eLife
·
2025
·
IF 0
Jing Lu,Hao Xu,Dongyue Wang,Yanlu Chen,Takeshi Inoue,Liang Gao,Kai Lei
The intricate coordination of the neural network in planarian growth and regeneration has remained largely unrevealed, partly due to the challenges of imaging the CNS in three dimensions (3D) with high resolution and within a reasonable timeframe. To address this gap in systematic imaging of the CNS in planarians, we adopted high-resolution, nanoscale imaging by combining tissue expansion and tiling light-sheet microscopy, achieving up to fourfold linear expansion. Using an automatic 3D cell segmentation pipeline, we quantitatively profiled neurons and muscle fibers at the single-cell level in over 400 wild-type planarians during homeostasis and regeneration. We validated previous observations of neuronal cell number changes and muscle fiber distribution. We found that the increase in neuron cell number tends to lag behind the rapid expansion of somatic cells during the later phase of homeostasis. By imaging the planarian with up to 120 nm resolution, we also observed distinct muscle distribution patterns at the anterior and posterior poles. Furthermore, we investigated the effects of β-catenin-1 RNAi on muscle fiber distribution at the posterior pole, consistent with changes in anterior-posterior polarity. The glial cells were observed to be close in contact with dorsal-ventral muscle fibers. Finally, we observed disruptions in neural-muscular networks in inr-1 RNAi planarians. These findings provide insights into the detailed structure and potential functions of the neural-muscular system in planarians and highlight the accessibility of our imaging tool in unraveling the biological functions underlying their diverse phenotypes and behaviors.
研究领域:
再生生物学
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神经科学
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显微成像技术
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产品关联
DOI
PubMed
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Liuyang Wang,Pei Guo,Xiaofang Zhang,Yun Duan,Jun Ning,Tao Zhang,Xinling Yang
In moths, sex pheromones are synthesized in pheromone glands (PGs) by a variety of enzymes. Desaturases (DESs) are critical for the introduction of double bonds into pheromones. In Mythimna loreyi, the specific DESs involved in sex pheromone biosynthesis remain unclear. In this study, we identified and characterized 25 putative DESs from the M. loreyi genome. Nineteen of them were expressed in the female PGs, with seven showing significant upregulation in response to pheromone biosynthesis activating neuropeptide (PBAN). RNAi-based knockdown of MlorDES2 significantly reduced the titer of pheromone components by 58.6–85.9%, while knockdown of MlorDES9 specifically reduced the production of (Z)-9-tetradecenyl acetate. Functional verification in yeast revealed that MlorDES2 and MlorDES9 exhibited Δ11 and Δ9 desaturase activities, respectively. Taken together, these results collectively demonstrate that MlorDES2 and MlorDES9 are involved in sex pheromone biosynthesis of M. loreyi, suggesting that DESs could be used as potential targets for pest management.
研究领域:
昆虫学
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分子生物学
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DOI
PubMed
高影响因子
VIROLOGY
·
2023
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IF 3.7
Xiaoping Huang,Xiao Wang,Yaqi Sun,Ling Li,Anna Li,Wentao Xu,Xiaolan Xie,Yong Diao
Because it is safe and has a simple genome, recombinant adeno-associated virus (rAAV) is an extremely appealing vector for delivery in in vivo gene therapy. However, its low transduction efficiency for some cells, limits its further application in the field of gene therapy. Bleomycin is a chemotherapeutic agent approved by the FDA whose effect on rAAV transduction has not been studied. In this study, we systematically investigated the effect of Bleomycin on the second-strand synthesis and used CRISPR/CAS9 and RNAi methods to understand the effects of Bleomycin on rAAV vector transduction, particularly the effect of DNA repair enzymes. The results showed that Bleomycin could promote rAAV2 transduction both in vivo and in vitro. Increased transduction was discovered to be a direct result of decreased cytoplasmic rAAV particle degradation and increased second-strand synthesis. TDP1 , PNKP , and SETMAR are required to repair the DNA damage gap caused by Bleomycin, TDP1, PNKP, and SETMAR promote rAAV second-strand synthesis. Bleomycin induced DNA-PKcs phosphorylation and phosphorylated DNA-PKcs and Artemis promoted second-strand synthesis. The current study identifies an effective method for increasing the capability and scope of in-vivo and in-vitro rAAV applications, which can amplify cell transduction at Bleomycin concentrations. It also supplies information on combining tumor gene therapy with chemotherapy.
研究领域:
分子生物学
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基因治疗
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癌症研究
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药理学
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DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-16
·
IF 15.7
Gao Zhou,Rensing Christopher,Wang Jie,Shen Chenhui,Elzaki Mohammed Esmail Abdalla,Li Xiaoyun,Tan Jinfang,Jiang Xiaoqian
RNA interference is an eco-friendly alternative to chemical pesticides, yet its efficacy in lepidopterans like Spodoptera frugiperda ( S. frugiperda ) is limited by poor uptake. Here, we report on ZIF-8 polydopamine nanoparticles that protect dsRNA against enzymatic degradation and active the endocytic/phagosome pathways for increased uptake. Furthermore, the uptake of nano-enabled dsRNA induces the overgrowth of Serratia marcescens , this reduces the S. frugiperda reactive oxygen species (ROS) immune response, increasing the effects of plant’s natural defenses, further inhibiting Enteroccous mundtii growth. This work shows the synergistic potential of nanoparticles for influencing the gut bacteria to prevent resistance mechanisms and for RNAi delivery for pest management.
研究领域:
昆虫学
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分子生物学
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农业科学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
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IF 9.7
Mingyu Xia,Songsong Zhao,Zhiwei Sun,Yan Shi,Wenhai Lin,Zhiyuan Zhong,Fenghua Meng
Glioblastoma (GBM) is among the most aggressive brain tumors, presenting significant therapeutic challenges due to intrinsic and acquired resistance to treatment, alongside a highly immunosuppressive tumor microenvironment (TME). While temozolomide (TMZ) is the standard chemotherapeutic agent with the ability to penetrate the blood–brain barrier (BBB), its clinical efficacy is often limited. Here, we report a strategy employing Apolipoprotein E (ApoE) peptide-functionalized polymersomes loaded with small interfering RNA (siRNA) targeting signal transducer and activator of transcription 3 (Apstat3) to amplify the anti-GBM effects of TMZ and immunotherapy. Apstat3 demonstrated small, uniform particle sizes, stability in siRNA encapsulation, and effective downregulation of STAT3 and O⁶-methylguanine-DNA methyltransferase (MGMT) in GL261 cells, sensitizing these tumor cells to TMZ. The combinatorial approach not only significantly inhibited GBM cell proliferation, migration and invasion but also improved dendritic cells (DCs) maturation under TME-mimicking environment. In orthotopic GL261 mouse models, intravenous injection of Apstat3 co-administered with oral TMZ resulted in a twofold increase in median survival and reshaped the TME. Notably, combined treatment with anti-CTLA4 therapy tripled median survival to 64 days, achieving complete remission observed in 20 % of the mice. This siSTAT3 delivery strategy holds promise for enhancing GBM treatment outcomes.
研究领域:
肿瘤学
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药剂学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science China-Chemistry
·
2025
·
IF 9.7
Jiang Yifan,Li Lisha,Fang Xiao,Zeng Tao,Su Lichao,Liu Yichang,Wu Ying,Li Jinyu,Lyu Peng,Lu Zhonglei,Lu Chunhua,Yang Huanghao
The development of RNA interference (RNAi) therapy offers a potential solution for Alzheimer’s disease (AD). However, the brain-blood barrier (BBB) with its selective permeability and pharmacokinetic-related challenges poses restrictions on the delivery of small interfering RNA (siRNA) to the central nervous system (CNS). In this study, we demonstrate that the incorporation of 2′-fluoro (2′-F) substitutions and L-carnitine modification facilitates the self-assembly of siRNA through triple interaction, leading to the formation of nanorings, called LCSF-NR. Based on the enhanced cellular uptake and lysosomal escape by 2′-F substitution and the transport across the BBB promoted by L-carnitine, the nanorings realized the improved brain-targeted delivery of siRNA, both in zebrafish and mice models. Moreover, our findings highlight the therapeutic potential of LCSF-NR formulation in an AD zebrafish model through a synergistic effect of downregulating the β-site APP cleavage enzyme 1 (BACE1) gene and L-carnitine-mediated neuroprotection, effectively inhibiting pathological processes. Overall, these results suggest that the chemical modification-based siRNA self-assembly strategy enables trans-BBB delivery and presents a concise approach for synergistic therapy of AD.
研究领域:
分子生物学
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神经科学
·
药物递送系统
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产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2022
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IF 10.723
Tian Wang,Boya Hao,Shilin Xu,Jie Meng,Tao Wen,Jian Liu,Haiyan Xu
RNA interference is a very useful tool for clinical treatment as well as mechanistic studies of leukemia. However, leukemia cells are known as hard-to-transfected by non-virus carriers. The low capacity of endocytosis and lysosomal escape of synthetic carriers are two obstacles for successful RNAi in leukemia cells. In this work, we established a universal powerful strategy for mediating effective RNAi in different types of leukemia cells by sequentially using spermine-modified pullulan (PS) as siRNA carrier and desloratadine (DL) to promote the lysosomal escape. It was shown that the complex of PS and siRNA could be largely internalized by human T-cell acute lymphoblastic leukemia cells, acute myeloid leukemia cells and chronic myeloid leukemia cells in serum-containing media, and the internalized complex was able to escape from the lysosomes by the aid of DL, resulting in effective RNAi against the key genes for the different leukemia cells.
研究领域:
肿瘤学
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分子生物学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Xianglong Tang,Zhen Wang,Yandong Xie,Yuyang Liu,Kun Yang,Taiping Li,Hong Shen,Mengjie Zhao,Juan Jin,Hong Xiao,Hongyi Liu,Ning Gu
Radiotherapy-resistant glioblastoma (rrGBM) remains a significant clinical challenge because of high infiltrative growth characterized by activation of antiapoptotic signal transduction. Herein, we describe an efficiently biodegradable selenium-engineered mesoporous silica nanocapsule, initiated by high-energy X-ray irradiation and employed for at-site RNA interference (RNAi) to inhibit rrGBM invasion and achieve maximum therapeutic benefit. Our radiation-triggered RNAi nanocapsule showed high physiological stability, good blood-brain barrier transcytosis, and potent rrGBM accumulation. An intratumoral RNAi nanocapsule permitted low-dose X-ray radiation-triggered dissociation for cofilin-1 knockdown, inhibiting rrGBM infiltration. More importantly, tumor suppression was further amplified by electron-affinity aminoimidazole products converted from metronidazole polymers under X-ray radiation-exacerbated hypoxia, which sensitized cell apoptosis to ionizing radiation by fixing reactive oxygen species-induced DNA lesions. In vivo experiments confirmed that our RNAi nanocapsule reduced tumor growth and invasion, prolonging survival in an orthotopic rrGBM model. Generally, we present a promising radiosensitizer that would effectively improve rrGBM-patient outcomes with low-dose X-ray irradiation.
研究领域:
纳米技术
·
癌症生物学
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放射生物学
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药学
·
神经肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomedicines
·
2024
·Vol. 12
·期 7
·1505
·
IF 3.9
Qi Zhang,Shuang Wu,Qiubing Chen,Yahong Zhang,Cai Zhang,Runting Yin,Zhen Ouyang,Yuan Wei
The prevalence of excessive drinking-related alcoholic liver disease (ALD) is rising, yet therapeutic options remain limited. High alcohol consumption and consequent oxidative metabolism by cytochrome P450 (CYP) can lead to extremely high levels of reactive oxygen species, which overwhelm cellular defenses and harm hepatocytes. Our previous investigations showed that inhibitingCyp2e1using RNA interference reduced the incidence of ALD. However, compensatory mechanisms other than CYP2E1 contribute to oxidative stress in the liver. Therefore, we coupled triple siRNA lipid nanoparticles (LNPs) targetingCyp2e1with two isoenzymesCyp4a10andCyp4a14to treat ALD mouse models fed with Lieber–Decarli ethanol liquid diet for 12 weeks at the early (1st week), middle (5th week), and late (9th week) stages. The administration of triple siRNA LNPs significantly ameliorated chronic alcoholic liver injury in mice, and early treatment achieved the most profound effects. These effects can be attributed to a reduction in oxidative stress and increased expression of antioxidant genes, includingGsh-Px,Gsh-Rd, andSod1. Moreover, we observed the alleviation of inflammation, evidenced by the downregulation ofIl-1β,Il-6,Tnf-α, andTgf-β, and the prevention of excessive lipid synthesis, evidenced by the restoration of the expression ofSrebp1c,Acc, andFas. Finally, triple siRNA treatment maintained normal metabolism in lipid oxidation. In brief, our research examined the possible targets for clinical intervention in ALD by examining the therapeutic effects of triple siRNA LNPs targetingCyp2e1,Cyp4a10, andCyp4a14. The in vivo knockdown of the three genes in this study is suggested as a promising siRNA therapeutic approach for ALD.
研究领域:
肝病学
·
分子生物学
·
药理学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
OncoTargets and Therapy
·
2023
·
IF 4
Liji Jiang,Gang Xu,Zihuang Li,Xiaowei Zeng,Zhuangling Li,Jingwen Liu,Lin Mei,Xianming Li
Although radiotherapy remains the most powerful as well as the primary treatment modality for nasopharyngeal carcinoma (NPC), approximately 20% of NPC patients still have local recurrence. Carbonic anhydrase IX (CAIX)-related signaling pathways that mediate radioresistance have been found in various kinds of cancer. However, the role of CAIX in NPC radioresistance is still unknown. In this study, we investigated the effect of CAIX silencing on sensitization to ionizing radiation in NPC by using Lipofectamine 2000, which delivers small interfering ribonucleic acid (siRNA) that targets CAIX. Results showed that Lipofectamine 2000 effectively delivered siRNA into the CNE-2 cells, which resulted in the decrease of CAIX expression and cell viability, decrease in cell proliferation and colony formation, and increase in the number of CNE-2 cells stuck in the G2/M phase of the cell cycle upon induction of ionizing radiation. Increased sensitivity of radiotherapy in CNE-2 cells under hypoxic conditions was correlated with the suppression of CAIX. Cells treated with irradiation in addition to CAIX-siRNA1 demonstrated reduced radiobiological parameters (survival fraction at 2 Gy [SF2]) compared with those treated with irradiation only, with a sensitization-enhancing ratio of 1.47. These findings suggest that CAIX can be a promising therapeutic target for the treatment of radioresistant human NPC.
研究领域:
肿瘤学
·
放射生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Science China-Life Sciences
·
2026
·
IF 9.5
Wang Xugang,Zhang Chenxi,Yang Chengjie,Guo Xiaotong,Hu Siyun,Qian Chaonan,Liao Bingrui,Ashraf Usama,Jin Weiwei,Yang Fei,Ouyang Hehao,Liu Yixin,Chen Huanchun,Huang Qiuying,Si Youhui,Zhu Bibo,Cao Shengbo,Ye Jing
Orthoflaviviruses are recognized as significant emerging mosquito-borne pathogens globally. Members of the Japanese encephalitis (JE) serogroup can be distinguished from other orthoflaviviruses by the presence of an additional non-structural protein (NS1’). However, the role of the NS1’ protein in the virus’s life cycle and transmission remains incompletely understood. This study demonstrates that the acquisition of the secretory NS1’ protein from JE serogroup viruses by mosquitoes from infected hosts significantly suppresses the antiviral effect of the RNA interference pathway, thereby facilitating viral infection in mosquitoes. Furthermore, immunization of mice with the NS1’ protein showed considerable efficacy in preventing the transmission of orthoflaviviruses from mice to mosquitoes. These findings indicate that targeting the NS1’ protein may represent a promising strategy for controlling the spread of JE serogroup viruses and other orthoflaviviruses between vertebrate hosts and mosquitoes.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2017
·
IF 8.766
Shuiqin Niu,Ling-Kun Zhang,Li Zhang,Siyi Zhuang,Xiuyu Zhan,Wu-Ya Chen,Shiwei Du,Liang Yin,Rong You,Chu-Hua Li,Yan-Qing Guan
Lewy bodies are considered as the main pathological characteristics of Parkinson's disease (PD). The major component of Lewy bodies is α-synuclein (α-syn). The use of gene therapy that targeting and effectively interfere with the expression of α-syn in neurons has received tremendous attention. In this study, we used magnetic Fe 3 O 4 nanoparticles coated with oleic acid molecules as a nano-carrier. N -isopropylacrylamide derivative (NIPAm-AA) was photo-immobilized onto the oleic acid molecules, and shRNA (short hairpin RNA) was absorbed. The same method was used to absorb nerve growth factor (NGF) to NIPAm-AA to specifically promote neuronal uptake via NGF receptor-mediated endocytosis. Additionally, shRNA plasmid could be released into neurons because of the temperature and pH sensitivity of NIPAm-AA interference with α-syn synthesis. We investigated apoptosis in neurons with abrogated α-syn expression in vitro and in vivo . The results demonstrated that multifunctional superparamagnetic nanoparticles carrying shRNA for α-syn could provide effective repair in a PD model.
研究领域:
神经科学
·
分子生物学
·
纳米技术
·
基因治疗
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）