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1.
Mol Ecol Resour ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010101

RESUMO

The blue king crab, Paralithodes platypus, which belongs to the Lithodidae family, is a commercially and ecologically important species. However, a high-quality reference genome for the king crab has not yet been reported. Here, we assembled the first chromosome-level blue king crab genome, which contains 104 chromosomes and an N50 length of 51.15 Mb. Furthermore, we determined that the large genome size can be attributed to the insertion of long interspersed nuclear elements and long tandem repeats. Genome assembly assessment showed that 96.54% of the assembled transcripts could be aligned to the assembled genome. Phylogenetic analysis showed the blue king crab to have a close relationship with the Eubrachyura crabs, from which it diverged 272.5 million years ago. Population history analyses indicated that the effective population of the blue king crab declined sharply and then gradually increased from the Cretaceous and Neogene periods, respectively. Furthermore, gene families related to developmental pathways, steroid and thyroid hormone synthesis, and inflammatory regulation, were expanded in the genome, suggesting that these genes contributed substantially to the environmental adaptation and unique body plan evolution of the blue king crab. The high-quality reference genome reported here provides a solid molecular basis for further study of the blue king crab's development and environmental adaptation.

2.
BMC Cancer ; 20(1): 957, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008389

RESUMO

BACKGROUND: Chromosome mis-segregation caused by spindle assembly checkpoint (SAC) dysfunction during mitosis is an important pathogenic factor in cancer, and modulating SAC function has emerged as a potential novel therapy for non-small cell lung cancer (NSCLC). UbcH10 is considered to be associated with SAC function and the pathological types and clinical grades of NSCLC. KIAA0101, which contains a highly conserved proliferating cell nuclear antigen (PCNA)-binding motif that is involved in DNA repair in cancer cells, plays an important role in the regulation of SAC function in NSCLC cells, and bioinformatics predictions showed that this regulatory role is related to UbcH10. We hypothesized KIAA0101 and UbcH10 interact to mediate SAC dysfunction and neoplastic transformation during the development of USCLC. METHODS: NSCLC cell lines were used to investigate the spatial-temporal correlation between UbcH10 and KIAA0101 expression and the downstream effects of modulating their expression were evaluated. Further immunoprecipitation assays were used to investigate the possible mechanism underlying the correlation between UbcH10 and KIAA0101. Eventually, the effect of modulating UbcH10 and KIAA010 on tumor growth and its possible mechanisms were explored through in vivo tumor-bearing models. RESULTS: In this study, we demonstrated that both UbcH10 and KIAA0101 were upregulated in NSCLC tissues and cells and that their expression levels were correlated in a spatial and temporal manner. Importantly, UbcH10 and KIAA0101 coordinated to mediate the premature degradation of various SAC components to cause further SAC dysfunction and neoplastic proliferation. Moreover, tumor growth in vivo was significantly inhibited by silencing UbcH10 and KIAA0101 expression. CONCLUSIONS: KIAA0101 and UbcH10 interact to cause SAC dysfunction, chromosomal instability and malignant proliferation in NSCLC, suggesting that UbcH10 and KIAA0101 are potential therapeutic targets for the treatment of NSCLC by ameliorating SAC function.

3.
Biomed Res Int ; 2020: 3178037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33015161

RESUMO

Osteosarcoma is a highly malignant bone cancer which primarily occurs in children and young adults. Increasing evidence indicates that long noncoding RNAs (lncRNAs), which function as competing endogenous RNAs (ceRNAs) that sponge microRNAs (miRNAs) and messenger RNAs (mRNAs), play a pivotal role in the pathogenesis and progression of cancers. The regulatory mechanisms of lncRNA-mediated ceRNAs in osteosarcoma have not been fully elucidated. In this study, we identified differentially expressed lncRNAs, miRNAs, and mRNAs in osteosarcoma based on RNA microarray profiles in the Gene Expression Omnibus (GEO) database. A ceRNA network was constructed utilizing bioinformatic tools. Kaplan-Meier survival analysis showed that lncR-C3orf35 and HMGB1 were associated with poor prognosis of osteosarcoma patients. Furthermore, results of Gene Set Enrichment Analysis (GSEA) suggested that lncR-C3orf35 may be involved in cellular invasion, the Toll-like receptor signaling pathway, and immune cell infiltration in the tumor microenvironment. Further analysis showed that patients with osteosarcoma metastasis expressed higher levels of lncR-C3orf35 and HMGB1 compared to metastasis-free patients. Moreover, the metastasis-free survival rate of the high lncR-C3orf35/HMGB1 expression group was significantly lower than that of the low expression group. The ESTIMATE algorithm was used to calculate the immune score and stromal scores for each sample. High lncR-C3orf35 and HMGB1 levels were correlated with low immune scores. ImmuCellAI analysis revealed that a low proportion of macrophage infiltration was associated with high lncR-C3orf35 and HMGB1 expression. The differential expression of lncR-C3orf35, miR-142-3p, and HMGB1 was further verified by quantitative real-time PCR. This study indicates that lncR-C3orf35 could be considered as a novel potential biomarker and therapeutic target of osteosarcoma, which may contribute to a better understanding of ceRNA regulatory mechanisms.

4.
Nat Cell Biol ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020597

RESUMO

PIWI-interacting RNAs (piRNAs) are abundantly expressed during cardiac hypertrophy. However, their functions and molecular mechanisms remain unknown. Here, we identified a cardiac-hypertrophy-associated piRNA (CHAPIR) that promotes pathological hypertrophy and cardiac remodelling by targeting METTL3-mediated N6-methyladenosine (m6A) methylation of Parp10 mRNA transcripts. CHAPIR deletion markedly attenuates cardiac hypertrophy and restores heart function, while administration of a CHAPIR mimic enhances the pathological hypertrophic response in pressure-overloaded mice. Mechanistically, CHAPIR-PIWIL4 complexes directly interact with METTL3 and block the m6A methylation of Parp10 mRNA transcripts, which upregulates PARP10 expression. The CHAPIR-dependent increase in PARP10 promotes the mono-ADP-ribosylation of GSK3ß and inhibits its kinase activity, which results in the accumulation of nuclear NFATC4 and the progression of pathological hypertrophy. Hence, our findings reveal that a piRNA-mediated RNA epigenetic mechanism is involved in the regulation of cardiac hypertrophy and that the CHAPIR-METTL3-PARP10-NFATC4 signalling axis could be therapeutically targeted for treating pathological hypertrophy and maladaptive cardiac remodelling.

5.
Anal Bioanal Chem ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33011840

RESUMO

A sensitive and portable microfluidic electrochemical array device (µFED) was developed for the immunoassay of trace amounts of human cardiac troponin I (cTnI), which is an attractive biomarker for acute myocardial infarction (AMI). The classical "sandwich" method was adopted for the immunoassay. The capture antibody was immobilized using a self-assembled monolayer (SAM) technique, and the process was reorganized to be compatible with the bonding process. The detection antibody was labeled with alkaline phosphatase (AP) for signal amplification. The performance of the µFED was improved by eliminating the shielding effect of the microelectrode array (MEA) integrated in the µFED. The effects of the interstice and the width of the MEA on the response peak current were analyzed and simulated. The concentration gradient, about 3% of the gradient at the surface, was considered as the criterion for estimation of the optimal interstice between electrodes, and its effectiveness was proved. A stable and miniaturized reference electrode was integrated in the µFED, and its potential deviation was less than 5 mV in 15 min. These efforts resulted in the enhanced immunoassay performance of the µFED. A low limit of detection of about 5 pg/mL was obtained in serum samples, and the response current was proportional to the logarithm of concentration from 50 pg/mL to 1 µg/mL. The immunoassay process was accomplished in 15 min. The µFED was thus qualified and is a promising candidate for point-of-care immunoassay of cTnI. Graphical abstract.

6.
Angiogenesis ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33011960

RESUMO

Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Increasing reports demonstrated that non-coding RNAs (ncRNAs) have been crucially involved in the development of CVDs. Piwi-interacting RNAs (piRNAs) are a novel cluster of small non-coding RNAs with strong uracil bias at the 5' end and 2'-O-methylation at the 3' end that are mainly present in the mammalian reproductive system and stem cells and serve as potential modulators of developmental and pathophysiological processes. Recently, piRNAs have been reported to be widely expressed in human tissues and can potentially regulate various diseases. Specifically, concomitant with the development of next-generation sequencing techniques, piRNAs have been found to be differentially expressed in CVDs, indicating their potential involvement in the occurrence and progression of heart diseases. However, the molecular mechanisms and signaling pathways involved with piRNA function have not been fully elucidated. In this review, we present the current understanding of the piRNAs from the perspectives of biogenesis, characteristics, biological function, and regulatory mechanisms, and highlight their potential roles and underlying mechanisms in CVDs, which will provide new insights into the potential applications of piRNAs in the clinical diagnosis, prognosis, and therapeutic strategies for heart diseases.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33038039

RESUMO

The ability to assemble intricately connected topologies from primary or secondary building units (SBUs) provides great prospective to expand the library of metal-organic frameworks (MOFs). Further development of MOFs requires an establishment of hierarchical interaction within the framework. Herein, we report a series of mesoporous rare-earth (RE) MOFs that are constructed from an unusual 12-connected π-stacked pyrene supramolecular building block and a typical 12-connected RE 6 cluster (RE = Eu, Y, Yb, Tb, and Ce). The judicious design of a butterfly-shape pyrene ligand with a tert-butyl substituent enables the formation of the disordered 12-connected organic SBUs on its strong intermolecular π-π interactions. The assembly of 12-connected inorganic cuboctahedron SBUs and 12-connected organic distorted hexagonal prism SBUs generates an unprecedented network that can be further simplified into a 4,4-connected pts net linked from planar square and tetrahedra. This work provides fresh insights into the design and synthesis of frameworks constructed from coordinatively, covalently and noncovalently linked building units, and also offers accesses to unknown MOF structures based on organic SBUs that still remains largely undiscovered.

8.
Acta Biomater ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007488

RESUMO

Zinc (Zn) and its alloys are receiving great attention as promising biodegradable materials due to their suitable corrosion resistance, good biocompatibility, and highly desirable biofunctionality. Nevertheless, the low mechanical strength of pure Zn impedes its practical clinical application and there have been calls for further research into the Zn alloys and thermomechanical processes to enhance their mechanical properties and biocompatibility. Here, we report on the alloying efficacy of rare earth elements (REEs) including erbium (Er), dysprosium (Dy), and holmium (Ho) on the microstructure, mechanical properties, corrosion and wear behavior, and in vitro biological properties of Zn-1Mg-0.1RE alloys. Microstructural characterization revealed that the addition of 0.1 wt.% REEs had a significant refining effect on the grain size of the α-Zn matrix and the second phases of the alloys. Alloying of the REEs and hot-rolling effectively improved the mechanical properties due to both precipitation strengthening of the second phases of ErZn5, DyZn5, and Ho2Zn17 and grain-refinement strengthening. The highest ultimate tensile strength of 259.4 MPa and yield strength of 234.8 MPa with elongation of 16.8% were achieved in the hot-rolled Zn-1Mg-0.1Ho. Alloying of REEs also improved the wear and corrosion resistance, and slowed down the degradation rate in Hanks' solution. Zn-1Mg-0.1Er showed the highest cytocompatibility of MC3T3-E1 cells cultured directly on the alloy surface and of MG-63 cells cultured in the alloy extract. Zn-1Mg-0.1Dy showed the best anticoagulant property among all the alloys. Overall, these Zn-1Mg-0.1RE (Er, Dy, and Ho) alloys can be considered promising biodegradable metallic materials for orthopedic applications.

10.
Chem Rev ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33049142

RESUMO

Metal-organic frameworks (MOFs), constructed from organic linkers and inorganic building blocks, are well-known for their high crystallinity, high surface areas, and high component tunability. The stability of MOFs is a key prerequisite for their potential practical applications in areas including storage, separation, catalysis, and biomedicine since it is essential to guarantee the framework integrity during utilization. However, MOFs are prone to destruction under external stimuli, considerably hampering their commercialization. In this Review, we provide an overview of the situations where MOFs undergo destruction due to external stimuli such as chemical, thermal, photolytic, radiolytic, electronic, and mechanical factors and offer guidelines to avoid unwanted degradation happened to the framework. Furthermore, we discuss possible destruction mechanisms and their varying derived products. In particular, we highlight cases that utilize MOF instability to fabricate varying materials including hierarchically porous MOFs, monolayer MOF nanosheets, amorphous MOF liquids and glasses, polymers, metal nanoparticles, metal carbide nanoparticles, and carbon materials. Finally, we provide a perspective on the utilization of MOF destruction to develop advanced materials with a superior hierarchy for various applications.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33052847

RESUMO

OBJECTIVE: the objective of this work is to develop a robust method for myoelectric control towards alleviating the in-terference of electrode shift. METHODS: In the proposed method, a preprocessing approach was first performed to convert high-den-sity surface electromyogram (HD-sEMG) signals into a series of images, and the electrode shift appeared as pixel shift in these im-ages. Next, a data augmentation approach was applied to the train-ing data from just one position (no shift), so as to simulate HD-sEMG images derived from fictitious shift positions. The dilated convolutional neural network (DCNN) was subsequently adopted for classification. Compared to common convolutional neural net-work, DCNN always contained a larger receptive field that was supposed to be adept at mining wider spatial contextual infor-mation in images. This property was further confirmed to facili-tate the classification of myoelectric patterns using HD-sEMG. The performance of the proposed method was evaluated with HD-sEMG data recorded by a 10 10 electrode array placed over forearm extensors of ten subjects during their performance of six wrist and finger extension tasks. RESULTS: Under a variety of actual electrode shift conditions, the proposed method achieved a mean classification accuracy of 95.34%, and it outperformed other com-mon methods. CONCLUSION: This work demonstrated feasibility and usability of combining data augmentation and DCNN in predict-ing myoelectric patterns in the context of electrode shifts. Signifi-cance: The proposed method is a practical solution for robust my-oelectric control against electrode array shifts.

12.
Occup Environ Med ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060188

RESUMO

OBJECTIVE: To explore the level and influencing factors of frontline nurses' post-traumatic growth (PTG) during COVID-19 epidemic. METHODS: A cross-sectional survey was conducted in February 2020 in three hospitals in China. The Post-traumatic Growth Inventory (PTGI) was used to investigate the PTG of frontline nurses. Data on related factors, including demographic characteristics and subjective variables, were collected. The Event-Related Rumination Inventory was used to assess rumination. Pearson's or Spearman's correlation was calculated for bivariate analysis. Independent sample t-tests or one-way analysis of variance and multiple linear regression analysis were used to examine the related factors. RESULTS: A total of 179 frontline nurses were recruited, and 167 were included in the analyses. The mean PTG score was 70.53±17.26. The bivariate analyses showed that deliberate rumination was modestly positively correlated with PTG (r=0.557, p<0.01), while intrusive rumination had a modest negative correlation with PTG (r=-0.413, p<0.01). Multiple linear regression demonstrated that working years, self-confidence in frontline work, awareness of risk, psychological intervention or training during the epidemic and deliberate rumination were the main influencing factors of PTG among frontline nurses and accounted for 42.5% of the variance (F=31.626, p<0.001). CONCLUSIONS: The PTG of frontline nurses was at a medium to high level and was influenced by working years, self-confidence in frontline work, awareness of risk, psychological intervention or training and deliberate rumination. It is necessary to strengthen psychological guidance and training for frontline nurses and promote their deliberate rumination on epidemic events to improve their PTG.

13.
Small ; : e2004188, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043586

RESUMO

In order to further overcome the shortage of electrodes with additive/binder and modulate the structure of NiCo2 O4 for supercapacitors, ultrathin NiCo2 O4 nanosheet arrays have been in situ grown on Ni foam by optimizing hydrothermal reactions based on crystal growth dynamics. The structure of ultrathin NiCo2 O4 nanosheet arrays can expose more active sites, provide abundant diffusion channels and buffer the stress caused by phase transition during charge-discharge process of supercapacitors. The optimized hydrothermal reactions can provide more ordered crystal orientations by keeping nanosheets on Ni foam completely coming from in situ growth, which will decrease the inner resistance of ultrathin NiCo2 O4 nanosheets and improve the efficiency and kinetics of electrons transfer. By the virtue of such remarkable features, the electrochemical results confirm the rationality of structural modulation and crystal orientations optimization with a drastically enhanced specific capacitance of 2017.8 F g-1 , admirable rate performance of 93.2% and outstanding stability retention of 90.9% after cycling 5000 times. More impressively, the assembled flexible solid-state asymmetric supercapacitor (ASC) shows superior energy density, power density, and high stability. The modification strategy in this paper may throw light on the rational design of new generation advanced electrode materials for high-performance flexible supercapacitors.

14.
J Colloid Interface Sci ; 583: 188-195, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33002691

RESUMO

Widespread approaches to fabricate surfaces with aligned nanostructured topographies have been stimulated by opportunities to enhance interface performance by combing physical and chemical effects, in which brush-coating technology (BCT) is a cost-effective and feasible method for aligned film and large-scale production. Here, we reported a BCT process to realize the alignment of various 1D nanostructures through mechanical design that provides a more precise and higher shear force. By regulating the viscosity of dispersion, shear force is proved to be 24 and 20.3 times larger (when the volume ratio of water and glycerol is 1:3) according to the theoretical calculation and ANSYS simulating calculation results respectively, which plays a vital role in brush coating process. The universality was demonstrated by the alignment of one-dimension nanomaterials with different diameters, including silver nanowires (~80 nm), molybdenum trioxide nanobelts (~150 nm), vanadium pentoxide nanobelts (~150 nm) and bismuth sulfide nanobelts (~200 nm), et al., which in consequence have different alignment ratios. Meanwhile, anisotropic and flexible electrical conductors (the resistance anisotropic ratio was 2) and thermoelectric films (Seebeck coefficient was calculated to be 56.7 µV/K) were demonstrated.

15.
Biosens Bioelectron ; 166: 112453, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32862845

RESUMO

Developing photoactive materials with wide spectral response is critical to improve the sensitivity of PEC biosensors. Herein, a sensitive photoelectrochemical (PEC) aptasensor was fabricated based on Bi surface plasmon resonance (SPR)-promoted BiVO4/g-C3N4 (Bi/BiVO4/g-C3N4) as photoactive material for the detection of oxytetracycline (OTC). Ternary Z-scheme Bi/BiVO4/g-C3N4 heterojunction exhibited widest spectral response and best PEC activity compared to g-C3N4, BiVO4, Bi/BiVO4, and BiVO4/g-C3N4. The wide spectral response and high PEC activity could be attributed to three reasons: Firstly, the SPR effect of Bi could greatly increase light harvesting; Secondly, Bi served as an electron conduction bridge between BiVO4 and g-C3N4 to form Z-scheme structure, significantly accelerating the separation of photogenerated carriers; Thirdly, the synergism of Z-scheme heterojunction and the SPR effect of Bi efficiently boosted the photoelectric response. Based on the above sensitization strategies, the proposed PEC aptasensor for OTC determination showed a wide linear range of 0.01-1000 nM and a low detection limit (S/N = 3) of 3.3 × 10-3 nM. Moreover, the high stability, satisfactory repeatability and favorable practicability of the fabricated PEC aptasensor revealed the potential applications for accurate monitoring of antibiotics in environmental media.

16.
Appl Opt ; 59(26): 7961-7967, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32976471

RESUMO

Direct reconstruction of the noncontact time-domain fluorescence molecular lifetime tomography (TD-FMLT) with current nonlinear algorithms has suffered from complexity and heavy computation loads of the physical model for a large imaging area in TD-FMLT. In this work, we discretize the system matrix along time points and apply a linearized reconstruction algorithm using the fused least absolute shrinkage and selection operator method. The reconstructed yield map and object geometry are used as a priori information to mitigate the ill conditions. This approach is implemented on a fully noncontact TD-FMLT system equipped with a femtosecond pulse laser and a high-speed, time-gated camera. We validate the methodology using both numerical simulations and inhomogeneous phantom experiments. The results exhibit good localization accuracy for fluorescent targets and an efficient computation capability for the reconstruction of fluorescence lifetime in noncontact TD-FMLT. We envision that the proposed linear scheme for the direct reconstruction method in noncontact TD-FMLT has a significant potential for in vivo preclinical studies.

17.
Global Spine J ; : 2192568220960406, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32975454

RESUMO

STUDY DESIGN: This was a prospective controlled study. OBJECTIVE: To compare the accuracy and clinical outcomes of robot-assisted (RA) and fluoroscopy-guided (FG) pedicle screw placement in posterior cervical surgery. METHODS: This study included 58 patients. The primary outcome measures were the 1-time success rate and the accuracy of pedicle screw placement according to the Gertzbein-Robbins scales. The secondary outcome measures, including the operative time, intraoperative blood loss, hospital stay, cumulative radiation time, radiation dose, intraoperative advent events, and postoperative complications, were recorded and analyzed. The Japanese Orthopedics Association (JOA) scores and Neck Disability Index (NDI) were used to assess the neurological function of patients before and at 3 and 6 months after surgery. RESULTS: The rate of grade A was significantly higher in the RA group than in the FG group (90.6% and 71.1%; P < .001). The clinically acceptable accuracy was 97.2% in the RA group and 90.7% in the FG group (P = .009). Moreover, the 1-time success rate was significantly higher in the RA group than in the FG group. The RA group had less radiation time (P < .001) and less radiation dose (P = .002) but longer operative time (P = .001). There were no significant differences in terms of intraoperative blood loss, hospital stay, intraoperative adverse events, postoperative complications, JOA scores, and NDI scores at each follow-up time point between the 2 groups. CONCLUSIONS: The RA technique achieved higher accuracy and 1-time success rate of pedicle screw placement in posterior cervical surgery while achieving comparable clinical outcomes.

18.
Global Spine J ; : 2192568220959036, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985251

RESUMO

STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the effects of percutaneous transforaminal endoscopic decompression (PTED) for lumbar stenosis associated with adult degenerative scoliosis and to analyze the correlation between preoperative radiological parameters and postoperative surgical outcomes. METHODS: Two years of retrospective data was collected from 46 patients with lumbar stenosis associated with adult degenerative scoliosis who underwent PTED. The visual analog scale (VAS), Oswestry Disability Index, and modified MacNab criteria were used to evaluate the clinical outcomes. Multiple linear regression analysis was used to analyze the correlation between radiological parameters and surgical outcomes. RESULTS: The mean age of the 33 female and 13 male patients was 73.5 ± 8.1 years. The mean follow-up was 27.6 ± 3.5 months (range from 24 to 36). The average coronal Cobb angle was 24.5 ± 8.2°. There were better outcomes of the VAS for leg pain and Oswestry Disability Index after surgery. Based on the MacNab criteria, excellent or good outcomes were noted in 84.78% of patients. Multiple linear regression analysis showed that Cobb angle and lateral olisthy may be the predictors for low back pain. CONCLUSION: Transforaminal endoscopic surgery may be an effective and safe method for geriatric patients with lumbar stenosis associated with degenerative scoliosis. The predictive factors of clinical outcomes were severe Cobb angle and high degree lateral subluxation. Transforaminal endoscopic surgery may not be recommended for patients with Cobb angle larger than 30° combined with lateral subluxation.

19.
J Nanobiotechnology ; 18(1): 138, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993684

RESUMO

BACKGROUND: Neutrophil-based drug delivery system possesses excellent advantages in targeting at tumour because neutrophils are easily recruited by chemotactic factor in tumor microenvironment. Herein, we developed a novel tactic of multistage neutrophils-based nanoparticle delivery system for promoting photothermal therapy (PTT) of lung cancer. RESULTS: Au nanorod (AuNR) was successfully modified with bovine serum albumin (AuNRB) and further conjugated with RGD (AuNRBR), followed by neutrophil internalisation to obtain neutrophils-based delivery system (AuNRBR/N). The engineered neutrophils efficiently migrated across the epithelial cells due to inflammatory signal. They exhibited better toxicity against Lewis cells with laser irradiation in vitro. Moreover, AuNRBR/N showed significantly more targetability to tumour tissue compared with cell carrier-free AuNRBR, as demonstrated in Lewis tumour-bearing mice. The enhanced tumour homing efficiency of AuNRBR/N together with subsequently released AuNRBR from the neutrophils was favourable for further deep tissue diffusion and contributed to the inhibition of the tumour growth in PTT and improved survival rate (over 120 days). CONCLUSIONS: Overall results illustrated that the design of cell-based nanoparticle delivery system for PTT of cancer is promising.

20.
Biochem Biophys Res Commun ; 532(2): 308-314, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-32868076

RESUMO

BACKGROUND: This study aimed to investigate the involvement of lncRNA CTBP1-AS2 in the progression of diabetic nephropathy (DN) by affecting high glucose (HG)-induced human glomerular mesangial cells (HGMCs). METHODS: HGMCs were selected for the establishment of cell injury induced by HG. The expression of CTBP1-AS2, miR-155-5p and FOXO1 was detected by real-time PCR and western blotting. The target association between miR-155-5p and CTBP1-AS2 or FOXO1 was confirmed by dual-luciferase reporter assays. Cell proliferation and oxidative stress were revealed by CCK-8 colorimetry, and the measurement of reactive oxygen species (ROS) and the activities of antioxidant enzymes. Extracellular matrix (ECM) protein accumulation and the production of inflammatory cytokines were investigated by western blotting and ELISA. RESULTS: The expression of CTBP1-AS2 was downregulated, and miR-155-5p was highly expressed in peripheral blood of DN patients and HG-treated HGMCs. Further investigation revealed that CTBP1-AS2 overexpression inhibited proliferation, oxidative stress, ECM accumulation and inflammatory response in HG-induced HGMCs. Mechanical analysis revealed that CTBP1-AS2 regulated FOXO1 expression via sponging miR-155-5p. Rescue experiments demonstrated that miR-155-5p overexpression or FOXO1 inhibition reversed the effects of CTBP1-AS2 in HG-stimulated HGMCs. CONCLUSION: Taken together, this study revealed CTBP1-AS2 attenuated HG-induced HGMC proliferation, oxidative stress, ECM accumulation, and inflammation through miR-155-5p/FOXO1 signaling.

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