JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
·
2022
·Vol. 78
·期 4
·777-791
·
IF 5.08
Li Ling,Bai Yu,Du Runyu,Tang Lei,Li Ling
Gestational diabetes mellitus (GDM) is a common pregnancy complication with a high incidence in women. Orphan nuclear receptor NUR77 is involved in regulating glucose metabolism. However, its role in GDM has not been fully elucidated yet. In this study, an animal model of GDM was established by feeding mice with a high-fat diet (HFD) before and during pregnancy. NUR77 expression was abnormally upregulated in placenta tissues of GDM mice. We performed gain- and loss-of-function studies of NUR77 in HTR-8/SVneo cells. Cells were incubated with 1 × 10 −6 M insulin for 48 h to induce insulin resistance (IR). The expression of NUR77 was downregulated in HTR-8/SVneo cells following IR induction. Overexpression of NUR77 promoted cell proliferation, migration, and invasion. Notably, NUR77 promoted glucose uptake and enhanced insulin sensitivity in vitro. NUR77 increased the ratio of p-insulin receptor β (IRβ) Tyr1361 /IRβ, p-insulin receptor substrate (IRS)-1 Tyr612 /IRS-1, p-Akt/Akt and decreased p-IRS-1 Ser307 /IRS-1, as well as lowered the expression of glucose transport protein type 1 (GLUT1) and elevated GLUT4. These results suggest the involvement of IRβ/IRS/Akt/GLUT4 signaling activation in the regulatory effects of NUR77 on IR in HTR-8/SVneo cells. Silencing of NUR77 displayed opposite effects. Besides, NUR77 enhanced the expression of autophagy-related protein Beclin 1 and the ratio of LC3II/LC3I. Further study demonstrated that the inhibitory effect of NUR77 on IR was partially attributed to the activation of autophagy. Therefore, we demonstrate that NUR77 enhances insulin sensitivity in HTR-8/SVneo cells likely through activating IRβ/IRS/Akt/GLUT4 pathway and regulating autophagy.
研究领域:
内分泌学
·
妇产科学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
EMBO Molecular Medicine
·
2025
·Vol. 18
·期 1
·275
·
IF 8.3
Huanhuan Gao,Yuecheng Zhan,Yuanqi Liu,Zhiyi Zhu,Yuxiu Zheng,Liqin Qian,Zhangzhi Xue,Honghan Cheng,Zongxiang Nie,Weigang Ge,Senlin Ruan,Jiaxu Liu,Jikai Zhang,Yingying Sun,Lei Zhou,Dongyue Xun,Yingrui Wang,Heyun Xu,Huiwen Miao,Yi Zhu,Tiannan Guo
Circulating blood proteomics enables minimally invasive biomarker discovery. Nanoparticle-based circulating plasma proteomics studies have reported varying number of proteins (ca 2000–7000), but it remains unclear whether a higher protein number is more informative. Here, we first develop OmniProt—a silica-nanoparticle workflow optimized through a systematic evaluation of nanoparticle types and protein corona formation parameters. Next, we present an Astral spectral library for 10,109 protein groups. Using the Astral with 60 sample-per-day throughput, OmniProt identifies ca 3000 to 6000 protein groups from human plasma. Platelet/erythrocyte/coagulation-related contamination artificially inflates protein identifications and compromises quantification accuracy in nanoparticle-enriched samples. Through controlled contamination experiments, we identified biomarkers for platelet/erythrocyte/coagulation-related contamination in nanoparticle-based plasma proteomics. We developed open-access software Baize for contamination assessment. We validated the pipeline in 193 patients with CT-indistinct benign nodules or early-stage lung cancers, flagging five contaminated samples. This study reveals that contamination alters protein identification/quantification in nanoparticle-based plasma proteomics and presents Baize software to evaluate it. In mass spectrometry-based plasma proteomics, blood platelet and erythrocyte contamination artificially inflates protein identification and compromises quantification. An open-source software, Baize, is developed to systematically evaluate this critical issue. In mass spectrometry-based plasma proteomics with nanoparticle enrichment, blood platelet and erythrocyte contamination artificially inflates protein identification and compromises quantification. The open-source software Baize is developed to systematically evaluate this critical issue.
研究领域:
蛋白质组学
·
临床蛋白质组学
·
纳米技术
·
生物医学工程
·
质谱分析
·
癌症生物标志物
·
液体活检
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·
IF 15.7
Yinglan Yu,Yongfeng Xu,Zehui Yu,Xinrui Liu,Jiayue Guo,Min Xiang,Junmeng Chen,Riyanto Teguh Widodo,Lei Luo
Oral antibiotics are a mainstay for treating bacterial infections, but unabsorbed portions can reach the caecum and colon, leading to gut dysbiosis. Herein, we engineer a biohybrid delivery system through the integration of milk extracellular vesicles with liposomes. The hybrid vesicles employ targeting mechanisms via neonatal Fc receptor and peptide transporter 1, facilitating antibiotic transport across the proximal small intestine. These vesicles exhibit superior drug encapsulation efficiency, stable release behavior, efficient mucus traversal, higher endocytosis, increased basolateral exocytosis, and improved oral absorption, achieving a 3.24-fold increase in oral bioavailability compared to free antibiotics. In lung bacterial infections and bacteremia models, hybrid vesicle-encapsulated cefdinir outperforms free antibiotics in eliminating infections. Notably, this approach also mitigates adverse effects on the intestinal microbiota, safeguarding the animals from dysbiosis-associated metabolic syndromes and opportunistic pathogen infections. This innovative hybrid vesicle system holds promise for the oral delivery of other drugs that suffer from limited absorption or cause gut dysbiosis. In this work, authors present a biohybrid delivery system aimed at overcoming low oral bioavailability and antibiotic-induced dysbiosis by enabling efficient antibiotic transport in the proximal small intestine.
研究领域:
药学
·
药物递送
·
纳米医学
·
微生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Clinical Epigenetics
·
2025
·Vol. 18
·期 1
·12
·
IF 4.4
Yu Chao,Yao Liyuan,Du Xinyu,Yu Jianjun,Wang Yanjin,Hou Xiying,Shen Fengchen,Liu Na,Zhuang Shougang
Background Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase that catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3), has been implicated in promoting renal fibrogenesis. Nevertheless, its precise role and underlying mechanisms remain incompletely defined. Methods To investigate the role of EZH2 in partial epithelial-mesenchymal transition (pEMT) and renal fibrosis, we utilized a mouse model with renal tubular cell-specific EZH2 deletion and administered gambogic acid (GA), a selective EZH2 degrader, following unilateral ureteral obstruction (UUO). In vitro, mouse renal epithelial cells were stimulated with TGF-β1 and treated with either EZH2-specific siRNA or GA to assess the effects on EMT and Notch1/3 signaling. In addition, chromatin immunoprecipitation (ChIP) assays were conducted to evaluate the binding of EZH2 and H3K27me3 to the promoters of Notch1 and Notch3. Results Compared with wild-type controls, mice with tubular cell-specific EZH2 deletion exhibited significantly reduced renal fibrosis, characterized by decreased expression of fibronectin, collagen III, vimentin, and Snail, while preserving E-cadherin levels in injured kidneys. Pharmacological degradation of EZH2 with GA produced comparable antifibrotic effects. UUO injury markedly upregulated Notch1, Notch3, the Notch intracellular domain, Hes1, Hey2, and Jagged-1; these increases were significantly suppressed by either EZH2 deletion or GA treatment. Similarly, in vitro, GA or EZH2-specific siRNA inhibited the expression of Notch signaling molecules in TGF-β1–treated renal epithelial cells. Chromatin immunoprecipitation analyses revealed direct binding of EZH2 and H3K27me3 to the Notch1 and Notch3 promoters. UUO injury enhanced EZH2 binding while reducing H3K27me3 enrichment at these sites, effects reversed by GA treatment. Conclusions These findings demonstrate that epithelial EZH2 contributes to pEMT in renal tubular cells and promotes renal fibrosis, at least in part through activation of Notch signaling. Targeting EZH2 may hold potential as a therapeutic approach for chronic kidney disease.
研究领域:
肾脏病学
·
分子生物学
·
表观遗传学
·
信号转导
·
纤维化研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 24
·期 1
·113
·
IF 12.6
Guan Shujuan,Yang Ruyue,Deng Danning,Long Huilin,Ou Zihao,Ge Xiaoxue,Jiang Xiujuan,Hu Xiumei,Chen Dingqiang
Bloodstream infections (BSIs) are life-threatening conditions with rising mortality, urgently requiring rapid pathogen identification to guide timely antibiotic therapy. Current methods (phenotypic identification, MALDI-TOF MS, molecular techniques) are faced with limitations in cost, turnaround time and accessibility. In this study, it was discovered that the drying of microbial suspensions on slides could lead to species-specific desiccation patterns, which reflects the physicochemical properties and complex interactions of microorganisms during evaporation. Inspired by this interesting phenomenon, an AI-powered platform is proposed for rapid pathogen identification through automated analysis of these patterns. By establishing an image dataset comprising 10,055 desiccation patterns of common BSIs pathogens ( Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecium and Candida albicans ), a ResNet-34 deep learning model is trained, achieving a classification accuracy of 91.8% and an area under the receiver operating characteristic curve (AUC-ROC) of 0.99. Following pure culture, identification is completed within 5 min after a simple drying step at 40 °C. With its minimal sample requirement, low cost, and operational simplicity, this platform demonstrates significant potential as a point-of-care diagnostic tool, particularly in resource-constrained regions. This technology offers a promising strategy to combat BSIs and improve patient outcomes. Graphical
研究领域:
微生物学
·
医疗人工智能
·
诊断医学
·
生物物理学
·
即时检测
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD SCIENCE AND BIOTECHNOLOGY
·
2025
·
IF 3.1
Park Chan-Hyeok,Ganbat Chinbat,Han Jung-Ah
Orally disintegrating films (ODFs) were prepared from five natural polymers—starch (STA), hyaluronic acid (HA), pectin (PEC), chitosan (CHI), and gelatin (GEL)—using literature‑based, polymer‑specific protocols. All films were cast to a uniform thickness of 1.00 ± 0.01 mm and then evaluated for physicochemical, mechanical, and dissolution properties, alongside a sensory assessment. STA, PEC, and CHI required glycerol as a plasticizer and consequently showed higher moisture contents, whereas GEL and HA formed stable films without plasticizers and exhibited higher tensile strength (51.70 and 76.77 MPa). STA displayed the highest opacity, moisture content (25.44%), and water‑vapor permeability (6.63 g·mm·m -2 ·h -1 ·kPa -1 ), indicating lower storage stability. Vitamin C release was fastest from PEC and GEL and slowest from HA; STA and CHI showed marked pH‑dependent dissolution. Sensory results mirrored instrumental trends: PEC was most preferred for rapid intraoral disintegration, whereas CHI was least favored. Overall, hydrocolloid selection governed water management, disintegration, and release profiles, directly linking material design with consumer‑relevant performance and offering guidance for polymer choice in functional‑food ODFs.
研究领域:
食品科学与技术
·
药用材料
·
高分子科学
·
感官科学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Cell Death & Disease
·
2025
·
IF 9.6
Huang Hongli,Chai Yihan,Wu Xuewei,Wang Sen,Li Binglin,Wang Yanyan,Zheng Wen,Wu Yuefeng,Meng Di,Wang Hua,Tu Zhengliang,Du Chengli,Lyu Xiayi,Li Guiying,Guo Wei
Non-genetic resistance of cancer remains poorly understood in clinical research and practice. To better understand resistant cancer cell heterogeneity, we isolated a novel riboflavin + NOTCH1 + population from cisplatin-naïve and -resistant lung cancer cell lines and patient specimens with or without immunotherapy and chemotherapy. This population was also identified as SLC52A2 (one of the riboflavin transporters) + NOTCH1 + cells in single-cell RNA sequencing (scRNA-seq) data derived from advanced lung tumors before therapy. Despite its therapy-naïve origin, the population, designated as stably resistant cancer cells (SRCC), exhibited the epithelial state, innate and stable resistance to therapy (chemotherapy, targeted therapy and immunotherapy), cell dormancy, elevated reactive oxygen species (ROS), and anti-apoptotic and anti-ferroptotic survival. These cellular and molecular characteristics distinguished SRCC from other resistant populations, including cancer stem-like cells (CSC), epithelial-mesenchymal transition (EMT) cells, and drug-tolerant persisters (DTP). The non-canonical NOTCH1 pathway, but not the inactivated canonical NOTCH1 pathway, played a critical role in the resistance of SRCC. Specifically, it modulates cell cycle, iron metabolism, EMT, and ferroptosis vulnerability in SRCC at the transcriptional level. It also controls the initiation of ferroptosis in lysosomes via a posttranslational NOTCH1-AKT-BAX axis. Inhibition of the non-canonical NOTCH1 pathway re-sensitizes these dormant and resistant cells to cisplatin-induced cell death in vitro and in vivo, including ferroptosis, apoptosis, and necroptosis. Our study contributes to a deeper understanding of cancer resistance and promotes the development of more effective therapeutic strategies against resistant cancer cells.
研究领域:
肿瘤学
·
分子生物学
·
癌症生物学
·
细胞信号转导
·
药物耐药性
·
铁死亡研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2025
·Vol. 30
·期 1
·1275
·
IF 3.4
Xu Long,Zhao Yuanyuan,Song Shuxi,Liu Junling,Li Jingyu,Zheng Zhendong
Background Lung adenocarcinoma (LUAD) is a major cause of cancer-related morbidity and mortality globally, with challenges in prognosis and treatment due to its complex pathogenesis and heterogeneous tumor microenvironment (TME). Neutrophil extracellular traps (NETs) and oxidative stress play critical roles in tumor progression: NETs promote tumor cell adhesion, migration, and immune suppression, while oxidative stress induces DNA damage and activates pro-tumor signaling pathways. Moreover, oxidative stress is an important inducer of NETs, and their crosstalk shapes the LUAD immune microenvironment. However, systematic exploration of LUAD immunotherapeutic response prediction based on NETs and oxidative stress-related genes remains lacking. Methods The gene set related to oxidative stress was obtained from MSigDB. The gene set related to NETs was sourced from relevant literature. Transcriptomic and clinical data were integrated from The Cancer Genome Atlas (TCGA)-LUAD (training set) and GSE31210 (validation set). Weighted Gene Co-Expression Network Analysis (WGCNA) was employed to screen gene modules and characteristic scores related to NETs and oxidative stress signatures. Differentially expressed genes (DEGs) were screened, and prognostic model was established using univariate and LASSO Cox regression. Immune infiltration was analyzed using ESTIMATE algorithm, MCP-counter and ssGSEA methods. And we developed a nomogram incorporating clinicopathological features and RiskScore model, and performed drug sensitivity analysis. Finally, the biological role of CPS1 in lung cancer cells was investigated through CCK-8, wound-healing, and Transwell experiments. Results 22 co-expression modules were screened, among which the brown module showed significant correlations with NETs and oxidative stress signature scores. This module was intersected with DEGs, yielding 624 overlapping genes implicated in immune-relevant pathways (like leukocyte differentiation, neutrophil activation involved in immune response). A prognostic model was established utilizing 8 key genes ( ADGRE3 , ARHGEF3 , CD79A , CLEC7A , CPS1 , EPHB2 , LARGE2 , and OAS3 ). In the TCGA database, the model demonstrated robust prognostic discrimination (area under the curve (AUC) > 0.6), with high-risk patients exhibiting shorter overall survival (OS) ( p < 0.05). Its stability was validated in GSE31210 (AUC > 0.6). The RiskScore showed negative correlations with immune infiltration (like T cells, CD8 T cells, and natural killer cells) as well as immune/stromal scores. A nomogram model combining RiskScore with N staging was developed and validated, demonstrating strong predictive accuracy through calibration and decision curve analyses. High-risk patients were more sensitive to drugs like BI-2536, BMS-509744, and Pyrimethamine. Finally, in vitro tests showed that CPS1 knockdown markedly decreased the viability, migration, and invasion of lung cancer cells. Conclusion The constructed prognostic model by NETs and oxidative stress-relevant genes effectively predicts LUAD prognosis, correlates with immune microenvironment characteristics, and guides drug sensitivity, providing novel insights for LUAD prognostic assessment and personalized therapy.
研究领域:
肿瘤学
·
分子生物学
·
免疫学
·
生物信息学
·
转化医学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·11509
·
IF 15.7
Chen Yigang,Ji Xiang,Zhang Ziyue,Zhu Zihao,Zhou Yuming,Su Chang,Lin Yang-Chi-Dung,Huang Hsi-Yuan,Wei Kangping,Lai Yi,Chen Ke,Lin Xingqiao,Zhang Yangyi,Fu Jiehui,Huang Yixian,Cui Shidong,Yen Shih-Chung,Zhang Tao,Warshel Arieh,Huang Hsien-Da
Deep learning-based drug-target interaction (DTI) prediction methods have demonstrated strong performance; however, real-world applicability remains constrained by limited data diversity and modeling complexity. To address these challenges, we propose SCOPE-DTI, a unified framework combining a large-scale, balanced semi-inductive human DTI dataset with advanced deep learning modeling. SCOPE-DTI is constructed from 13 public repositories and expands data volume by up to 100-fold compared to common benchmarks such as the Human dataset. The SCOPE model integrates three-dimensional protein and compound representations, graph neural networks, and bilinear attention mechanisms to effectively capture cross domain interaction patterns and outperform state-of-the-art methods across various DTI prediction tasks. Additionally, SCOPE-DTI provides a user-friendly interface and database. We further demonstrate its effectiveness by experimentally identifying anticancer targets of two bioactive natural compounds. By offering comprehensive data, advanced modeling, and accessible tools, SCOPE-DTI accelerates drug discovery research.
研究领域:
生物信息学
·
计算生物学
·
药物发现
·
机器学习
·
结构生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 17
·期 1
·88
·
IF 15.7
Zhang Peng,Chen Dinghao,Fang Yu,Li Sangshuang,Zhou Ziao,Lu Huanfen,Cheng Jianjun,Wang Huaimin
Osteoporosis therapies remain limited by non-specific osteoclast inhibition, which disrupts physiological bone remodeling and increases fracture risk. Here we show that selectively targeting mature osteoclasts via enzyme-responsive nanoparticles could eliminate pathological bone resorption while generating apoptotic bodies (ABs) to promote regeneration. We design OsteoSAVE, a peptide-based nanoparticle integrating a cathepsin K (CTSK)-cleavable linker, a bone-targeting motif, and a self-assembling biphenyl core. Upon CTSK-mediated hydrolysis, OsteoSAVE transforms into nanofibers within osteoclast lysosomes, inducing apoptosis and releasing ABs enriched with PDGF-BB. Mechanistic studies confirm CTSK-selective cleavage and charge-driven cellular specificity. In ovariectomized mice, OsteoSAVE restores bone density by coupling osteoclast elimination with ABs-mediated osteogenesis via PI3K/AKT activation in mesenchymal stem cells. This work establishes enzyme-triggered supramolecular self-assembly as a paradigm for dual-action therapies that recalibrate bone homeostasis without disrupting physiological processes.
研究领域:
骨骼生物学
·
纳米医学
·
再生医学
·
分子治疗学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMER BULLETIN
·
2025
·Vol. 83
·期 1
·31
·
IF 4
Huang Ruoxi,Yi Yaxin,Zhang Shiyu,Wang Jiaxin,Yuan Haikuan,Lu Jie
A stimulus-responsive drug delivery system holds promise for reducing adverse effects and enhancing the bioavailability of chemotherapeutic agents. In this study, amino-terminated dextran was utilized as a macromolecular initiator to prepare a range of amphiphilic dextran-b-poly(ε-benzyloxycarbonyl- l -lysine) (Dex-b-PZLL) copolymers with varying hydrophobic segment lengths via ring-opening polymerization (ROP). Folic acid (FA) was further grafted onto the dextran side chains via esterification (FA-Dex-b-PZLL), offering the potential tumor-specific recognition. The resulting copolymers were able to self-assemble into stable spherical micelles via dialysis and efficiently encapsulated the hydrophobic drug letrozole (LTZ). A systematic assessment was conducted on the drug encapsulation efficiency/loading capacity, drug release performance in vitro, and biocompatibility of the copolymers under aqueous conditions, indicating that these properties of the FA-Dex-b-PZLL micelles mainly depended on the copolymer composition. The optimized micelles, with a balanced hydrophilic/hydrophobic ratio, achieved a drug loading capacity with approximately 8.49% and an encapsulation efficiency with about 46.39%. Moreover, LTZ/FA-Dex-b-PZLL micelles exhibited pH-responsive release, with cumulative release rates within 72 h of 20.74%, 27.14% and 62.96% in phosphate buffer at pH 7.4, 6.5 and 4.5, respectively, indicating the accelerated release under acidic conditions. In addition, the micelles showed good cytocompatibility according to the CCK-8 assay. Graphical abstract
✓ 已验证
产品关联
DOI
高影响因子
MICROCHIMICA ACTA
·
2025
·Vol. 193
·期 1
·31
·
IF 5.3
Zhang Yukai,Yang Mo,Liu Juan
A novel artificial mineralized bioprobe was developed through a templated strategy, enabling highly sensitive and rapid detection of neuron-specific enolase (NSE) in serum samples. This probe was based on a nitrogen-doped carbon porous hollow shell as a carrier, loaded with Fe-Cu nanoparticles exhibiting highly efficient peroxidase-like activity. The Fe-Cu nanoparticles demonstrated outstanding catalytic decomposition of hydrogen peroxide, while the unique porous structure provided an ideal confined space for immobilizing the native enzyme. The acidic microenvironment generated by the enzymatic products of anchored glucose oxidase activates adjacent Fe-Cu bimetallic nanozymes, enabling cascade catalytic reactions under near-neutral conditions. Furthermore, due to the confining effect of the porous carbon shell layer, immobilized natural enzymes showed superior stability in response to temperature changes (10–50 °C) and during storage (30 days). In the presence of NSE targets, immunocomplex formed and catalyzed the cascade decomposition of substrate glucose, which attacked the chromogenic substrate to induce color change. Under optimized conditions, the developed sensor exhibited an ultra-wide linear response range (0.1–100 ng mL − 1 ) and a low detection limit (LOD = 0.0486 ng mL − 1 ). This work provides new insights for developing highly efficient enzyme-catalyzed probes.
Section
Graphical
✓ 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）