ACS Nano
·
2023
·
IF 17.1
Hongwei Liao,Shengfei Yang,Zeyu Liang,Lin Xiao,Shangzhi Xie,Peihua Lin,Fan Xia,Chunyan Fang,Qian Chen,Daishun Ling,Fangyuan Li
Replication stress (RS) induced by DNA damage plays a significant role in conferring the anticancer effects of radiotherapy and is tightly associated with radioresistance of cancer cells. Amplification of RS represents an effective approach to improving the efficacy of radiotherapy, although the development of selective RS amplifiers remains an unexplored frontier. We herein present an RS nano amplifier (RSNA) consisting of a catalytic FePt nanoparticle loaded with the chemotherapeutic doxorubicin (DOX), which selectively exacerbates RS in cancer cells by promoting replication fork (RF) catastrophe. RSNA converts the excessive reactive oxygen species (ROS) in cancer cells into oxygen, enhancing the DNA-damaging effects of radiotherapy to create more template lesions that impede RF progression in coalition with DOX. After radiation, ROS scavenging by RSNA accelerates RF progression through damaged template strands, increasing the frequency of RF collapse into double-strand breaks. Moreover, pretreatment with RSNA accumulates cancer cells in the S phase, exposing more RFs to radiation-induced RS. These effects of RSNA convergently maximize RS in cancer cells, effectively overcoming the radioresistance of cancer cells without affecting normal cells. Our study demonstrates the feasibility of selectively amplifying RS to boost radiotherapy.
研究领域:
肿瘤学
·
纳米技术
·
辐射生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF IMMUNOLOGY
·
2025
·
IF 3.4
Huang Wenji,Wang Yafang,Ji Ning,Xiao Hehe,Chen Kangyong,Guo Jiahong,Feng Jianhua,Mustafa Nageen,Wang Junya,Feng Hao,Zou Jun
A balanced IFN response, tightly regulated at multiple levels, is essential for host defense against viral infection. Tripartite motif-containing (TRIM) proteins are a large group of E3 ubiquitin ligases, and have been shown to be involved in the regulation of IFN response. However, the regulatory functions of individual TRIM proteins remain controversial. Here, we show that a virus-inducible TRIM2 homolog acts as a negative regulator for IFN production in zebrafish. Zebrafish Trim2a was upregulated in response to spring viremia of carp virus (SVCV) infection, and knockout of Trim2a significantly increased the expression of antiviral genes, leading to enhanced resistance to SVCV. Overexpression of Trim2a resulted in pronounced ubiquitination of IFN regulatory factor 3 (IRF3) via K11, K27, K29, and K48, promoting IRF3 degradation and stability of SVCV phosphoprotein to favor viral replication. Moreover, TRIM2a induced ubiquitination of autophagic cargo receptor p62, which then interacted with IRF3, instigating IRF3 degradation. Further, the inhibitory effects of TRIM2a on IFN production were also observed in human HEK293 cells, suggesting that the regulatory functions of TRIM2 are likely to be conserved during evolution. Collectively, our findings demonstrate that TRIM2a is a negative regulator of IFN production, and could serve as a potential target to dampen exacerbated IFN response triggered by aberrant activation of retinoic acid-inducible gene 1 (RIG-I)-like receptors. Our study provides insights into a previously uncharacterized role of TRIM2 in the regulation of IFN signaling.
研究领域:
免疫学
·
病毒学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANTIVIRAL RESEARCH
·
2015
·
IF 3.938
Shaoyang Zhang,Limei Zhong,Bing Chen,Ting Pan,Xue Zhang,Liting Liang,Qianwen Li,Ziying Zhang,Hui Chen,Jie Zhou,Haihua Luo,Hui Zhang,Chuan Bai
HIV-1 Vif protein is one of the most crucial accessory proteins for viral replication. It efficiently counteracts the important host restriction factor APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G, A3G) which is lethal to HIV-1 by causing G to A mutation of viral genome. Vif protein mediates degradation of APOBEC3G via the complicated protein–protein interactions of Vif, APOBEC3G, Elongin C/B and Cullin 5. The importance of Vif–APOBEC3G complex makes it a good potential target to develop new therapeutics of HIV-1. We identified a potent HIV-1 replication inhibitor (ZBMA-1, IC 50 = 1.01 μM) that efficiently protected APOBEC3G protein by targeting Vif–APOBEC3G complex. The co-immunoprecipitation and docking studies indicated that compound ZBMA-1 affected the binding of Elongin C with Vif protein.
研究领域:
病毒学
·
分子生物学
·
药物开发
✓ 已验证
DOI
PubMed
高影响因子
PLANT JOURNAL
·
2018
·Vol. 94
·期 2
·288-303
·
IF 5.775
Jie Qian,Yueyue Chen,Ying Hu,Yingtian Deng,Yang Liu,Gang Li,Wenxuan Zou,Jie Zhao
Summary Replication factor C (RFC) is a conserved eukaryotic complex consisting of RFC1/2/3/4/5. It plays important roles in DNA replication and the cell cycle in yeast and fruit fly. However, it is not very clear how RFC subunits function in higher plants, except for the Arabidopsis ( At ) subunits AtRFC1 and AtRFC3 . In this study, we investigated the functions of AtRFC4 and found that loss of function of AtRFC4 led to an early sporophyte lethality that initiated as early as the elongated zygote stage, all defective embryos arrested at the two- to four-cell embryo proper stage, and the endosperm possessed six to eight free nuclei. Complementation of rfc4-1 /+ with AtRFC4 expression driven through the embryo-specific DD45pro and ABI3pro or the endosperm-specific FIS2pro could not completely restore the defective embryo or endosperm, whereas a combination of these three promoters in rfc4-1 /+ enabled the aborted ovules to develop into viable seeds. This suggests that AtRFC4 functions simultaneously in endosperm and embryo and that the proliferation of endosperm is critical for embryo maturation. Assays of DNA content in rfc4-1 /+ verified that DNA replication was disrupted in endosperm and embryo, resulting in blocked mitosis. Moreover, we observed a decreased proportion of late S-phase and M-phase cells in the rfc4-1 /– FIS 2; DD 45; ABI 3pro::At RFC 4 seedlings, suggesting that incomplete DNA replication triggered cell cycle arrest in cells of the root apical meristem. Therefore, we conclude that AtRFC4 is a crucial gene for DNA replication.
研究领域:
植物学
·
遗传学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Nanomaterials
·
2023
·Vol. 13
·期 2
·346
·
IF 5.3
Wenning Zhao,Fan Lin,Xiuxun Han
The replication of nano-patterns is a significant means of nanomanufacturing. However, there is still a dearth of nano-replication methods that meet the requirements of both high precision and low cost. Therefore, a new strategy to achieve the replication of nano-patterns, namely centrifugal-force-driven nano-replication (CFDNR), is proposed here. An easily obtained centrifugal force which is perpendicular to the plane of a nanostructured template is designed as a driving power, to compel the dynamic polymer to fully fill the space of the template; then, the nano-pattern can be replicated on a polymer film. Anodic aluminum oxide (AAO) templates with nanohole periods of ~450 nm and ~100 nm were employed as the original masters to investigate the nano-replication behaviors. The results of morphology measurements demonstrate excellent precision. The size deviations between the nanohole in the template and the nanopillar on the polymer film are less than 4%. Furthermore, a vacuum-assisted CFDNR scheme is proposed to prevent the formation of cavitation on the polymer replica. This work provides new possibilities and choices for facile, inexpensive and high-precision nanomanufacturing.Keywords:nano-replication;centrifugal force;polymer;anodic aluminum oxide
研究领域:
纳米制造
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED OPTICS
·
2022
·Vol. 61
·期 15
·4558-4566
·
IF 1.905
Jian Jin,Jian Jin,Zhong Wang,Jun Wu,ZhenHua Yu,XiaoBao Cao,XiaoBao Cao,XuDi Wang,XuDi Wang
Polydimethylsiloxane (PDMS) and polyurethane acrylate (PUA) are excellent pattern transfer materials. In this study, PDMS-PUA bi-directional replication technology is explored using the PDMS grating as a template, and relevant technical issues are discussed in detail. Special surface treatment and process optimization are applied to solve the problems of demolding, PDMS polymerization inhibition, and substrate flatness. Further experiments show that the technology can be employed to replicate nanoscale structures and has the potential value of prolonging the longevity of the original template. Additionally, utilizing the advantage of the high elasticity of PDMS materials, two applications of bi-directional replication technology are demonstrated. One is to increase the line-density of the grating by stretching, and the experimental results show that the line-density of the grating increased by 26.6%. The other one is to fabricate the convex grating. Compared with the original planar PDMS grating, the resolution of the first-order diffraction spectrum of the convex grating at the focal point has been greatly improved. Since this technology requires simple equipment, and PDMS and PUA are reusable, it has the advantages of low cost, simplicity, and rapid fabrication. The two application examples also indicate that the technology has good application value.
研究领域:
材料科学
·
纳米技术
·
光学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Xin Peng,Xin Huang,Shaolu Zhang,Naixin Zhang,Shengfan Huang,Yingying Wang,Zhenxing Zhong,Shan Zhu,Haiwang Gao,Zixiang Yu,Xiaotong Yan,Zhennan Tao,Yuxiang Dai,Zhe Zhang,Xi Chen,Feng Wang,Francois X. Claret,Moshe Elkabets,Ning Ji,Yuxu Zhong,Dexin Kong
PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair. Through in vitro experiments using established GBM cell lines and patient-derived primary GBM cells, as well as in vivo orthotopic transplantation tumor experiments in zebrafish and nude mice, it is demonstrated that the concurrent administration of PARPi and BETi can synergistically inhibit GBM. Intriguingly, it is observed that DNA damage lingers after discontinuation of PARPi monotherapy, implying that sequential administration of PARPi followed by BETi can maintain antitumor efficacy while reducing toxicity. In GBM cells with elevated baseline replication stress, the sequential regimen exhibits comparable efficacy to concurrent treatment, protecting normal glial cells with lower baseline replication stress from DNA toxicity and subsequent death. This study provides compelling preclinical evidence supporting the development of innovative drug administration strategies focusing on PARPi for GBM therapy.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-10
·
IF 5.228
Huang Wuren,Zhang Jie,Yang Bing,Beerntsen Brenda T.,Song Hongsheng,Ling Erjun
Invertebrate animals have the capacity of repairing wounds in the skin and gut via different mechanisms. Gastrointestinal perforation, a hole in the human gastrointestinal system, is a serious condition and surgery is necessary to repair the perforation to prevent an abdominal abscess or sepsis. Here we report the repair of gastrointestinal perforation made by a needle-puncture wound in the silkworm larval midgut. Following insect gut perforation, only a weak immune response was observed because the growth of Escherichia coli alone was partially inhibited by plasma collected at 6 h after needle puncture of the larval midgut. However, circulating hemocytes did aggregate over the needle-puncture wound to form a scab. While, cell division and apoptosis were not observed at the wound site, the needle puncture significantly enhanced DNA duplication in cells surrounding the wound, which was essential to repair the midgut perforation. Due to the repair capacity and limited immune response caused by needle puncture to the midgut, this approach was successfully used for the injection of small compounds (ethanol in this study) into the insect midgut. Consequently, this needle-puncture wounding of the insect gut can be developed for screening compounds for use as gut chemotherapeutics in the future.
研究领域:
昆虫学
·
医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICAL VIROLOGY
·
2022
·Vol. 94
·期 6
·2519-2527
·
IF 20.693
Lu Lv,Haoran Cui,Zhiyang Chen,Yixuan Zhou,Leiliang Zhang
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus affecting human health globally. G-quadruplex secondary structures attract great attention as potential targets for antiviral strategy. In this study, we show that the CHIKV genome possesses several conserved potential G-quadruplex sequences. G-quadruplex ligands BRACO-19 and TMPyP4 could stabilize the CHIKV G-quadruplex and inhibit the transcription of constructs containing CHIKV G-quadruplex sequences. Importantly, BRACO-19 and TMPyP4 suppress CHIKV replication. Our study not only reinforces the presence of viral G-quadruplex sequences but also suggests that targeting G-quadruplex structure could represent a novel strategy to inhibit CHIKV. Highlights CHIKV possesses conserved G-quadruplexes G-quadruplex ligands stabilize CHIKV G-quadruplexes with high affinities G-quadruplex structures reduce the transcription of the GFP reporter gene containing CHIKV G-quadruplex G-quadruplex ligands BRACO-19 and TMPyP4 inhibit CHIKV replication
研究领域:
病毒学
·
分子生物学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 9
·5478-5486
·
IF 3.119
Xiawei Yun,Zhiyuan Xiong,Yaning He,Xiaogong Wang
In this work, reduced graphene oxide (RGO) was used as a material to fabricate superhydrophobic lotus-leaf-like surfaces through soft-lithographic duplication. In the process, a polydimethylsiloxane (PDMS) stamp was prepared by replica molding against the surfaces of fresh lotus leaves that functioned as masters. A dispersion of octadecylamine-modified reduced graphene oxide (ODA-RGO) in tetrahydrofuran (THF) was used as “ink”. The lotus-leaf-like surfaces were fabricated by microcontact printing on the solid substrates. The results showed that due to the good processibility of the ODA-RGO dispersion, the printed layers display papillary micro/nano-structures with high fidelity to the surfaces of lotus leaves. The RGO-based lotus-leaf-like surfaces possess superhydrophobic characteristics with a water contact angle larger than 160° and the contact angle hysteresis less than 5°. Due to the excellent chemical stability of the RGO sheets, as-prepared surfaces show remarkable superhydrophobic stability. The lotus-leaf-like surfaces maintain the superhydrophobicity after heating treatment at 150 °C for 24 h or being exposed to corrosive solutions with different pH values for 12 h. The present findings prove that the RGO-based material is an ideal candidate for fabrication of environment-durable lotus-leaf-like surfaces, which can be expected to have applications in different areas.
研究领域:
材料科学
·
表面工程学
✓ 已验证
DOI
PubMed
高影响因子
VIROLOGY
·
2024
·
IF 2.8
Ping Yang,Zheng-Jian Wang,Hai-Tao Lu,Xu-Meng Feng,Jing-Long Ye,Guangchuan Wang,Cheng-Feng Qin,Qing Ye,Zhong-Yu Liu
The knowledge on the life cycle of flaviviruses is still incomplete, and no direct-acting antivirals against their infections are clinically available. Herein, by screening via a Zika virus (ZIKV) replicon assay, we found that the N-terminus of NS2A exhibited great tolerance to the insertions of different split fluorescent proteins (split-FPs). Furthermore, both ZIKV and dengue virus encoding a split-FP-tagged NS2A propagated efficiently, and the split-FP-tagged ZIKVs had good genetic stability. Robust green fluorescence was observed in the reporter cell lines infected with these viruses and the fluorescence responded to anti-flavivirus chemicals with high specificity and sensitivity. Moreover, the sites of viral RNA replication were illuminated in live cells. Interestingly, by blocking viral RNA synthesis with an NS5 inhibitor, we found a correlation between the morphological characteristics of potential replication organelles and RNA amplification, highlighting that the NS2A-tagged viruses are of great value for the in-depth understanding of flavivirus replication mechanisms.
研究领域:
病毒学
·
分子生物学
·
药物研发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Xin Zhao,Wenji Huang,Yanjie Shi,Jiahong Guo,Hehe Xiao,Ning Ji,Jianhua Feng,Huifeng Dang,Jun Zou
PLAAT1 is a member of the PLAAT protein family and plays important roles in tumor suppression, transglutaminase activation and peroxisomal biogenesis. Recently, PLAAT1 has been shown to promote degradation of p53 protein and cellular organelles such as mitochondria, endoplasmic reticulum and lysosome. In this study, we show that PLAAT1 inhibits the production of type I interferon and promotes virus replication in zebrafish. Overexpression of Plaat1 in zebrafish cells suppresses antiviral responses and promotes virus replication. Mechanistically, PLAAT1 interacts with IRF3 and IRF7 to initiate degradation of IRF3 and IRF7, which can be attenuated by 3-methyladenine, an inhibitor of autophagosome. Our study provides novel insights into the functions of PLAAT1 in host immune response to viral infection.
研究领域:
免疫学
·
病毒学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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