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1.
J Enzyme Inhib Med Chem ; 35(1): 414-423, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31899991

RESUMO

A novel series of cyclin-dependent kinases (CDKs) inhibitors, which play critical roles in the cell cycle control and regulation of cell transcription, were synthesised. A systematic study of enzymatic and cellular assays led to the identification of compound X22 with a nanomolar potency against CDK4 and CDK9 and potent antiproliferative activities against a panel of tumour cell lines. X22 could induce cell cycle arrest and cell apoptosis in cancer cell lines. X22 dose-dependently inhibits signalling pathways downstream of CDKs in cancer cells. In vivo antitumor activity assays, oral administration of X22 led to significant tumour regression in mouse model without obvious toxicity. Superior anti-cancer efficacy in vitro and in vivo of X22 demonstrated combined depletion of cell cycle and transcriptional CDK all contributed to antitumor activity. Taken together, concomitant inhibition of cell cycle and transcriptional CDK activities provided valuable guide for further structural optimisation.

2.
Life Sci ; : 117300, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31953162

RESUMO

MiR-346-5p is overexpressed in several cancers, including colorectal cancer (CRC). However, the effects of miR-346-5p on CRC progression have not yet been clarified. In our study, miR-346-5p levels in four CRC cell lines and normal human colon epithelial cells were determined by real-time PCR. SW620 and HCT116 cells were selected and then transfected with miR-346-5p mimic, miR-346-5p inhibitor, or specific siRNAs targeting F-box/LRR-repeat protein 2 (FBXL2). Cell proliferation, cell cycle distribution and cell cycle regulators were examined by CCK-8 assay, flow cytometry, and western blot. The binding of miR-346-5p on 3' untranslated region (UTR) of FBXL2 were verified by dual-luciferase reporter assay. CRC cells were co-transfected with miR-346-5p inhibitor and siFBXL2 to investigate the involvement of FBXL2. Interaction of FBXL2 with forkhead box M1 (FoxM1) was examined by co-immunoprecipitation (Co-IP) assay. The effect of miR-346-5p knockdown on CRC tumorigenesis in vivo was investigated. Here, we found that miR-346-5p overexpression promoted, while miR-346-5p knockdown inhibited cell proliferation and G1-S transition. Inhibition of FBXL2 showed similar effects as miR-346-5p overexpression. Moreover, we verified that FBXL2 was a direct target of miR-346-5p. FBXL2 interacted with FoxM1, and then negatively regulated both FoxM1 and nuclear ß-catenin levels. Additionally, FBXL2 knockdown reversed the effects of miR-346-5p inhibitor. In xenograft models, miR-346-5p knockdown significantly inhibited tumor growth, increased FBXL2 expression, and downregulated the levels of FoxM1 and nuclear ß-catenin. In conclusion, miR-346-5p may promote CRC growth by targeting FBXL2 and activating the ß-catenin signaling pathway. MiR-346-5p may be a novel target in cancer therapy.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31943586

RESUMO

The enantioselective ketimine-ene reaction represents one of the most challenging stereo-controlled reaction type in organic synthesis. In this article, catalytic enantioselective ketimine-ene reactions of 2-aryl-3 H -indol-3-ones with α-methylstyrenes are achieved by utilizing a B(C 6 F 5 ) 3 /chiral phosphoric acid complex catalyst. These ketimine-ene reactions proceed well with low catalyst loading (B(C 6 F 5 ) 3 /CPA = 2 mol%/ 2 mol%) under mild conditions, providing a rapid and facile access to a series of functionalized 2-allyl-indolin-3-ones with very good reactivities (up to 99% yield) and excellent enantioselectivities (up to 99% ee ). Theoretical calculations reveal enhancement of the acidity of chiral phosphoric acid by B(C 6 F 5 ) 3  significantly reduce the activation free energy barrier. And the collective favorable hydrogen bonding interactions, especially the enhanced N-H•••O hydrogen bonding interaction differentiate the free energy between the transition states of CPA and B(C 6 F 5 ) 3 /CPA inducing the improvement of stereoselectivity.

5.
Mol Cell ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31954095

RESUMO

A comprehensive catalog of cancer driver mutations is essential for understanding tumorigenesis and developing therapies. Exome-sequencing studies have mapped many protein-coding drivers, yet few non-coding drivers are known because genome-wide discovery is challenging. We developed a driver discovery method, ActiveDriverWGS, and analyzed 120,788 cis-regulatory modules (CRMs) across 1,844 whole tumor genomes from the ICGC-TCGA PCAWG project. We found 30 CRMs with enriched SNVs and indels (FDR < 0.05). These frequently mutated regulatory elements (FMREs) were ubiquitously active in human tissues, showed long-range chromatin interactions and mRNA abundance associations with target genes, and were enriched in motif-rewiring mutations and structural variants. Genomic deletion of one FMRE in human cells caused proliferative deficiencies and transcriptional deregulation of cancer genes CCNB1IP1, CDH1, and CDKN2B, validating observations in FMRE-mutated tumors. Pathway analysis revealed further sub-significant FMREs at cancer genes and processes, indicating an unexplored landscape of infrequent driver mutations in the non-coding genome.

6.
Int J Biol Macromol ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31954126

RESUMO

We reported an ecofriendly and cost-effective way to prepare carbon aerogels that were derived from sodium lignin sulfonate using κ-carrageenan as a skeleton for efficient dye adsorption. The scanning electron microscopy, nitrogen adsorption and desorption methods were used to analyze the surface configuration and porous structure of the samples. The specific surface area of the as-prepared carbon aerogels based on the Brunauer-Emmet-Teller method reached 594.6 m2/g and the average pore diameter based on the Barrett-Joyner-Halenda method was 2.2118 nm. X-ray energy dispersive spectroscopy, X-ray photoelectron spectroscopy and Raman spectroscopy were used to analyze the elements and functional groups in the samples. The interaction between the as-prepared carbon aerogels and methylene blue (MB) involved π-π electron-donor-acceptor interaction, hydrogen bonding, and electrostatic interaction. The adsorption data at different conditions fitted the pseudo-second-order and Freundlich models well. ∆S° data demonstrated the increased randomness during adsorption. ∆H° and ∆G° data indicated that the interaction between MB and carbon aerogel was endothermic and spontaneous. The adsorption capacity of the as-prepared carbon aerogels for MB removal reached 421.94 mg/g. This work is promising for multi-valued use of lignin sulfonate from pulping wastewater and MB dye wastewater treatment.

7.
Neurosci Lett ; 718: 134745, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31923521

RESUMO

BACKGROUND: Most studies assessing brain-personality mechanisms have used Western personality questionnaires. However, Western personality questionnaires may not objectively reflect the personality characteristics of individuals in Eastern cultures such as China. Hence, we adopted the functional magnetic resonance imaging (fMRI) and the Chinese localized scale, FPPI, to explore the brain mechanisms differences of typical yin and typical yang personalities of individuals in China. METHODS: 30 typical yin personality participants (TYI) and 34 typical yang personality participants (TYA) were enrolled according to the FPPI. The group differences of the functional brain networks among 90 specific brain regions were mapped using fMRI data and then analyzed by the conventional network metrics (CNM) and frequency subgraph mining (FSM). RESULTS: The CNM and FSM differences between two typical personality groups were traced to the frontal, temporal, and parietal cortices. The yin group, reflecting the rich emotions and feelings of individuals, showed higher betweenness centrality (BCi) and nodal efficiency (Ei) values in putamen and middle frontal gyrus. The yang group, reflecting active behaviors and tendency to adapting to the changing surroundings, showed higher BCi and Ei values in precuneus, posterior cingulate gyrus, and inferior parietal lobule, brain areas in the default mode network (DMN). CONCLUSION: These results supplied evidence for the neurobiological differences between typical yin and typical yang personality participants based on Chinese culture. These results also provide a new perspective to help researchers understand brain mechanism differences between yin and yang personality groups in the Chinese culture.

8.
Sci Total Environ ; 706: 135807, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862593

RESUMO

The traditional fluorinated porous material with super-hydrophobicity and super-oleophilicity is an effective strategy for oil-water separation. However, in recent years, fluorinated materials have been classified as "Emerging Environmental Pollutants" by U. S. Environmental Protection Agency because of difficult degradation and bio-accumulation. It is unacceptable to introduce new pollutants while solving environmental disasters. Therefore, it is great requirement to explore a low-cost, environmentally friendly, and renewable technique for the fabrication of novel porous materials with super-hydrophobicity and super-oleophilicity to separate oil-water mixtures. In this work, renewable beeswax, lignin, and cotton have been chosen to prepare the biomass-based porous materials with super-hydrophobicity and super-oleophilicity for oil-water separation. The mixture of beeswax and lignin is modified on the surface of cotton to obtain the biomass-based porous materials with super-hydrophobicity and super-oleophilicity. The beeswax and lignin provide low surface energy and micro/nanoscale structures, respectively. The introduction of lignin effectively improves the thermal stability of the porous materials. The apparent contact angle still remains to be above 150° after a long-time heating. The porous materials effectively separate oil-water mixtures and have good absorption effect for heavy oil (density greater than water). Moreover, the porous materials are easily recyclable after reactivation. This strategy of preparing oil-water separation materials from renewable natural polymers not only helps to clean the environment, but also helps to recover valuable oil.

9.
Food Chem ; 311: 125911, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31869650

RESUMO

Milk allergenic proteins are the main reason of cow's milk allergy. The most common method for removing milk allergenic proteins is enzymatic hydrolysis. However, the direct application of protease to hydrolyze allergens will lead to the introduction of new allergenic proteins. An ideal strategy for removing milk allergenic proteins without introducing new allergenic proteins is immobilization of protease. Herein, we established a simple method to synthesize a novel papain-Cu3(PO4)2·3H2O-magnetic nanoflowers (PCMNs). The PCMNs demonstrated 1556% higher activity than the free alkaline papain. Moreover, the PCMNs could hydrolyze most of allergenic proteins in cow's milk, generating low-sensitive milk. In cycle analysis, the PCMNs also exhibited good reusability and were easily separated from the product.

10.
ACS Appl Mater Interfaces ; 12(1): 1210-1221, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31845573

RESUMO

In this work, a simple phosphating process was proposed to modify cellulose-acetate (CA) and lignin for a novel energy storage precursor material. The prepared precursor fibers exhibited good thermal stability of lignin and flexibility of CA. Subsequently, the precursor fibers undergo a short preoxidation and carbonization treatment process to obtain the biomass-based carbon fibers (CFs) with complete fibrous morphology, uniform fiber diameter, high surface areas, good flexibility, and excellent power storage capacity. The specific capacitance of 346.6 F/g was obtained by using CFs-5 (prepared with 40% H3PO4 content) as a supercapacitor. Simultaneously, the biomass-based CF supercapacitor device delivers a high-energy density of 31.5 Wh/kg at the power density of 400 W/kg. These results indicate that the introduction of H3PO4 can effectively reduce the energy consumption of the preoxidation treatment process for the preparation of the biomass-based CFs, while increasing the energy storage properties significantly. This novel strategy showed a successful route for the preparation of high-quality and low-consumption biomass-based CFs.

11.
Chemosphere ; 238: 124695, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31545215

RESUMO

As the effective adsorbents, carbon materials (CMs) are typically used in the removal of disinfection byproduct (DBP) precursors during the water treatment by adding CMs before disinfection procedure. However, after the separation of CMs from the treated water by flocculation, sedimentation, and filtration, a small amount of loaded activated carbon could be released into the water treatment system and affect the DBP formation in the following disinfection. In this study, three CMs, including coal-made activated carbon (CAC), sawdust charcoal (SCC), and hydroxylated multiwall carbon nanotubes (OH-MWCNT), were used to explore the effects of residual CMs in the formation of DBPs. The results indicated that some DBP precursors could be irreversibly adsorbed into the pore structure of CMs and hardly to be extracted and determined, then affected the DBP formation in the water system. In the chlorination process of surface water samples, CMs have similar effects on the formation of DBPs. However, given that water samples contain a variety of complex substances, the effects of residual CMs on the formation of DBPs were also slightly changed.


Assuntos
Carvão Vegetal/química , Cloro/análise , Nanotubos de Carbono/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Desinfecção/métodos , Floculação , Halogenação
12.
J Cell Biochem ; 121(1): 385-393, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31222822

RESUMO

In this study, we aimed to study the effect of miR-33b in regulating sensitivity to daunorubicin (DNR) in acute myelocytic leukemia (AML). We used quantitative real-time polymerase chain reaction and Cell Counting Kit-8 assay to detect the level of miR-33b and cell viability. Cell apoptosis and the expression of eIF5A-2 and MCL-1 protein were detected by flow cytometry analysis and Western Blot analysis, respectively. MiR-33b mimic increased sensitivity of AML cells against DNR, while miR-33b inhibitor had the opposite effect. Furthermore, the results showed that the eIF5A-2 gene was a direct target of miR-33b, and miR-33b regulated eIF5A-2 mRNA and protein expression. Silencing of eIF5A-2 by RNA interference increased the sensitivity of AML cells against DNR. We also found that MCL-1 contributed to the regulation of DNR sensitivity, which was dependent on downregulation of eIF5A-2. Finally, knockdown of eIF5A-2 eliminated the effects of miRNA-33b mimic or inhibitor on DNR sensitivity. These findings indicate that miR-33b maybe as a new therapeutic target in AML cells.

13.
Ecotoxicol Environ Saf ; 190: 110063, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31846860

RESUMO

Arsenic is a toxic metalloid that can cause male reproductive malfunctions and is widely distributed in the environment. The aim of this study was to investigate the cytotoxicity of arsenic trioxide (ATO) induced GC-1 spermatogonial (spg) cells. Our results found that ATO increased the levels of catalase (CAT) and malonaldehyde (MDA) and reactive oxygen species (ROS), while decreasing glutathione (GSH) and the total antioxidant capacity (T-AOC). Therefore, ATO triggered oxidative stress in GC-1 spg cells. In addition, ATO also caused severe mitochondrial dysfunction that included an increase in residual oxygen consumption (ROX), and decreased the routine respiration, maximal and ATP-linked respiration (ATP-L-R), as well as spare respiratory capacity (SRC), and respiratory control rate (RCR); ATO also damaged the mitochondrial structure, including mitochondrial cristae disordered and dissolved, mitochondrial vacuolar degeneration. Moreover, degradation of p62, LC3 conversion, increasing the number of acidic vesicle organelles (AVOs) and autophagosomes and autolysosomes are demonstrated that the cytotoxicity of ATO may be associated with autophagy. Meanwhile, the metabolomics analysis results showed that 20 metabolites (10 increased and 10 decreased) were significantly altered with the ATO exposure, suggesting that maybe there are the perturbations in amino acid metabolism, lipid metabolism, glycan biosynthesis and metabolism, metabolism of cofactors and vitamins. We concluded that ATO was toxic to GC-1 spg cells via inducing oxidative stress, mitochondrial dysfunction and autophagy as well as the disruption of normal metabolism. This study will aid our understanding of the mechanisms behind ATO-induced spermatogenic toxicity.

14.
ACS Appl Mater Interfaces ; 12(2): 2910-2915, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31852182

RESUMO

We demonstrate a photoexcitation-friction coupling in bilayered black phosphorus, a two-dimensional semiconductor crystallized via van der Waals interaction, using density functional theory and the Prandtl-Tomlinson model. Under an experimentally accessible electron-hole density of 5 × 1013 cm-2, the energy barrier for interlayer sliding can be reduced by 13% and the resultant reduction of critical force for stick-slip transition can be up to 4.7%. With the carrier density being doubled, the frictional anisotropy can even be eliminated. Analysis based on Born-Oppenheimer approximation shows that photoexcitation-friction coupling can be universal for van der Waals crystals with interlayer electronic states responsive to both photoexcitation and interlayer sliding.

15.
Nat Commun ; 10(1): 5510, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796745

RESUMO

The study of transition metal clusters exhibiting fast electron hopping or delocalization remains challenging, because intermetallic communications mediated through bridging ligands are normally weak. Herein, we report the synthesis of a nanosized complex, [Fe(Tp)(CN)3]8[Fe(H2O)(DMSO)]6 (abbreviated as [Fe14], Tp-, hydrotris(pyrazolyl)borate; DMSO, dimethyl sulfoxide), which has a fluctuating valence due to two mobile d-electrons in its atomic layer shell. The rate of electron transfer of [Fe14] complex demonstrates the Arrhenius-type temperature dependence in the nanosized spheric surface, wherein high-spin centers are ferromagnetically coupled, producing an S = 14 ground state. The electron-hopping rate at room temperature is faster than the time scale of Mössbauer measurements (<~10-8 s). Partial reduction of N-terminal high spin FeIII sites and electron mediation ability of CN ligands lead to the observation of both an extensive electron transfer and magnetic coupling properties in a precisely atomic layered shell structure of a nanosized [Fe14] complex.

16.
Chin J Nat Med ; 17(11): 842-857, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31831131

RESUMO

Astrapterocarpan (AP) is a bioactive constituent of Astragali Radix and was selected as a model compound for investigating the in vitro metabolism of pterocarpans in this study. Its in vitro metabolism was conducted by incubation with rat hepatic 9000g supernatant (S9) in the presence of an NADPH-generating system. At first, four compounds were isolated and their structures were elucidated as 6a-hydroxy-AP (M1), astrametabolin I [M2, 1a-hydroxy-9, 10-dimethoxy-pterocarp-1(2), 4-diene-3-one], 9-demethyl-AP (M3, nissolin) and 4-methoxy-astraisoflavan (M4, 7, 2'dihydroxy-4, 3', 4'-trimethoxy-isoflavan) on the basis of NMR data, respectively. Among them, M1, M2 and M4 were new compounds. Next, the metabolite profile of AP in rat hepatic S9 was obtained via HPLC-DAD-ESI-IT-TOF-MSn, and 40 new metabolites were tentatively identified. These newly identified metabolites included 9 monohydroxylated metabolites, 1 demethylated metabolite, 7 demethylated and monohydroxylated metabolites, 4 dihydroxylated metabolites, 1 hydration metabolite, 1 didemethylated metabolite, 2 glucosylated metabolites, 1 monohydroxylated and dehydrogenated metabolite, 2 monohydroxylated and demethylated and dehydrogenated metabolites, 2 dimerized metabolites, 3 dimerized and monohydroxylated metabolites, 2 dimerized and didemethylated metabolites, and 5 dimerized and demethylated metabolites. Finally, the major metabolic reactions of AP in rat hepatic S9 were summarized and found to be hydroxylation, demethylation, dimerization, hydration, and dehydrogenation. More importantly, the biotransformation from AP to M2 and the dimerization of AP by incubation with hepatic S9 were reported for the first time. In conclusion, this is the first report on the metabolism of a pure pterocarpan in animal tissues, and these findings will provide a solid basis for further studies on the metabolism of other pterocarpans.

17.
Sci Total Environ ; : 135254, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31810705

RESUMO

The application of graphene oxide (GO) and its derivatives as adsorbents to remove heavy metal contaminants from industrial wastewaters has attracted increasing attention worldwide. Here, we investigated the role of oxidative debris (OD) on GO surfaces in the adsorption of Pb(II) under natural conditions. OD attached to GO surfaces can be removed under alkaline conditions, and plays a critical role in the adsorption of Pb(II) by GO. Specifically, the maximum adsorption capacity of Pb(II) on GO decreased from 926.50 to 357.64 mg·g-1 after OD removal. Under simulated natural alkaline groundwater conditions, some adsorbed Pb(II) was released with OD that was stripped from spent GO adsorbents (i.e., GO-Pb(II)). Further, batch experiments indicated that 1.30-1.43% of adsorbed Pb(II) could stably disperse in water as dissolved PbCO3 and OD-Pb(II) complexes, at a pH of ~8.3. The stripping and dissociation of OD under alkaline conditions promoted the mobility of Pb(II) on GO adsorbents. This study enhances our understanding of heavy metal transport in natural alkaline groundwater environments that contain GO particles.

18.
J Cell Mol Med ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31815360

RESUMO

Atrial fibrosis is an important factor in the initiation and maintenance of atrial fibrillation (AF); therefore, understanding the pathogenesis of atrial fibrosis may reveal promising therapeutic targets for AF. In this study, we successfully established a rapid atrial pacing canine model and found that the inducibility and duration of AF were significantly reduced by the overexpression of c-Ski, suggesting that this approach may have therapeutic effects. c-Ski was found to be down-regulated in the atrial tissues of the rapid atrial pacing canine model. We artificially up-regulated c-Ski expression with a c-Ski-overexpressing adenovirus. Haematoxylin and eosin, Masson's trichrome and picrosirius red staining showed that c-Ski overexpression alleviated atrial fibrosis. Furthermore, we found that the expression levels of collagen III and α-SMA were higher in the groups of dogs subjected to right-atrial pacing, and this increase was attenuated by c-Ski overexpression. In addition, c-Ski overexpression decreased the phosphorylation of smad2, smad3 and p38 MAPK (p38α and p38ß) as well as the expression of TGF-ß1 in atrial tissues, as shown by a comparison of the right-atrial pacing + c-Ski-overexpression group to the control group with right-atrial pacing only. These results suggest that c-Ski overexpression improves atrial remodelling in a rapid atrial pacing canine model by suppressing TGF-ß1-Smad signalling and p38 MAPK activation.

19.
Anal Chem ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31786915

RESUMO

Cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) are genotoxic DNA lesions and mainly generated on thymine-thymine (T-T) dinucleotides upon UV irradiation. Regarding the sensitivity, specificity, and accuracy of analytical methods, it is of first choice to develop a reliable assay for simultaneous detection of these DNA lesions using liquid chromatography-tandem mass spectrometry (LC-MS/MS). However, the dilemma is the low detection sensitivity of the phosphate-containing dimeric photoproducts even using most favorable negative-ion mode for LC-MS/MS analysis. Unexpectedly, we observed that the detection sensitivity of T-T CPD and 6-4PP could be significantly improved using formic acid/acetic acid (∼ppm) as an additive of the mobile phase for reversed-phase LC-MS/MS analysis. This is the first demonstration of the enhancement of LC-MS/MS signals by formic acid/acetic acid in negative-ion mode. Of note, these acidic agents are often used for positive-ion mode in LC-MS assays. Benefited from the developed method, we could quantify both T-T CPD and 6-4PP in mouse embryonic stem cells upon UVC irradiation at low dosage. This sensitive method is applicable to the screening and identification of genes involved in formation, signaling, and repair of UV lesion.

20.
Adv Mater ; : e1905145, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31788896

RESUMO

Rapid cut-off of blood supply in diseases involving thrombosis is a major cause of morbidity and mortality worldwide. However, the current thrombolysis strategies offer limited results due to the therapeutics' short half-lives, low targeting ability, and unexpected bleeding complications. Inspired by the innate roles of platelets in hemostasis and pathological thrombus, platelet membrane-camouflaged polymeric nanoparticles (nanoplatelets) are developed for targeting delivery of the thrombolytic drug, recombinant tissue plasminogen activator (rt-PA), to local thrombus sites. The tailor-designed nanoplatelets efficiently accumulate at the thrombi in pulmonary embolism and mesenteric arterial thrombosis model mice, eliciting a significantly enhanced thrombolysis activity compared to free rt-PA. In addition, the nanoplatelets exhibit improved therapeutic efficacy over free rt-PA in an ischemic stroke model. Analysis of in vivo coagulation indicators suggests the nanoplatelets might possess a low risk of bleeding complications. The hybrid biomimetic nanoplatelets described offer a promising solution to improve the efficacy and reduce the bleeding risk of thrombolytic therapy in a broad spectrum of thrombosis diseases.

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