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1.
J Phys Chem Lett ; : 567-573, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35014840

RESUMO

Phosphorylation for ribonucleotide formation is a critical step in the origin of life but has had limited success due to the thermodynamic and kinetic constraints in aqueous media. Here, we report that the production of ribonucleotides from ribonucleosides in the presence of monopotassium phosphate (KH2PO4) spontaneously proceeded in aqueous microdroplets under ambient conditions and without using a catalyst. A full set of ribonucleotides including adenosine monophosphate (AMP), guanosine monophosphate (GMP), uridine monophosphate (UMP), and cytidine monophosphate (CMP) were generated on the scale of a few milliseconds. The aqueous microdroplets could transfer the ribonucleotides to oligoribonucleotides and showed mutual compatibility for individual phosphorylation. Conditions established the dependence of the conversion ratio on the droplet size and suggested that the condensation reactions occurred at or near the microdroplets' surface. This aqueous microdroplet approach also provides a route for elucidating phosphorylation chemistry in the prebiotic era.

2.
Cancer Manag Res ; 14: 135-155, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35027848

RESUMO

Background: The use of machine learning (ML) in predicting disease prognosis has increased, and scientists have adopted different methods for cancer classification to optimize the early screening of cancer to determine its prognosis in advance. In this study, we aimed at improving the prediction accuracy of gastric cancer in postoperation patients by constructing a highly effective prognostic model. Methods: The study used postoperative gastric cancer patient data from the SEER database. The LASSO regression method was used to construct a clinical prognostic model, and four machine learning methods (Boruta algorithm, neural network, support vector machine, and random forest) were used to screen and recombine the features to construct an ML prognostic model. Clinical information on 955 postoperative gastric cancer patients collected from the Affiliated Tumor Hospital of Harbin Medical University was used for external verification. Results: Experimental results showed that the AUC values of 1, 3 and 5 years in the training set, validation set and external validation set of clinical prognosis model and ML prognosis model directly established by LASSO regression are all around 0.8. Conclusion: Both models can accurately evaluate the prognosis of postoperative patients with gastric cancer, which may be helpful for accurate and personalized treatment of postoperative patients with gastric cancer.

3.
Opt Lett ; 47(1): 190-193, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34951914

RESUMO

Strong light-matter coupling manifested by Rabi splitting has drawn considerable interest owing to its fundamental significance for impressive interaction enhancement in the fields of ultrafast active plasmonic devices and quantum information. In this paper, we investigate the coherent optical properties of a plasmonic system consisting of periodic metal nanoparticle arrays covered by a WS2 thin film of atomic layer thickness. The coupling factor, energy splitting, and temporal dynamics of this coherent coupling phenomenon are quantitatively revealed by finite-difference time-domain (FDTD) simulation and a full quantum mechanical model proves that the exciton behavior of the fermionic quantum emitter WS2 is carefully modulated by bosonic surface lattice resonances. This work may pave the way for coherent modulation of polariton and plasmon devices and can potentially open up diverse exciting possibilities like nanoscale light sources, single-photon emitters, and all-optical transistors.

4.
Nanotechnology ; 33(13)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34929679

RESUMO

Structural color has been studied through various methods due to its distinguished features of stability, durability, high information storage density and high integration. However, the artificial structural color samples do not exhibit superior performance in color saturation and low angular dependence. Here, we present an approach to acquire additive reflective color based on a metal-dielectric-metal (MDM) stack. The upper layer composed of Ag particles is perforated in a hexagonal arrangement which profits from the dielectric anodic aluminium oxide (AAO) membrane. The size and shape of the Ag particles are getting inhomogeneous as the deposition thickness of the upper layer increasing, which expands the desired absorption range of surface plasmons. The residual non-anodized Al foil serves as a highly reflective substrate for efficient color presenting through the thin-film interference in this plasmonic MDM system. As a result, the color gamut area of this MDM stack is extended 8 times in CIE chromaticity coordinates. Finally, a wafer-scale (diameter of 83 mm) badge of Harbin Engineering University (HEU) with highly saturated colors and a pattern characterized with low angle-dependent property (up to 60°) are presented, which exhibit promising prospects in commercial coloring and imaging.

5.
Front Bioeng Biotechnol ; 9: 742135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869257

RESUMO

The rapidly increasing resistance of bacteria to currently approved antibiotic drugs makes surgical interventions and the treatment of bacterial infections increasingly difficult. In recent years, complementary strategies to classical antibiotic therapy have, therefore, gained importance. One of these strategies is the use of medicinal honey in the treatment of bacterially colonized wounds. One of the several bactericidal effects of honey is based on the in situ generation of hydrogen peroxide through the activity of the enzyme glucose oxidase. The strategy underlying this work is to mimic this antibacterial redox effect of honey in an injectable, biocompatible, and rapidly forming hydrogel. The hydrogel was obtained by thiol-ene click reaction between hyperbranched polyethylene glycol diacrylate (HB PEGDA), synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization, and thiolated hyaluronic acid (HA-SH). After mixing 500 µL HB PEGDA (10%, w/w) and 500 µL HA-SH (1%, w/w) solutions, hydrogels formed in ∼60 s (HB PEGDA/HA-SH 10.0-1.0), as assessed by the tube inverting test. The HB PEGDA/HA-SH 10.0-1.0 hydrogel (200 µL) was resistant to in vitro dissolution in water for at least 64 days, absorbing up to 130 wt% of water. Varying glucose oxidase (GO) amounts (0-500 U/L) and constant glucose content (2.5 wt%) were loaded into HB PEGDA and HA-SH solutions, respectively, before hydrogel formation. Then, the release of H2O2 was evaluated through a colorimetric pertitanic acid assay. The GO content of 250 U/L was selected, allowing the formation of 10.8 ± 1.4 mmol H2O2/L hydrogel in 24 h, under static conditions. The cytocompatibility of HB PEGDA/HA-SH 10.0-1.0 hydrogels loaded with different GO activities (≤ 500 U/L) at a constant glucose amount (2.5 wt%) was investigated by in vitro assays at 24 h with L929 and HaCaT cell lines, according to DIN EN ISO 10993-5. The tests showed cytocompatibility for GO enzyme activity up to 250 U/L for both cell lines. The antibacterial activity of HB PEGDA/HA-SH 10.0-1.0 hydrogels loaded with increasing amounts of GO was demonstrated against various gram-positive bacteria (S. aureus and S. epidermidis), antibiotic-resistant gram-positive bacteria (MRSA and MRSE), gram-negative bacteria (P. aeruginosa, E. coli, and A. baumanii), and antibiotic-resistant gram-negative strains (P. aeruginosa and E. coli) using agar diffusion tests. For all gram-positive bacterial strains, increasing efficacy was measured with increasing GO activity. For the two P. aeruginosa strains, efficacy was shown only from an enzyme activity of 125 U/L and for E. coli and A. baumanii, efficacy was shown only from 250 U/L enzyme activity. HB PEGDA/HA-SH 10.0-1.0 hydrogels loaded with ≤250 U/L GO and 2.5 wt% glucose are promising formulations due to their fast-forming properties, cytocompatibility, and ability to produce antibacterial H2O2, warranting future investigations for bacterial infection treatment, such as wound care.

6.
Int J Mol Sci ; 22(23)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34884578

RESUMO

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare autosomal inherited skin disorder caused by mutations in the COL7A1 gene that encodes type VII collagen (C7). The development of an efficient gene replacement strategy for RDEB is mainly hindered by the lack of vectors able to encapsulate and transfect the large cDNA size of this gene. To address this problem, our group has opted to use polymeric-based non-viral delivery systems and minicircle DNA. With this approach, safety is improved by avoiding the usage of viruses, the absence of bacterial backbone, and the replacement of the control viral cytomegalovirus (CMV) promoter of the gene with human promoters. All the promoters showed impressive C7 expression in RDEB skin cells, with eukaryotic translation elongation factor 1 α (EF1α) promoter producing higher C7 expression levels than CMV following minicircle induction, and COL7A1 tissue-specific promoter (C7P) generating C7 levels similar to normal human epidermal keratinocytes. The improved system developed here has a high potential for use as a non-viral topical treatment to restore C7 in RDEB patients efficiently and safely, and to be adapted to other genetic conditions.

7.
Chem Commun (Camb) ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34859797

RESUMO

A novel theranostic probe called CX-B-DF is constructed for precise chemotherapy guided by near-infrared (NIR) fluorescence imaging. Moreover, the theranostic probe shows high cytotoxicity to cancer cells under dual activation (H2O2 and TP), which causes the accuracy of drug release to be improved and the toxic side effects to be reduced.

8.
Biomed Eng Online ; 20(1): 131, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34965854

RESUMO

BACKGROUND: Image registration is an essential step in the automated interpretation of the brain computed tomography (CT) images of patients with acute cerebrovascular disease (ACVD). However, performing brain CT registration accurately and rapidly remains greatly challenging due to the large intersubject anatomical variations, low resolution of soft tissues, and heavy computation costs. To this end, the HSCN-Net, a hybrid supervised convolutional neural network, was developed for precise and fast brain CT registration. METHOD: HSCN-Net generated synthetic deformation fields using a simulator as one supervision for one reference-moving image pair to address the problem of lack of gold standards. Furthermore, the simulator was designed to generate multiscale affine and elastic deformation fields to overcome the registration challenge posed by large intersubject anatomical deformation. Finally, HSCN-Net adopted a hybrid loss function constituted by deformation field and image similarity to improve registration accuracy and generalization capability. In this work, 101 CT images of patients were collected for model construction (57), evaluation (14), and testing (30). HSCN-Net was compared with the classical Demons and VoxelMorph models. Qualitative analysis through the visual evaluation of critical brain tissues and quantitative analysis by determining the endpoint error (EPE) between the predicted sparse deformation vectors and gold-standard sparse deformation vectors, image normalized mutual information (NMI), and the Dice coefficient of the middle cerebral artery (MCA) blood supply area were carried out to assess model performance comprehensively. RESULTS: HSCN-Net and Demons had a better visual spatial matching performance than VoxelMorph, and HSCN-Net was more competent for smooth and large intersubject deformations than Demons. The mean EPE of HSCN-Net (3.29 mm) was less than that of Demons (3.47 mm) and VoxelMorph (5.12 mm); the mean Dice of HSCN-Net was 0.96, which was higher than that of Demons (0.90) and VoxelMorph (0.87); and the mean NMI of HSCN-Net (0.83) was slightly lower than that of Demons (0.84), but higher than that of VoxelMorph (0.81). Moreover, the mean registration time of HSCN-Net (17.86 s) was shorter than that of VoxelMorph (18.53 s) and Demons (147.21 s). CONCLUSION: The proposed HSCN-Net could achieve accurate and rapid intersubject brain CT registration.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Algoritmos , Encéfalo/diagnóstico por imagem , Humanos , Tomografia Computadorizada por Raios X
9.
Molecules ; 26(24)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34946568

RESUMO

Taxilli Herba (TAXH) is an important traditional Chinese medicine with a long history, dating from the Eastern Han Dynasty to the present times. However, the active constituents in it that parasitize different hosts vary, affecting its clinical efficacy. Given the complexity of the host origins, evaluating the quality of TAXH is critical to ensure the safety and effectiveness of clinical medication. In the present study, a quantitative method based on ultra-fast liquid chromatography tandem triple quadrupole mass spectrometry (UFLC-QTRAP-MS/MS) was established, which simultaneously determined the content of 33 active constituents, including 12 flavonoids, 4 organic acids, 12 amino acids, and 5 nucleosides in 45 samples. Orthogonal partial least squares discriminant analysis (OPLS-DA) was employed to classify and distinguish between TAXH and its adulterants, Tolypanthi Herba (TOLH). A hierarchical clustering analysis (HCA) was conducted combined with a heatmap to visually observe the distribution regularity of 33 constituents in each sample. Furthermore, gray relational analysis (GRA) was applied to evaluate the quality of samples to get the optimal host. The results demonstrated that TAXH excelled TOLH in quality as a whole. The quality of TAXH parasitizing Morus alba was also better, while those that were parasitic on Cinnamomum camphora and Glyptostrobus pensilis had relatively poor quality. This study may provide comprehensive information that is necessary for quality control and supply a scientific basis for further exploring the quality formation mechanism of TAXH.

10.
J Colloid Interface Sci ; 608(Pt 2): 1685-1695, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34742083

RESUMO

Though the function of peptide based nanotubes are well correlated with its shape and size, controlling the dimensions of nanotubes still remains a great challenge in the field of peptide self-assembly. Here, we demonstrated that the shell structure of nanotubes formed by a bola peptide Ac-KI3VK-NH2 (KI3VK, in which K, I, and V are abbreviations of lysine, isoleucine, and valine) can be regulated by mixing it with the salt sodium tartrate (STA). The ratio of KI3VK and STA had a great impact on shell structure of the nanotubes. Bilayer nanotubes can be constructed when the molar ratio of KI3VK and STA was less than 1:2. Both the two hydroxyls and the negative charges carried by STA were proved to play important roles in the bilayer nanotubes formation. Observations of different intermediates provided obvious evidence for the varied pathway of the bilayer nanotubes formation. Based on these experimental results, the possible mechanism for bilayer nanotubes formation was proposed. Such a study provides a simple and effective way for regulating the shell structure of the nanotubes and may expand their applications in different fields.

11.
Molecules ; 26(21)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34770782

RESUMO

Taxilli Herba (TH) is a well-known traditional Chinese medicine (TCM) with a wide range of clinical application. However, there is a lack of comprehensive research on its chemical composition in recent years. At the same time, Taxillus chinensis (DC) Danser is a semi parasitic plant with abundant hosts, and its chemical constituents varies due to hosts. In this study, the characterization of chemical constituents in TH was analyzed by ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry (UFLC-Triple TOF-MS/MS). Moreover, partial least squares discriminant analysis (PLS-DA) was applied to reveal the differential constituents in TH from different hosts based on the qualitative information of the chemical constituents. Results showed that 73 constituents in TH were identified or tentatively presumed, including flavonoids, phenolic acids and glycosides, and others; meanwhile, the fragmentation pathways of different types of compounds were preliminarily deduced by the fragmentation behavior of the major constituents. In addition, 23 differential characteristic constituents were screened based on variable importance in projection (VIP) and p-value. Among them, quercetin 3-O-ß-D-glucuronide, quercitrin and hyperoside were common differential constituents. Our research will contribute to comprehensive evaluation and intrinsic quality control of TH, and provide a scientific basis for the variety identification of medicinal materials from different hosts.

12.
Int J Mol Med ; 48(6)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34664683

RESUMO

Matrix metalloproteinase (MMP)­9 is associated with the severity of ventilator­associated pneumonia (VAP), while an rs1056629 SNP located in the 3'­untranslated region (UTR) of MMP­9 affects the microRNA (miRNA/miR)­491­mediated regulation of MMP­9 expression. In the present study, the effect of rs1056629 on the development of VAP in patients with chronic obstructive pulmonary disease (COPD) was investigated. Patients with COPD were enrolled in the study and their genotypes of rs1056629 (CC, CA or AA) were determined. ELISA was used to analyze the levels of TNF­α and IL­6 in the monocytes of patients with COPD carrying differential genotypes of rs1056629. Reverse transcription­quantitative PCR was carried out to evaluate the expression of miR­491 and MMP­9 mRNA in the different groups of patients with COPD. Luciferase assay was used to confirm the inhibitory role of miR­491 in MMP­9 expression. Western blot analysis was carried out to assess the expression of MMP­9 protein in A549 and H1299 cells transfected with miR­491 mimics. The risk and severity of VAP were significantly elevated in patients with COPD carrying the CC and AC genotypes of rs1056629. Although there was no difference in the expression of miR­491 in patients carrying different genotypes of rs1056629, the expression levels of TNF­α, IL­6 and MMP­9 were increased in patients with COPD carrying the CC and AC genotypes of rs1056629. The results of luciferase assay revealed that miR­491 inhibited the expression of MMP­9 through direct binding to the 3'UTR of MMP­9. Transfection of miR­491 mimics into A549 and H1299 cells markedly suppressed the expression of MMP­9 in a concentration­dependent manner. On the whole, the findings of the present study confirm that the CC and AC genotypes of rs1056629 increase the risk of developing VAP in patients with COPD by increasing the expression of MMP­9.

13.
Materials (Basel) ; 14(20)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34683575

RESUMO

Due to their biodegradability and biocompatibility, chitosan-based hydrogels have great potential in regenerative medicine, with applications such as bacteriostasis, hemostasis, and wound healing. However, toxicity and high cost are problems that must be solved for chitosan-based hydrogel crosslinking agents such as formaldehyde, glutaraldehyde, and genipin. Therefore, we developed a biocompatible yet cost-effective chitosan-based hydrogel system as a candidate biomaterial to prevent infection during wound healing. The hydrogel was fabricated by crosslinking chitosan with dialdehyde chitosan (CTS-CHO) via dynamic Schiff-base reactions, resulting in a self-healable and injectable system. The rheological properties, degradation profile, and self-healable properties of the chitosan-based hydrogel were evaluated. The excellent antibacterial activity of the hydrogel was validated by a spread plate experiment. The use of Live/Dead assay on HEK 293 cells showed that the hydrogel exhibited excellent biocompatibility. The results demonstrate that the newly designed chitosan-based hydrogel is an excellent antibacterial wound dressing candidate with good biocompatibility.

14.
Adv Mater ; : e2106908, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34676921

RESUMO

The underwater superoleophobicity of a coating is often caused by its preferential water affinity, which, however, normally weakens the substrate adhesion property. In this work, a new strategy is reported for achieving strong underwater adhesion between a well-designed amphiphilic polyurethane coating and a diverse range of substrates while also rendering the coating surface's superoleophobicity. When the coating, which is a mixture of an amphiphilic polyurethane and a water miscible solvent, is immersed in water, the hydrophobic segments aggregate to orientate and pile along the surface of substrates via a segment orientation mechanism triggered by solvent exchange with water penetration to exert strong adhesion. At the same time, the hydrophilic segments will physically crosslink to form a hydrogel coating, endowing the substrate with underwater superoleophobicity. This work provides a facile, versatile, and scalable approach for the future design of superoleophobic coatings in a water environment.

15.
Cell Metab ; 33(10): 1943-1956.e2, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478633

RESUMO

Metabolic dysfunction is becoming a predominant risk for the development of many comorbidities. Ischemic heart disease (IHD) still imposes the highest disease burden among all cardiovascular diseases worldwide. However, the contributions of metabolic risk factors to IHD over time have not been fully characterized. Here, we analyzed the global disease burden of IHD and 15 associated general risk factors from 1990 to 2019 by applying the methodology framework of the Global Burden of Disease Study. We found that the global death cases due to IHD increased steadily during that time frame, while the mortality rate gradually declined. Notably, metabolic risk factors have become the leading driver of IHD, which also largely contributed to the majority of IHD-related deaths shifting from developed countries to developing countries. These findings suggest an urgent need to implement effective measures to control metabolic risk factors to prevent further increases in IHD-related deaths.

16.
Acta Biomater ; 135: 289-303, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34474179

RESUMO

Critical bone defects are a common yet challenging orthopedic problem. Tissue engineering is an emerging and promising strategy for bone regeneration in large-scale bone defects. The precise on-demand release of osteogenic factors is critical for controlling the osteogenic differentiation of seed cells with the support of appropriate three dimensional scaffolds. However, most of the effective osteogenic factors are biomacromolecules with release behaviors that are difficult to control. Here, the cholesterol-modified non-coding microRNA Chol-miR-26a was used to promote the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Chol-miR-26a was conjugated to an injectable poly(ethylene glycol) (PEG) hydrogel through an ultraviolet (UV)-cleavable ester bond. The injectable PEG hydrogel was formed by a copper-free click reaction between the terminal azide groups of 8-armed PEG and dibenzocyclooctyne-biofunctionalized PEG, into which UV-cleavable Chol-miR-26a was simultaneously conjugated via a Michael addition reaction. Upon UV irradiation, Gel-c-miR-26a (MLCaged) released Chol-c-miR-26a selectively and exhibited significantly improved efficacy in bone regeneration compared to the hydrogel without UV irradiation and UV-uncleavable MLControl. MLCaged significantly enhanced alkaline phosphatase activity and promoted calcium nodule deposition in vitro and repaired critical skull defects in a rat animal model, demonstrating that injectable implantation with the precise release of osteogenic factors has the potential to repair large-scale bone defects in clinical practice. STATEMENT OF SIGNIFICANCE: Provide a novel and practical strategy via hydrogel for efficient delivery and precisely controlled release of miRNAs into bone defect sites. The hydrogel is formed by polyethylene glycol (PEG), which is crosslinked by 'click' reaction. Cholesterol-modified miR-26a loading on the hydrogel is covalently patterned onto the fibers of hydrogel through a UV light-cleavable linker, which prevents undesired release of miRNA. This hydrogel could realize the controlled release of miRNA under light regulation both in vitro and in vivo, thus realize bone regeneration.


Assuntos
Hidrogéis , MicroRNAs , Animais , Regeneração Óssea , Diferenciação Celular , Hidrogéis/farmacologia , MicroRNAs/genética , Osteogênese , Ratos
17.
ACS Appl Mater Interfaces ; 13(39): 47262-47271, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34553898

RESUMO

Ceaselessly increasing demands for elaborate nanostructures prompt advanced structure fabrication with good practicability, especially, subwavelength ordered structures in simple lattices even in superlattices over a large area, namely, large-scale photonic lattices, in which lattice arrangement, geometry, and components of unit cells are key factors for their macroscopic optical properties. Moreover, exciting properties always occur at high symmetry points of the lattice; therefore, straightforward modulation of symmetry points over a large area is very important for the investigation and application of photonic lattices. Here, this work establishes a lithography-free approach of undervoltage oxidation (UVO) for regulating high symmetry points in the reciprocal space of a dielectric alumina superlattice. Embedding subunit cells at high symmetry points Γ (M) result in the degenerate energy changing from 1.34 eV (924.6 nm) to 1.87 eV (662.6 nm) under normal excitation at the Γ point, and the degeneracy lifting under off-normal excitation along the Γ-X high symmetry orientation. Furthermore, systematic characterizations of the alumina membrane are presented to learn its dynamic evolution of the morphology on a centimeter scale, and the pore array changes from a hierarchical period to a form of hexagonal close packing, especially at Γ and M points of the square lattice. Therefore, the reported lithography-free alumina-based nanofabrication offers an ability for varying the spatial structure at high symmetry points of photonic lattices, which is of great significance in the fields of nanomanufacturing and has great potential to bring about preferable performances in nanodevices.

18.
Mikrochim Acta ; 188(9): 287, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34350511

RESUMO

A near-infrared (NIR) fluorescence nanoprobe named RhI-DOX@ZIF-90 has been synthesized by wrapping the guest molecule (RhI and DOX) into ZIF-90 framework. The nanoprobe itself is non-fluorescent and the drug (DOX) is inactive. Upon the addition of ATP, the structure of RhI-DOX@ZIF-90 is degraded. The fluorescence of RhI is recovered and DOX is released. The nanoprobe can detect ATP with high sensitivity and selectivity. There is good linear relationship between the nanoprobe and ATP concentration from 0.25 to 10 mM and the detection limit is 0.10 mM. The nanoprobe has the ability to monitor the change of ATP level in living cells and DOX is released inducing apoptosis of cancer cells. RhI-DOX@ZIF-90 is capable of targeting mitochondria, which provides a basis for improving the efficiency of drug delivery by mitochondrial administration. In particular, the nanoprobe is preferentially accumulated in the tumor sites and detect ATP in tumor mice by fluorescence imaging using near-infrared fluorescence. At the same time, DOX can be released accurately in tumor sites and have good anti-tumor efficiency. So, this nanoprobe is a reliable tool to realize early diagnosis of cancer and improve effect of anticancer drug.

19.
Eur J Med Chem ; 224: 113736, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34384944

RESUMO

Pyrazolopyrimidinones are fused nitrogen-containing heterocyclic systems, which act as a core scaffold in many pharmaceutically relevant compounds. Pyrazolopyrimidinones have been demonstrated to be efficient in treating several diseases, including cystic fibrosis, obesity, viral infection and cancer. In this study using glioblastoma U-251MG cell line, we tested the cytotoxic effects of 15 pyrazolopyrimidinones, synthesised via a two-step process, in combination with cold atmospheric plasma (CAP). CAP is an adjustable source of reactive oxygen and nitrogen species as well as other unique chemical and physical effects which has been successfully tested as an innovative cancer therapy in clinical trials. Significantly variable cytotoxicity was observed with IC50 values ranging from around 11 µM to negligible toxicity among tested compounds. Interestingly, two pyrazolopyrimidinones were identified that act in a prodrug fashion and display around 5-15 times enhanced reactive-species dependent cytotoxicity when combined with cold atmospheric plasma. Activation was evident for direct CAP treatment on U-251MG cells loaded with the pyrazolopyrimidinone and indirect CAP treatment of the pyrazolopyrimidinone in media before adding to cells. Our results demonstrated the potential of CAP combined with pyrazolopyrimidinones as a programmable cytotoxic therapy and provide screened scaffolds that can be used for further development of pyrazolopyrimidinone prodrug derivatives.

20.
Anal Chem ; 93(34): 11826-11835, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34461732

RESUMO

Cancer ranks as a leading cause of death in every country of the world. However, if they are discovered early, a lot of cancers can be prevented or cured. Discovering and monitoring cancer markers are the main methods for early diagnosis of cancer. To date, many fluorescent probes designed and used for early cancer diagnosis can only react with a single marker, which always causes insufficient accuracy in complex systems. Herein, a novel near-infrared (NIR) fluorescent probe (CyO-DNP) for the sequential detection of H2S and H+ is synthesized. In this probe, a heptamethine dye is selected as the fluorophore and a 2,4-dinitrophenyl (DNP) ether is chosen as recognition group. In the presence of H2S, CyO-DNP is transformed into CyO, which exhibits an intense fluorescence at 663 nm. Then, H+ induces the protonation of CyO to obtain CyOH, and the final fluorescence emission at 793 nm significantly enhances. Owing to the low cytotoxicity and the NIR fluorescence emission, CyO-DNP can sequentially monitor endogenous H2S and H+ in cancer cells and image exogenous and endogenous H2S and H+ in mice. It is worth mentioning that CyO-DNP can effectively avoid the false positive signal caused by the liver and kidney and discriminate normal mice and tumor mice accurately. For all we know, CyO-DNP is the first fluorescent probe for early accurate diagnosis of cancer by sequentially detecting H2S and H+.


Assuntos
Sulfeto de Hidrogênio , Neoplasias , Animais , Corantes Fluorescentes , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Microscopia de Fluorescência , Neoplasias/diagnóstico
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