Search

Aggregation-induced emission (AIE) molecules that can avoid the aggregation-caused quenching (ACQ) effect and break the concentration limit have been widely used for biosensing. Similar to fluorescence dyes, AIE molecules can be chemiexcited simply by a peroxyoxalate-based chemiluminescence (CL) reaction, but the hydrolysis of peroxyoxalate is often a problem in an aqueous solution. Herein, we report an AIE effect within peroxyoxalate-loaded silica nanoparticles (PMSNs) for an efficient harvest of CL energy as well as alleviation of bis(2,4,5-trichloro-6-carbopentoxyphenyl) oxalate (CPPO) hydrolysis. Peroxyoxalate (i.e., CPPO) and AIE molecules (i.e., 1,2-benzothiazol-2-triphenylamino acrylonitrile, BTPA) were loaded together within the mesoporous silica nanoparticles (MSNs) to synthesize the BTPA-PMSN nanocomposite. The BTPA-PMSNs not only allowed CPPO to be dispersed well in an aqueous solution but also avoided the hydrolysis of CPPO. Meanwhile, the proximity between BTPA and CPPO molecules in the mesopores of MSNs facilitated the BTPA aggregate to harvest the energy from CL intermediates. Hence, the CL system of BTPA-PMSNs can work efficiently in aqueous solutions at a physiological pH. The CL quantum yield of the BTPA-PMSN system was measured to be 9.91 × 10

Chemiluminescence (CL) has been widely used for bioanalysis owing to its high sensitivity, low background and simplicity. However, most of the CL systems need acidic/alkaline conditions or organic solvent to enhance their luminescent efficiency, and the non-physiological conditions can usually lead to the misfunction of biomolecules during biosensing. Herein, we report a highly luminous CL system under physiological conditions based on carbon dots-bis(2-carbopentyloxy-3,5,6-trichlorophenyl) oxalate (CDs-CPPO) micelles, and further used it in biosensing application. In the CL system, the amphiphilic surfactant packed CPPO and hydrophobic CDs together to form CDs-CPPO micelles. Such micelles solution not only isolated the CPPO from water to prevent its hydrolysis but also made the close proximity between CPPO and CDs, thus significantly enhancing the CDs quantum yield. The CL quantum yield was calculated to be 5.26 × 10−4 einsteins/mol, about 200-fold higher than that of the most commonly used luminol CL system. The oxidases (e.g., glucose oxidase) were tested to be susceptible to the organic solvent and non-physiological pH. Hence, the CL system was used for the detection of oxidase substrates (exemplified by glucose) in serum samples, and the limit of detection was as low as 8.4 nmol/L. The highly luminous CL system that can work under physiological conditions is promising for biosensing applications

Non-viral carrier nanomaterials are commonly used for molecular targeted therapy. This study explored the effects of miR-27 on cervical cancer using nanoparticles as a carrier. Hela cells were used to build cervical cancer tumor model. 20 nude mice were randomly assigned into control group, empty vector group (treated with glucopyranosyl lipid adjuvant-human serum albumin (GLA-HSA), miR-27 group (treated with GLA-HSAencapsulated miR-27), and 17-AAG group (treated with GLA-HSA-encapsulated miR-27 and 17-AAG mixed culture medium), followed by analysis of tumor morphology, apoptosis and expression of Wnt/β-catenin and apoptosis factors (Bcl-2, caspase-3). The size of transplanted tumor was smallest in 17-AAG group on 7th day, followed by miR-27 group (P < 0.05) compared to control group and empty carrier group without different between them (P > 0.05). The miR-27 group and 17-AAG group had highest tumor inhibition rate and apoptotic cell number and apoptosis index compared to other two groups without difference between them (P > 0.05). miR-27 group and 17-AAG group showed lowest expression of CA125, CEA, Wnt, β-catenin, Bcl-2, and caspase-3 with lower level in 17-AAG group than miR-27 group (P > 0.05). Loading miR-27 small molecule substance inhibited cervical cancer tumor growth and promoted tumor cell apoptosis with decreased CA125 and CEA expression, indicating that the miR-27 coated with nanoparticles may inhibit Wnt/β-catenin signal pathway, thereby up-regulating Bcl-2 and caspase-3, and finally exerting an anti-tumor effect.

To explore the genetic basis for a fetus with club foot detected upon mid-pregnancy ultrasonography.Amniotic fluid of the fetus and peripheral blood samples of its parents were collected and subjected to G-banding karyotype analysis and copy number variation sequencing (CNV-seq). The result was verified by fluorescence in situ hybridization (FISH).The fetus and its parents all had a normal karyotype. CNV-seq analysis revealed that the fetus has harbored a 23.12 Mb on chromosome 5 and a 21.46 Mb duplication on chromosome 7. FISH assay has verified that its mother has carried a cryptic t(5;7)(p14.3;q33) translocation.CNV-seq combined with FISH can effectively detect cryptic chromosome aberrations, and can help to reduce severe birth defects and provide a basis for prenatal genetic counseling.

The participation of circular RNAs (circRNAs) in carcinogenesis is widely established. Numerous circRNAs with aberrant expression in cervical cancer (CC) are identified by RNA sequencing, whereas the function of these circRNAs remains unclear. We thus aimed to unveil the effects and mechanisms of circ_0042986 in CC. Circ_0042986 with aberrant downregulation in CC was obtained from GSE10286 dataset. qPCR and western blotting were employed for the detection of circ_0042986, miR-582-3p, and paternally expressed 3 (PEG3) expressions. EdU assay, colony formation assay, wound healing assay, transwell assay, tube formation assay, and flow cytometry assay were applied for functional analyses. The potential binding site was ensured by dual-luciferase reporter analysis, and their binding relationship was verified by pull-down assay. The transplanted tumor models were constructed for in vivo function verification of circ_0042986. Our findings exposed that the downregulation of circ_0042986 was verified in clinical CC samples. Circ_0042986 overexpression largely attenuated CC cell growth, invasiveness, angiogenesis, and survival. MiR-582-3p was targeted by circ_0042986, and the inhibitory roles of circ_0042986 presence were partly abolished by miR-582-3p enrichment. MiR-582-3p combined with PEG3, and circ_0042986 increased PEG3 expression via decoying miR-582-3p. The interaction between miR-582-3p and PEG3 on CC cell functions was confirmed, evidenced by the reversal effects of PEG3 knockdown on miR-582-3p deficiency-inhibited cancer cell malignant behaviors. Circ_0042986 overexpression also limited tumorigenesis of CC in animal models. In summary, circ_0042986 overexpression decoyed miR-582-3p to increase PEG3 expression, thereby blocking the malignant progression of CC.

Aggregation-induced emission (AIE) is a powerful method to produce fluorescence for a diverse range of applications. While most previous work induced aggregation by change of solvent, ionic strength, pH, or self-assembly, we herein explored adsorption-induced aggregation using 4,4′-(hydrazine-1,2-diylidene bis(methanylylidene)) bis(3-hydroxybenzoic acid) (HDBB) as an AIE luminogen. HDBB is known to aggregate with AIE at low pH but not at neutral pH, and its aggregation facilitates excited state intramolecular proton transfer for enhanced emission. Using a nonquenching nanomaterial, Y2O3 nanoparticles, HDBB showed sevenfold fluorescence increase at pH 7.0. Fluorescence lifetime showed that HDBB was in the aggregated state in the presence of Y2O3. For comparison, a fluorescent porphyrin compound showed that adsorption caused quenching after mixing with Y2O3, whereas other dyes such as fluorescein, calcein, and rhodamine B failed to be adsorbed by Y2O3. Adsorption did not follow a Langmuir isotherm, but it s...

The co-immobilization of two enzymes onto single support commonly exhibits low efficiency due to the competition against limited sites. Water-stable metal–organic frameworks (MOFs) [i.e., PCN-333(Al)] with a high surface area and ultra-large cavities were employed to efficiently adsorb cholesterol oxidase (ChOx) and encapsulate horseradish peroxidase (HRP), respectively. The prepared PCN-333/ChOx&HRP was characterized through SEM, XRD, confocal microscopy, N2 adsorption isotherms, and thermal gravity analysis (TGA). The high surface area and high concentration of mesoporous cages resulted in the high loadings of both ChOx and HRP. The absorbed ChOx and the encapsulated HRP presented excellent activities without additional chemical modification. The immobilized enzymes were stable against protease digestion, organic solvents, temperature changes, and pH variation. Thus, a colorimetric biosensor for cholesterol detection was fabricated depending on cascade catalytic reactions of the immobilized bi-enzymes. An extended linear range from 0.0 to 40.0 μM with a low detection limit of 0.6 μM was obtained using the biosensor. The co-immobilization of the enzymes onto the surface and into the mesopores of MOFs provided a new and excellent platform for the development of highly stable and sensitive colorimetric biosensors.

Objection: Cumulative studies have identified the effectiveness of cardiac shock wave therapy (CSWT) in treating heart failure after acute myocardial infarction (AMI), but little have been discussed with regard to the beneficial effects of CSWT on anti-fibrosis along with the underlying mechanism. In this study, we investigated whether CSWT could reduce post-AMI fibrosis and further explored the molecular mechanism.Methods: Rat heart failure (HF) models induced by ligating the left anterior descending coronary artery were established and validated by echocardiography. Eligible animals were randomly categorized into five groups: the sham group, the HF group, the HF + CSWT group, the HF + LY294002 group, and the HF + CSWT + LY294002 group. The cardiac weight, serum level of BNP, NT-pro BNP and echocardiography parameters were measured to assess cardiac function in different groups. Masson's trichrome staining was used to assess the proportions of the fibrotic area. The expression level of CD34, αSMA was measured by RT-PCR, Immunohistochemistry and Immunofluorescent analyses and the level of PI3K/Akt was quantified by Immunohistochemistry and Western blotting.Results: The application of CSWT significantly improved cardiac function and reduced myocardial fibrosis and level of CD34 and αSMA, compared to the HF group. CSWT led to significant elevations of p-PI3K and p-Akt expression levels compared to that of the HF group and the inhibition of the PI3K/Akt pathway abolished the observed beneficial effects of CSWT.Conclusion: CSWT can facilitate the alleviation of cardiac fibrosis induced by AMI through the activation of PI3K/Akt signaling pathway.

Background Global longitudinal strain (GLS) echo has been regarded as a sensitive and reproducible indicator for detection of subclinical cardiac dysfunction in children with Kawasaki disease (KD), but whether it can assist in differentiating KD patients with different severity of coronary artery lesions (CALs) has been rarely reported. The purpose of this study was to determine the feasibility of GLS derived from rest and exercise stress echo in risk stratification in patients with KD. Methods 43 children with KD and 50 healthy controls were enrolled. KDs was divided into 3 groups according to the severity of CALs based on Z score, which was measured at the 3-year follow-up, G1 = KD without CALs (Z Results 38 KDs and 50 HCs had normal exercise tolerance. There were 18, 8, and 12 patients in G1, G2, and G3, respectively. LA, LV, LVPW, IVS and LVEF, were not significantly different in the KDs at the onset and 3-year follow-up, and so did that between KDs and HCs (all p>0.05). Both GLSrest and GLSstress in the KDs were significantly decreased compared with HCs (GLSrest: −17.2±9.1% vs. −22.3±0.7%, p0.05, seen in Fig.1C). GLSstress in the G3 decreased significantly compared with that in G1 and G2 (G3 vs. G1: −16.8±2.6% vs. −22.8±1.9%, p Conclusions GLS derived from rest and exercise stress speckle-tracking echo can detect subclinical cardiac dysfunction in KD patients with normal LV systolic function by conventional measurements, but rest GLS could not assist in differentiating KD patients with different severity of CALs. Exercise stress GLS, which correlated well with Z score, has the potential in risk stratification in children with KD, and thus may provide prognostic value in multidisciplinary treatment strategy. Statistics and echo, CMR imaging Funding Acknowledgement Type of funding source: None

Thiolated DNA (DNA-SH) was employed as a template in the synthesis and stabilization of AgNCs (DNA-SH-AgNCs). Resulting from the synergistic protective effect of specific Ag+-DNA interactions and Ag-S bonding, DNA-SH-AgNCs exhibited high quantum yields and resistance to oxidation.

Recent global military events, such as the conflict in Syria, have emphasized the need to find effective strategies to rapidly destroy organophosphorus-based nerve agents. In this work, we designed active site-engineered graphene oxide (GO) via polymerization (polymer bead-GOs) as organophosphorus hydrolase (OPH) mimetic hotspots for the rapid degradation of nerve agents. This hybrid catalyst has a high total turnover frequency value of 0.65 s–1 and good stability (94.8% activity maintained after 5 cycles). Mechanism investigations suggested that the high catalytic performance could be attributed to the synergistic effect among the clusters of imidazole and the presence of – COOH groups on the GO surface and Zn2+.

Dens Invaginatus (DI) is a congenital development malformation. The complex anatomy of DI aids in the retention of food and bacteria, which leads to pulp necrosis and develops into periapical inflammation. The histopathology of DI is not very clear. This study reports an unusual case of a 6-year-old boy who had a malformed immature permanent mandibular central incisor with DI Type III and apical periodontitis. The malformed tooth was extracted due to the severe infection and short tooth root. Histological results showed that typical pulp tissues were in the main root canal whereas a typical granuloma existed in the invaginated part. This case report indicate that the apical periodontitis in DI Type III was mainly induced by the invaginatus canal and the pertinent treatment for the invaginatus canal was the key for DI Type III.

Thrombin has been implicated in atherosclerotic disease development. However, thrombin activity detection is currently limited because of the lack of convenient fluorescent probes. We developed a label-free fluorescent method to assay thrombin activity on the basis of a designed peptide probe with a thrombin-cleavable peptide sequence and a cysteine terminus. The peptide probe can be conjugated to DNA-templated silver nanoclusters (DNA-AgNCs) through Ag-S bonding; as a result, the fluorescence of DNA-AgNCs was enhanced. As the DNA-AgNCs-peptide conjugate was adsorbed to graphene oxide (GO), the enhanced fluorescence of DNA-AgNCs was quenched. Once the peptide probe was cleaved by thrombin, the resulting release of the DNA-AgNCs from the surface of GO restored the enhanced fluorescence. Thrombin can be determined with a linear range of 0.0-50.0 nM with a detection limit of 1 nM. The thrombin-sensitive probe with a cysteine terminus may be developed into probes to detect other proteases.

Different from popular mimics of bimetallic nuclear centers bridged by a hydroxide, a total coordination sphere of the active center of organophosphorus hydrolase was assembled in metal–organic frameworks by rational design and combination of ligands, which resulted in efficient destruction of nerve agent stimulants without a base as a co-catalyst.

The present study was performed to determine whether there are variants in TBX20 and genes of the Ras-MAPK pathway associated with nonsyndromic congenital heart disease (ns-CHD).A total of 223 ns-CHD patients and 273 healthy controls from China were selected as study subjects to perform an association analysis using 22 tag single-nucleotide polymorphisms (tag SNPs) located either in one of three genes in the Ras-MAPK pathway (MAP2K2, BRAF, and RAF1) or the TBX20 gene that have previously been associated with syndromic congenital heart disease.The results showed that none of these tag SNPs are associated with ns-CHD.The results suggested that these disease-causing genes, which were previously discovered in familial cases, might not be the major genetic factors causing the development of ns-CHD in Chinese.

Pancreatic function tests are used to determine the presence of chronic pancreatitis, particularly in the early stage of the disease. Chymotrypsin is an indicator of pancreatic function and is thus related to pancreatic diseases. A new fluorescent biosensing method for assay of chymotrypsin activity was developed using DNA (dC12)-templated silver nanoclusters and graphene oxide (GO). A peptide probe was also designed using chymotrypsin-cleavable amino acid sequence and a cysteine terminus. The peptide probe formed Ag-S bond to dC12-AgNCs to enhance the fluorescence of dC12-AgNCs. After the addition of GO, the peptide was adsorbed to the negative GO surface and the fluorescence of dC12-AgNCs was quenched by FRET. The peptide was then degraded into amino acid fragments upon addition of chymotrypsin; these fragments were released from the GO surface, and the FRET was terminated. The developed label-free method features lower cost and higher sensitivity to chymotrypsin activity assay compared with conventional fluorescence analysis. The method can be used to analyze chymotrypsin (as low as 3 ng/mL, signal/noise =3) across a dynamic range of 0.0–50.0 ng/mL. The proposed biosensing strategy can also be extended to other proteases by using different peptide substrates.