CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Qiufang Chen,Bin Deng,Qing Luo,Guanbin Song
Cancer stem cells (CSCs), which are resistant to the traditional therapies, have been considered to account for the development, metastasis, and relapse of various malignant tumors, and therefore, must be eliminated to cure cancer. However, they can reside in deep tumor regions away from the blood vessels, and are typically inaccessible owing to the low delivery efficiency and limited tumor penetrating ability of drug carriers. To overcome these problems, we designed a tumor-penetrating peptide (tLyP-1)-conjugated ZIF-90 nanosystem loaded with doxorubicin (DOX) and N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT) to penetrate and eradicate differentiated cancer cells and CSCs simultaneously. The nanosystem exhibited beneficial biocompatibility, enhanced tissue penetration, high blood circulation stability, and pH-responsive drug release for favoring cancer therapy. It was found that the nanosystem could kill both cancer cells and CSCs in vitro . The in vivo results demonstrated that the ZIF-90 nanosystem can effectively accumulate in tumor tissues after long blood circulation and flexibly permeate throughout the tumor tissues. In the HCCLM3 xenograft model, the ZIF-90 nanosystem presented high-efficiency tumor suppression and drastically eradicated the CSCs in the tumor tissues with low systemic toxicity. Overall, the deep tumor-penetrating nanosystem exhibits outstanding potential for improving curative effect.
研究领域:
肿瘤学
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药学
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纳米技术
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生物医学工程
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产品关联
DOI
高影响因子
Theranostics
·
2024
·
IF 12.4
Ke Wang,Xing-Yang Liu,Sui-Feng Liu,Xiao-Xia Wang,Yi-Hua Wei,Jun-Rong Zhu,Jing Liu,Xiu Qin Xu,Lei Wen
Rationale: Adult neurogenesis in the subventricular zone (SVZ) is essential for maintaining neural homeostasis, and its dysregulation contributes to anosmia and delayed tissue healing in neurological disorders, such as Parkinson's disease (PD). Despite intricate regulatory networks identified in SVZ neurogenesis, the molecular mechanisms dynamically maintaining neural stem/progenitor cells (NSPCs) in response to physiological and pathological stimuli remain incompletely elucidated. Methods: We generated an RNA binding motif protein 24 (Rbm24) knockout model to investigate its impact on adult neurogenesis in the SVZ, employing immunofluorescence, immunoblot, electrophysiology, RNA-sequencing, and in vitro experiments. Further investigations utilized a PD mouse model, along with genetic and pharmacological manipulations, to elucidate Rbm24 involvement in PD pathology. Results: Rbm24, a multifaceted post-transcriptional regulator of cellular homeostasis, exhibited broad expression in the SVZ from development to aging. Deletion of Rbm24 significantly impaired NSPC proliferation in the adult SVZ, ultimately resulting in collapsed neurogenesis in the olfactory bulb. Notably, Rbm24 played a specific role in maintaining Notch1 mRNA stability in adult NSPCs. The Rbm24/Notch1 signaling axis was significantly downregulated in the SVZ of PD mice. Remarkably, overexpression of Rbm24 rescued disruption of adult neurogenesis and olfactory dysfunction in PD mice, and these effects were hindered by DAPT, a potent inhibitor of Notch1. Conclusions: Our findings highlight the critical role of the Rbm24/Notch1 signaling axis in regulating adult SVZ neurogenesis under physiological and pathological circumstances. This provides valuable insights into the dynamic regulation of NSPC homeostasis and offers a potential targeted intervention for PD and related neurological disorders.
研究领域:
神经科学
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分子生物学
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神经退行性疾病
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干细胞生物学
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产品关联
DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2023
·Vol. 80
·期 8
·1-19
·
IF 8
Dong Yuechao,Ma Guixing,Hou Xiaoting,Han Yingying,Ding Zhen,Tang Wanze,Chen Litong,Chen Yangshan,Zhou Bo,Rao Feng,Lv Kaosheng,Du Changzheng,Cao Huiling
Kindlin-2 is critical for development and homeostasis of key organs, including skeleton, liver, islet, etc., yet its role in modulating angiogenesis is unknown. Here, we report that sufficient KINDLIN-2 is extremely important for NOTCH-mediated physiological angiogenesis. The expression of KINDLIN-2 in HUVECs is significantly modulated by angiogenic factors such as vascular endothelial growth factor A or tumor necrosis factor α. A strong co-localization of CD31 and Kindlin-2 in tissue sections is demonstrated by immunofluorescence staining. Endothelial-cell-specific Kindlin-2 deletion embryos die on E10.5 due to hemorrhage caused by the impaired physiological angiogenesis. Experiments in vitro show that vascular endothelial growth factor A-induced multiple functions of endothelial cells, including migration, matrix proteolysis, morphogenesis and sprouting, are all strengthened by KINDLIN-2 overexpression and severely impaired in the absence of KINDLIN-2. Mechanistically, we demonstrate that KINDLIN-2 inhibits the release of Notch intracellular domain through binding to and maintaining the integrity of NOTCH1. The impaired angiogenesis and avascular retinas caused by KINDLIN-2 deficiency can be rescued by DAPT, an inhibitor of γ-secretase which releases the intracellular domain from NOTCH1. Moreover, we demonstrate that high glucose stimulated hyperactive angiogenesis by increasing KINDLIN-2 expression could be prevented by KINDLIN-2 knockdown, indicating Kindlin-2 as a potential therapeutic target in treatment of diabetic retinopathy. Our study for the first time demonstrates the significance of Kindlin-2 in determining Notch-mediated angiogenesis during development and highlights Kindlin-2 as the potential therapeutic target in angiogenic diseases, such as diabetic retinopathy.
研究领域:
分子生物学
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细胞生物学
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发育生物学
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血管生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Jiuyan Zhang,Yuan Zhao,Ning Sun,Manyu Song,Yongping Chen,Lin Li,Hailin Cui,Haotian Yang,Chuqiao Wang,Haiyang Zhang,Honggang Fan
Chronic stress induction in immunosuppression and splenocyte apoptosis is commonly associated with increased susceptibility to various diseases. Lycopene (LYC) is a member of the carotenoid family with immune restoration and anti-apoptotic function. However, little is known about the mechanisms underlying the protective roles of LYC against spleen injury induced by chronic stress. Herein, male Wistar rats were undergoing chronic restraint stress and/or administered LYC (10 mg/kg) for 21 days. The effective model establishment was validated by open-field tests and levels of corticosterone in serum. Histopathological staining observation displayed that LYC could reduce chronic stress-induced spleen structure damage. Furthermore, LYC treatment significantly reduced the number of apoptotic-positive splenocytes caused by chronic stress via the death receptor apoptotic pathway. We detected the interleukin 4 and interferon γ levels in serum and spleen to determine the ratio of Th1 and Th2 and found that LYC can alleviate the immunosuppression induced by chronic stress. Notably, western blot and real-time polymerase chain reaction indicated that LYC can reduce the expression of the Notch-pathway-related proteins and mRNA in rats exposed to chronic stress. Further study of the potential mechanisms by adding the Notch pathway inhibitor DAPT revealed that LYC alleviates the structure damage, apoptosis, and immunosuppression caused by chronic stress via the suppression of the Notch pathway. Overall, this study presents a strong rationale to target LYC as a treatment strategy to relieve chronic stress-induced spleen injury.
研究领域:
免疫学
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药理学
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分子生物学
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应激生理学
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产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2024
·Vol. 16
·期 38
·6529-6537
·
IF 2.7
Na Li,Baokun Tang,Tao Zhu
Carbendazim (CBZ) is widely used for crop protection and its residues threaten human health and the environment. Therefore, developing an effective electrocatalyst is important for the extremely sensitive detection of CBZ. Lattice-strain engineering is an effective strategy to change its electronic structure and ultimately optimize the catalytic performance of materials, which can be used as a modification method to improve the detection performance of electrochemical sensors. Herein, a NiFeLDH@HsGY-NH2/MWCNTs heterojunction with strain effect is prepared by the electrostatic self-assembly method. The structure, morphology, composition, crystallinity and electrochemical performance of NiFeLDH@HsGY-NH2/MWCNTs are analyzed using various instrumental techniques, in which geometric phase analysis (GPA) and X-ray diffraction (XRD) images confirm the lattice-strain generated in NiFeLDH@HsGY-NH2/MWCNTs. The results indicate that the prepared electrochemical sensor exhibited an excellent response for carbendazim (CBZ) in the linear range of 0.05–50.00 μM with a detection limit of 10.00 nM (S/N = 3) under the optimal detection conditions. By analyzing the reasons for the improvement of the catalytic performance of the composite material, it is found that the composite of MWCNTs not only improves the conductivity of NiFeLDH but also regulates the electronic structure of metal atoms through double effects. This study provides new insights into the design of efficient and low-cost catalysts to facilitate electrochemical sensor applications.
研究领域:
材料科学
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环境科学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Peipei Li,Jing Kang,Xiaojie Wu,Duo Wang,Yongjun Li,Nan Liang,Rui Du,Minjie Wang,Alideertu Dong,Yuliang Li
Bacterial keratitis (BK) is one of the most threatening ocular diseases, leading to stromal injury, corneal perforation, or even blindness. Avoiding side effect is necessary for efficient BK treatment. Herein, we develop GDY-Ag@AgCl heterojunction catalysts to achieve BK treatment via mild phototherapy strategy. Mild photothermal therapy (PTT) can greatly enhance the generation of ROS produced by photocatalytic therapy (PCT), which can decrease the dosage of photosensitizer, as well as solve the issue of uncontrolled local overheating and the accumulation of PTT agents, minimizing side effects and avoiding secondary injuries. The results demonstrate that lower dosage of PTT/PCT agents, and milder and controlled thermal effect of GDY-Ag@AgCl exhibits excellent inactivation performance against ampicillin-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, this phototherapy strategy not only achieves more effective treatment of BK induced by MRSA with no side effects but also shows a superior ability to alleviate inflammation. This strategy offers a safe and promising theragnostic approach for treating ocular drug-resistant bacterial infections.
研究领域:
眼科学
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光疗
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纳米技术
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传染病
·
耐药性
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Tang Xu,Wenshuai Hao,Ran Du,Dai Dai,Cuixia Wang,Suhua Li,Carol Sze Ki Lin,Ruitao Cha,Jianbin Yan,Chong Li
Plant pathogenic fungi pose a substantial challenge to agricultural production, but the conventional fungicide-based approaches are losing importance. As agents with broad-spectrum antibacterial effects, gold nanoparticles (Au NPs) are found to have antifungal effects; however, no study has examined their application in agriculture as fungicides. Accordingly, this study investigates the activity of 2-mercaptoimidazole-capped Au NPs (MI-Au NPs) against the ‘top’ plant pathogenic fungi, finding that they could inhibit Magnaporthe oryzae, Botrytis cinerea, Fusarium pseudograminearum and Colletotrichum destructivum by inducing cytoplasmic leakage. Moreover, MI-Au NPs are found to protect plants from infection by B. cinerea. Specifically, pot experiments demonstrate that MI-Au NPs decrease the incidence rate of B. cinerea infection in Arabidopsis thaliana from 74.6% to 6.2% and in Solanum lycopersicum from 100% to 10.9%, outperforming those achieved by imazalil. Furthermore, the biosafety assays reveal that MI-Au NPs cannot penetrate the cuticle of plant cells or negatively influence plant growth, and it is safe to mammalian cells. In summary, the findings of this study will support the development of NP-based antifungal agents for use in agriculture.
研究领域:
农业科学
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纳米技术
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植物病理学
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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2026
·
IF 4.8
Haixia Yang,Fanghui Ma,Minghui Yang,Xiaoqing Li
Copper nanoclusters (CuNCs) that display aggregation-induced emission (AIE) properties has promising applications in biosensing areas due to their good optical properties and good biocompatibility. But common AIE inducing strategies such as solvent effects and domain confinement effects lack specificity or require complex design, which limits their practical biosensing applications. To address these issues, this study designed a fluorescent biosensor based on the complexation of CuNCs with adenosine triphosphate (ATP) for the efficient detection of acid phosphatase (ACP). ATP induces CuNCs aggregation through electrostatic interactions and hydrogen bonding, forming a sheet-like assembly structure and triggering the AIE effect, resulting in a significant increase in system fluorescence. In the presence of ACP, ATP is catalytically hydrolyzed to adenosine diphosphate (ADP) and inorganic phosphate, leading to the dissociation of the aggregates and a decrease in fluorescence intensity. This strategy utilizes ATP as a bridge to directly convert enzymatic reactions into changes in fluorescence signals, which is simple to operate and has high sensitivity.
✓ 已验证
产品关联
DOI
高影响因子
CHINESE MEDICAL JOURNAL
·
2025
·
IF 7.3
Li Na,Mao Jingwei,Tang Haiying,Tan Xiaoyan,Bi Jian,Wu Hao,Chen Xiuli,Wang Yingde
Background: Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process. Methods: DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 − T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice. Results: CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 − T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice. Conclusion: The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
研究领域:
免疫学
·
分子生物学
·
医学
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产品关联
DOI
PubMed
高影响因子
POLYMER DEGRADATION AND STABILITY
·
2025
·
IF 7.4
Huimin Chen,Xin Li,Wenjiang Li,Aoao Lu,Chenguang Li,Qiang Li,Dabin Liu,Hongfei Ma,Binbin Wang
The safe long-term storage of nitrocellulose (NC) has become increasingly challenging under extreme environmental conditions due to accelerated NO x release, which promotes self-catalytic decomposition of NC. In this study, Tröger’s base (TB) was integrated into porous organic polymers (POPs) to achieve dual functionality: efficient physical adsorption and stable in-situ chemical fixation of NO x within confined pore spaces. Solid-state CP/MAS 13 C NMR spectroscopy and quantum chemical calculations were employed to confirm that NO x immobilization occurs preferentially at the ortho positions of tertiary amine moieties on aromatic rings. Among the synthesized materials, the polymer resulting from the Trögerization of the Tetrakis (4-aminophenyl) methane (TAPM-TB) was identified as the optimal adsorbent, characterized by accessible ortho-active sites, a microporous structure, and an exceptional NO x uptake capacity of 3.31 mmol/g under standard conditions. Furthermore, TAPM-TB was demonstrated to extend the stability time of NC by 3.23 times in methyl violet tests. These findings highlight a novel strategy for designing materials capable of simultaneous physical adsorption and stable chemical immobilization of NO x or other gases.
研究领域:
材料科学
·
环境化学
·
高分子化学
·
物理化学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Chunxia Pang,Huanhuan You,Sijie Lei,Fan Su,Lili Liang,Zhanguo Li,Xiaoyan Lin,Yaping Zhang,Hao Zhang,Xunhai Pan,Yang Hu
The surface chemical composition of materials is essential for regulating their charge trapping and storage capabilities, which directly affect their electret performance. Although chemical modification of materials to alter electret performance has been investigated, the mechanism through which electret properties are regulated more systematically via chemical customization has not been elucidated in detail. Herein, p -phenylenediamine, benzidine and 4,4′-diaminotriphenyl, which have different conjugated strength functional groups, were selected to chemically tailor the surface of bamboo pulp fibers to regulate the electret properties and elucidate the regulatory mechanism more systematically. The results showed that the charge trapping and storage properties of materials could be regulated by introducing functional groups with different conjugated strengths to their surfaces, realizing the regulation of the electret properties. Moreover, the charge trapping and storage ability could be tailored more specifically by regulating the number of functional groups. By chemical customization to provide electrostatic effects to the materials, the purification time was reduced by approximately 45 %–52 %. More importantly, a relatively systematic mechanism was proposed to elucidate the effect of the conjugate group strength on the charge trapping and charge storage properties of the material. These findings will provide guidance for the investigation of chemical modifications to regulate the electret performance of materials.
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Wenshuai Hao,Ruitao Cha,Mingzheng Wang,Juanjuan Li,Hongbo Guo,Ran Du,Fengshan Zhou,Xingyu Jiang
Intestinal metabolism-related diseases, such as constipation, inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, could be associated with the dysfunction of intestinal mitochondria. The mitochondria of intestinal epithelial cells are of great significance for promoting intestinal motility and maintaining intestinal metabolism. It is necessary for the prophylaxis and therapy of intestinal metabolism-related diseases to improve mitochondrial function. We investigated the effect of 4,6-diamino-2-pyrimidinethiol-modified gold nanoparticles (D-Au NPs) on intestinal mitochondria and studied the regulatory role of D-Au NPs on mitochondria metabolism-related disease. D-Au NPs improved the antioxidation capability of mitochondria, regulated the mitochondrial metabolism, and maintained intestinal cellular homeostasis via the activation of AMPK and regulation of PGC-1α with its downstream signaling (UCP2 and DRP1), enhancing the intestinal mechanical barrier. D-Au NPs improved the intestinal mitochondrial function to intervene in the emergence of constipation, which could help develop drugs to treat and prevent mitochondrial metabolism-related diseases. Our findings provided an in-depth understanding of the mitochondrial effects of Au NPs for improving human intestinal barriers.
研究领域:
纳米技术
·
药理学
·
胃肠病学
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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