whereas rotundic acid was easily metabolized. Eight pedunculoside metabolites and six rotundic acid metabolites were detected and tentatively identified through hydroxylation, glucuronidation, acetylation, and glucose conjugation. Hydroxylation of pedunculoside is mainly catalyzed by CYP3A4/5 and partly by CYP2C8. Hydroxylation of rotundic acid is almost exclusively catalyzed by CYP3A4/5, and its glucuronidation reaction is mediated by UGT1A4. Neither pedunculoside nor rotundic acid showed CYP inhibition (IC50 values > 50 μM) with the probe substrates of major CYP isoforms during incubation with human liver microsomes. This study is the first investigation into the in vitro metabolism of pedunculoside and rotundic acid using human liver microsomes. It also aims to assess their potential as perpetrators of drug–drug interactions involving CYP enzymes. The comprehensive metabolism and drug interaction studies of pedunculoside and rotundic acid enable us to evaluate and manage potential risks with their use in pharmacotherapy. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Identification of Dendrobium Using Laser-Induced Breakdown Spectroscopy in Combination with a Multivariate Algorithm Model
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Zhang, Tingsong, primary, Liu, Ziyuan, additional, Ma, Qing, additional, Hu, Dong, additional, Dai, Yujia, additional, Zhang, Xinfeng, additional, and Zhou, Zhu, additional
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- 2024
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23. Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease
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Tang, Yifang, primary, Liu, Tao, additional, Sun, Shibo, additional, Peng, Youbo, additional, Huang, Xiaoxiao, additional, Wang, Shuangquan, additional, and Zhou, Zhu, additional
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- 2024
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24. A spontaneous hyperglycaemic cynomolgus monkey presents cognitive deficits, neurological dysfunction and cataract
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Huang, Hongdi, primary, Pu, Jianglin, additional, Zhou, Yufang, additional, Fan, Yang, additional, Zhang, Yali, additional, Li, Yanling, additional, Chen, Yangzhuo, additional, Wang, Yun, additional, Yu, Xiaomei, additional, Dmitry, Bulgin, additional, Zhou, Zhu, additional, and Wang, Jianhong, additional
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- 2024
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25. CBD and THC in Special Populations: Pharmacokinetics and Drug–Drug Interactions
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Qian, Lixuan, primary, Beers, Jessica L., additional, Jackson, Klarissa D., additional, and Zhou, Zhu, additional
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- 2024
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26. Patient, industry, and regulatory perspective on antibody‐drug conjugates dose optimization
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Hamed, Salaheldin, primary, Li, Chunze, additional, Liao, Michael Z., additional, Warwick, Lorna, additional, and Zhou, Zhu, additional
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- 2024
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27. Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease
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Tang,Yifang, Liu,Tao, Sun,Shibo, Peng,Youbo, Huang,Xiaoxiao, Wang,Shuangquan, Zhou,Zhu, Tang,Yifang, Liu,Tao, Sun,Shibo, Peng,Youbo, Huang,Xiaoxiao, Wang,Shuangquan, and Zhou,Zhu
- Abstract
Yifang Tang,1,* Tao Liu,2,* Shibo Sun,3 Youbo Peng,1 Xiaoxiao Huang,4 Shuangquan Wang,4 Zhu Zhou1 1Department of Nephrology, the First Affiliated Hospital, Kunming Medical University, Kunming, Peopleâs Republic of China; 2Organ Transplantation Center, the First Affiliated Hospital, Kunming Medical University, Kunming, Peopleâs Republic of China; 3Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital, Kunming Medical University, Kunming, Peopleâs Republic of China; 4Department of Nephrology, Xishuangbanna Dai Autonomous Prefecture Peopleâs Hospital, Xishuangbanna, Peopleâs Republic of China*These authors contributed equally to this workCorrespondence: Zhu Zhou, Department of Nephrology, The First Affiliated Hospital of Kunming Medical University and Yunnan Province Clinical Research Center for Chronic Kidney Disease, No. 295, Xichang Road, Wuhua District, Kunming, Peopleâs Republic of China, Email zhouzhu21@163.com Shibo Sun, Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital, Kunming Medical University, No. 295, Xichang Road, Wuhua District, Kunming, Peopleâs Republic of China, Email shibosunky@126.comAbstract: GDF-15 is an essential member of the transforming growth factor-beta superfamily. Its functions mainly involve in tissue injury, inflammation, fibrosis, regulation of appetite and weight, development of tumor, and cardiovascular disease. GDF-15 is involved in various signaling pathways, such as MAPK pathway, PI3K/AKT pathway, STAT3 pathway, RET pathway, and SMAD pathway. In addition, several factors such as p53, ROS, and TNF-α participate the regulation of GDF-15. However, the specific mechanism of these factors regulating GDF-15 is still unclear and more research is needed to explore them. GDF-15 mainly improves the function of kidneys in CKD and plays an important role in the prediction of CKD progression and cardiovascular complications. In addition, the role of GDF-1
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- 2024
28. Effect of Oregon grape root extracts on P-glycoprotein mediated transport in in vitro cell lines
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Fan, Ying, primary, Zhou, Zhu, additional, and Zhang, Lei, additional
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- 2024
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29. Risk Factors Associated Pneumoconiosis: A Meta-Analysis
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zou, min, primary, Wang, Fenghua, additional, Tian, Shen, additional, Hu, Xiongfei, additional, Huang, Lei, additional, Yuan, Huamin, additional, Zhou, Zhu, additional, Feng, Juan, additional, and Deng, Xiaobin, additional
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- 2024
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30. Effect of miR-1297 on Kidney Injury in Rats with Diabetic Nephropathy through the PTEN/PI3K/AKT Pathway
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Chen, Na, primary, Liu, Hailing, primary, Jiang, Xiaobo, primary, Tang, Nina, primary, Fan, Wenxing, primary, Ji, Wenxuan, primary, and Zhou, Zhu, primary
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- 2024
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31. De Novo Mutations Promote Inflammation in Children with Stat3 Gain-of-Functionsyndrome by Affecting Il-1β Expression
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Chen, Jiyu, primary, Li, Yanfang, additional, Zhou, Zhu, additional, Jiang, XueMei, additional, Bi, Xin, additional, Yang, Mifeng, additional, and Zhao, Bo, additional
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- 2024
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32. Application and Development of Electrochemical Spectroscopy Methods.
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Yue-Zhou Zhu, Kun Wang, Shi-Sheng Zheng, Hong-Jia Wang, Jin-Chao Dong, and Jian-Feng Li
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- 2024
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33. Prediction of an impaired myocardial work using infarct size in acute myocardial infarction.
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Xiao-Ting He, Jie Zhang, Yang Pan, Fan Yu, Ge Tang, Li-Zhou Zhu, Yi-Nan Qin, and Xiao-Zhi Zheng
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- 2024
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34. Advances and Challenges in Modeling Cannabidiol Pharmacokinetics and Hepatotoxicity
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Beers, Jessica L., Zhou, Zhu, and Jackson, Klarissa D.
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Cannabidiol (CBD) is a pharmacologically active metabolite of cannabis that is US Food and Drug Administration approved to treat seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex in children aged 1 year and older. During clinical trials, CBD caused dose-dependent hepatocellular toxicity at therapeutic doses. The risk for toxicity was increased in patients taking valproate, another hepatotoxic antiepileptic drug, through an unknown mechanism. With the growing popularity of CBD in the consumer market, an improved understanding of the safety risks associated with CBD is needed to ensure public health. This review details current efforts to describe CBD pharmacokinetics and mechanisms of hepatotoxicity using both pharmacokinetic models and in vitro models of the liver. In addition, current evidence and knowledge gaps related to intracellular mechanisms of CBD-induced hepatotoxicity are described. The authors propose future directions that combine systems-based models with markers of CBD-induced hepatotoxicity to understand how CBD pharmacokinetics may influence the adverse effect profile and risk of liver injury for those taking CBD.SIGNIFICANCE STATEMENTThis review describes current pharmacokinetic modeling approaches to capture the metabolic clearance and safety profile of cannabidiol (CBD). CBD is an increasingly popular natural product and US Food and Drug Administration–approved antiepileptic drug known to cause clinically significant enzyme-mediated drug interactions and hepatotoxicity at therapeutic doses. CBD metabolism, pharmacokinetics, and putative mechanisms of CBD-induced liver injury are summarized from available preclinical data to inform future modeling efforts for understanding CBD toxicity.
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- 2024
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35. Hydrolytic endonucleolytic ribozyme (HYER) is programmable for sequence-specific DNA cleavage.
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Zi-Xian Liu, Shouyue Zhang, Han-Zhou Zhu, Zhi-Hang Chen, Yun Yang, Long-Qi Li, Yuan Lei, Yun Liu, Dan-Yuan Li, Ao Sun, Cheng-Ping Li, Shun-Qing Tan, Gao-Li Wang, Jie-Yi Shen, Shuai Jin, Caixia Gao, and Gogo Liu, Jun-Jie
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- 2024
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36. Asymmetric Synthesis of Rupestonic Acid and Pechueloic Acid
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Han, Pan, Zhou, Zhu, Si, Chang-Mei, Sha, Xian-Yi, Gu, Zheng-Yi, Wei, Bang-Guo, and Lin, Guo-Qiang
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In this report, the originally proposed rupestonic acid (5) and pechueloic acid (3) were efficiently synthesized. The chiral lactone 13, recycled from the degradation of saponin glycosides, was utilized to prepare the key chiral fragment 11. During the exploration of this convergent assembly strategy, the ring-closing metathesis (RCM), SmI2-prompted intermolecular addition, and [2,3]-Wittig rearrangement proved to be effective transformations for the synthesis of subunits.
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- 2024
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37. Application of physiologically‐based pharmacokinetic modeling to inform dosing decisions for geriatric patients.
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Qian, Lixuan, Wang, Ziteng, Paine, Mary F., Chan, Eric Chun Yong, and Zhou, Zhu
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- *
GENERATIVE artificial intelligence , *OLDER people , *ORGANIC anion transporters , *CULTURAL pluralism , *AGE - Abstract
This article explores the application of physiologically-based pharmacokinetic (PBPK) modeling in determining appropriate drug dosing for geriatric patients. Geriatric patients often have multiple health conditions and are typically excluded from clinical trials, resulting in suboptimal dosing. PBPK modeling has been used to simulate drug exposure in older adults, but there are still gaps in knowledge. The article emphasizes the importance of considering changes in anatomy, physiology, and organ function in older adults when using PBPK models. It also discusses the use of PBPK modeling in evaluating drug-drug interactions and optimizing dosing regimens for geriatric patients. However, the article acknowledges the limitations of current PBPK models, such as the lack of consideration for age-related physiological changes and the limited diversity in the databases used. The authors suggest that incorporating clinical data and refining the models with new information can improve the accuracy of drug dosing for geriatric patients. [Extracted from the article]
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- 2024
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38. First report of basal stem rot on sugarcane (var. Badila) caused by Sclerotium rolfsii in China.
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Lao SC, Lao SJ, Huang JH, Zhou ZG, and Lin SH
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Badila (Saccharum officinarum) is one of the important chewing cane in south China. During the year 2019-2020, as much as 60.2%-87.5% of sugarcane plants stem showed red rot developments were observed in the fields of Yongning District, Nanning city, Guangxi province. Symptomatic plants showed red rot at basal stem nodes and sheath, when the disease serious, the epidermis and aerial roots decomposed and exfoliated, then formed sclerotiums, the upper stem also occurred the symptom. Infected plant tissues were dissected into small pieces with 0.1 × 0.1cm in size and surface sterilized in 0.1% HCl2 for 2 min, followed by 75% ethanol for 30 s, rinsed three times with sterile distilled water. Then the tissues were placed onto potato dextrose agar (PDA) plates and incubated at 25 °C for 3 days. Numerous white globoid sclerotia were formed on PDA after 5 days of growth. The sclerotia (2 to 3 mm in diameter) were white at first and then gradually turned dark brown. Aerial mycelia usually formed many narrow hyphal strands 4 to 9 μm wide. Five uniform isolates were obtained from diseased sugarcane plants. Pathogenicity of representative strain W1 was confirmed by inoculating 120-day-old Badila plants grown in field. Five plants were inoculated with colonized agar discs (6mm in diameter) by applying toothpick tips to the lower part of the stem. Five non-inoculated plants served as control. The inoculated and non-inoculated plants were sprayed sterile water then incubated with plastic film for maintained high moisture. All the plants were placed inside of a growth chamber at 26 ± 2°C with a 14-h photoperiod and 80% relative humidity. All inoculated plants showed red rot at stem and sheath after 2 weeks, whereas the control plants were symptomless. By the third week, mycelium and sclerotia developed on the crown on the inoculated plants. The fungus was re-isolated from the artificially inoculated plants. To confirm the species-level identification, partial of the ribosomal DNA internal transcribed spacer (ITS), mitocondrial small subunit (SSU), and nuclear ribosomal large subunit (LSU) regions of representative strain W1 were amplified and sequenced using the primers pairs ITS1/ITS4 (White et al. 1990), ITS-Fu-F /ITS-Fu-R and SRLSU1//SRLSU2 (Kumar et al., 2016), respectively. The resulting ITS, SSU and LSU sequences were deposited in GenBank (GenBank accession no. MW620994, MW617878, and MW617872) and shared 99.42%, 100% and 100% sequence identity with Athelia rolfsii isolate (JN017199, OM319631, and MT225781). Phylogenetic analysis conducted with neighbor-joining (NJ) method using MEGA6.0 revealed that the isolate share a common clade with reference sequence of A. rolfsii in GenBank Data Library. Based on morphological and molecular characteristics, the fungus was identified as A. rolfsii (anamorph: Sclerotium rolfsii) (Paul et al. 2017; Paparu et al. 2020). Although S. rolfsii has been reported causing sugarcane sett rot in Australia (Bhuiyan et al., 2019) and seedlings of sugarcane in Indian (Gopi et al., 2023), as we know, this is the first report of sugarcane basal stem rot disease caused by this fungus in China. This study will be helpful for the prevention and control sugarcane basal stem rot in the future.
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- 2024
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39. Preclinical metabolism and metabolic drug-drug interaction profile of pedunculoside and rotundic acid.
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Wu L, Dong L, Zhou Z, Wang X, Lin Y, Shi X, Wang P, Xu S, and Fang Z
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- Humans, Drug Interactions, Cytochrome P-450 Enzyme System metabolism, Hydroxylation, Tandem Mass Spectrometry, Herb-Drug Interactions, Drug Evaluation, Preclinical, Microsomes, Liver metabolism, Triterpenes metabolism, Triterpenes pharmacokinetics
- Abstract
Pedunculoside and rotundic acid, the most abundant components in plants of the genus Ilex L. (Aquifoliaceae), exhibit biological and pharmacological significance in the treatment of cardiovascular diseases. However, there have been few studies on their metabolism. This study performed a systematic metabolism study of pedunculoside and rotundic acid and evaluated their potential for herb-drug interaction. Pedunculoside or rotundic acid was incubated with human liver microsomes and recombinant human metabolic enzymes, and analyzed using LC-Q-TOF/MS and LC-MS/MS. Pedunculoside was found to be the most stable in human liver microsomes, whereas rotundic acid was easily metabolized. Eight pedunculoside metabolites and six rotundic acid metabolites were detected and tentatively identified through hydroxylation, glucuronidation, acetylation, and glucose conjugation. Hydroxylation of pedunculoside is mainly catalyzed by CYP3A4/5 and partly by CYP2C8. Hydroxylation of rotundic acid is almost exclusively catalyzed by CYP3A4/5, and its glucuronidation reaction is mediated by UGT1A4. Neither pedunculoside nor rotundic acid showed CYP inhibition (IC
50 values > 50 μM) with the probe substrates of major CYP isoforms during incubation with human liver microsomes. This study is the first investigation into the in vitro metabolism of pedunculoside and rotundic acid using human liver microsomes. It also aims to assess their potential as perpetrators of drug-drug interactions involving CYP enzymes. The comprehensive metabolism and drug interaction studies of pedunculoside and rotundic acid enable us to evaluate and manage potential risks with their use in pharmacotherapy., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)- Published
- 2024
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