CHEMOSPHERE
·
2024
·
IF 8.1
Qiuhui Qian,Qian Pu,Xin Li,XingCheng Liu,Anyu Ni,Xiaowen Han,Zejun Wang,Xuedong Wang,Jin Yan,Huili Wang
Triclosan (TCS), a prevalent contaminant in aquatic ecosystems, has been identified as a potential threat to both aquatic biota and human health. Despite its widespread presence, research into the immunotoxic effects of TCS on aquatic organisms is limited, and the underlying mechanisms driving these effects remain largely unexplored. Herein, we investigated the developmental and immune toxicities of environmentally relevant concentrations of TCS in zebrafish, characterized by morphological anomalies, histopathological impairments, and fluctuations in cytological differentiation and biomarkers following both acute (from 6 to 72/120 hpf) and chronic exposure periods (from 30 to 100 dpf). Specifically, acute exposure to TCS resulted in a significant increase in innate immune cells, contrasted by a marked decrease in T cells. Furthermore, we observed that TCS exposure elicited oxidative stress and a reduction in global m 6 A levels, alongside abnormal expressions within the m 6 A modification enzyme system in zebrafish larvae. Molecular docking studies suggested that mettl3 might be a target molecule for TCS interaction. Intriguingly, the knock-down of mettl3 mirrored the effects of TCS exposure, adversely impacting the growth and development of zebrafish, as well as the differentiation of innate immune cells. These results provide insights into the molecular basis of TCS-induced immunotoxicity through m 6 A-RNA epigenetic modification and aid in assessing its ecological risks, informing strategies for disease prevention linked to environmental contaminants.
研究领域:
水生毒理学
·
分子生物学
·
环境科学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANTI-CANCER DRUGS
·
2023
·Vol. 34
·期 9
·1046
·
IF 2.3
Zhou Qidong,Wu Hao,Miao Fengze,Cao Yirui,Liang Lifei,Huang Jiahua,Qian Zhiyu
Cisplatin-based chemotherapy plays a vital role in the management of muscle-invasive bladder cancer (MIBC); however, off-tumor toxicity and resistance often lead to cancer recurrence and eventual treatment failure. The loss of function of the nucleotide excision repair gene excision repair cross-complementing rodent repair deficiency gene 2 ( ERCC2 ) in cancer cells correlates with sensitivity to cisplatin, while its overexpression causes cisplatin resistance. Small interfering RNA (siRNA) knockdown of ERCC2 combined with cisplatin treatment may improve therapeutic outcomes in patients with bladder cancer. Here, we aimed to develop macrophage-derived mimetic nanovesicles (MNVs) as a nanoplatform for the simultaneous delivery of cisplatin and ERCC2 siRNA for enhancing the efficacy of bladder cancer chemotherapy. The cellular uptake, gene down-regulation, tumor inhibition effects, and biosafety of the synthesized nanodrugs (MNV-Co) as a synergistic therapeutic strategy for MIBC were evaluated in vitro and in vivo . The results indicated high efficacy of MNV-Co against MIBC and low off-tumor toxicity. Furthermore, by down-regulating ERCC2 mRNA and protein levels, MNV-Co improved chemosensitivity, promoted cancer cell apoptosis, and effectively suppressed tumor growth. This study presents a potential approach for delivering cisplatin and ERCC2 siRNA concurrently to treat bladder cancer using a biomimetic nanosystem.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Sensors
·
2025
·
IF 9.1
Yu Luo,Bicheng Zhu,Congcong Zhu,Penghui Lai,John Taylor,Claire Honney,Ashley Nutsford,Chaofeng Ma,Hailong Chen,Kean C. Aw,Rui Wu,Erasmus Smit,Peikai Zhang,Jadranka Travas-Sejdic
Herein, a novel and simple electrospray (ES) printing technique was developed for the fabrication of ultrathin graphene layers with precisely controlled nanometer-scale thickness, where graphene oxide (GO) was electrosprayed on wafers and subsequently chemically reduced into reduced GO (rGO). Utilizing that technique, we prepared ultrathin rGO in-plane graphene field-effect transistor (GFET)-based biosensors coupled with a portable prototype measuring system for point-of-care detection of pathogens. We illustrate the use of such prepared GFETs to detect COVID-19, using the SARS-CoV-2 nucleocapsid protein antigen (N-protein) and genomic viral RNA as detection targets. The electrosprayed and chemically reduced rGO films enhance the molecular detection in GFET sensors through significant local gating effects. The device detects the N-protein from the SARS-CoV-2 Omicron variant in a culture medium with an LOD of 1.44 PFU/mL and in clinical oropharyngeal samples with an LOD of 45 genome copies/mL in 5 min. It also successfully detects viral RNA in oropharyngeal swabs within 10 min. The GFET sensor responses were further analyzed using our proprietary wireless, miniaturized, and portable FET analyzer, coupled with a smartphone detecting app. Altogether, we present low-cost and mass-producible GFETs with high-quality graphene channels, enabling a portable, efficient, and accurate solution for point-of-care pathogen detection and in clinical testing. This technology has the potential to become a crucial tool in preventing future global epidemic outbreaks.
研究领域:
生物传感器
·
医学诊断
·
纳米技术
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Zhihao Zhang,Feng Liu,Xin Lan,Fuhai Wang,Jiahao Sun,Honglong Wei
Objective This study explores the impact of pyroptosis-related genes (PRG) on the prognosis of liver cancer (LC). Methods 421 samples (371 tumor samples and 50 normal samples) from the Cancer Genome Atlas (TCGA) were included in this study. GSE14520 dataset (data of RNA expression and relevant clinicopathological features), GSE125449 dataset (single-cell data in LC) and HCCDB18 dataset (validation on the reliability of the model) were downloaded as appropriate. Download the PRG and its corresponding pathway information from the gene set enrichment analysis (GSEA) website. The consensus clustering was performed by ConsensusClusterPlus package. Differentially expressed genes (DEGs) were identified using limma package, and prognostic features were constructed using un/multivariate and Lasso Cox regression. Pathway enrichment analysis was conducted by ssGSEA method. Receiver Operating Characteristic and the survival analysis were conducted by timeROC and Survminer packages. The Seurat package was used for single-cell RNA sequencing (scRNA-seq) analysis. For cellular validation, following the quantification on the key genes via reverse-transcription quantitative PCR, the Transwell and scratch assays were applied to evaluate the in-vitro invasion and migration of LC cells Huh-7. Results 12 prognosis-related genes were identified to be related to the progression of LC. Three subtypes including C1, C2 and C3 were categorized using the 12 prognosis-related genes and PRGs significantly related to the prognosis of LC patients. The worst and best prognosis was seen in C3 subtype and C2 subtype, respectively. Hallmark pathway enrichment analysis has shown the concurrent immunoactivation and immune escape in C3 subtype. A RiskScore model was constructed using 8 key genes (KPNA2, UCK2, FTCD, CBX2, RAB32, HMMR, S100A9 and ANXA10) from the DEGs of three subtypes. The RiskScore system as an independent prognostic factor dividing the patients into high and low risk groups, and patients of the high-risk group had poor prognosis in both test set and validation set. A nomogram model combining the risk score had the extreme higher benefit. Further, 6 subclusters were identified from scRNA-seq analysis, where the highest PYROPTOSIS score was seen in Monocytic-Macrophages. The quantification on the key genes has suggested the high expressions of KPNA2, UCK2, CBX2, RAB32, HMMR and S100A9 and the low expressions of FTCD and ANXA10 in LC cells Huh-7. Particularly, UCK2 knockdown evidently diminished the number of invaded and migrated LC cells in vitro . Conclusion The risk model associated with pyproptosis is crucial for the tumor immunity of LC and may serve as a prognostic indicator for patients suffering from LC. Our findings will offer new perspectives for immunotherapies targeting LC.
研究领域:
肿瘤学
·
分子生物学
·
生物信息学
·
癌症基因组学
·
细胞免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Dong-xuan Zheng,Qiang Hou,Tao-tao Xue,Xiang Gao,Ruo-yu Geng,Li-mei Wen,Zhi Wang,Qiang Yin,Hai-long Yin,Jun-ping Hu,Jian-hua Yang
Ethnopharmacological relevance Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a crucial component of this disease spectrum. The Yanxiao Di'naer formula (YXDNE) is an Uyghur medical extract that has been used in folk medicine to treat hepatitis for a long time. However, the role and mechanism of action of YXDNE in NASH treatment remains unclear. Objective The objective of this study was to assess the effectiveness of YXDNE in treating NASH induced by injections of carbon tetrachloride combined with a high-fat high-cholesterol diet (HFHCD), and to clarify the underlying mechanisms. Methods The compounds in the YXDNE extract were analysed for classification and proportions using ultra-performance liquid chromatography-mass spectrometry. The efficacy of YXDNE in treating abnormal lipid metabolism was evaluated in L02 cells in vitro . In addition, a C57BL/6 mouse model of NASH was established to evaluate the therapeutic efficacy of YXDNE in vivo . Metabolomics and RNA sequencing were used to analyse the therapeutic effects of YXDNE on the liver. The corresponding signalling pathways were found to target AMPKα1, PPARα, and NF-κB. The efficacy of YXDNE was validated using inhibitors or silencing RNA (siRNA) against AMPKα1 and PPARα. Results This study confirmed that YXDNE treatment ameliorated NASH in a murine model of this disease. Metabolomics analysis suggested that YXDNE efficacy was associated with fatty acid catabolism and AMPK signalling pathways. RNA sequencing results showed that YXDNE efficacy in treating NASH was highly correlated with the AMPK, PPARα and NF-κB pathways. Both in vitro and in vivo experimental data demonstrated that YXDNE affected the expression of p-AMPKα1, PPARα, p–NF–κB, IκB, and p-IκB. The efficacy of YXDNE in treating NASH in vitro was cancelled when AMPK was inhibited with Compound C or PPARα was modulated via siRNA. Conclusions YXDNE may have a therapeutic effect on abnormal lipid metabolism in L02 cells and in a murine model of NASH by affecting the AMPKα1/PPARα/NF-κB signalling pathway. Therefore, YXDNE has the potential for clinical application in the prevention and treatment of NASH.
研究领域:
药理学
·
代谢组学
·
分子生物学
·
民族药理学
·
肝病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2017
·
IF 7.78
Junchun Wang,Jinjin Guo,Junjun Zhang,Wenjuan Zhang,Yuzhong Zhang
C-reactive protein (CRP) is a widely accepted biomarker of cardiovascular disease and inflammation. In this study, a RNA aptamer-based electrochemical sandwich type aptasensor for CRP detection was described using the functionalized silica microspheres as immunoprobes. Silica microspheres (Si MSs), which have good monodispersity and uniform shape, were firstly synthesized. The silica microspheres functionlized with gold nanoparticles (Au NPs) provided large surface area for immobilizing signal molecules (Zinc ions, Zn 2+ ) and antibodies (Ab). RNA aptamers, which were specific recognized to CRP, were assembled on the surface of Au NPs modified electrode via gold-sulfur affinity. In the presence of CRP, a sandwich structure of aptamer-CRP-immunoprobe was formed. Square wave voltammetry (SWV) was employed to record the sensing signal, and a clearly reductive peak corresponding to Zn 2+ at about −1.16 V (vs. SCE) was obtained. Under optimal conditions, the aptasensor showed wide linear range (0.005 ng mL −1 to 125 ng mL −1 ) and low detection limit (0.0017 ng mL −1 at a signal-to-noise ratio of 3). Some possible interfering substance was also investigated, and the results obtained showed that the aptasensor possessed good selectivity . When the aptasensor was applied to real serum samples analysis, the satisfied results were obtained, indicating that the aptasensor possessed potential real application ability.
研究领域:
生物传感器
·
电化学
·
分析化学
·
生物工程
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 45
·32883-32892
·
IF 3.9
Xuehui Pang,Rui Liu,Xiaoyi Lv,Wenjun Lu,Lebin Sun,Qiuyan Wang,Zhen Li,Qing Kang,Jiandong Xie,Yingxin Pang,Feimeng Zhou
A photoelectrochemical (PEC) sensor based on the poly-2,2,5,2-terthiophene (pTTh)/Cu2O heterojunction was constructed and applied for the detection of long non-coding RNA (lncRNA) TROJAN, a biomarker of triple-negative breast cancer. Cu2O and pTTh were electrodeposited in situ and sequentially onto an indium tin oxide substrate. The bandgap of the resultant type II heterojunction was measured spectroscopically and the morphology was found to effectively separate photogenerated holes from electrons. A photocurrent density as high as 250 μA cm−2 was attained, which is about three times higher than those of only pTTh or Cu2O. Owing to the close contact between pTTh and Cu2O, this PEC sensor is highly stable. Oligonucleotide probes for lncRNA can be cross-linked to carboxyl moieties of mercaptopropionic acid molecules adsorbed on pTTh/Cu2O. The desirable band structure and the high density of probe molecules collectively yielded a linear range of 0.1–10 000 pM. Our PEC sensor has been demonstrated to be amenable for detection of lncRNA markers with excellent analytical performance.
研究领域:
材料科学
·
生物化学
·
分析化学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Peihua Lin,Zhouyang Qian,Shanbiao Liu,Xin Ye,Pengpeng Xue,Yangjie Shao,Jing Zhao,Yunan Guan,Zhichao Liu,Yuhua Chen,Qiyue Wang,Zhigao Yi,Mingjian Zhu,Mengfei Yu,Daishun Ling,Fangyuan Li
Conventional bone tissue engineering materials struggle to reinstate physiological bone remodeling in a diabetic context, primarily due to the compromised repolarization of proinflammatory macrophages to anti-inflammatory macrophages. Here, leveraging single-cell RNA sequencing (scRNA-seq) technology, the pivotal role of nitric oxide (NO) and reactive oxygen species (ROS) is unveiled in impeding macrophage repolarization during physiological bone remodeling amidst diabetes. Guided by scRNA-seq analysis, we engineer a multienzymatic bone tissue engineering hydrogel scaffold (MEBTHS) composed is engineered of methylpropenylated gelatin hydrogel integrated with ruthenium nanozymes, possessing both Ru 0 and Ru 4+ components. This design facilitates efficient NO elimination via Ru 0 while simultaneously exhibiting ROS scavenging properties through Ru 4+ . Consequently, MEBTHS orchestrates macrophage reprogramming by neutralizing ROS and reversing NO-mediated mitochondrial metabolism, thereby rejuvenating bone marrow-derived mesenchymal stem cells and endothelial cells within diabetic mandibular defects, producing newly formed bone with quality comparable to that of normal bone. The scRNA-seq guided multienzymatic hydrogel design fosters the restoration of self-regenerative repair, marking a significant advancement in bone tissue engineering.
研究领域:
生物医学工程
·
组织工程
·
分子生物学
·
材料科学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Zhiwen Wang,Yu Li,Borui Zhang,Xiang Gao,Mengru Shi,Sicong Zhang,Shan Zhong,Yang Zheng,Xili Liu
Spray-induced gene silencing (SIGS) represents an attractive avenue for plant protection, but limited uptake efficiency of double-stranded RNA (dsRNA) has restricted its application against the notorious oomycetes, Phytophthora . To control Phytophthora , dsRNAs targeting two essential genes in Phytophthora are screened for their ability to partially decrease Phytophthora capsici ( P. capsici ) infection and fecundity. To further facilitate SIGS for Phytophthora control, functionalized carbon dots (CDs) are complexed with the screened dsRNAs (dsRNA-CDs) through electrostatic interaction. dsRNA-CDs significantly enhanced the control efficacy of dsRNA against Phytophthora infestans , Phytophthora sojae , and both the wild-type and fungicide-resistant P. capsici . The synergism is based on enhancing dsRNA stability and internalization. Dual treatment with dsRNA-CDs and the corresponding fungicide reduced the amount of fungicide required to achieve the same protective effect by 90%. Plant RdRP1 is the main effector in processing various lengths of small RNAs to induce translation inhibition in Phytophthora . Notably, here the first application of a nano-delivery system to improve the effect of SIGS against Phytophthora pathogens is reported. Moreover, the elucidation of how CD facilitates dsRNA internalization in recipient cell and the molecular mechanism of SIGS can benefit the application of dsRNA-CDs in other plant-pathogen pathosystems through improving dsRNA bioactivity and reducing chemical fungicides application.
研究领域:
植物病理学
·
分子生物学
·
纳米技术
·
农业科学
✓ 已验证
DOI
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Tong Yu,Yeqing Wang,Yi Kong,Jianwei Wang,Hong Yun,Yunchao Wang,Fuqiang Hu,Zhongxin Zhu,Hong Yuan
Drug delivery system (DDS) is an important branch of pharmaceutics. Rational modification of the physicochemical properties of DDSs can further improve their targeting efficiency. Herein, a bionic DDS is reported for AKI that is scRNA-seq-guided, custom-designed, and prepared, targeting the Key Cell Subtype for Pathological Progression (KCS-PP) of acute kidney injury (AKI). Specifically, scRNA-seq is utilized to identify a specific renal tubular epithelial cell subtype (PTIs) as the KCS-PP for AKI from numerous cellular subtypes. Additionally, specific cell adhesion molecules (VCAM1 and ICAM1) are identified as the Targeting Drug Delivery Mediators (TDDMs) for PTIs from a list of 1000 marker genes of PTIs. Based on this progress, PTI-targeting bionic DDS, named BRNCs@AMMOs is custom-designed and prepared, and used them for AKI treatment in vitro and in vivo. In vitro, BRNCs@AMMOs shows that its adhesion ability in PTI model cells is 3.2 times that in normal cells. In vivo, 6 h after renal pelvis injection, the MFI of BRNCs@AMMOs-DiI in AKI kidneys is 3.7 times that of sham kidneys. The findings demonstrate that BRNCs@AMMOs exhibits prolonged retention in PTI model cells and AKI kidneys. Overall, the custom-designed and prepared PTI-targeting bionic DDS, may promote the customized design and preparation of DDSs for different diseases and targets, is reported.
研究领域:
药剂学
·
药物递送
·
分子医学
·
纳米技术
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYHEDRON
·
2025
·
IF 2.6
Keliang Wan,Lifeng Tan
Double-stranded RNA determines and regulates many biological processes in cells, plays a vital role in cell information transmission and gene regulation, and is a key target for the treatment of certain diseases. Here, we synthesized and characterized two novel ruthenium(II) complexes [Ru(phen) 2 ( o -CNPIP)] 2+ (Ru 1 ) and [Ru(phen) 2 ( o -CH 3 PIP)] 2+ (Ru 2 , phen = 1,10-phenanthroline, o -CNPIP = (2-(4-cyanodipyrido)-imidazo-[4,5- f ][1,10]-phenanthroline, o -CH 3 PIP = 2-(4-methyl)-imidazo-[4,5- f ][1,10]-phenanthroline). The interaction of the two Ru (II) complexes with double-stranded RNA poly(rA)•poly(rU) under dilute solution and molecular crowding conditions was studied by various spectroscopic methods and viscosity measurements. The results of UV–vis absorption spectroscopy and steady-state emission spectroscopy studies show that Ru 1 showed stronger binding and stabilizing ability to poly(rA)•poly(rU) and the binding affinity of Ru 1 and Ru 2 to poly(rA)•poly(rU) was weakened under molecular crowding conditions. Subsequently, the results of circular dichroism spectroscopy studies, thermal denaturation measurements and viscosity measurements also confirmed the results of our UV–vis absorption spectroscopy and steady-state emission spectroscopy studies. The results also showed that the two Ru(II) complexes bind, stabilize and perturb the structure of poly(rA)•poly(rU) by intercalation under dilute solution and molecular crowding conditions. In addition, it was found that the strength of these abilities was closely related to the binding affinity of the Ru(II) complexes to poly(rA)•poly(rU) by comparing the results of these studies. Furthermore, the thermodynamic parameters for the binding of Ru(II) complexes to poly(rA)•poly(rU) under the two conditions indicate that the binding process is spontaneous, is an enthalpy-driven process, and that hydrogen bonding serves as the dominant force. The purpose of this work is to explore the substituent effect of Ru(II) complexes and the effect of solution environment on the ability of Ru(II) complexes to bind and stabilize poly(rA)•poly(rU). Some insights resulting from this work are expected to facilitate the design of highly selective double-stranded RNA binders based on Ru(II) complexes. Interestingly, the phosphorescence intensity of Ru 2 after binding to poly(rA)•poly(rU) is significantly higher than that of Ru 1 under both solution conditions, with even stronger phosphorescence emission observed under molecular crowding conditions. This indicates that Ru 2 possesses the potential to serve as a nucleic acid luminescent probe for nucleic acid imaging in biological cells. To enhance its luminescent properties and specific binding capacity, further structural modification of Ru 2 is essential, which will be one of the key focuses of our future research efforts.
研究领域:
无机化学
·
生物无机化学
·
核酸化学
·
分子光谱学
·
生物物理化学
✓ 已验证
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Jingyu Cui,Jiafang Piao,Houyu Han,Weipan Peng,Mengyao Lin,Dianming Zhou,Cheng Zhu,Xiaoqun Gong
Circulating microRNAs (miRNAs) have recently emerged as noninvasive disease biomarkers. Quantitative detection of circulating miRNAs could offer significant information for clinical diagnosis due to its significance in the development of biological processes. In response to the current challenges of circulating miRNA detection, we introduce a sensitive, selective, and versatile circulating miRNA detection strategy using terminal deoxynucleotidyl transferase (TdT)-catalyzed RNA-primed DNA polymerization (TCRDP) coupled with semiarbitrary qPCR (SAPCR). Semiarbitrary qPCR was first developed here to detect long fragment targets with only a short-known sequence or to detect a short fragment target after extension with terminal transferase. Besides, the subsequent results show that TdT has a preference for RNA, particularly for extending RNAs with purine-rich and unstructured ends. Consequently, utilizing this assay, we have successfully applied it to the quantitative analysis of circulating miR-122 in animal models, a sensitive and informative biomarker for drug-induced liver injury, and as low as 200 zmol of the target is detected with desirable specificity and sensitivity, indicating that the TCRDP-SAPCR can offer a promising platform for nucleic acids analysis.
研究领域:
分子生物学
·
临床诊断
·
生物技术
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）