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| 1 | Molecular mechanisms and clinical management of cancer bone metastasis显示文摘As one of the most common metastatic sites of malignancies,bone has a unique microenvironment that allows metastatic tumor cells to grow and flourish.The fenestrated capillaries in the bone,bone matrix,and bone cells,including osteoblasts and osteoclasts,together maintain the homeostasis of the bone microenvironment.In contrast,tumor-derived factors act on bone components,leading to subsequent bone resorption or excessive bone formation.The various pathways involved also provide multiple targets for therapeutic strategies against bone metastases.In this review,we summarize the current understanding of the mechanism of bone metastases.Based on the general process of bone metastases,we specifically highlight the complex crosstalk between tumor cells and the bone microenvironment and the current management of cancer bone metastases. | Manni Wang Fan Xia Yuquan Wei Xiawei Wei | 2020 | Bone Research2020，8，3： | 7 |
| 2 | Role of tumor gene mutations in treatment response to immune checkpoint blockades显示文摘Early studies shed light on the immune suppression of immune checkpoint molecules in the cancer microenvironment,with later studies applying immune checkpoint blockade(ICB)in treatment of various malignancies.Despite the encouraging efficacy of ICBs in a substantial subset of cancer patients,the treatment response varies.Gene mutations of both tumor cells and immune cells in the tumor microenvironment have recently been identified as potential predictors of the ICB response.Recent developments in gene expression profiling of tumors have allowed identification of a panel of mutated genes that may affect tumor cell response to ICB treatment.In this review,we discuss the association of the ICB response with gene expression and mutation profiles in tumor cells,which it is hoped will help to optimize the clinical application of ICBs in cancer patients. | Manni Wang Liu Yu Xiawei Wei Yuquan Wei | 2019 | Precision Clinical Medicine2019，2，2： | 2 |
| 3 | DNA-PK inhibition by M3814 enhances chemosensitivity in non-small cell lung cancer显示文摘A significant proportion of non-small cell lung cancer(NSCLC) patients experience accumulating chemotherapy-related adverse events,motivating the design of chemosensitizating strategies.The main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks(DSB).It is thus conceivable that DNA-dependent protein kinase(DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy.The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC.We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis.M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549,H460 and H1703 NSCLC cell lines.In the four combinations based on two NSCLC xenograft models and two chemotherapy,we also observed tumor regression at tolerated doses in vivo.Moreover,we identified a P53-dependent accelerated senescence response by M3814 following treatment with paclitaxel/etoposide.The present study provides a theoretical basis for the use of M3814 in combination with paclitaxel and etoposide in clinical practice,with hope to aid the optimization of NSCLC treatment. | Manni Wang Siyuan Chen Yuquan Wei Xiawei Wei | 2021 | Acta Pharmaceutica Sinica B2021，11，12： | 2 |
| 4 | Nanoparticles targeting tumor-associated macrophages:A novel anti-tumor therapy显示文摘The immunosuppressive tumor microenvironment(TME)is crucial in the occurrence of tumorigenesis,metastasis,and drug resistance.Among all stromal cells,tumor-associated macrophages(TAMs)are recognized as vital components causing the TME to be favorable for cancer cells and are also main targets in cancer immunotherapy.To date,nanoparticle(NP)-based drug delivery systems,as new technology platforms,have exhibited considerable advantages,such as targeted drug delivery at tumor sites,enhanced drug transport efficiency,and controllable drug release profiles,which provide new approaches for cancer therapy.Regarding TAM-targeting nanoparticles,various therapeutic strategies have been developed by varying their design,namely,by blocking TAM recruitment,promoting TAM transformation,and directly diminishing existing TAMs.In the current review,we provide a brief overview of the role of TAMs in the tumor microenvironment and their functions and highlight strategies for TAM targeting.Moreover,the applications of nanoparticles in targeting TAMs to improve cancer therapeutic efficiency are summarized. | Siyuan Chen Furong Qin Manni Wang Yuquan Wei Zhiyong Qian Xiawei Wei | 2022 | Nano Research2022，15，3： | 1 |
| 5 | Study of the decorporation efficacy and toxicity of tetradentate 3-hydroxy- 2-pyridinone ligands at the cellular level显示文摘Objective:A series of experiments were carried out to study the comparative decorporation efficacy and toxicity of three tetradentate hydroxypyridinone ligands(3LI-1-Cm-3,2-HOPO,5LIO-1-Cm-3,2-HOPO,and 7LIO-1-Cm-3,2-HOPO)with the variation of the linker length and the substituents.Methods:Three ligands were obtained from a 4-step synthesis via the amidation of HOPO unit and different backbones.Potentiometric titrations were carried out to evaluate the formation constants of their corresponding uranyl complexes.CCK-8 and colony formation assays were used to compare the cytotoxicity of the three ligands and uranyl using renal proximal tubular epithelial(NRK-52E)cells.In vitro uranium removal assays were performed to assess decorporation efficiencies of those ligands by co-incubating uranium and chelators with NRK-52E cells for 48 h.Results:Among the three ligands,5LIO-1-Cm-3,2-HOPO exhibits the highest uranyl affinity(logβ110?18.6(7))in comparison to the other two ligands(logβ110?14.9(2)for 3LI-1-Cm-3,2-HOPO and logβ110?16.7(1)for 7LIO-1-Cm-3,2-HOPO).The results of CCK-8 tests and colony formation assays further elucidate that 5LIO-1-Cm-3,2-HOPO and 7LIO-1-Cm-3,2-HOPO both show a similar level of cytotoxicity compared with ZnNa3-DTPA at relatively low ligand concentrations.In contrast,in the 3LI-1-Cm-3,2-HOPO treated group,the cell viability decreased markedly with the increase of the ligand concentrations,and the colony formation capability of NRK-52E cells was inhibited.Furthermore,the comparative decorporation efficacy of the three ligands was obtained from in vitro uranium removal assays,suggesting that these ligands could significantly inhibit the cellular uptake and prompt the cellular release of uranium from NRK-52E cells by the level of 81.9%,91.8%,and 87.1%,respectively.Conclusion:Our current results demonstrate that the linker/backbone species would significantly affect the decorporation efficacy and toxicity of the tetradentate 3-hydroxy-2-pyridinone ligands,which is informative for the future design and modification of novel decorporation ligands. | Xiaomei Wang Cen Shi Manni Gao Ying Xu Yang Jiao Jianmei Wan Jianping Cao Zhifang Chai Juan Diwu | 2020 | Radiation Medicine and Protection2020，1，4： | 1 |
| 6 | Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials显示文摘Epigenetic alternations concern heritable yet reversible changes in histone or DNA modifications that regulate gene activity beyond the underlying sequence.Epigenetic dysregulation is often linked to human disease,notably cancer.With the development of various drugs targeting epigenetic regulators,epigenetic-targeted therapy has been applied in the treatment of hematological malignancies and has exhibited viable therapeutic potential for solid tumors in preclinical and clinical trials.In this review,we summarize the aberrant functions of enzymes in DNA methylation,histone acetylation and histone methylation during tumor progression and highlight the development of inhibitors of or drugs targeted at epigenetic enzymes. | Yuan Cheng Cai He Manni Wang Xuelei Ma Fei Mo Shengyong Yang Junhong Han Xiawei Wei | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 1 |
| 7 | Clonal replacement of novel T cells: a new phenomenon in the tumor microenvironment following PD-1 blockade显示文摘In a recent study published in Nature Medicine,Yost et al.1 described the clonal replacement of tumor-specific T cells after treatment with PD-1 antibodies.This finding reveals the intrinsic ability of the tumor microenvironment to attract new T cells,which has crucial applications for the design of immune checkpoint blockade(ICB)therapies(Fig.1).Over the past few decades,ICB therapies have been successful in some patients with different types of cancer by blocking inhibitory checkpoint receptors on T cells,and thus restoring T cell-mediated immune responses as well as recruiting more T cells into the tumor environment. | Xue Li Manni Wang Rong Xiang | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 1 |
| 8 | Sensitive direct-conversion X-ray detectors formed by ZnO nanowire field emitters andβ-Ga_(2)O_(3)photoconductor targets with an electron bombardment induced photoconductivity mechanism显示文摘Sensitive X-ray detection is needed in diverse areas motivated by a common desire to reduce radiation dose.Cold cathode X-ray detectors operating with a photoelectron multiplication mechanism called electron bombardment induced photoconductivity(EBIPC)have emerged as promising candidates for low-dose X-ray detection.Herein,the cold cathode detectors formed by ZnO nanowire field emitters andβ-Ga_(2)O_(3)photoconductor targets were proposed for sensitive direct-conversion X-ray detection.The charge carrier transport mechanism of EBIPC effect in X-ray detectors was investigated to achieve a high internal gain(2.9×10^(2))and high detection sensitivity(3.0×10^(3)μCGy^(−1)_(air)cm^(−2))for a 6 keV X-ray at the electric field of 22.5 Vμm−1.Furthermore,the proposed X-ray detectors showed the features of fast response time(40 ms),long-term stability(0.6%for 1 h),and low detection limit(0.28 mGy_(air)s^(−1)),suggesting that the direct-conversion cold cathode X-ray detectors are ideal candidates for low-energy X-ray detecting and imaging applications. | ZHIPENG ZHANG MANNI CHEN XINPENG BAI KAI WANG HUANJUN CHEN SHAOZHI DENG JUN CHEN | 2021 | Photonics Research2021，9，12： | 1 |
| 9 | Wide temperature range-and damage-tolerant microsupercapacitors from salt-tolerant, anti-freezing and self-healing organohydrogel via dynamic bonds modulation显示文摘The advance of microelectronics requires the micropower of microsupercapacitors(MSCs) to possess wide temperature-and damage-tolerance beyond high areal energy density.The properties of electrolyte are crucial for MSCs to meet the above requirements.Here,an organohydrogel electrolyte,featured with high salt tolerance,ultralow freezing point,and strong self-healing ability,is experimentally realized via modulating its inner dynamic bonds.Spectroscopic and theoretical analysis reveal that dimethyl sulfoxide has the ability to reconstruct Li^(+)solvation structure,and interact with free water and polyvinyl alcohol chains via forming hydrogen bonds.The organohydrogel electrolyte is employed to build MSCs,which show a boosted energy density,promising wide temperature range-and damage-tolerant ability.These attractive features make the designed organohydrogel electrolyte have great potential to advance MSCs. | Cheng Tang Manni Li Yaling Wang Yan Zhang Yinzhuo Yao Guolong Wang Jiamei Liu Lei Li | 2023 | Journal of Energy Chemistry2023，，3： | 0 |
| 10 | FcγRIIb blockage:a promising immunotherapy target for severe COVID-19显示文摘A recent study published in Nature by Combes et al.1 introduced a whole-blood-preserving single-cell analysis strategy to explore the contributions of the immune cells,including neutrophils,monocytes,platelets,and lymphocytes.The team comprehensively analyzed a variety of cellular and serological immune features between severe and mild to moderate phenotypes of patients with coronavirus disease 2019(COVID-19),in order to identify potential targets of immunotherapies for the severe COVID-19 patients who need prompt and effective treatments. | Xuemei He Manni Wang Min Wu | 2021 | Signal Transduction and Targeted Therapy2021，6，5： | 0 |
| 11 | Constrained surfaces: promising therapeutic targets for COVID-19 determined by systematically mutational analysis显示文摘A recent study published in Cell by Tyler N.Starr et al. presented a quantitative deep mutational scanning platform that allowed for the characterization of potential amino acid(AA)mutations to the SARS-CoV-2 receptor binding domain(RBD).The mutationphenotype maps provided in this work determined the influence of RBD expression and binding affinity to human cell-surface protein angiotensin-converting enzyme 2(ACE2)induced by fully random substitution for each AA of RBD.This work identified pivotal positions for virus binding and entry into cells,facilitating the development of countermeasures for COVID-19,such as vaccines. | Manni Wang Tianxia Lan Wei Wang | 2021 | Signal Transduction and Targeted Therapy2021，6，2： | 0 |
| 12 | Electrode structure enabling dendrite inhibition for high cycle stability quasi-solid-state lithium metal batteries显示文摘Lithium(Li)metal batteries(LMBs)are widely regarded as the ultimate choice for the next generation of high-energy–density batteries.However,the uncontrollable growth of Li dendrites formed by inhomogeneous deposition seriously hinders its commercialization.Although many studies have achieved significant results in inhibiting the formation of Li dendrites,it is still impossible to eradicate them completely.Therefore,regulating the deposition behavior,such as the growth direction of unevenly deposited Li,is preferable to unilaterally suppressing them in some cases.Here we report a structured anode that can confine the deposited Li within holes and tune it to become vertical-up/horizontal-centripetal mixed growth mode by optimizing the electric field/Li^(+)concentration gradient.The Li^(+) adsorbed by the poly(amic acid)(PAA)insulating layer coated on the anode surface can form the Li^(+)concentration gradient pointing to the center of the hole.Combined with the special electric field formed by the hole structure,it is favorable for the Li^(+)to move into the vertically arrayed holes and simultaneously deposit on the bottom and walls.Furthermore,both in-situ and ex-situ observations confirm that the growth mode is changed and the Li deposition morphology is denser,which can greatly delay capacity fading and prolong cycle life in both liquid and quasi-solid-state LMBs.All the results show that the novel anode provides a new perspective for deep research into solid-state LMBs. | Kaiming Wang Ao Yu Zhiyi Zhou Fei Shen Manni Li Liang Zhang Weichang Guo Yifei Chen Le Shi Xiaogang Han | 2023 | Journal of Energy Chemistry2023，，4： | 0 |
| 13 | JMJD family proteins in cancer and inflammation显示文摘The occurrence of cancer entails a series of genetic mutations that favor uncontrollable tumor growth.It is believed that various factors collectively contribute to cancer,and there is no one single explanation for tumorigenesis.Epigenetic changes such as the dysregulation of enzymes modifying DNA or histones are actively involved in oncogenesis and inflammatory response.The methylation of lysine residues on histone proteins represents a class of post-translational modifications.The human Jumonji C domain-containing(JMJD)protein family consists of more than 30 members.The JMJD proteins have long been identified with histone lysine demethylases(KDM)and histone arginine demethylases activities and thus could function as epigenetic modulators in physiological processes and diseases.Importantly,growing evidence has demonstrated the aberrant expression of JMJD proteins in cancer and inflammatory diseases,which might serve as an underlying mechanism for the initiation and progression of such diseases.Here,we discuss the role of key JMJD proteins in cancer and inflammation,including the intensively studied histone lysine demethylases,as well as the understudied group of JMJD members.In particular,we focused on epigenetic changes induced by each JMJD member and summarized recent research progress evaluating their therapeutic potential for the treatment of cancer and inflammatory diseases. | Wang Manni Xue Jianxin Hong Weiqi Chen Siyuan Shi Huashan | 2022 | Signal Transduction and Targeted Therapy2022，7，10： | 0 |
| 14 | Deletion of the RNA-editing enzyme ADAR1A: new strategy to potentiate responses to PD-1 immune checkpoint blockade显示文摘In a recent study in Nature,Ishizuka et al.1 proposed a new strategy to restore sensitivity to immune checkpoint blockades(ICBs)through the loss of RNA-editing enzyme ADAR1(adenine deaminase acting on RNA 1).This finding identifies ADAR1 as an attractive target to improve the treatment response in ICB-resistant patient. | Manni Wang Xiawei Wei | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 0 |
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