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23篇 您的检索式:作者名="Tiantian LUO"
    题名 作者 年代 出处 被引量
1Reversing drug resistance of soft tumor-repopulating cells by tumor cell-derived chemotherapeutic microparticles显示文摘颠倒使人重新住入肿瘤的房间(TRC ) 的药抵抗或起源的发展中的新奇途径像房间的癌症房间是迫切临床的需要改进癌症病人的结果。这里,我们显示出用肿瘤颠倒 TRC 的药抵抗的一条创新途径包含反肿瘤药的导出房间的 microparticles (T-MPs ) 。由比区分的癌症房间更可变形的优点, TRC 优先地收起 T-MPs 在进入房间以后释放反肿瘤药,它接着导致 TRC 的死亡。内在的机制包括防碍药流出并且支持这些药的原子入口。我们的调查结果在用有希望的临床的应用程序颠倒 TRC 的药抵抗在 T-MPs 的举起和一条新奇途径的有效性表明肿瘤房间柔软的重要性。Jingwei Ma Yi Zhang Ke Tang Huafeng Zhang Xiaonan Yin Yong Li Pingwei Xu Yanling Sun Ruihua Ma Tiantian Ji Junwei Chen Shuang Zhang Tianzhen Zhang Shunqun Luo Yang Jin Xiuli Luo Chengyin Li Hongwei Gong Zhixiong Long Jinzhi Lu Zhuowei Hu Xuetao Cao Ning Wang Xiangliang Yang Bo Huang 2016Cell Research2016,26,6:17
2Parthenogenetic haploid embryonic stem cells produce fertile mice显示文摘Haifeng Wan Zhengquan He Mingzhu Dong Tiantian Gu Guan-Zheng Luo Fei Teng Baolong Xia Wei Li Chunjing Feng Xin Li Tianda Li Ling Shua Rui Fu Liu Wang Xiu-Jie Wang Xiao-Yang Zhao Qi Zhou 2013Cell Research2013,23,11:13
3A double crosslinking MXene/cellulose nanofiber layered film for improving mechanical properties and stable electromagnetic interference shielding performance显示文摘With the discovery of the two-dimensional(2D) MXene, it shows a great application potential in the field of electromagnetic interference(EMI) shielding, but the mechanical brittleness and easy oxidation of MXene limit its wide application. For this reason, a double crosslinking strategy is provided to solve the above problems in a nacre-like “brick-mortar” layered MXene/cellulose nanofiber(MXene/CNF) film.Typically, the film was firstly suffered by dopamine modification, then was further reinforced by secondary Ca^(2+)bridging, so as to obtain excellent mechanical properties and antioxidative EMI shielding performance. Comparing with the single crosslinking, the double crosslinking strategy reveals a higher efficiency in improving the mechanical property. The mechanical strength and toughness of the double crosslinking MXene/CNF film can increase to 142.2 MPa and 9.48 MJ/m^(3), respectively. More importantly, while achieving good mechanical properties, the MXene composite film still holds a very stable EMI shielding performance of more than 44.6 dB when suffering from the oxidation treatment of hightemperature annealing, showing excellent anti-oxidation ability and environment tolerance. Therefore,this work provides a universal but effective double crosslinking strategy to solve the mechanical brittleness and easy oxidation of MXene-based composites, thus showing a huge potential in flexible EMI shielding applications.Shilu Luo Tiantian Xiang Jingwen Dong Fengmei Su Youxin Ji Chuntai Liu Yuezhan Feng 2022Journal of Materials Science & Technology2022,,34:4
4Hierarchical graphene@MXene composite foam modified with flower-shaped FeS for efficient and broadband electromagnetic absorption显示文摘Developing high-performance broadband microwave absorption material becomes an urgent concern in the field of electromagnetic protection.In this work,an ultralight magnetic composite foam was con-structed by electrostatic self-assembly of MXene on the surface of graphene skeletons,and subsequent hydrothermal anchoring of flower-shaped FeS clusters.Under the synergistic effect of MXene coating in-creasing conductive loss and FeS clusters improving magnetic loss,the rational construction of hierarchi-cal impedance structure in foam can effectively promote the entrance and consumption of more incident electromagnetic waves.The minimum reflection loss(RL min)reaches-47.17 dB at a thickness of 4.78 mm,and the corresponding effective absorption bandwidth(EAB)is up to 6.15 GHz.More importantly,the microwave absorption performance of composite foam can be further optimized by controlling the load-ing of MXene and thermal treatment at a low temperature.The maximum of EAB for GMF-300 can be extended to an unprecedented value of 11.20 GHz(covering 6.10-17.30 GHz).Shuangshuang Li Xinwei Tang Xu Zhao Shijie Lu Jiangtao Luo Zheyuan Chai Tiantian Ma Qianqian Lan Piming Ma Weifu Dong Zicheng Wang Tianxi Liu 2023Journal of Materials Science & Technology2023,,2:4
5Multi-channel phase regeneration of QPSK signals based on phase sensitive amplification显示文摘In this paper,we propose and demonstrate simultaneous phase regeneration of four different channels of QPSK signal based on phase sensitive amplification.The configuration can be divided into two parts.The first one uses four wave mixing in high nonlinear fiber(HNLF)to generate the corresponding three harmonic conjugates precisely at the frequency of the original signals.The other one uses optical combiner to realize coherent addition which is aimed at completely removing the interaction in phase regeneration stage.The simulation results suggest that this scheme can optimize signal constellation to a large extend especially in high noise environment.Besides,optical signal to noise ratio(OSNR)can improve more than 3 dB while the bit-error-rate(BER)reaches 10 – 3 with a constant white noise and 15° phase noise.Hongxiang WANG Tiantian LUO Yuefeng JI 2019Frontiers of Optoelectronics2019,12,1:3
6HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression显示文摘Diffuse large B-cell lymphoma(DLBCL) is an aggressive type of non-Hodgkin’s lymphoma. A total of 10%-15% of DLBCL cases are associated with myelocytomatosis viral oncogene homolog(MYC) and/or B-cell lymphoma-2(BCL2) translocation or amplification. BCL2 inhibitors have potent anti-tumor effects in DLBCL;however, resistance can be acquired through up-regulation of alternative anti-apoptotic proteins. The histone deacetylase(HDAC) inhibitor chidamide can induce BIM expression, leading to apoptosis of lymphoma cells with good efficacy in refractory recurrent DLBCL. In this study, the synergistic mechanism of chidamide and venetoclax in DLBCL was determined through in vitro and in vivo models. We found that combination therapy significantly reduced the protein levels of MYC, TP53, and BCL2 in activated apoptotic-related pathways in DLBCL cells by increasing BIM levels and inducing cell apoptosis. Moreover, combination therapy regulated expression of multiple transcriptomes in DLBCL cells, involving apoptosis, cell cycle, phosphorylation, and other biological processes, and significantly inhibited tumor growth in DLBCL-bearing xenograft mice. Taken together, these findings verify the in vivo therapeutic potential of chidamide and venetoclax combination therapy in DLBCL, warranting pre-clinical trials for patients with DLBCL.Cancan LUO Tiantian YU Ken H.YOUNG Li Yu 2022Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2022,23,8:2
7Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization显示文摘Currently,stem cell transplantations in cardiac repair are limited owing to disadvantages,such as immunological rejection and poor cell viability.Although direct injection of exosomes can have a curative effect similar to that of stem cell transplantation,high clearance hinders its application in clinical practice.Previous reports suggested that induction of coronary collateralization can be a desired method of adjunctive therapy for someone who had missed the optimal operation time to attenuate myocardial ischemia.In this study,to mimic the paracrine and biological activity of stem cells,we developed artificial stem cells that can continuously release Tβ4-exosomes(Tβ4-ASCs)by encapsulating specific exosomes within microspheres using microfluidics technology.The results show that Tβ4-ASCs can greatly promote coronary collateralization in the periphery of the myocardial infarcted area,and its therapeutic effect is superior to that of directly injecting the exosomes.In addition,to better understand how it works,we demonstrated that the Tβ4-ASC-derived exosomes can enhance the angiogenic capacity of coronary endothelial cells(CAECs)via the miR-17-5p/PHD3/Hif-1αpathway.In brief,as artificial stem cells,Tβ4-ASCs can constantly release functional exosomes and stimulate the formation of collateral circulation after myocardial infarction,providing a feasible and alternative method for clinical revascularization.Peier Chen Xiaodong Ning Weirun Li Yuxuan Pan Ling Wang Hekai Li Xianglin Fan Jiexin Zhang Tiantian Luo Yaobin Wu Caiwen Ou Minsheng Chen 2022Bioactive Materials2022,7,8:2
8Nitrogen content diagnosis of apple trees canopies using hyperspectral reflectance combined with PLS variable extraction and extreme learning machine显示文摘Nitrogen(N)is an important mineral element in apple production.Rapid estimation of apple tree N status is helpful for achieving precise N management.The objective of this work was to explore partial least squares(PLS)regression in dimensional reduction of spectral data and build the diagnostic model.The spectral reflectance data were collected from Fuji apple trees with 4 levels of N fertilizer treatment in the Loess Plateau in 2018 and 2019 using an ASD portable spectroradiometer,and leaf total N content was obtained at the same time.The raw spectra were pretreated using Savitzky-Golay(SG)smoothing and a combination of SG and first-order derivative(SG_FD)or second-order derivative(SG_SD).The samples were divided into a calibration dataset and a prediction dataset using SPXY.Based on 4 factors of PLS regression,including latent variables(LVs),X-loading,variable importance in projection(VIP)and regression coefficients(RC),the 6 methods(LVs,X-loading,VIP_01,VIP_02,RC_01 and RC_02)were derived and used for variable extraction,based on which PLS model and ELM model were established.The results indicated that the spectral data processed by SG_FD had the highest signal-to-noise ratio and was selected for subsequent analysis.The amounts of variables extracted by LVs,X-loading,VIP_01,VIP_02,RC_01 and RC_02 were 6,11,18,305,26 and 88,respectively.The method of extracting variables with an RC threshold based on the minimum RMSEP(RC_02)could effectively avoid the omission of effective information.The RC_02 method was recommended for related research which required accurate wavelength information as a variable.The variable extraction method based on LVs generated an ELM model with a simple structure.The prediction results showed that the ELM model outperformed the PLS model.The PLS(LVs)_ELM model was the best;R2P,RMSEP and RPD were 0.837,2.393 and 2.220,respectively.Shaomin Chen Lihui Ma Tiantian Hu Lihua Luo Qiong He Shaowu Zhang 2021International Journal of Agricultural and Biological Engineering2021,14,3:2
9On Latency Reductions in Vehicle-to-Vehicle Networks by Random Linear Network Coding显示文摘In the Internet of vehicles(IoV),direct communication between vehicles,i.e.,vehicle-tovehicle(V2V)may have lower latency,compared to the schemes with help of Road Side Unit(RSU)or base station.In this paper,the scenario where the demands of a vehicle are satisfied by cooperative transmissions from those one in front is considered.Since the topology of the vehicle network is dynamic,random linear network coding is applied in such a multisource single-sink vehicle-to-vehicle network,where each vehicle is assumed to broadcast messages to others so that the intermediate vehicles between sources and sink can reduce the latency collaboratively.It is shown that the coding scheme can significantly reduce the time delay compared with the non-coding scheme even in the channels with high packet loss rate.In order to further optimize the coding scheme,one can increase the generation size,where the generation size means the number of raw data packets sent by the source node to the sink node in each round of communication.Under the premise of satisfying the coding validity,we can dynamically select the Galois field size according to the number of intermediate nodes.It is not surprised that the reduction in the Galois field size can further reduce the transmission latency.Tiantian Zhu Congduan Li Yanqun Tang Zhiyong Luo 2021China Communications2021,18,6:1
10A Vaccine Based on the Receptor-Binding Domain of the Spike Protein Expressed in Glycoengineered Pichia pastoris Targeting SARS-CoV-2 Stimulates Neutralizing and Protective Antibody Responses显示文摘In 2020 and 2021,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel coronavirus,caused a global pandemic.Vaccines are expected to reduce the pressure of prevention and control,and have become the most effective strategy to solve the pandemic crisis.SARS-CoV-2 infects the host by binding to the cellular receptor angiotensin converting enzyme 2(ACE2)via the receptor-binding domain(RBD)of the surface spike(S)glycoprotein.In this study,a candidate vaccine based on a RBD recombinant subunit was prepared by means of a novel glycoengineered yeast Pichia pastoris expression system with characteristics of glycosylation modification similar to those of mammalian cells.The candidate vaccine effectively stimulated mice to produce high-titer anti-RBD specific antibody.Furthermore,the specific antibody titer and virus-neutralizing antibody(NAb)titer induced by the vaccine were increased significantly by the combination of the double adjuvants Al(OH)_(3) and CpG.Our results showed that the virus-NAb lasted for more than six months in mice.To summarize,we have obtained a SARS-CoV-2 vaccine based on the RBD of the S glycoprotein expressed in glycoengineered Pichia pastoris,which stimulates neutralizing and protective antibody responses.A technical route for fucose-free complex-type N-glycosylation modified recombinant subunit vaccine preparation has been established.Bo Liu Ying Yin Yuxiao Liu Tiantian Wang Peng Sun Yangqin Ou Xin Gong Xuchen Hou Jun Zhang Hongguang Ren Shiqiang Luo Qian Ke Yongming Yao Junjie Xu Jun Wu 2022Engineering2022,8,6:1
11Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3显示文摘Intercellular cross-talk plays important roles in cancer progression and metastasis.Yet how these cancer cells interact with each other is still largely unknown.Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators.We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma(HCC).Exosomes were extracted from HCC cells of different metastatic potentials.The metastatic effects of exosomes derived from highly metastatic HCC cells(HMH)were evaluated both in vitro and in vivo.Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines,xenograft tumor samples,and functional analyses.Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells(LMH).S100 calcium-binding protein A4(S100A4)was identified as a functional factor in exosomes derived from HMH.S100A4r,ch exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4^(rich) exosomes or controls.Moreover,exosomal S100A4 could induce expression of osteopontin(OPN),along with other tumor metastasis/stemness-related genes.Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation.HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis.In conclusion,exosomes from HMH could promote the metastatic potential of LMH,and exosomal S100A4 is a key enhancer for HCC metastasis,activating STAT3 phosphorylation and up-regulating OPN expression.This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.Haoting Sun Chaoqun Wang Beiyuan Hu Xiaomei Gao Tiantian Zou Qin Luo Mo Chen Yan Fu Yuanyuan Sheng Kaili Zhang Yan Zheng Xudong Ren Shican Yan Yan Geng Luyu Yang Qiongzhu Dong Lunxiu Qin 2021Signal Transduction and Targeted Therapy2021,6,6:1
12Durable pluripotency and haploidy in epiblast stem cells derived from haploid embryonic stem cells in vitro显示文摘Haploid pluripotent stem cells,such as haploid embryonic stem cells(haESCs),facilitate the genetic study of recessive traits.In vitro,fish haESCs maintain haploidy in both undifferentiated and differentiated states,but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested.Here,wereport thatmousehaESCs can differentiate in vitro into haploid epiblast stem cells(haEpiSCs),which maintain an intact haploid genome,unlimited self-renewal potential,and durable pluripotency to differentiate into various tissues in vitro and in vivo.Mechanistically,the maintenance of self-renewal potential depends on the Activin/bFGF pathway.We further show that haEpiSCs can differentiate in vitro into haploid progenitor-like cells.When injected into the cytoplasm of an oocyte,androgenetic haEpiSC(ahaEpiSCs)can support embryonic development until midgestation(E12.5).Together,these resultsdemonstrate durable pluripotency inmousehaESCs andhaEpiSCs,aswell asthe valuable potential of using these haploid pluripotent stem cells in high-throughput genetic screening.Ling Shuai Yukai Wang Mingzhu Dong Xuepeng Wang Lisi Sang Mei Wang Haifeng Wan Guanzheng Luo Tiantian Gu Yan Yuan Chunjing Feng Fei Teng Wei Li Xiuying Liu Tianda Li Liu Wang Xiu-Jie Wang Xiao-Yang Zhao Qi Zhou 2015Journal of Molecular Cell Biology2015,7,4:1
13Molecular characterization of glutaredoxin 2 from Ostrinia furnacalis显示文摘Glutaredoxins(GRXs)play very important roles in maintaining intracellular redox homeostasis.In the present study,the full-length cDNA sequence encoding GRX2,named OfurGRX2(GenBank accession no.GU393246),was obtained from Ostrinia furnacalis,using reverse transcription polymerase chain reaction and rapid amplification of cDNA ends.Sequence analysis revealed that the open reading frame of OfurGRX2 consists of 351 nucleotides encoding 116 amino acid residues with a predicted molecular weight of 12.6 kDa.Homolog research revealed that OfurGRX2 shares a common active site,CPYC/CPFC,with other insect counterparts.Expression profiles revealed that OfurGRX2 is a ubiquitous gene expressed in insect heads,fat bodies,epidermises,mid guts and muscles.The OfurGRX2 transcript peaked in 36-h larvae of 4th instars,and then suddenly declined in the molting stage.Hormone treatment experiments revealed that 20-hydroxyecodyson(20e)significantly induces the expression of the OfurGRX2 transcript,whereas juvenile hormone(JH)counteracts 20e effects.Adverse stress factors(including starvation,ultraviolet light,mechanical injury,Escherichia coli exposure,and high and low temperatures)dramatically induced OfurGRXGRX2 transcript expression,which confirmed for the first time that GRX2 play important roles in insecta during exposure to adverse environments.Shiheng AN Ying ZHANG Tiantian WANG Meihao LUO Chaohai LI 2013Integrative Zoology2013,8,1:0
14Reflectin基因起源及其蛋白质逐级组装的性质显示文摘文章简介在自然界中,头足纲动物以动态变色和拟态隐形而著称。这其中涉及两种类型的颜色,分别是色素色彩和结构色彩。Reflectin是一类只存在于头足纲动物体内的特殊蛋白质家族,其构成了它们结构色变化的物质基础,然而其基因来源以及如何介导结构色彩变化的分子机理尚不清楚。Zhe Guan Tiantian Cai Zhongmin Liu Yunfeng Dou Xuesong Hu Peng Zhang Xin Sun Hongwei Li Yao Kuang Qiran Zhai Hao Ruan Xuanxuan Li Zeyang Li Qihui Zhu Jingeng Mai Qining Wang Luhua Lai Jianguo Ji Haiguang Liu Bin Xia Taijiao Jiang Shu-Jin Luo Hong-Wei Wang 谢灿 2018科学新闻2018,0,4:0
15A cell transcriptomic profile p ovides insights into adipocytes of porcine mammary gland across development显示文摘Background Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on the gene expression of multiple cell types. Most studies focused on epithelial cells, disregarding the role of neighboring adipocytes.Results Here, we constructed the largest transcriptomic dataset of porcine mammary gland cells thus far. The dataset captured 126,829 high-quality nuclei from physiological mammary glands across five developmental stages(d 90 of gestation, G90;d 0 after lactation, L0;d 20 after lactation, L20;2 d post natural involution, PI2;7 d post natural involution, PI7). Seven cell types were identified, including epithelial cells, adipocytes, endothelial cells, fibroblasts cells, immune cells, myoepithelial cells and precursor cells. Our data indicate that mammary glands at different developmental stages have distinct phenotypic and transcriptional signatures. During late gestation(G90), the differentiation and proliferation of adipocytes were inhibited. Meanwhile, partly epithelial cells were completely differentiated. Pseudo-time analysis showed that epithelial cells undergo three stages to achieve lactation, including cellular differentiation, hormone sensing, and metabolic activation. During lactation(L0 and L20), adipocytes area accounts for less than 0.5% of mammary glands. To maintain their own survival, the adipocyte exhibited a poorly differentiated state and a proliferative capacity. Epithelial cells initiate lactation upon hormonal stimulation. After fulfilling lactation mission, their undergo physiological death under high intensity lactation. Interestingly, the physiological dead cells seem to be actively cleared by immune cells via CCL21-ACKR4 pathway. This biological process may be an important mechanism for maintaining homeostasis of the mammary gland. During natural involution(PI2 and PI7), epithelial cell populations dedifferentiate into mesenchymal stem cells to maintain the lactation potential of mammary glands for the next lactation cycle.Conclusion The molecular mechanisms of dedifferentiation, proliferation and redifferentiation of adipocytes and epithelial cells were revealed from late pregnancy to natural involution. This cell transcriptomic profile constitutes an essential reference for future studies in the development and remodeling of the mammary gland at different stages.Yongliang Fan Long Jin Zhiping He Tiantian Wei Tingting Luo Jiaman Zhang Can Liu Changjiu Dai Chao A Yan Liang Xuan Tao Xuebin Lv Yiren Gu Mingzhou Li 2024Journal of Animal Science and Biotechnology2024,15,1:0
16AcWRKY28 mediated activation of AcCPK genes confers salt tolerance in pineapple(Ananas comosus)显示文摘Unfavorable environmental cues severely affect crop productivity resulting in significant economic losses to farmers. In plants, multiple regulatory genes, such as the WRKY transcription factor (TF) family, modulate the expression of defense genes. However, the role of the pineapple WRKY genes is poorly understood. Here, we studied the pineapple WRKY gene, AcWRKY28, by generating AcWRKY28 over-expressing transgenic pineapple plants. Overexpression of AcWRKY28 enhanced the salt stress resistance in transgenic pineapple lines. Comparative transcriptome analysis of transgenic and wild-type pineapple plants showed that “plant-pathogen interaction” pathway genes, including 9calcium-dependent protein kinases (CPKs), were up-regulated in AcWRKY28 over-expressing plants. Furthermore, chromatin immunoprecipitation and yeast one-hybrid assays revealed AcCPK12, AcCPK3, AcCPK8, AcCPK1, and AcCPK15 as direct targets of AcWRKY28. Consistently, the study of AcCPK12 over-expressing Arabidopsis lines showed that AcCPK12 enhances salt, drought, and disease resistance. This study shows that AcWRKY28 plays a crucial role in promoting salt stress resistance by activating the expression of AcCPK genes.Qiao Zhou Samaranayaka Vidana Gamage Nirosha Priyadarshani Rongjuan Qin Han Cheng Tiantian Luo Myat Hnin Wai Mohammad Aqa Mohammadi Yanhui Liu Chang Liu Hanyang Cai Xiaomei Wang Yeqiang Liu Yuan Qin Lulu Wang 2024Horticultural Plant Journal2024,10,2:0
17An injectable bioactive dressing based on platelet-rich plasma and nanoclay:Sustained release of deferoxamine to accelerate chronic wound healing显示文摘Delayed diabetic wound healing has placed an enormous burden on society.The key factors limiting wound healing include unresolved inflammation and impaired angiogenesis.Platelet-rich plasma(PRP)gel,a popular biomaterial in the field of regeneration,has limited applications due to its non-injectable properties and rapid release and degradation of growth factors.Here,we prepared an injectable hydrogel(DPLG)based on PRP and laponite by a simple one-step mixing method.Taking advantages of the non-covalent interactions,DPLG could overcome the limitations of PRP gels,which is injectable to fill irregular injures and could serve as a local drug reservoir to achieve the sustained release of growth factors in PRP and deferoxamine(an angiogenesis promoter).DPLG has an excellent ability in accelerating wound healing by promoting macrophage polarization and angiogenesis in a full-thickness skin defect model in typeⅠdiabetic rats and normal rats.Taken together,this study may provide the ingenious and simple bioactive wound dressing with a superior ability to promote wound healing.Jiao Zhang Qian Luo Qian Hu Tiantian Zhang Jingyu Shi Li Kong Dehao Fu Conglian Yang Zhiping Zhang 2023Acta Pharmaceutica Sinica B2023,13,10:0
18Design, synthesis, molecular modeling, and biological evaluation of acrylamide derivatives as potent inhibitors of human dihydroorotate dehydrogenase for the treatment of rheumatoid arthritis显示文摘Human dihydroorotate dehydrogenase(DHODH) is a viable target for the development of therapeutics to treat cancer and immunological diseases, such as rheumatoid arthritis(RA), psoriasis and multiple sclerosis(MS). Herein, a series of acrylamide-based novel DHODH inhibitors as potential RA treatment agents were designed and synthesized. 2-Acrylamidobenzoic acid analog 11 was identified as the lead compound for structureeactivity relationship(SAR) studies. The replacement of the phenyl group with naphthyl moieties improved inhibitory activity significantly to double-digit nanomolar range.Further structure optimization revealed that an acrylamide with small hydrophobic groups(Me, Cl or Br)at the 2-position was preferred. Moreover, adding a fluoro atom at the 5-position of the benzoic acid enhanced the potency. The optimization efforts led to potent compounds 42 and 53-55 with IC50 values of 41, 44, 32, and 42 nmol/L, respectively. The most potent compound 54 also displayed favorable pharmacokinetic(PK) profiles and encouraging in vivo anti-arthritic effects in a dose-dependent manner.Fanxun Zeng Shiliang Li Guantian Yang Yating Luo Tiantian Qi Yingfan Liang Tingyuan Yang Letian Zhang Rui Wang Lili Zhu Honglin Li Xiaoyong Xu 2021Acta Pharmaceutica Sinica B2021,11,3:0
193D bioprinted breast tumor model for structure–activity relationship study显示文摘In this paper,we present a 3D printed tumor spheroidal model suitable for drug discovery.This model is based on a hydroxyethyl cellulose/alginate/gelatin(HCSG)composite biomaterial that has three distinct properties:(1)the HCSG is similar to the commercial basement membrane extract in Ki67,MUC1,and PARP1 expressions of MCF-7 cells for embedding culture;(2)the HCSG is printable at room temperature;and(3)the HCSG can be large-scale manufactured at an ultralow cost.We printed a 3D MCF-7 spheroid model with HCSG and characterized it in terms of cell viability,spheroid size,key protein expression,and mitochondrial metabolic activity.We used the 3D MCF-7 spheroid model to evaluate the anti-breast cancer activity of 13 amino acid-based flavone phosphoramidates and found that the alanine structure induced a stronger drug resistance,whereas phenylalanine hardly caused drug resistance in the MCF-7 cells.This is the first time that 3D bioprinting technology has been used in a structure–activity relationship study.Xiaorui Li Quanfeng Deng Tiantian Zhuang Yao Lu Tingjiao Liu Weijie Zhao Bingcheng Lin Yong Luo Xiuli Zhang 2020Bio-Design and Manufacturing2020,3,4:0
20Epigenetic modification mechanisms of chloroplasts mutants in pineapple leaves during somatic regeneration显示文摘Somaclonal variation in tissue culture is a common phenomenon induced by various external or internal environmental conditions,resulting in heritable or non-heritable alterations in gene expression. One crucial mechanism involved in plant growth and development is epigenetic regulation. A highly dynamic epigenome can respond to environmental changes by regulating gene expression. DNA methylation is one of these epigenetic modifications that can alter gene expression in tissue-cultured pineapple plants. The underlying mechanism of such somaclonal variations in pineapple and the epigenetic regulation involvement in somaclonal variations has not been studied. This study performed DNA methylome and transcriptome sequencing of wild-type(WT) and mutant pineapple plants(WS, HW, and TW). We observed altered DNA methylation patterns in chlorophyll development in the mutants. Specifically, we noticed that the methylation levels in the CHG and CHH contexts were lower in the gene body regions compared to the upstream and downstream regions. We identified several thousand differentially methylated regions(DMRs) located at the gene body regions, some of which overlapped with the differentially expressed genes(DEGs). Functional enrichment analyses suggested that these genes were involved in chlorophyll metabolism. Thus, our results revealed that the transcriptional regulation of many chlorophyll metabolic essential genes could be regulated by DNA methylation caused by somaclonal variations and provided insights into epigenetic mechanisms underlying the regulation of chlorosis in pineapple plants.Yanhui Liu S.V.G.N.Priyadarshani Meirong Chi Maokai Yan Mohammad Aqa Mohammadi Man Zhang Qiao Zhou Lulu Wang Tiantian Luo Myat Hnin Wai Xiaomei Wang Hanyang Cai Haifeng Wang Yuan Qin 2023Horticultural Plant Journal2023,9,3:0
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