Publications by authors named "Na Na"

119 Publications

One-Step Prepared Water-Resistant Organic-Inorganic-Hybrid Perovskite Quantum Dots with Zn-Oxygen Vacancies for Attempts at Nitrogen Fixation.

Small 2021 Sep 23:e2103773. Epub 2021 Sep 23.

Key Laboratory of Radiopharmaceuticals, Key Laboratory of Theoretical and Computational Photochemistry, College of Chemistry, Beijing Normal University, No.19, Xinjiekouwai Street, Haidian District, Beijing, 100875, P. R. China.

Applying organic-inorganic hybrid perovskite quantum dots (PQDs) to photocatalytic nitrogen fixation is hindered long-term by the inherent instability in water and tedious preparations. Here, to realize PQD-catalyzed photocatalytic N reduction reaction (NRR), water-resistant PQDs are simply prepared through one-step electrospray synthesis in microseconds. During the fast electrospray, PQDs of Zn/PbO-doped methylammonium lead bromide (Zn/PbO/PC-Zn/MAPbBr , MA: CH NH ) are prepared and part-encapsulated by polycarbonate. The synthesis maintains good water resistance, whose restriction on charge transport is overcome skillfully. Simultaneously, substitution of Zn with Pb on water-resistant surface is also achieved, which fabricates new Zn-oxygen vacancies (Zn-OVs) with Zn/PbO-Zn/MAPbBr type I heterojunction. This facilitates efficient electron transfer from internal heterojunction interface of Zn/MAPbBr PQDs to the surface of Zn/PbO. Demonstrated by theoretical calculations, Zn-OVs promote chemisorption and polarization of N . In addition, s-electrons in exposed Zn become active due to changes of electron filling of Zn orbitals under OVs' co-doping. Thus, photocatalytic N reduction reaction catalyzed by organic-inorganic hybrid PQDs is first achieved in aqueous phase without sacrificial agents being added. This initiates possibilities for photocatalytic applications of organic-inorganic hybrid PQDs in aqueous phase.
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http://dx.doi.org/10.1002/smll.202103773DOI Listing
September 2021

Value of refined care in patients with acute exacerbation of chronic obstructive pulmonary disease.

World J Clin Cases 2021 Jul;9(21):5840-5849

Department of Respiratory and Critical Care Medicine, Jinan Central Hospital, Jinan 250013, Shandong Province, China.

Background: Under physiological conditions, sputum produced during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can move passively with the cilia in the airway; the sputum is gradually excreted from the depth of the airways through the stimulation of the coughing reflex on the sensory nerve on the surface of the airway. However, when the sputum is thick, the cough is weak, or the tracheal cilia are abnormal, sputum accumulation may occur and affect the exchange of oxygen and carbon dioxide in the lung. Furthermore, the presence of pathogenic microorganisms in sputum may cause or aggravate the symptoms of pulmonary infection in patients, which is the main factor leading to AECOPD. Therefore, promoting effective drainage of sputum and maintaining airway opening are key points requiring clinical attention.

Aim: To explore the effect of refined nursing strategies in patients with AECOPD and dysphagia.

Methods: We selected 126 patients with AECOPD and difficulty of expectoration at our hospital, and divided them into a refined care group and a routine care group, with 63 cases each, using a random number table. The two groups of patients were treated with expectorant, anti-infection, oxygen inhalation, and other basic treatment measures; patients in the refined care group were given refined nursing intervention during hospitalization, and the routine care group received conventional nursing intervention. The differences in sputum expectoration, negative pressure suction rate, blood gas parameters, dyspnea score measured through the tool developed by the Medical Research Council (MRC), and quality of life were compared between the two groups.

Results: After 7 d of intervention, the sputum expectoration effect of the refined care group was 62.30%, the effective rate was 31.15%, and the inefficiency rate was 6.56%. The sputum expectoration effect of the routine care group was 44.07%, the effective rate was 42.37%, and the inefficiency rate was 13.56%. The refined care group had better sputum expectoration than the routine care group ( < 0.05). The negative pressure suction rate in the refined care group was significantly lower than that of the routine care group during the treatment (22.95% 44.07%, < 0.05). Before the intervention, the arterial oxygen saturation (PaO) and arterial carbon dioxide saturation (PaCO) values were not significantly different between the two groups ( > 0.05); the PaO and PaCO values in the refined care group were comparable to those in the routine care group after 7 d of intervention ( > 0.05). Before the intervention, there was no significant difference in the MRC score between the two groups ( > 0.05); the MRC score of the refined care group was lower than that of the routine care group after 7 d of intervention, but the difference was not statistically significant ( > 0.05). Before intervention, there was no significant difference in the symptoms, activities, disease impact, or St. George's Respiratory questionnaire (SGRQ) total scores between the two groups ( > 0.05). After 7 days of intervention, the symptoms, activities, and total score of SGRQ of the refined care group were higher than those of the routine care group, but the difference was not statistically significant ( > 0.05).

Conclusion: AECOPD with thick sputum, weak coughing reflex, and abnormal tracheal cilia function will lead to sputum accumulation and affect the exchange of oxygen and carbon dioxide in the lung. Patients with AECOPD who have difficulty expectorating sputum may undergo refined nursing strategies that will promote expectoration, alleviate clinical symptoms, and improve the quality of life.
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http://dx.doi.org/10.12998/wjcc.v9.i21.5840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316959PMC
July 2021

Dynamics of Bacterial and Fungal Communities and Metabolites During Aerobic Exposure in Whole-Plant Corn Silages With Two Different Moisture Levels.

Front Microbiol 2021 15;12:663895. Epub 2021 Jun 15.

Inner Mongolia Engineering Research Center of Development and Utilization of Microbial Resources in Silage, Inner Mongolia Academy of Agriculture and Animal Husbandry Science, Hohhot, China.

The study was aimed to investigate the effect of moisture content on microbial communities, metabolites, fermentation quality, and aerobic stability during aerobic exposure in whole-plant corn silages preserved long time to improve the quality and aerobic stability of the silage during feed-out. Corn plants with two different moisture levels (high-moisture content, 680 g/kg; low-moisture content, 620 g/kg) were harvested at one-third and two-thirds milk-line stages, respectively, ensiled in laboratory-scale silos, and then sampled at 350 day after ensiling and at 2 and 5 day after opening to investigate bacterial and fungal communities, metabolites, and aerobic stability. High-moisture content increased aerobic stability and pH and decreased lactic acid and microbial counts in silages ( < 0.05). During aerobic exposure, the low-moisture silages had higher pH and lactic acid bacterial count and lower lactic acid than the high-moisture silages ( < 0.05); sp. was the most main bacterial species in the silages; and unclassified had an increasing abundance and negatively correlation with aerobic stability of high-moisture silages ( < 0.05), while , , unclassified , and unclassified negative correlated with aerobic stability of low-moisture silages ( < 0.05) with a rising ; the silages had a reducing concentration of total metabolites ( < 0.05). Moreover, the high-moisture silages contained greater total metabolites, saturated fatty acids (palmitic and stearic acid), essential fatty acids (linoleic acid), essential amino acids (phenylalanine), and non-essential amino acids (alanine, beta-alanine, and asparagine) than the low-moisture silages at 5 day of opening ( < 0.05). Thus, the high-moisture content improved the aerobic stability. sp. and sp. dominated the bacterial and fungal communities, respectively; sp. resulted in the aerobic deterioration in high-moisture silages, while the combined activities of sp. and sp. caused the aerobic deterioration in low-moisture silages. The greater aerobic stability contributed to preserve the palmitic acid, stearic acid, linoleic acid, phenylalanine, alanine, beta-alanine, and asparagine during aerobic exposure.
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http://dx.doi.org/10.3389/fmicb.2021.663895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239417PMC
June 2021

Target-triggered and controlled release plasmon-enhanced fluorescent AIE probe for conformational monitoring of insulin fibrillation.

J Mater Chem B 2021 07 15;9(25):5128-5135. Epub 2021 Jun 15.

Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

In this work, we constructed a target-triggered and controlled-release plasmon-enhanced fluorescent AIE probe to realize the purpose of conformational monitoring of insulin fibrillation. We synthesized a novel water-soluble anthracene derivative, 4,4',4'',4'''-(anthracene-9,10-diylbis(ethene-2,1,1-triyl))tetrakis(N,N,N-trimethylbenzenaminium) iodide (BDVAI), with AIE properties, high biocompatibility and good self-assembly effect. Gold nanocages (AuNCs) were selected as the substrate for PEF, and the inner space of hollow AuNCs was filled with BDVAI. Thiol-modified DNA chains were bonded to the surface of AuNCs by Au-S bonds, and an insulin aptamer was combined with the sulfhydryl chain to seal the AuNCs. This PEF-AIE sensor produces different fluorescence signals when interacting with native insulin and fibrillar insulin; thus, monitoring conformational changes in insulin can be realized by detecting fluorescence intensity changes during insulin fibrillation. Based on this design, this system realized sensitive detection of fibrillar insulin with a detection limit of 23.6 pM. This AIE molecular-based PEF fluorescence enhancement system improves the optical properties of fluorescent substances, which is of great significance in improving the detection sensitivity of amyloid fibrils conformational changes and providing a reliable basis for further understanding the pathogenesis of amyloidosis.
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http://dx.doi.org/10.1039/d1tb00712bDOI Listing
July 2021

Inhibition of HMGB1 alleviates myocardial ischemia/reperfusion injury in diabetic mice via suppressing autophagy.

Microvasc Res 2021 Nov 10;138:104204. Epub 2021 Jun 10.

Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention, Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, Guangxi, China. Electronic address:

Background: Diabetes aggravates myocardial ischemia/reperfusion (I/R) injury (MI/RI). The association between high mobility group box 1 protein (HMGB1) and autophagy in diabetic MI/RI remains unknown. Therefore, we investigated whether inhibiting HMGB1 can regulate autophagy in diabetic mice (DM) after I/R injury.

Methods: I/R models of C57BL/KsJ mice and db/db mice were established. Histological changes, infarct size (IS), HMGB1 protein, and autophagy-related proteins were detected after 24h of reperfusion. In DM treatment groups, anti-HMGB1 antibody (H-Ig) was injected via tail vein after reperfusion for 15min, and the above-mentioned experimental methods were performed at the end of reperfusion.

Results: Compared with the I/R group, the pathological myocardial damage and IS were significantly increased in the I/R (DM) group. Additionally, the levels of HMGB1, Beclin1, and LC3II/LC3I ratio were remarkably higher in the I/R (DM) group than those in the I/R group, while p62 level was lower. In the H-Ig (DM) group, injection of H-Ig significantly reduced the IS, as well as alleviated pathological myocardial damage. Moreover, Beclin1, LC3II/LC3I ratio, and p62 levels were notably reversed after this treatment.

Conclusions: I/R-induced myocardium was aggravated by diabetes, which may be related to increased release of HMGB1 and activated autophagy. Inhibition of HMGB1 alleviates diabetic MIRI which was associated with reduced autophagy.
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http://dx.doi.org/10.1016/j.mvr.2021.104204DOI Listing
November 2021

Exosomally derived Y RNA fragment alleviates hypertrophic cardiomyopathy in transgenic mice.

Mol Ther Nucleic Acids 2021 Jun 20;24:951-960. Epub 2021 Apr 20.

Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.

Cardiosphere-derived cell exosomes (CDC) and YF1, a CDC-derived non-coding RNA, elicit therapeutic bioactivity in models of myocardial infarction and hypertensive hypertrophy. Here we tested the hypothesis that YF1, a 56-nucleotide Y RNA fragment, could alleviate cardiomyocyte hypertrophy, inflammation, and fibrosis associated with hypertrophic cardiomyopathy (HCM) in transgenic mice harboring a clinically relevant mutation in cardiac troponin I (cTnI). By quantitative PCR, YF1 was detectable in bone marrow, spleen, liver, and heart 30 min after intravenous (i.v.) infusion. For efficacy studies, mice were randomly allocated to receive i.v. YF1 or vehicle, monitored for ambulatory and cardiac function, and sacrificed at 4 weeks. YF1 (but not vehicle) improved ambulation and reduced cardiac hypertrophy and fibrosis. In parallel, peripheral mobilization of neutrophils and proinflammatory monocytes was decreased, and fewer macrophages infiltrated the heart. RNA-sequencing of macrophages revealed that YF1 confers substantive and broad changes in gene expression, modulating pathways associated with immunological disease and inflammatory responses. Together, these data demonstrate that YF1 can reverse hypertrophic and fibrotic signaling pathways associated with HCM, while improving function, raising the prospect that YF1 may be a viable novel therapeutic candidate for HCM.
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http://dx.doi.org/10.1016/j.omtn.2021.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141670PMC
June 2021

Multifunctional Spiky Topological Nanocapsules for the Discrimination and Differential Inhibition of Inflammation and Cancer.

ACS Appl Mater Interfaces 2021 Jun 28;13(22):25727-25737. Epub 2021 May 28.

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

Accurate discrimination of inflammations and cancers as well as differential inhibition of cancers are significant for early diagnoses and timely treatments. Nanoparticles have become new modalities for diagnosis and therapy. However, they are still challenged by the efficient delivery of multiple reagents into living cells, discriminating multisignals without any interference, and differential treatments of different diseases. Here, multifunctional spiky topological nanocapsules (STNs) are prepared for the discrimination and differential inhibition of inflammation and cancer. With unique spiky hollow architectures, STNs' advantages including excellent loading capacity, enhanced cellular uptake, DNAs' protection against degradation, target-controlled drug release, and efficient endo-/lysosome escape are demonstrated. Therefore, sequential detection of inflammation-related miR-155 (by external modified hairpin DNAs) and the cancer target of monocarboxylate transporter 1 (MCT1) (by internal loaded pH-sensitive carbon dots and MCT1 inhibitor-AZD3965) are achieved. Furthermore, the release of AZD3965 from the cavities of STNs is controlled by the miR-155 amount (first target). Therefore, the released drug of AZD3965 realizes the stage-dependent differential treatment of diseases via cellular acidosis induced by MCT1 inhibition. Via in vivo evaluations of normal, inflammatory, and liver cancer cells/mice, as well as the efficient inhibition of tumor growth, the possibility of STN-based discrimination and differential treatment is confirmed. This would encourage new strategies for multidiagnosis and differential treatment of early-stage cancer.
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http://dx.doi.org/10.1021/acsami.1c04737DOI Listing
June 2021

Particle-in-a-frame gold nanomaterials with an interior nanogap-based sensor array for versatile analyte detection.

Chem Commun (Camb) 2021 May;57(37):4520-4523

Key Laboratory of Theoretical and Computational Photochemistry, College of Chemistry, Beijing Normal University, Beijing 100875, China.

In this work, we studied the catalytic performance of gold nanomaterials, specifically a particle-in-a-frame nanostructure (PIAF) with interior nanogaps. Au PIAF was used to catalyse the 3,3',5,5'-tetramethylbenzidine (TMB) reaction. This array could accurately identify 7 proteins, 5 antioxidants, and 3 cell types.
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http://dx.doi.org/10.1039/d1cc01094hDOI Listing
May 2021

Observation of intermediates by online mass spectrometry to demonstrate the multiple mechanisms of dye-sensitized photocatalysis.

Chem Commun (Camb) 2021 Apr 23;57(32):3921-3924. Epub 2021 Mar 23.

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, P. R. China.

Online mass spectrometry was applied to reveal multiple mechanisms of visible-light irradiated dye-sensitized photocatalysis for o-phenylenediamine oxidation. The reactants, products and short-lived intermediates were recorded and dynamically tracked. Dimer and unexpected trimer intermediates were observed to deduce the stepwise aerobic photooxidation mechanism with multiple routes, which was supported by theoretical calculations.
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http://dx.doi.org/10.1039/d1cc00908gDOI Listing
April 2021

Succession of Bacterial Community During the Initial Aerobic, Intense Fermentation, and Stable Phases of Whole-Plant Corn Silages Treated With Lactic Acid Bacteria Suspensions Prepared From Other Silages.

Front Microbiol 2021 26;12:655095. Epub 2021 Mar 26.

Inner Mongolia Academy of Agriculture and Animal Husbandry Science, Hohhot, China.

The present study was aimed at investigating the bacterial community in lactic acid bacteria (LAB) suspensions prepared from whole-plant corn silage (LAB suspension-CS) and silage (LAB suspension-ES) and the bacterial community succession of whole-plant corn silages inoculated with LAB suspension-CS or LAB suspension-ES during initial aerobic phase, intense fermentation phase, and stable phase. The LAB suspensions were cultured in sterile Man, Rogosa, Sharpe broth at 37°C for 24 h and used as inoculants for ensiling. The chopped whole-plant corn was treated with distilled water (CK), LAB suspension-CS (CSL), or LAB suspension-ES (ESL) and then ensiled in vacuum-sealed plastic bags containing 500 g of fresh forage. Silages were sampled at 0 h, anaerobic state (A), 3 h, 5 h, 10 h, 24 h, 2 days, 3 days, 10 days, 30 days, and 60 days of ensiling with four replicates for each treatment. The results showed that , , and _5 dominated the bacterial community in LAB suspension-CS; was the most predominant bacterial genus in LAB suspension-ES. During the initial aerobic phase (from 0 h to A) of whole-plant corn silage, the pH and the abundances of , , , , and increased. During the intense fermentation phase (from A to 3 days), the pH decreased rapidly, and the microbial counts increased exponentially; the most predominant bacterial genus shifted from to , and then to ; inoculating LAB suspensions promoted the bacterial succession and the fermentation process, and LAB suspension-CS was more effective than LAB suspension-ES. During the stable phase (from 3 to 60 days), the pH and the microbial counts decreased, and dominated the bacterial community with a little decrease. The results also confirmed the existence of LAB fermentation relay during fermentation process, which was reflected by , , and in the first 5 h; , , , , and between 5 and 24 h; and from 24 h to 60 days.
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http://dx.doi.org/10.3389/fmicb.2021.655095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032959PMC
March 2021

Understanding of TEMPO-electrocatalyzed acceptorless dehydrogenation of tetrahydroquinoline by extractive electrospray ionization mass spectrometry.

Chem Commun (Camb) 2021 Mar;57(23):2955-2958

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

The TEMPO-electrocatalyzed acceptorless dehydrogenation of tetrahydroquinoline, a transformation in green synthesis and hydrogen storage, has been investigated by coupling of an electrocatalytic system with in situ extraction electrospray ionization mass spectrometry. Dynamic changes in important species and intermediates were monitored, which evoked an updated AD understanding.
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http://dx.doi.org/10.1039/d0cc08209kDOI Listing
March 2021

Diagnostic Value of Serum N1-Methylnicotinamide in Cervical Cancer Patients.

Clin Lab 2021 Feb;67(2)

Background: The current study evaluated the level of serum N1-methylnicotinamide (me-NAM) in cervical cancer patients and further explored whether serum me-NAM was related to the prognosis of cervical cancer.

Methods: Fifty-eight cases of cervical intraepithelial neoplasia patients, 78 cases of cervical cancer patients, and 52 healthy women were included in the present study. Serum me-NAM concentrations were determined by liquid chromatography with tandem mass spectrometry. Receiver operating characteristic (ROC) curve was used to assess me-NAM as a biomarker and Kaplan-Meier analysis was carried out to evaluate the survival rate.

Results: Our data showed that the level of serum me-NAM in cervical cancer patients was significantly higher than that in the cervical intraepithelial neoplasia group and the healthy control group. Furthermore, the level of me-NAM in cervical cancer tissues of stage I, II, III, and IV was higher than that of those without lymph node metastasis. The area under the receiver operating characteristic curve (ROC) for me-NAM was higher than that of squamous cell carcinoma antigen (SCC Ag) and carbohydrate antigen 125 (CA125) when comparing cervical cancer from CIN or healthy control. The combination of me-NAM and SCC Ag or CA125 could improve the diagnostic efficiency better than SCC Ag or CA125 alone. Compared with me-NAM low expression group, the survival rate and time of me-NAM high expression group were lower and shorter.

Conclusions: Altogether, elevated serum me-NAM levels contribute to the progression of cervical cancer and may be used as a marker for the prognosis of patients with cervical cancer.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200422DOI Listing
February 2021

Integrating Near-Infrared Visual Fluorescence with a Photoelectrochemical Sensing System for Dual Readout Detection of Biomolecules.

Anal Chem 2021 02 5;93(7):3486-3492. Epub 2021 Feb 5.

Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

Compared with traditional visible light-driven fluorescence visualization (FV), near-infrared (NIR)-induced FV is an interesting and promising method, while photoelectrochemical (PEC) immunoassay sensing possesses the advantages of high sensitivity, low cost, and simple instrumentation. We combined PEC sensing with NIR-induced FV together and developed a dual readout sensing platform. In this protocol, based on the antibody-analyte (i.e., antigen, DNA, and RNA) reaction and the sandwich-type structure, CuInS microflowers as the matrix provided the original background photocurrent; chlorin e6 (Ce6) was conjugated to antibody-modified upconversion nanoparticles and formed a signal label for the PEC sensing and naked-eye readout. Different from traditional PEC immunosensors, under NIR illumination, the developed dual mode sensing platform could achieve quick qualitative analysis and quantitative analysis. Preliminary application performance of the proposed biosensor in prostate-specific antigen analysis is acceptable, indicating its promising potential in clinical/biological studies.
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http://dx.doi.org/10.1021/acs.analchem.0c04802DOI Listing
February 2021

CircRNA hsa_circ_0005909 Promotes Cell Proliferation of Osteosarcoma Cells by Targeting miR-338-3p/HMGA1 Axis.

Cancer Manag Res 2021 27;13:795-803. Epub 2021 Jan 27.

Department of Spine Surgery, Zibo Central Hospital, Zibo 255000, People's Republic of China.

Objective: Osteosarcoma (OS) is the most common malignant bone tumor in the pediatric population. The main goal of this study is to investigate the role of hsa_circ_0005909 and the underlying signaling pathway involved in OS.

Methods: Cell proliferation was measured using a CCK-8 assay kit and clone formation assay. Change of RNA and protein expression was determined using RNA extract and quantitative real time PCR (RT-qPCR) assay and Western blotting, respectively. CircInteractome was used to predict the target of circRNA and starBase v2.0 was used to predict the target of miRNAs. Luciferase assay was used to confirm the predicted results from CircInteractome, starBase v2.0, and MirTarget2.

Results: Expression of circ_0005909 was upregulated in both OS tissues and cell lines. The predicted results from CircInteractome, starBase v2.0, and MirTarget2 demonstrated that circ_0005909 could sponge miR-338-3p and that HGMA1 was the direct target of miR-338-3p. Cell viability and cell clones were inhibited by knockdown of circ_0005909 but increased by dual inhibition of circ_0005909 and miR-338-3p. Phosphorylation of ERK, Akt, and PI3K was inhibited by sh-circ_0005909, while this inhibition was repressed by co-transfection of sh-circ_0005909 and HGMA1.

Conclusion: Expression of circ_0005909 was upregulated in both OS tissues and cell lines which upregulated expression of HGMA1 through sponging miR-338-3p, resulting in the activation of MAPK-ERK and PI3K-Akt signaling pathways to promote the development of OS.
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http://dx.doi.org/10.2147/CMAR.S285118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850455PMC
January 2021

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries.

Authors:

Lancet 2021 Jan 21;397(10272):387-397. Epub 2021 Jan 21.

Background: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality.

Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494.

Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70-8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39-8·80) and upper-middle-income countries (2·06, 1·11-3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26-11·59) and upper-middle-income countries (3·89, 2·08-7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications.

Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications.

Funding: National Institute for Health Research Global Health Research Unit.
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http://dx.doi.org/10.1016/S0140-6736(21)00001-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846817PMC
January 2021

Role of First-Trimester Serum C1q/TNF-Related Protein 9 in Gestational Diabetes Mellitus.

Authors:
Na Na Mei Ji

Clin Lab 2020 Dec;66(12)

Background: The current study aims to explore the relationship between gestational diabetes mellitus (GDM) and C1q/TNF-related protein 9 (CTRP9) level in early pregnancy.

Methods: Clinical data of 63 GDM patients and 70 normal pregnant women were included in the present study. Binary logistic regression analysis was used to explore the risk factors for GDM. To determine the value of CTPR9 for predicting GDM, the area under the receiver operating characteristic curve (AUC-ROC) was analyzed. Pearson's correlation assay was performed to explore the relationship between serum CTRP9 and body mass index (BMI) or oral glucose tolerance test (OGTT).

Results: Our data showed that the age, median maternal prepregnancy BMI, and fasting blood glucose during pregnancy of GDM group were significantly higher than those of the control group. ELISA showed the level of first-trimester serum CTRP9 was significantly decreased in GDM patients compared with that of healthy controls. Multiple logistic regression analysis showed that first-trimester serum CTRP9 and BMI were risk factors of GDM. The AUC-ROC showed that the diagnostic efficiency of CTRP9 + BMI was much higher than that of BMI alone. Moreover, first-trimester serum CTRP9 was found to be negatively correlated with BMI or OGTT in GDM patients.

Conclusions: Serum CTRP9 was an independent risk factor for the progression of GDM in pregnant women. Combined use of first-trimester serum CTRP9 and maternal pre-pregnancy BMI may be able to more accurately predict the occurrence of GDM.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200434DOI Listing
December 2020

CHEMICAL REACTION MONITORING BY AMBIENT MASS SPECTROMETRY.

Mass Spectrom Rev 2020 Dec 1. Epub 2020 Dec 1.

Key Laboratory of Radiopharmaceuticals Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, People's Republic of China.

Chemical reactions conducted in different media (liquid phase, gas phase, or surface) drive developments of versatile techniques for the detection of intermediates and prediction of reasonable reaction pathways. Without sample pretreatment, ambient mass spectrometry (AMS) has been applied to obtain structural information of reactive molecules that differ in polarity and molecular weight. Commercial ion sources (e.g., electrospray ionization, atmospheric pressure chemical ionization, and direct analysis in real-time) have been reported to monitor substrates and products by offline reaction examination. While the interception or characterization of reactive intermediates with short lifetime are still limited by the offline modes. Notably, online ionization technologies, with high tolerance to salt, buffer, and pH, can achieve direct sampling and ionization of on-going reactions conducted in different media (e.g., liquid phase, gas phase, or surface). Therefore, short-lived intermediates could be captured at unprecedented timescales, and the reaction dynamics could be studied for mechanism examinations without sample pretreatments. In this review, via various AMS methods, chemical reaction monitoring and mechanism elucidation for different classifications of reactions have been reviewed. The developments and advances of common ionization methods for offline reaction monitoring will also be highlighted.
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http://dx.doi.org/10.1002/mas.21668DOI Listing
December 2020

Metal-DNA coordination based bioinspired hybrid nanospheres for amplification and sensing of microRNA.

J Mater Chem B 2020 12;8(48):11074-11081

Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

Sufficient delivery of biomolecules into cells with high loading efficiency and easy cleavability would be significant for the visualization of biomolecules in living cells. Herein, a facile approach based on nano-wire balls (NWs) for efficient loading, intracellular delivery of nucleic acids and in situ targeted miRNA bioimaging is proposed, by feeding of Zn ions for generating DNA-inorganic hybrid structures with large surface areas and good stability. Given that the versatile and robust hybridization chain reaction (HCR) amplification strategy combines DNA assembly with intracellular assay, the resulting NWs without any complicated modification are capable of enhanced signals for the targeted imaging of cancer cells. This method realized a linear detection range of 100 fM to 10 nM, with a low detection limit of 83.6 fM in vitro, and could be used to effectively differentiate the expression levels of miRNA-21 in living cells. Due to its high loading efficiency, excellent biocompatibility and low toxicity, this system can be used to construct a coordination-based delivery nanoplatform for in situ enzyme-free amplified imaging of miRNAs, expanding the application of DNA-based nanomaterials for cellular delivery and intracellular molecule analysis.
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http://dx.doi.org/10.1039/d0tb02315aDOI Listing
December 2020

Chemiluminescence Resonance Energy Transfer-Based Mesoporous Silica Nanosensors for the Detection of miRNA.

ACS Sens 2020 09 26;5(9):2800-2805. Epub 2020 Aug 26.

Key Laboratory of Radiopharmaceuticals, College of Chemistry, Beijing Normal University, Beijing 100875, China.

The chemiluminescence resonance energy transfer (CRET)-based method is free of autofluorescence interference, which can achieve an extremely high signal-to-background ratio for detection. Nevertheless, this method is still hindered by the inner filter effect, quenching effect, and nonspecific absorption of reported nanoparticles. Herein, mesoporous silica nanomaterials (MSNs) acted as carriers to load both the donor (horseradish peroxidase, HRP) and the acceptor (a functional DNA duplex). This approach realized the construction of a new CRET-based nanosensor for the sensitive detection of miRNA. By controlling the energy-transfer distance with the designed DNAs, the donor emission at 430 nm could be quenched by the adsorption of the dye labeled on the acceptor DNA. The CRET system could be destroyed by releasing acceptor DNA from linker DNA via the competitive hybridization of target miRNA, resulting in emission recovery for quantification. With the cancer biomarker miR-155 as the model, the sensitive and selective detection of miR-155 was achieved, which showed high energy-transfer efficiency, good specificity, favorable biodegradability, and low toxicity. This work provides a potential pathway for biological detection and clinical diagnosis.
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http://dx.doi.org/10.1021/acssensors.0c00747DOI Listing
September 2020

Visualizations of Mercury Methylation and Dynamic Transformations by In Vivo Imaging.

Small 2020 08 8;16(33):e2000072. Epub 2020 Jul 8.

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.

Visualization of Hg(II) and MeHg in their native contexts is significant for examining mercury poisoning, while it is challenging because of indistinguishable fluorescent (FL) signals during FL imaging. Herein, visualizations of mercury methylation and dynamic transformations of Hg(II) and MeHg are achieved in living biological systems. Well distinguishable FL responses (blue emission for Hg(II), yellow emission for MeHg) are obtained by a double-response FL probe (DPAHB) without any interference. As demonstrated by experimental and computational studies, the distinguishable signals are attributed to selective binding with DPAHB and different inhibition of excited-state proton transfer. Through control tests for live-dead markers, mercury methylation is demonstrated to be employed in living biological systems. Therefore, the methylation and dynamic transformations of both ions are monitored in zebrafish by imaging, and these results are confirmed by traditional high-performance liquid chromatography-based methods. The methylation of Hg(II) to MeHg, dynamic transformations and final accumulations of both species in zebrafish tissues are visualized successfully. This method is also convenient for fast evaluation of detoxification reagents. This is the first visualization of in vivo mercury methylation and dynamic transformation of both species and is effective for studying pathological processes in their native contexts.
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http://dx.doi.org/10.1002/smll.202000072DOI Listing
August 2020

Multi-Dimensionally Extended Functionalization Innovates to an Entropy-Driven Detection of Multi-miRNAs for One-Step Cancer Screening and Diagnosis in Living Cells.

Anal Chem 2020 06 22;92(12):8125-8132. Epub 2020 May 22.

Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

Compared with tedious multi-step detections, multi-functional nanoprobes are effective for one-step screening and diagnosis of cancers by multi-detection of microRNAs (miRNAs). However, limited probe density, spatial mutual interference, and low target-triggered hybridization efficiency of nanoprobes will hinder intracellular applications. Here, for obtaining high loading density but low spatial mutual interference between functional biomolecules on nanoprobes, an extended biofunctionalization in three dimensions (the two-dimensional surface and a special "height" direction) is designed. Therefore, a multi-functional probe is constructed for one-step detection of multi-miRNAs for cancer screening and diagnosis. With linker-bridged multiple single-stranded DNAs swung out rigidly, multi-dimensionally extended upconversion nanorods (ME-UCNRs) covered by chitosan are constructed to load and deliver multiple biomolecules into living cells. Escaping from endolysosomes, ME-UCNRs maintain good biological activities of functionalized DNAs for effective detection of multi-miRNAs in living cells. Thereby, with multiple targets of miRNAs, toehold-mediated entropy-driven strand displacements are employed to give respectively changed fluorescent signals via fluorescence resonance energy transfer. Thus, a universal cancer biomarker of miR-21 and two specific liver-cancer biomarkers (miR-199a and miR-224) are efficiently detected through a one-step detection. By discriminating cancer cells from normal ones and determining liver-cancer cells simultaneously, this work innovates an efficient and definite one-step strategy for fast screening and early cancer diagnosis.
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http://dx.doi.org/10.1021/acs.analchem.0c00045DOI Listing
June 2020

Sequencing of Small DNA Fragments with Aggregated-Induced-Emission Molecule-Labeled Nucleotides.

Anal Chem 2020 05 6;92(10):7179-7185. Epub 2020 May 6.

Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.

Sequencing by synthesis is a significant method for high-throughput DNA sequencing. Herein, we synthesized terminal aggregated-induced-emission luminogen (AIEgen) labeled nucleotides (dNTPs-HCAP) that could serve as substrates for some polymerases and applied them into the sequencing of small DNA fragments. In the process of DNA amplification, ratiometric AIEgens are released from dNTPs-HCAP and aggregate through the effects of phosphatase, which results in changes in the ratiometric fluorescent signals. With the AIEgen-labeled nucleotides, we accomplished the sequencing of small DNA fragments through double changes in fluorescence. In addition, we achieved the differentiation of single nucleotide polymorphisms through rolling circle amplification reactions without the addition of signal probes, which is fast and cost-effective. The introduction of ratiometric AIEgens into DNA synthesis makes the detection of DNA sequences more efficient and accurate. Therefore, the development of AIEgen-labeled nucleotides is meaningful for the study of DNA sequencing methods.
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http://dx.doi.org/10.1021/acs.analchem.0c00707DOI Listing
May 2020

Target-Triggered Assembly of Nanogap Antennas to Enhance the Fluorescence of Single Molecules and Their Application in MicroRNA Detection.

Small 2020 05 20;16(19):e2000460. Epub 2020 Apr 20.

State Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.

Nanogap antennas are plasmonic nanostructures with a strong electromagnetic field generated at the gap region of two neighboring particles owing to the coupling of the collective surface plasmon resonance. They have great potential for improving the optical properties of fluorophores. Herein, nanogap antennas are constructed using an aqueous solution-based method to overcome the defects of weak fluorescence and photobleaching associated with traditional organic dyes, and a highly sensitive nanogap antenna-based sensing strategy is presented for the detection of low-abundance nucleic acid biomarkers via a target-triggered strand displacement amplification (SDA) reaction between two DNA hairpins that are tagged to the tips of gold nanorods (Au NRs). In the presence of targets, end-to-end Au NR dimers gradually form, and the fluorophores quenched by the Au NRs exhibit a dramatic fluorescence enhancement due to the plasmon-enhanced fluorescence effect of nanogap antennas. Meanwhile, the SDA reaction results in secondary amplification of fluorescence signals. Combined with single-molecule counting, this method applied in miRNA-21 detection can achieve a low detection limit of 97.2 × 10 m. Moreover, accurate discrimination between different cells through miRNA-21 imaging demonstrates the potential of this method in monitoring the expression level of low-abundance nucleic acid biomarkers.
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http://dx.doi.org/10.1002/smll.202000460DOI Listing
May 2020

Ginkgolic acid inhibits the growth of renal cell carcinoma cells via inactivation of the EGFR signaling pathway.

Exp Ther Med 2020 Apr 27;19(4):2949-2956. Epub 2020 Feb 27.

Department of Urology, 900th Hospital of The Joint Logistics Support Force (People's Liberation Army), Fuzhou, Fujian 350000, P.R. China.

Renal cell carcinoma (RCC) is one of the most common urological malignancies occurring in adult human kidneys worldwide. Recent research on antitumor drugs has focused on plant extracts, a class of compounds that play critical roles in cancer treatment. The present study aimed to investigate the potential antitumor effect of ginkgolic acid (GA) in RCC. Transwell invasion assay, cell counting kit-8 assay and flow cytometry were used to measure cell migration, cell viability and apoptosis, respectively. A network pharmacology approach was applied to identify pathway information, combining molecular docking techniques to screen for key target information. In the present study, GA inhibited the viability and proliferation of RCC cells (786-O and A498), both and , via G arrest. GA also reduced RCC cell invasion and migration. In addition, the epidermal growth factor receptor (EGFR) was identified as a critical target protein of GA, which significantly inactivated EGFR signaling in RCC (P<0.05). Collectively, the present study provided evidence that GA exerts its anticancer function by directly targeting the EGFR signaling pathway, revealing the potential of GA therapy for RCC.
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http://dx.doi.org/10.3892/etm.2020.8570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086188PMC
April 2020

In Situ HO Meter by Visualization in Hydrogels.

ACS Appl Mater Interfaces 2020 Apr 14;12(17):19307-19312. Epub 2020 Apr 14.

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

The solvent content strongly affects the viscoelastic properties and network structure of hydrogels. Because of the gels' structural susceptibility and autofluorescence background, there is still no visual method to evaluate the water content in micropores. Herein, a colorimetric molecular probe (DHBYD) was synthesized for in situ visualization of water content in the micropores of hydrogels. The rapid and reversible colorimetric responses of DHBYD to solvents were obtained, which resulted a full linearity range (0 to 100%) for detecting water content in real time. Demonstrated by theoretical calculations, the sensing was attributed to changes in intramolecular charge transfer via deprotonation of phenol group. A cubic polynomial, on correlation of RGB values with water content, was established for real detection of water content in hydrogels. It reveals a new pathway for simple, in situ, and full-range evaluation of solvent content in micropores of hydrogels without any complicated procedures or expensive instruments. This would achieve fast and in situ monitoring of hydrogels to improve gel properties for better applications. It can be extended to evaluate the solvent content in other fields such as synthesis and industrial applications.
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http://dx.doi.org/10.1021/acsami.0c03116DOI Listing
April 2020

An Acetone Sensor Based on Plasma-Assisted Cataluminescence and Mechanism Studies by Online Ionizations.

Anal Chem 2019 12 27;91(24):15763-15768. Epub 2019 Nov 27.

Key Laboratory of Theoretical and Computational Photochemistry, College of Chemistry , Beijing Normal University , Beijing 100875 , China.

The new development of noninvasive diagnosis in breath analysis requires the fabrication of inexpensive and rapid sensing technologies, whose sensing mechanisms are further encouraged to be studied. Here based on the dramatically enhanced plasma-assisted cataluminescence (PA-CTL) signals, a new sensor was constructed for the detection of acetone, an important biomarker of diabetes mellitus in breath. As demonstrated, the PA-CTL-based sensor showed good sensitivity, repeatability, and selectivity in acetone detection, which also displayed good recovery and stability in exhaled breath. An online ionization system of low-temperature plasma mass spectrometry was designed to couple with the PA-CTL sensor for examining changes of molecules during the sensing. For the first time, some important ions were recorded in real time, which helped to clear the reaction mechanism of radical-based catalytic oxidation combined with the CTL data. By the fabrication and relative comprehensive understanding of the PA-CTL sensor for acetone detection, this work would promote the development of CTL sensing techniques and inspire a potential pathway for rapid and noninvasive diagnosis.
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http://dx.doi.org/10.1021/acs.analchem.9b04023DOI Listing
December 2019

Ultrasensitive detection of prostate specific antigen using a personal glucose meter based on DNA-mediated immunoreaction.

Analyst 2019 Oct;144(20):6019-6024

Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.

With the increase in cancer risk, early immunodiagnosis is of great significance for timely therapy. In this work, a DNA-mediated immunosensor for the highly sensitive detection of prostate specific antigen (PSA) is proposed, which is mainly based on a portable personal glucose meter (PGM). Gold nanoparticles (AuNPs) functionalized with PSA detection antibodies and DNA primers are introduced. When the target of the PSA is present, rolling circle amplification (RCA) reactions on AuNPs are triggered and numerous repeated RCA products hybridize with the DNA-conjugated invertase; thus the signal of the PGM is generated and the PSA is quantified indirectly. With the use of a portable PGM, our method realizes a linear detection range of 0.003-50 ng mL-1, with a low detection limit of 0.1 pg mL-1, which is comparable to that of the traditional methods using expensive apparatus. Besides, the analysis of clinical human serum samples is performed to investigate its good practicability. This simple, low-cost, and miniaturized immunosensor is promising for the point-of-care testing of cancer markers.
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http://dx.doi.org/10.1039/c9an01558bDOI Listing
October 2019

A versatile single-molecule counting-based platform by generation of fluorescent silver nanoclusters for sensitive detection of multiple nucleic acids.

Nanoscale 2019 Sep 28;11(35):16606-16613. Epub 2019 Aug 28.

State Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

The good photostability and strong brightness of individual DNA-templated silver nanoclusters (DNA-AgNCs) have been confirmed by single-molecule imaging in this work and DNA-AgNCs as a new class of outstanding fluorophores are applied in the construction of single-molecule counting-based probes for the first time. Based on the fluorescent AgNC-generating molecular beacons (AgNC-MBs), we present a versatile method for simultaneous analysis of multiple nucleic acids. Distinct from previous designs in which a AgNC stabilizing sequence is incorporated into the stem of a hairpin DNA to form the AgNC-MB, we prepared a nicked MB in which the AgNC stabilizing sequence is hybridized with the longer stem of a single-stranded DNA (ssDNA) with a stem-loop structure. Our proposed AgNC-MB is activated by probe-target hybridization then releasing the AgNC stabilizing sequence via a toehold-mediated strand displacement reaction, the versatility of which has been greatly improved because bases in the target-binding region are not involved in the formation of DNA-AgNCs. As a proof of concept, the simultaneous detection of two breast cancer-related MicroRNAs (miR-21 and let-7a miRNA) has been achieved with total internal reflection fluorescence (TIRF)-based imaging and the detection sensitivity of our method has been demonstrated to be improved by at least two orders of magnitude compared with conventional AgNC-MBs. Furthermore, in the single-nucleotide mutation identification assay, the simultaneous detection strategy introduces a competitive reaction between the two probe-target hybridizations, resulting in the excellent discrimination ability of the AgNC-MB sensing platform and the mutant-type targets can be successfully detected at low abundance. The new AgNC-MB sensing platform demonstrated potential to make AgNCs an attractive alternative to conventional organic dyes for single-molecule studies.
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http://dx.doi.org/10.1039/c9nr04608aDOI Listing
September 2019

Biodegradable nanosyringes for intracellular amplification-based dual-diagnosis and gene therapy in single living cells.

Chem Sci 2019 Jun 6;10(24):6113-6119. Epub 2019 May 6.

Key Laboratory of Theoretical and Computational Photochemistry , College of Chemistry , Beijing Normal University , Beijing 100875 , China . Email:

The efficient delivery of biomolecules into living cells as well as their easy biodegradation have been challenges for the application of intracellular amplification for sensitive multiple-diagnosis and gene therapy for cancer. Herein, new strategies of amplification-based dual-detection of cancer biomarkers (Let-7a miRNA and VEGF) and gene therapy for cancers are put forward. These are achieved through biodegradable nanosyringes (NSs), rigid and sharp but degradable , which are applied for the efficient loading, delivery and release of biomolecules (enzymes, nucleic acids, and even silencing RNA) into living cells. After penetrating cell membranes and escaping from endosomes through their rigid and sharp tips, NSs release biomolecules for fast and easy "one-step" rolling circle amplification (ring formation and amplification) in single living cells. Therefore, based on signals from two probes, FAM-Probe and Cy5-Probe, that selectively bind to amplification products, 100 aM of Let-7a and 100 fM of VEGF could be detected, which are much lower than reported values. Furthermore, siRNAs can also be delivered by NSs for gene therapy, and their therapeutic effect was evaluated by their antitumor efficacy in CCRF-CEM subcutaneous xenograft nude mice. Rigid and degradable , NSs show potential for achieving fast, sensitive and safe cancer diagnosis and efficient therapy.
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http://dx.doi.org/10.1039/c9sc01894hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585592PMC
June 2019

V211D Mutation in MEK1 Causes Resistance to MEK Inhibitors in Colon Cancer.

Cancer Discov 2019 09 21;9(9):1182-1191. Epub 2019 Jun 21.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

We report the emergence of the novel gatekeeper mutation in a patient with colon cancer treated with the allosteric MEK inhibitor binimetinib and the anti-EGFR antibody panitumumab. The mutation concurrently occurs in the same cell with and leads to RAF-independent activity but remains regulated by RAF. The V211D mutation causes resistance to binimetinib by both increasing the catalytic activity of MEK1 and reducing its affinity for the drug. Moreover, the mutant exhibits reduced sensitivity to all the allosteric MEK inhibitors tested. Thus, this mutation serves as a general resistance mutation for current MEK inhibitors; however, it is sensitive to a newly reported ATP-competitive MEK inhibitor, which therefore could be used to overcome drug resistance. SIGNIFICANCE: We report a resistance mechanism to allosteric MEK inhibitors in the clinic. A mutation developed in a patient with colon cancer on MEK and EGFR inhibitors. This mutant increases the catalytic activity of MEK1 and reduces its affinity for binimetinib, but remains sensitive to ATP-competitive MEK inhibitors..
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http://dx.doi.org/10.1158/2159-8290.CD-19-0356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726556PMC
September 2019
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