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| 1 | “Pincer movement”:Reversing cisplatin resistance based on simultaneous glutathione depletion and glutathione S-transferases inhibition by redox-responsive degradable organosilica hybrid nanoparticles显示文摘The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers.Intracellular glutathione(GSH)detoxification of cisplatin under the catalysis of glutathione S-transferases(GST)plays important roles in the development of cisplatin resistance.Herein,a strategy of“pincer movement”based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy.Specifically,a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid(EA),a GST inhibitor.Responding to high level of intracellular GSH,the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds,which further promotes drug release.Meanwhile,the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance.Moreover,the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma.The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion,GST inhibition,and consequent tumor growth suppression.Overall,this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance,which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers. | Boyi Niu Yixian Zhou Kaixin Liao Ting Wen Sixian Lao Guilan Quan Xin Pan Chuanbin Wu | 2022 | Acta Pharmaceutica Sinica B2022，12，4： | 3 |
| 2 | Developing rat testicular organoid models for assessing the reproductive toxicity of antidepression drugs in vitro显示文摘With the increasing incidence of depression worldwide,antidepressant medications are commonly used in males of reproductive age for long-term treatment of depression,as well as other disorders[1].Antidepressants are known to be associated with sexual side effects[2],such as decreased libido and impotence.Their effects on semen parameters and other markers of male fertility have been less thoroughly described,such as sperm motility and fertilization ability.Therefore,it is critical to determine the potential toxic effects of antidepressants on reproductive organs.A recent study systemically determined the effect of different drugs on the telomere-related DNA damage response of germ cells[3].In addition,another study showed that mirtazapine has less toxic effects than amitriptyline and other drugs[4].However,these studies used germ cell lines to determine the phenotype,which limits their potential translational value in toxicity studies in humans.Given the widespread and often long-term use of antidepressant medications,there is an urgent need for further data regarding their impact on semen quality and subsequent male fertility. | Sixian Wu Xiaoliang Li Peiyu Li Tongtong Li Gelin Huang Qun Sun Andras Dinnyés Lijun Shang Wenming Xu | 2022 | Acta Biochimica et Biophysica Sinica2022，54，11： | 1 |
| 3 | The novel BRDT inhibitor NHWD870 shows potential as a male contraceptive in mice显示文摘Small molecule inhibitors of the bromodomain and extraterminal domain(BET)family proteins have emerged as promising options not only for the treatment of multiple cancers but also for disturbing the process of sperm maturation with potential for use as viable contraceptive targets.In this study,we find that the BET family inhibitor NHWD870 and BRDT can bind well in vitro through bioinformatics software prediction and protein binding inhibition experiments.NHWD870 can produce a good contraceptive effect through animal experiments in vivo,and the fertility can be restored to normal after drug withdrawal.Transcriptomics and proteomics results suggest that NHWD870 affects pathways related to spermatogenesis and maturation,further contributing to the male infertility phenotype.Our results show that NHWD870 can induce a complete and reversible contraceptive effect in mice,which is stronger than that of JQ1 and its synthesized derivatives.This study is expected to eventually lead to clinical trials. | Sixian Wu Xiaoliang Li Lijun Shang Lvying Wu Tongtong Li Peiyv Li Zhiliang Ji Jianwen Hou Mingzhu Yin Wenming Xu | 2022 | Acta Biochimica et Biophysica Sinica2022，54，12： | 1 |
| 4 | Digital twins in smart farming:An autoware-based simulator for autonomous agricultural vehicles显示文摘Digital twins can improve the level of control over physical entities and help manage complex systems by integrating a range of technologies.The autonomous agricultural machine has shown revolutionary effects on labor reduction and utilization rate in field works.Autonomous vehicles in precision agriculture have the potential to improve competitiveness compared to current crop production methods and have become a research hotspot.However,the development time and resources required in experiments have limited the research in this area.Simulation tools in unmanned farming that are required to enable more efficient,reliable,and safe autonomy are increasingly demanding.Inspired by the recent development of an open-source virtual simulation platform,this study proposed an autoware-based simulator to evaluate the performance of agricultural machine guidance based on digital twins.Oblique photogrammetry using drones is used to construct threedimensional maps of fields at the same scale as reality.A communication format suitable for agricultural machines was developed for data input and output,along with an inter-node communication methodology.The conversion,publishing,and maintenance of multiple coordinate systems were completed based on ROS(Robot Operating System).Coverage path planning was performed using hybrid curves based on Bézier curves,and it was tested in both a simulation environment and actual fields with the aid of Pure Pursuit algorithms and PID controllers. | Xin Zhao Wanli Wang Long Wen Zhibo Chen Sixian Wu Kun Zhou Mengyao Sun Lanjun Xu Bingbing Hu Caicong Wu | 2023 | International Journal of Agricultural and Biological Engineering2023，16，4： | 0 |
| 5 | Learning Discriminatory Information for Object Detection on Urine Sediment Image显示文摘In clinical practice,the microscopic examination of urine sediment is considered an important in vitro examination with many broad applications.Measuring the amount of each type of urine sediment allows for screening,diagnosis and evaluation of kidney and urinary tract disease,providing insight into the specific type and severity.However,manual urine sediment examination is labor-intensive,time-consuming,and subjective.Traditional machine learning based object detection methods require hand-crafted features for localization and classification,which have poor generalization capabilities and are difficult to quickly and accurately detect the number of urine sediments.Deep learning based object detection methods have the potential to address the challenges mentioned above,but these methods require access to large urine sediment image datasets.Unfortunately,only a limited number of publicly available urine sediment datasets are currently available.To alleviate the lack of urine sediment datasets in medical image analysis,we propose a new dataset named UriSed2K,which contains 2465 high-quality images annotated with expert guidance.Two main challenges are associated with our dataset:a large number of small objects and the occlusion between these small objects.Our manuscript focuses on applying deep learning object detection methods to the urine sediment dataset and addressing the challenges presented by this dataset.Specifically,our goal is to improve the accuracy and efficiency of the detection algorithm and,in doing so,provide medical professionals with an automatic detector that saves time and effort.We propose an improved lightweight one-stage object detection algorithm called Discriminatory-YOLO.The proposed algorithm comprises a local context attention module and a global background suppression module,which aid the detector in distinguishing urine sediment features in the image.The local context attention module captures context information beyond the object region,while the global background suppression module emphasizes objects in uninformative backgrounds.We comprehensively evaluate our method on the UriSed2K dataset,which includes seven categories of urine sediments,such as erythrocytes(red blood cells),leukocytes(white blood cells),epithelial cells,crystals,mycetes,broken erythrocytes,and broken leukocytes,achieving the best average precision(AP)of 95.3%while taking only 10 ms per image.The source code and dataset are available at https://github.com/binghuiwu98/discriminatoryyolov5. | Sixian Chan Binghui Wu Guodao Zhang Yuan Yao Hongqiang Wang | 2024 | Computer Modeling in Engineering & Sciences2024，138，1： | 0 |
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