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1.
J Colloid Interface Sci ; 593: 251-265, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33744535

RESUMO

In this work, we fabricated vanadium/zinc metal-organic frameworks (V/Zn-MOFs) derived from self-assembled metal organic frameworks, to further disperse ultrasmall Zn2VO4 nanoparticles and encapsulate them in a nitrogen-doped nanocarbon network (ZVO/NC) under in situ pyrolysis. When employed as an anode for lithium-ion batteries, ZVO/NC delivers a high reversible capacity (807 mAh g-1 at 0.5 A g-1) and excellent rate performance (372 mAh g-1 at 8.0 A g-1). Meanwhile, when used in sodium-ion batteries, it exhibits long-term cycling stability (7000 cycles with 145 mAh g-1 at 2.0 A g-1). Additionally, when employed in potassium-ion batteries, it also shows outstanding electrochemical performance with reversible capacities of 264 mAh g-1 at 0.1 A g-1 and 140 mAh g-1 at 0.5 A g-1 for 1000 cycles. The mechanism by which the pseudocapacitive behaviour of ZVO/NC enhances battery performance under a suitable electrolyte was probed, which offers useful enlightenment for the potential development of anodes of alkali-ion batteries. The performance of Zn2VO4 as an anode for SIBs/PIBs was investigated for the first time. This work provides a new horizon in the design ZVO/NC as a promising anode material owing to the intrinsically synergic effects of mixed metal species and the multiple valence states of V.

2.
Biomed Res Int ; 2021: 8868700, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33728345

RESUMO

Several theories on the origin of adenomyosis (ADS) have been proposed, of which the most widely accepted is the fundamental pathogenic role of uterine eutopic endometrium. Emerging evidence suggests that circular RNAs participate in the multiple tumorgenesis. The vital importance of circular RNA PVT1 (circPVT1) in the pathological progress like malignancies has been well documented. Nevertheless, its underlying correlation with ADS remains elusive yet. The purpose of this study was to investigate the expression pattern, regulatory effect, and internal mechanism of circPVT1 in ADS. qRT-PCR was performed to detect the relative mRNA expression of circPVT1, miR-145, and Talin1 in ADS endometrial tissue and cells. The protein level of Talin1 was measured by Western blot and immunochemistry. Immunofluorescence was used to identify the primary endometrial epithelial and stromal cells. circPVT1 knockdown in vitro was achieved by transfecting with specific lentivirus vector CCK-8, and colony formation assays were utilized to assess cell proliferation; meanwhile, the transwell assay was employed for evaluating cell invasion ability. By conducting bioinformatics, dual-luciferase reporter assay, or RNA immunoprecipitation (RIP) experiment, the interaction between miR-145 and circPVT1 or Talin1 was verified. Rescue experiments further determined the regulatory effect of circPVT1/miR-145/Talin1 axis. We found both circPVT1 and Talin1 were markedly upregulated in ADS endometrial tissue and cells, whereas miR-145 was decreased. Elevated expression of circPVT1 was closely related to the severity of dysmenorrhea, menorrhagia, and uterine enlargement of patients with ADS. Knockdown of circPVT1 inhibited adenomyotic epithelial and stromal cell proliferation and invasion. Further mechanistic experiments revealed that circPVT1 negatively regulated miR-145 through serving as a molecular sponge. And the facilitating effect of circPVT1 was partially reversed by miR-145. Talin1 was demonstrated to be a down target of miR-145 and indirectly affected by circPVT1. Our findings unveiled that enhanced circPVT1 may be involved in the pathogenesis of ADS via stimulating endometrial cell proliferation and invasion. The establishment of circPVT1/miR-145/Talin1 pathway might present a novel therapeutic insight for ADS.

3.
Rheumatol Ther ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666893

RESUMO

INTRODUCTION: The objective of this study is to identify the potential risk factors for progression from subclinical to clinical psoriatic arthritis (PsA). METHODS: A retrospective, longitudinal, case-control study was conducted at a single hospital, including 25 patients with clinically confirmed PsA in the case group and 137 controls without confirmed PsA. All patients in both groups had a medical history of subclinical PsA. Various baseline covariates were collected from all patients when they had a status of subclinical PsA. Univariate, multivariate, stratified, and interaction analyses were employed to identify potential risk factors of transiting to clinical PsA from subclinical PsA. RESULTS: In multivariate logistic regression analysis, older age (OR 10.15, 95% CI 2.79-36.91, p = 0.00), alcohol drinking (OR 3.43, 95% CI 1.17-10.12, p = 0.03), elevated high-sensitivity C-reactive protein (hs-CRP) (OR 1.05, 95% CI 1.01-1.09, p = 0.03) were identified as risk factors for transition from subclinical to clinical PsA. Stratified and logistic regression analyses suggest a significant interaction between age and fatty liver. For patients aged less than 45 years old, the association between fatty liver and clinical PsA was statistically significant. CONCLUSIONS: Older age, alcohol drinking, elevated hs-CRP, and the presence of fatty liver at less than 45 years old appear to increase the risk of transition from subclinical to clinical PsA. These findings call for a need to manage these risk factors.

4.
Reprod Sci ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33537874

RESUMO

Adenomyosis (ADS) is a commonly encountered benign gynecological disorder. Epithelial-mesenchymal transition (EMT) may serve a pivotal role in the pathogenesis of ADS. Talin1 has been identified to be implicated in multiple human carcinomas, probably through inducing EMT process. However, available data on the precise molecular mechanism of Talin1 in the pathogenesis of ADS remain extremely scanty. In the present study, we aim to investigate the clinical roles of Talin1 and its effects on uterine endometrial cell migration, invasion, and EMT in ADS. Relative mRNA expression of Talin1, microRNA-145-5p (miR-145-5p), and EMT-related markers was determined by qRT-PCR. Immunohistochemistry and immunofluorescence were performed to examine the distribution of Talin1 in ADS endometrium. Protein levels of Talin1, EMT-related markers, and wnt/ß-catenin pathway were measured by western blot. Wound healing assay and transwell assay were utilized for evaluating cell migration and invasion respectively. Dual-luciferase reporter assay was performed to verify the relationship between Talin1 and miR-145-5p. We found Talin1 was markedly overexpressed in ADS endometrial tissue and cells, whereas miR-145-5p was downregulated. Elevated Talin1 mRNA level might be closely related to some clinicopathological features of ADS. Through functional experiments, we demonstrated that overexpression of Talin1 induced EMT and enhanced migration and invasion ability of ADS eutopic and ectopic endometrial epithelial cells (ADS_Eu_EEC and ADS_Ec_EEC) in vitro through activating the canonical wnt/ß-catenin pathway. From a mechanistic perspective, Talin1 was inversely regulated by miR-145-5p as a direct target. Our findings unveiled that under the regulation of miR-145-5p, Talin1 might promote endometrial cell migration and invasion through inducing EMT, presenting a novel insight for elucidating the pathogenesis of ADS.

5.
Theranostics ; 11(5): 2395-2409, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500732

RESUMO

Alzheimer's disease (AD) is currently ranked as the third leading cause of death for eldly people, just behind heart disease and cancer. Autophagy is declined with aging. Our study determined the biphasic changes of miR-331-3p and miR-9-5p associated with AD progression in APPswe/PS1dE9 mouse model and demonstrated inhibiting miR-331-3p and miR-9-5p treatment prevented AD progression by promoting the autophagic clearance of amyloid beta (Aß). Methods: The biphasic changes of microRNAs were obtained from RNA-seq data and verified by qRT-PCR in early-stage (6 months) and late-stage (12 months) APPswe/PS1dE9 mice (hereinafter referred to as AD mice). The AD progression was determined by analyzing Aß levels, neuron numbers (MAP2+) and activated microglia (CD68+IBA1+) in brain tissues using immunohistological and immunofluorescent staining. MRNA and protein levels of autophagic-associated genes (Becn1, Sqstm1, LC3b) were tested to determine the autophagic activity. Morris water maze and object location test were employed to evaluate the memory and learning after antagomirs treatments in AD mice and the Aß in the brain tissues were determined. Results: MiR-331-3p and miR-9-5p are down-regulated in early-stage of AD mice, whereas up-regulated in late-stage of AD mice. We demonstrated that miR-331-3p and miR-9-5p target autophagy receptors Sequestosome 1 (Sqstm1) and Optineurin (Optn), respectively. Overexpression of miR-331-3p and miR-9-5p in SH-SY5Y cell line impaired autophagic activity and promoted amyloid plaques formation. Moreover, AD mice had enhanced Aß clearance, improved cognition and mobility when treated with miR-331-3p and miR-9-5p antagomirs at late-stage. Conclusion: Our study suggests that using miR-331-3p and miR-9-5p, along with autophagic activity and amyloid plaques may distinguish early versus late stage of AD for more accurate and timely diagnosis. Additionally, we further provide a possible new therapeutic strategy for AD patients by inhibiting miR-331-3p and miR-9-5p and enhancing autophagy.

6.
Reprod Biomed Online ; 42(3): 651-660, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33431336

RESUMO

RESEARCH QUESTION: Does connective tissue growth factor (CTGF) expression relate to adenomyotic fibrosis and determine the correlation between fibrosis with adenomyosis-associated dysmenorrhoea? DESIGN: Protein and mRNA expression of CTGF was detected by Western blots and real-time quantitative polymerase chain reaction in the endometrium of the control group and the eutopic and ectopic endometrium of the adenomyosis group. Collagen fibres and type I collagen in the myometrium were detected by immunohistochemistry and Masson's trichrome staining, and the correlations of CTGF protein and mRNA levels with the degree of fibrosis were analysed. Furthermore, the relationship between the severity of dysmenorrhoea and the degree of fibrosis was determined, and the correlation between uterus size and the degree of fibrosis was also analysed. RESULTS: Levels of CTGF mRNA and protein were significantly higher in patients with adenomyosis than in controls, and CTGF mRNA and protein expression in adenomyosis was positively correlated with fibrosis severity (r = 0.57, P < 0.001 and r = 0.39, P = 0.012), which correlated positively with dysmenorrhoea and uterus size (r = 0.42 and r = 0.6, P < 0.002). CONCLUSIONS: Increased CTGF may contribute to the occurrence and fibrogenic progression of adenomyosis and may play an important role in dysmenorrhoea. The present study may provide ideas for treating adenomyosis-associated dysmenorrhoea.

7.
J Biophotonics ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33389817

RESUMO

Due to the disruption of intraocular pressure (IOP) and central corneal thickness (CCT), diurnal variation in normal young human corneal elasticity is not clear. Using the custom-built air-puff optical coherence elastography, one eye of twenty-one normal subjects is enrolled randomly to measure the central corneal elasticity, IOP, and CCT in different time points within a day. Based on the multi-level model, the corneal elastic modulus is found to have a linear positive relation with IOP (P<0.01) but not CCT (P=0.175) and time point (P=0.174-0.686). A new indicator, corneal elasticity change rate, is proposed to present the magnitude of corneal elasticity change caused by 1 mmHg IOP, which can correct the interference effect of IOP. The results show that the corneal elasticity in the normal young human doesn't have the characteristics of diurnal variation under IOP control. Furthermore, IOP plays an important role in the corneal elasticity, and corneal elasticity change rate can increase the comparability of results between individuals. This article is protected by copyright. All rights reserved.

8.
Reprod Biomed Online ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33189575

RESUMO

RESEARCH QUESTION: Is abnormal gene module expression in the eutopic endometrium related to the occurrence of endometriosis? DESIGN: Nine datasets of normal and eutopic endometrium were searched and collected through the National Center for Biotechnology Information Gene Expression Omnibus, which included genome-wide expression studies of 71 normal cases and 142 endometriosis cases. Surrogate variable analysis was used for dataset integration. The network module and hub genes were selected by weighted gene co-expression network analysis. Machine learning was used to establish a diagnostic model of endometriosis. RESULTS: A gene module that was most relevant to endometriosis was selected through weighted gene co-expression network analysis. After further analysis of this module, four hub genes that represent the function of this module were selected: SCAF11, KRAS, MDM2 and KIF3A. Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the four hub genes revealed that all of them were most highly correlated with genes enriched in the ubiquitin-mediated proteolysis pathway. Moreover, in the correlation analysis between hub genes and Jab1, SCAF11 was found to be closely related to Jab1. Furthermore, hub genes were effective indicators for clinical diagnosis. The deep machine learning diagnostic model based on hub genes was highly sensitive. CONCLUSIONS: The gene module identified is highly correlated with endometriosis. The four hub genes in this module degrade p27kip1 through the ubiquitin-mediated proteolysis pathway to regulate the endometrium cell cycle and affect the development of endometriosis. The hub genes and the deep learning model based on them are valuable for clinical diagnosis.

9.
Autophagy ; : 1-17, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33143524

RESUMO

Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Herein, we identified Optn as a critical molecule of cell fate decision for bone marrow mesenchymal stem cells (MSCs), whose expression decreased in aged mice. Aged mice revealed osteoporotic bone loss, elevated senescence of MSCs, decreased osteogenesis, and enhanced adipogenesis, as well as optn- / - mice. Importantly, restoring Optn by transplanting wild-type MSCs to optn- / - mice or infecting optn- / - mice with Optn-containing lentivirus rescued bone loss. The introduction of a loss-of-function mutant of OptnK193R failed to reestablish a bone-fat balance. We further identified FABP3 (fatty acid binding protein 3, muscle and heart) as a novel selective autophagy substrate of OPTN. FABP3 promoted adipogenesis and inhibited osteogenesis of MSCs. Knockdown of FABP3 alleviated bone loss in optn- / - mice and aged mice. Our study revealed that reduced OPTN expression during aging might lead to OP due to a lack of FABP3 degradation via selective autophagy. FABP3 accumulation impaired osteogenesis of MSCs, leading to the occurrence of OP. Thus, reactivating OPTN or inhibiting FABP3 would open a new avenue to treat senile OP. Abbreviations: ADIPOQ: adiponectin, C1Q and collagen domain containing; ALPL: alkaline phosphatase, liver/bone/kidney; BGLAP/OC/osteocalcin: bone gamma carboxyglutamate protein; BFR/BS: bone formation rate/bone surface; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A/p21: cyclin-dependent kinase inhibitor 1A; CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CDKN2B/p15: cyclin dependent kinase inhibitor 2B; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; COL1A1: collagen, type I, alpha 1; Ct. BV/TV: cortical bone volume fraction; Ct. Th: cortical thickness; Es. Pm: endocortical perimeter; FABP4/Ap2: fatty acid binding protein 4, adipocyte; H2AX: H2A.X variant histone; HE: hematoxylin and eosin; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MAR: mineral apposition rate; MSCs: bone marrow mesenchymal stem cells; NBR1: NBR1, autophagy cargo receptor; OP: osteoporosis; OPTN: optineurin; PDB: Paget disease of bone; PPARG: peroxisome proliferator activated receptor gamma; Ps. Pm: periosteal perimeter; qRT-PCR: quantitative real-time PCR; γH2AX: Phosphorylation of the Serine residue of H2AX; ROS: reactive oxygen species; RUNX2: runt related transcription factor 2; SA-GLB1: senescence-associated (SA)-GLB1 (galactosidase, beta 1); SP7/Osx/Osterix: Sp7 transcription factor 7; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 (human T cell leukemia virus type I) binding protein 1; Tb. BV/TV: trabecular bone volume fraction; Tb. N: trabecular number; Tb. Sp: trabecular separation; Tb. Th: trabecular thickness; µCT: micro computed tomography.

10.
Sci Adv ; 6(43)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33097529

RESUMO

Poor wound healing after diabetes or extensive burn remains a challenging problem. Recently, we presented a physical approach to fabricate ultrasmall silver particles from Ångstrom scale to nanoscale and determined the antitumor efficacy of Ångstrom-scale silver particles (AgÅPs) in the smallest size range. Here we used the medium-sized AgÅPs (65.9 ± 31.6 Å) to prepare carbomer gel incorporated with these larger AgÅPs (L-AgÅPs-gel) and demonstrated the potent broad-spectrum antibacterial activity of L-AgÅPs-gel without obvious toxicity on wound healing-related cells. Induction of reactive oxygen species contributed to L-AgÅPs-gel-induced bacterial death. Topical application of L-AgÅPs-gel to mouse skin triggered much stronger effects than the commercial silver nanoparticles (AgNPs)-gel to prevent bacterial colonization, reduce inflammation, and accelerate diabetic and burn wound healing. L-AgÅPs were distributed locally in skin without inducing systemic toxicities. This study suggests that L-AgÅPs-gel represents an effective and safe antibacterial and anti-inflammatory material for wound therapy.

11.
Proc Conf Assoc Comput Linguist Meet ; 2020: 177-185, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33060888

RESUMO

Many clinical assessment instruments used to diagnose language impairments in children include a task in which the subject must formulate a sentence to describe an image using a specific target word. Because producing sentences in this way requires the speaker to integrate syntactic and semantic knowledge in a complex manner, responses are typically evaluated on several different dimensions of appropriateness yielding a single composite score for each response. In this paper, we present a dataset consisting of non-clinically elicited responses for three related sentence formulation tasks, and we propose an approach for automatically evaluating their appropriateness. Using neural machine translation, we generate correct-incorrect sentence pairs to serve as synthetic data in order to increase the amount and diversity of training data for our scoring model. Our scoring model uses transfer learning to facilitate automatic sentence appropriateness evaluation. We further compare custom word embeddings with pre-trained contextualized embeddings serving as features for our scoring model. We find that transfer learning improves scoring accuracy, particularly when using pre-trained contextualized embeddings.

12.
Dalton Trans ; 49(41): 14536-14542, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33048101

RESUMO

In pursuit of a one-dimensional (1D) porous carbon framework to restrain selenium for advanced lithium-selenium batteries, the Se-hierarchical porous carbon fiber composite (Se-HPCF) is synthesized via a liquid-solution route followed by calcination treatment. The unique architecture of the HPCF, which exhibits a large surface area and high pore volume, is fabricated using sodium lignosulfonate (LN) as a green pore-forming agent via electrospinning. As a cathode material for Li-Se batteries, the Se-HPCF composite exhibits superior electrochemical performance. A reversible capacity of 533 mA h g-1 is maintained at a rate of 0.2C after 50 cycles. In addition, the Se-HPCF composite delivers high rate performance with a high specific capacity of 351 mA h g-1 at 5C. The enhanced capacity retention and rate performance of Se-HPCF is generated by the 1D structure characteristics, and the liquid phase melting diffusion method could be applied to produce other related materials.

13.
Front Microbiol ; 11: 1178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117296

RESUMO

Various endogenous and exogenous agents cause DNA damage, including apurinic/apyrimidinic (AP) sites. Due to their cytotoxic effects, AP sites are usually cleaved by AP endonuclease through the base excision repair (BER) pathway. Deinococcus radiodurans, an extraordinary radiation-resistant bacterium, is known as an ideal model organism for elucidating DNA repair processes. Here, we have investigated a unique AP endonuclease (DrXth) from D. radiodurans and found that it possesses AP endonuclease, 3'-phosphodiesterase, 3'-phosphatase, and 3'-5' exonuclease but has no nucleotide incision repair (NIR) activity. We also found that Mg2+ and Mn2+ were the preferred divalent metals for endonuclease and exonuclease activities, respectively. In addition, DrXth were crystallized and the crystals diffracted to 1.5 Å. Structural and biochemical analyses demonstrated that residue Gly198 is the key residue involved in the substrate DNA binding and cleavage. Deletion of the drxth gene in D. radiodurans caused elevated sensitivity to DNA damage agents and increased spontaneous mutation frequency. Overall, our results indicate that DrXth is an important AP endonuclease involved in BER pathway and functions in conjunction with other DNA repair enzymes to maintain the genome stability.

14.
Am J Physiol Cell Physiol ; 319(4): C657-C666, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32783654

RESUMO

Human flap endonuclease 1 (FEN1) is a structure-specific, multifunctional endonuclease essential for DNA replication and repair. Our previous study showed that in response to DNA damage, FEN1 interacts with the PCNA-like Rad9-Rad1-Hus1 complex instead of PCNA to engage in DNA repair activities, such as stalled DNA replication fork repair, and undergoes SUMOylation by SUMO-1. Here, we report that succinylation of FEN1 was stimulated in response to DNA replication fork-stalling agents, such as ultraviolet (UV) irradiation, hydroxyurea, camptothecin, and mitomycin C. K200 is a key succinylation site of FEN1 that is essential for gap endonuclease activity and could be suppressed by methylation and stimulated by phosphorylation to promote SUMO-1 modification. Succinylation at K200 of FEN1 promoted the interaction of FEN1 with the Rad9-Rad1-Hus1 complex to rescue stalled replication forks. Impairment of FEN1 succinylation led to the accumulation of DNA damage and heightened sensitivity to fork-stalling agents. Altogether, our findings suggest an important role of FEN1 succinylation in regulating its roles in DNA replication and repair, thus maintaining genome stability.

15.
Blood Adv ; 4(15): 3659-3667, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32766856

RESUMO

Many mutations in the signal peptide and propeptide of factor IX (FIX) cause hemophilia B. A FIX variants database reports 28 unique missense mutations in these regions that lead to FIX deficiency, but the underlying mechanism is known only for the mutations on R43 that interfere with propeptide cleavage. It remains unclear how other mutations result in FIX deficiency and why patients carrying the same mutation have different bleeding tendencies. Here, we modify a cell-based reporter assay to characterize the missense mutations in the signal peptide and propeptide of FIX. The results show that the level of secreted conformation-specific reporter (SCSR), which has a functional γ-carboxyglutamate (Gla) domain of FIX, decreases significantly in most mutations. The decreased SCSR level is consistent with FIX deficiency in hemophilia B patients. Moreover, we find that the decrease in the SCSR level is caused by several distinct mechanisms, including interfering with cotranslational translocation into the endoplasmic reticulum, protein secretion, γ-carboxylation of the Gla domain, and cleavage of the signal peptide or propeptide. Importantly, our results also show that the SCSR levels of most signal peptide and propeptide mutations increase with vitamin K concentration, suggesting that the heterogeneity of bleeding tendencies may be related to vitamin K levels in the body. Thus, oral administration of vitamin K may alleviate the severity of bleeding tendencies in patients with missense mutations in the FIX signal peptide and propeptide regions.

16.
Theranostics ; 10(20): 8996-9031, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802176

RESUMO

Silver nanoparticles (AgNPs) have been one of the most attractive nanomaterials in biomedicine due to their unique physicochemical properties. In this paper, we review the state-of-the-art advances of AgNPs in the synthesis methods, medical applications and biosafety of AgNPs. The synthesis methods of AgNPs include physical, chemical and biological routes. AgNPs are mainly used for antimicrobial and anticancer therapy, and also applied in the promotion of wound repair and bone healing, or as the vaccine adjuvant, anti-diabetic agent and biosensors. This review also summarizes the biological action mechanisms of AgNPs, which mainly involve the release of silver ions (Ag+), generation of reactive oxygen species (ROS), destruction of membrane structure. Despite these therapeutic benefits, their biological safety problems such as potential toxicity on cells, tissue, and organs should be paid enough attention. Besides, we briefly introduce a new type of Ag particles smaller than AgNPs, silver Ångstrom (Å, 1 Å = 0.1 nm) particles (AgÅPs), which exhibit better biological activity and lower toxicity compared with AgNPs. Finally, we conclude the current challenges and point out the future development direction of AgNPs.

17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(8): 811-814, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32761584

RESUMO

OBJECTIVE: To develop a cell-based system for the diagnosis of vitamin K-dependent coagulation factor deficiency 1 (VKCFD1). METHODS: In HEK293 cells stably expressing the reporter gene FIX-Gla-PC, the gamma-glutamyl carboxylase (GGCX) gene was knocked out by using CRISPR/Cas9 technology. Enzyme-linked immunosorbent assay (ELISA), DNA sequencing and Western blotting were used to identify the GGCX gene knockout cells. A quickchange point variant method was used to construct the GGCX variant. ELISA was used to assess the influence of GGCX variant on the activity of reporter gene. RESULTS: Two monoclonal cell lines with no reporter activity by ELISA was identified. Edition and knockout of the GGCX gene was confirmed by DNA sequencing and Western blotting. The activity of the reporter gene was recovered by transfection of the wild-type GGCX gene. Thereby two monoclonal cells with GGCX knockout were obtained. By comparing the wild-type and pathogenic GGCX variants, the reporter activity was decreased in the pathogenic variants significantly. CONCLUSION: A cell-based system for the detection of GGCX activity was successfully developed, which can be used for the diagnosis of VKCFD1 caused by GGCX variants.


Assuntos
Transtornos Herdados da Coagulação Sanguínea/genética , Carbono-Carbono Ligases/genética , Vitamina K 1 , Sequência de Bases , Transtornos Herdados da Coagulação Sanguínea/diagnóstico , Sistemas CRISPR-Cas , Técnicas de Inativação de Genes , Células HEK293 , Humanos
18.
Theranostics ; 10(17): 7710-7729, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32685015

RESUMO

Osteosarcoma is a common malignant bone cancer easily to metastasize. Much safer and more efficient strategies are still needed to suppress osteosarcoma growth and lung metastasis. We recently presented a pure physical method to fabricate Ångstrom-scale silver particles (AgÅPs) and determined the anti-tumor efficacy of fructose-coated AgÅPs (F-AgÅPs) against lung and pancreatic cancer. Our study utilized an optimized method to obtain smaller F-AgÅPs and aimed to assess whether F-AgÅPs can be used as an efficient and safe agent for osteosarcoma therapy. We also investigated whether the induction of apoptosis by altering glucose metabolic phenotype contributes to the F-AgÅPs-induced anti-osteosarcoma effects. Methods: A modified method was developed to prepare smaller F-AgÅPs. The anti-tumor, anti-metastatic and pro-survival efficacy of F-AgÅPs and their toxicities on healthy tissues were compared with that of cisplatin (a first-line chemotherapeutic drug for osteosarcoma therapy) in subcutaneous or orthotopic osteosarcoma-bearing nude mice. The pharmacokinetics, biodistribution and excretion of F-AgÅPs were evaluated by testing the levels of silver in serum, tissues, urine and feces of mice. A series of assays in vitro were conducted to assess whether the induction of apoptosis mediates the killing effects of F-AgÅPs on osteosarcoma cells and whether the alteration of glucose metabolic phenotype contributes to F-AgÅPs-induced apoptosis. Results: The newly obtained F-AgÅPs (9.38 ± 4.11 nm) had good stability in different biological media or aqueous solutions and were more effective than cisplatin in inhibiting tumor growth, improving survival, attenuating osteolysis and preventing lung metastasis in osteosarcoma-bearing nude mice after intravenous injection, but were well tolerated in normal tissues. One week after injection, about 68% of F-AgÅPs were excreted through feces. F-AgÅPs induced reactive oxygen species (ROS)-dependent apoptosis of osteosarcoma cells but not normal cells, owing to their ability to selectively shift glucose metabolism of osteosarcoma cells from glycolysis to mitochondrial oxidation by inhibiting pyruvate dehydrogenase kinase (PDK). Conclusion: Our study suggests the promising prospect of F-AgÅPs as a powerful selective anticancer agent for osteosarcoma therapy.

19.
J Biophotonics ; 13(8): e202000104, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32368840

RESUMO

Current elastography techniques are limited in application to accurately assess spatially resolved corneal elasticity in vivo for human eyes. The air-puff optical coherence elastography (OCE) with an eye motion artifacts correction algorithm is developed to distinguish the in vivo cornea vibration from the eye motion and visualize the Lamb wave propagation clearly in healthy subjects. Based on the Lamb wave model, the phase velocity dispersion curve in the high-frequency is calculated to obtain spatially resolved corneal elasticity accurately with high repeatability. It is found that the corneal elasticity has regional variations and is correlated with intraocular pressure, which suggests that the method has the potential to provide noninvasive measurement of spatially resolved corneal elasticity in clinical practice.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32283327

RESUMO

STUDY OBJECTIVE: To report a new improved laparoscopic Vecchietti vaginoplasty in patients with congenital vaginal agenesis and to investigate its efficacy and safety. DESIGN: A retrospective descriptive and case-control study. SETTING: Single academic institution. PATIENTS: Women who were diagnosed with Mayer-Rokitansky-Küster-Hauster (MRKH) syndrome and underwent our new improved laparoscopic Vecchietti procedure from July 2010 to June 2019 were selected as the study group. The eligible participants had congenital vaginal agenesis with normal 46,XX karyotype and ovarian function. Age-matched, nulliparous, sexually active women were selected as the control group. INTERVENTIONS: Women with MRKH syndrome in the study group underwent the novel improved laparoscopic Vecchietti procedure. All participants in both groups were required to complete Female Sexual Function Index and Female Genital Self-Image Scale questionnaires. MEASUREMENTS AND MAIN RESULTS: The effects of our procedure, including the anatomic and functional efficacy of the neovagina, were the primary outcomes. The secondary outcomes consisted of the perioperative complications, surgical morbidities, and long-term postoperative discomfort. A total of 79 patients with MRKH syndrome underwent our new improved Vecchietti vaginoplasty, of whom 44 (55.7%) were diagnosed as Type I MRKH syndrome, whereas 35 (44.3%) were Type II MRKH syndrome. At a 30-month follow-up after surgery, an anatomic neovagina measuring 10.44 cm in length and 1.30 cm in width was achieved. All 79 patients obtained anatomic success with 92.41% of functional efficacy. Compared with 81 age-matched, nulliparous women in the control group, there was no statistical difference regardless of individual measure or total Female Sexual Function Index scores (p >.05). The Female Genital Self-Image Scale assessment showed a significantly lower score in patients undergoing the vaginoplasty (20.14 ± 3.05 vs 22.95 ± 2.12; p <.001). There were no severe perioperative complications except 1 mild bladder injury and 1 transient fever. CONCLUSION: Our novel improved laparoscopic Vecchietti vaginoplasty is a relatively safe and effective method for surgical treatment of congenital vaginal agenesis. It may be an alternative to neovagina creation for reaching satisfying anatomic and functional efficacy and improving patients' sexual function.

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