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| 1 | SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer显示文摘SIRT7,a sirtuin family member implicated in aging and disease,is a regulator of metabolism and stress responses.It remains elusive how human somatic stem cell populations might be impacted by SIRT7.Here,we found that SIRT7 expression declines during human mesenchymal stem cell(hMSC)aging and that SIRT7 deficiency accelerates senescence.Mechanistically,SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins,thus maintaining the repressive state of heterochromatin at nuclear periphery.Accordingly,deficiency of SIRT7 results in loss of heterochromatin,derepression of the LINE1 retrotransposon(LINE1),and activation of innate immune signaling via the cGAS-STING pathway.These agingassociated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor.Together,these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging. | Shijia Bi Zunpeng Liu Zeming Wu Zehua Wang Xiaoqian Liu Si Wang Jie Ren Yan Yao Weiqi Zhang Moshi Song Guang-Hui Liu Jing Qu | 2020 | Protein & Cell2020，11，7： | 10 |
| 2 | Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration显示文摘Accumulating evidence indicates an association between the circadian clock and the aging process.However,it remains elusive whether the deregulation of circadian clock proteins underlies stem cell aging and whether they are targetable for the alleviation of aging-associated syndromes.Here,we identified a transcription factor-independent role of CLOCK,a core component of the molecular circadian clock machinery,in counteracting human mesenchymal stem cell(hMSC)decay.CLOCK expression was decreased during hMSC aging.In addition,CLOCK deficiency accelerated hMSC senescence,whereas the overexpression of CLOCK,even as a transcriptionally inactive form,rejuvenated physiologically and pathologically aged hMSCs.Mechanistic studies revealed that CLOCK formed complexes with nuclear lamina proteins and KAP1,thus maintaining heterochromatin architecture and stabilizing repetitive genomic sequences.Finally,gene therapy with lentiviral vectors encoding CLOCK promoted cartilage regeneration and attenuated age-related articular degeneration in mice.These findings demonstrate a noncanonical role of CLOCK in stabilizing heterochromatin,promoting tissue regeneration,and mitigating aging-associated chronic diseases. | Chuqian Liang Zunpeng Liu Moshi Song Wei Li Zeming Wu Zehua Wang Qiaoran Wang Si Wang Kaowen Yan Liang Sun Tomoaki Hishida Yanning Cai Juan Carlos lzpisua Belmonte Pedro Guillen Piu Chan Qi Zhou Weiqi Zhang Jing Qu Guang-Hui Liu | 2021 | Cell Research2021，31，2： | 8 |
| 3 | Surgical‐pathologic risk factors of pelvic lymph node metastasis in stage Ib1‐IIb cervical cancer显示文摘 | DONGLIN LI JING CAI YAN KUANG JIN CAO ZEHUA WANG | 2012 | Acta Obstetricia et Gynecologica Scandinavica2012，，7： | 1 |
| 4 | MiR-27a modulates MDR1/P-glycoprotein expression by targeting HIPK2 in human ovarian cancer cells显示文摘 | Zhimin Li Sha Hu Jing Wang Jing Cai Lan Xiao Lili Yu Zehua Wang | 2010 | Gynecologic Oncology2010，，1： | 1 |
| 5 | An invasive zone in human liver cancer identified by Stereo-seq promotes hepatocyte–tumor cell crosstalk,local immunosuppression and tumor progression显示文摘Dissecting and understanding the cancer ecosystem,especially that around the tumor margins,which have strong implications for tumor cell infiltration and invasion,are essential for exploring the mechanisms of tumor metastasis and developing effective new treatments.Using a novel tumor border scanning and digitization model enabled by nanoscale resolution-SpaTial Enhanced REsolution Omics-sequencing(Stereo-seq),we identified a 500µm-wide zone centered around the tumor border in patients with liver cancer,referred to as“the invasive zone”.We detected strong immunosuppression,metabolic reprogramming,and severely damaged hepatocytes in this zone.We also identified a subpopulation of damaged hepatocytes with increased expression of serum amyloid A1 and A2(referred to collectively as SAAs)located close to the border on the paratumor side.Overexpression of CXCL6 in adjacent malignant cells could induce activation of the JAK-STAT3 pathway in nearby hepatocytes,which subsequently caused SAAs’overexpression in these hepatocytes.Furthermore,overexpression and secretion of SAAs by hepatocytes in the invasive zone could lead to the recruitment of macrophages and M2 polarization,further promoting local immunosuppression,potentially resulting in tumor progression.Clinical association analysis in additional five independent cohorts of patients with primary and secondary liver cancer(n=423)showed that patients with overexpression of SAAs in the invasive zone had a worse prognosis.Further in vivo experiments using mouse liver tumor models in situ confirmed that the knockdown of genes encoding SAAs in hepatocytes decreased macrophage accumulation around the tumor border and delayed tumor growth.The identification and characterization of a novel invasive zone in human cancer patients not only add an important layer of understanding regarding the mechanisms of tumor invasion and metastasis,but may also pave the way for developing novel therapeutic strategies for advanced liver cancer and other solid tumors. | Liang Wu Jiayan Yan Yinqi Bai Feiyu Chen Xuanxuan Zou Jiangshan Xu Ao Huang Liangzhen Hou Yu Zhong Zehua Jing Qichao Yu Xiaorui Zhou Zhifeng Jiang Chunqing Wang Mengnan Cheng Yuan Ji Yingyong Hou Rongkui Luo Qinqin Li Liang Wu Jianwen Cheng Pengxiang Wang Dezhen Guo Waidong Huang Junjie Lei Shang Liu Yizhen Yan Yiling Chen Sha Liao Yuxiang Li Haixiang Sun Na Yao Xiangyu Zhang Shiyu Zhang Xi Chen Yang Yu Yao Li Fengming Liu Zheng Wang Shaolai Zhou Huanming Yang Shuang Yang Xun Xu Longqi Liu Qiang Gao Zhaoyou Tang Xiangdong Wang Jian Wang Jia Fan Shiping Liu Xinrong Yang Ao Chen Jian Zhou | 2023 | Cell Research2023，33，8： | 1 |
| 6 | MiR-27a modulates MDR1/P-glycoprotein expression by targeting HIPK2 in human ovarian cancer cells显示文摘 | Zhimin Li Sha Hu Jing Wang Jing Cai Lan Xiao Lili Yu Zehua Wang | 2010 | Gynecologic Oncology2010，，1： | 1 |
| 7 | Direct characteristic-function tomography of the quantum states of quantum fields显示文摘Herein,we propose a novel strategy for implementing a direct readout of the symmetric characteristic function of the quantum states of quantum fields without the involvement of idealized measurements,an aspect that has always been deemed ill-defined in quantum field theory.This proposed scheme relies on the quantum control and measurements of an auxiliary qubit locally coupled to the quantum fields.By mapping the expectation values of both the real and imaginary parts of the field displacement operator to the qubit states,the qubit's readout provides complete information regarding the symmetric characteristic function.We characterize our technique by applying it to the Kubo-Martin-Schwinger(thermal)and squeezed states of a quantum scalar field.In addition,we have discussed general applications of this approach to analogue-gravity systems,such as Bose-Einstein condensates,within the scope of state-of-the-art experimental capabilities.This proposed strategy may serve as an essential in understanding and optimizing the control of quantum fields for relativistic quantum information applications,particularly in exploring the interplay between gravity and quantum,for example,the relation to locality,causality,and information. | Zehua Tian Jiliang Jing Jiangfeng Du | 2023 | Science China(Physics,Mechanics & Astronomy)2023，66，11： | 0 |
| 8 | Direct oxidative C(sp^3)-H cyanation of secondary benzylic ethers显示文摘Current studies on the oxidative C--H functionalization of benzylic ethers for C--C forging process dominantly focus on primary ethers. The corresponding reaction of secondary ethers remains underdeveloped. Herein, a practical and efficient oxidative C--H cyanation of secondary benzylic ethers with TMSCN in the presence of DDQ is described. The metal-free process is well tolerated with a wide variety of electronically varied α-monosubstituted isochromans, facilely furnishing a library of isochromans bearing α-aryl α-cyano substituent patterns for further diversification and bioactive small molecule identification. | Zehua Wang Ying Mao Honghao Guan Min Cao Jing Hua Lei Feng Lei Liu | 2019 | Chinese Chemical Letters2019，30，6： | 0 |
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