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| 1 | Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions显示文摘Brain tumors are dynamic complex ecosystems with multiple cell types.To model the brain tumor microenvironment in a reproducible and scalable system,we developed a rapid three-dimensional(3D)bioprinting method to construct clinically relevant biomimetic tissue models.In recurrent glioblastoma,macrophages/microglia prominently contribute to the tumor mass.To parse the function of macrophages in 3D,we compared the growth of glioblastoma stem cells(GSCs)alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel,with or without macrophage.Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival,maintenance of stemness,invasion,and drug resistance.Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs,relative to sphere culture.Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity,cellular crosstalk,invasion,context-specific functional dependencies,as well as immunologic interactions in a species-matched neural environment. | Min Tang Qi Xie Ryan C.Gimple Zheng Zhong Trevor Tam Jing Tian Reilly L.Kidwell Qiulian Wu Briana C.Prager Zhixin Qiu Aaron Yu Zhe Zhu Pinar Mesci Hui Jing Jacob Schimelman Pengrui Wang Derrick Lee Michael H.Lorenzini Deobrat Dixit Linjie Zhao Shruti B.hargava Tyler E.Miller Xueyi Wan Jing Tang Bingjie Sun Benjamin F.Cravatt Alysson R.Muotri Shaochen Chen Jeremy N.Rich | 2020 | Cell Research2020，30，10： | 6 |
| 2 | Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy显示文摘The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death(ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment(ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin(DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels(DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful antitumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines. | Xianbin Ma Shaochen Yang Tian Zhang Shuo Wang Qichao Yang Yao Xiao Xiaoxiao Shi Peng Xue Yuejun Kang Gang Liu Zhi-Jun Sun Zhigang Xu | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 1 |
| 3 | Glyphosate exposure deteriorates oocyte meiotic maturation via induction of organelle dysfunctions in pigs显示文摘Background:Recently,defects in mammalian oocytes maturation induced by environmental pollution results in the decreasing animal reproduction.Animal exposed to glyphosate is largely unavoidable because glyphosate is one of the most widely used herbicide worldwide due to its high-efficiency and broad-spectrum effects,which causes glyphosate an environmental contaminant found in soil,water and food.During the last few years,the growing and wider use of glyphosate has raised great concerns about its effects of reproductive toxicity.In this study,using porcine models,we investigated effects of glyphosate on organelle functions during oocyte meiosis.Results:The results showed glyphosate exposure disrupted porcine oocyte maturation.Expression levels of cumulus expansion-related genes were interfered,further indicating the meiotic defects.The damaging effects were mediated by destruction of mitochondrial distribution and functions,which induced ROS accumulation and oxidative stress,also indicated by the decreased mRNA expression of related antioxidant enzyme genes.We also found an interference of endoplasmic reticulum(ER)distribution,disturbance of Ca^(2+)homeostasis,as well as fluctuation of ER stress,showing with the reduced ER stress-related mRNA or protein expression,which could indicate the dysfunction of ER for protein processing and signal transduction in glyphosate-exposed oocytes.Moreover,glyphosate exposure induced the disruption of lysosome function for autophagy,showing with the decrease of LAMP2 expression and autophagy-related genes mRNA expression.Additionally,our data showed the distribution of Golgi apparatus and the functions of ribosome were disturbed after glyphosate exposure,which might affect protein synthesis and transport.Conclusions:Collectively,our study showed that exposed to glyphosate could affect animal reproduction by compromising the quality of oocytes through its wide toxic effects on organelle functions. | Chunhua Xing Shun Chen Yue Wang Zhennan Pan Yuanjing Zou Shaochen Sun Zili Ren Yu Zhang | 2022 | Journal of Animal Science and Biotechnology2022，13，6： | 1 |
| 4 | DRP1 deficiency induces mitochondrial dysfunction and oxidative stress-mediated apoptosis during porcine oocyte maturation显示文摘Background: Environmental pollution induces oxidative stress and apoptosis in mammalian oocytes, which can cause defects in reproduction;however, the molecular regulation of oxidative stress in oocytes is still largely unknown. In the present study, we identified that dynamin-related protein 1(DRP1) is an important molecule regulating oocyte mitochondrial function and preventing oxidative stress/apoptosis. DRP1 is a member of the dynamin GTPase superfamily localized at the mitochondrial-endoplasmic reticulum interaction site, where it regulates the fission of mitochondria and other related cellular processes.Results: Our results show that DRP1 was stably expressed during different stages of porcine oocyte meiosis, and might have a potential relationship with mitochondria as it exhibited similar localization. Loss of DRP1 activity caused failed porcine oocyte maturation and cumulus cell expansion, as well as defects in polar body extrusion.Further analysis indicated that a DRP1 deficiency caused mitochondrial dysfunction and induced oxidative stress,which was confirmed by increased reactive oxygen species levels. Moreover, the incidence of early apoptosis increased as detected by positive Annexin-V signaling.Conclusions: Taken together, our results indicate that DRP1 is essential for porcine oocyte maturation and that a DRP1 deficiency could induce mitochondrial dysfunction, oxidative stress, and apoptosis. | Haolin Zhang Zhennan Pan Jiaqian Ju Chunhua Xing Xiaohan Li Mengmeng Shan Shaochen Sun | 2021 | Journal of Animal Science and Biotechnology2021，12，1： | 1 |
| 5 | Aluminum exposure impairs oocyte quality via subcellular structure disruption and DNA damage-related apoptosis in mice显示文摘Aluminum(Al)can lead to an exposure of creature in varieties ways for its universality,and it could disturb normal physiological metabolism,with the damage to multisystem including reproduction.Since the oocyte quality is critical for female reproduction,we inspected the toxicity of Al on mouse oocyte maturation.We constructed in vitro exposure mouse model,and we found that 5 mmol/L Al had adverse effects on oocyte maturation by impairing organelle and cytoskeleton.Aberrant spindle and misaligned chromosomes which might be considered to be caused by elevated levels of acetylation,as well as abnormal distribution of actin dynamics could hinder normal meiosis of oocytes.Organelle dysfunction indicated that Al affected proteins synthesis,transport and digestion,which would further damage oocyte maturation.In order to explore the mechanism of Al toxicity,our further investigation demonstrated that Al caused mitochondrial dysfunction and imbalance calcium homeostasis,resulting in limited energy supply.Moreover,high level of reactive oxygen species,DNA damage and apoptosis caused by oxidative stress were also the manifestation of Al toxicity on oocytes.In conclusion,our study provided the evidence that Al exposure affected oocyte quality through its effects on spindle organization,actin dynamics,organelle function and the induction of DNA damage-related apoptosis with mouse model. | Hongge Li Jingcai Liu Weihua Nong Mengying Shen Sheng Dou Shaochen Sun Junli Wang | 2024 | Journal of Environmental Sciences2024，，5： | 0 |
| 6 | Engineering prodrug nanomicelles as pyroptosis inducer for codelivery of PI3K/mTOR and CDK inhibitors to enhance antitumor immunity显示文摘Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response.However,single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways.The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications.To circumvent this issue,we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle(PNM)for cancer therapy.PNM was engineered by integrating the PI3K/m TOR inhibitor PF-04691502(PF)and the broad spectrum CDK inhibitor flavopiridol(Flav)into a single nanoplatform,which showed tumor-specific accumulation,activation and deep penetration in response to the high glutathione(GSH)tumoral microenvironment.The codelivery of PF and Flav could trigger gasdermin E(GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response.Furthermore,the combination of PNM-induced immunogenic pyroptosis with antiprogrammed cell death-1(a PD-1)immunotherapy further boosted the antitumor effect and prolonged the survival time of mice.Collectively,these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/m TOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy. | Qichao Yang Xianbin Ma Yao Xiao Tian Zhang Leilei Yang Shaochen Yang Mengyun Liang Shuo Wang Zhizhong Wu Zhigang Xu Zhijun Sun | 2022 | Acta Pharmaceutica Sinica B2022，12，7： | 0 |
| 7 | Experimental investigation of flame propagation characteristics in the in-line crimped-ribbon flame arrester显示文摘An experimental system that consisted was of gas mixing equipment,a sensor detection flame system,a data and acquisition quenching device,and an electric spark ignition device set in up to investigate fuel/air deflagration propagation suppression processes through when a crimped-ribbon concentration flame arrester an was enclosed close horizontal the pipe.Deflagration ratio,experiments showed that the the four of and flammable ethylene-air combustion,gas to stoichiometric pipe the evolution processes of and explosion could pressure divided for propane-air stages:premixed slow gases in the diameter(DN32–DN400)and were similar be into isobaric pressure was rise,quick pressure and rise,pressure oscillation.However,high.the explosion duration quickly of the the hydrogen-air premixed gas stage.relatively short,the peak be explosion pressure three was The pipe pressure diameter rose after isobaric combustion speed Therefore,the the process can divided into stages increased in the and(DN15–DN150).Deflagration increases results indicated that propane-air flame speed initially eventually decreased along with in the pipe diameter(DN32–DN400);however,the of ethylene-air flame speed gradually flame increased with the increase the of the pipe diameter(DN80–DN400).No notable pattern change speed in the hydrogen-air at speed was observed in pipe diameter(DN15–DN150).The maximum happened propane-air when flame occurred 5%concentration.The the maximum conditions flame of speed same for size ethylene-air of and hydrogen-air tube the mixture ignition was close to but stoichiometric different ratio.Under or the experimental configuration experimental and the same distance flame pipe lengths,stopped the same flames pipe length high but different ignition low distances,results showed that the arrester successfully the at flame speed and explosion pressure,but failed at low flame speed and high explosion pressure. | SUN ShaoChen DING ChunHui HU XiYu LIU Gang YE Chen BI MingShu | 2017 | Science China(Technological Sciences)2017，60，5： | 0 |
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