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Anisotropic nanomaterials, such as gold nanorods (AuNRs), could be employed as an orientation platform due to their polarization-dependent surface plasmon resonance. However, a variety of factors would affect the dark-field light scattering imaging of anisotropic nanomaterials, resulting in an unstable signal, which is not advantageous to its further application. In this work, the localized surface plasmon resonance properties of a few AuNRs at different angles were excited by polarization with a conventional dark-field microscope, in which it was found that the ratio of AuNRs' light scattering intensity at different polarization angles (

Objective To investigate if inhibitory effects of propofol on proliferation, invasion and migration of non-small cell lung carcinoma (NSCLC) cells was associated with the regulation of miR-199a/PAK4 axis. Methods Human NSCLC A549 and H1299 cells were treated with propofol of different concentrations at different time points. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to evaluate miR-199a expression. A549 and H1299 cells were divided into Control, Propofol, Propofol + miR-NC and Propofol + miR-199a inhibitor groups. The proliferation, apoptosis, migration, and invasion were examined by CCK-8, flow cytometry, wound healing, and Transwell, respectively. Western blotting was used to measure the protein expression of PAK4. Xenograft model was established in nude mice to observe if propofol can mediate miR-199a expression to regulate the growth of subcutaneous xenograft tumor. Results Propofol can effectively enhance the expression of miR-199a in NSCLC. Compared with Control group, H1299 and A549 cells in Propofol group decreased in viability, invasion and migration, and increased in apoptosis. The inhibitory effect of propofol on NSCLC growth was reversed by miR-199a. In comparison with Propofol group, Propofol + miR-199a inhibitor group was declined in miR-199a expression and increased in PAK4 protein expression. According to dual-luciferase reporter assay, PAK4 was a target gene of miR-199a. Experiment in vivo revealed propofol can inhibit the growth and reduce the weight of xenograft tumor, which can be reversed by miR-199a inhibitor. Conclusion Propofol can suppress PAK4 expression by inducing miR-199a up-regulation, thereby inhibiting the proliferative, invasive and migrating abilities of NSCLC.

A range of circular (Circ) RNAs have been demonstrated to be of therapeutic significance for the treatment of acute lymphoblastic leukemia (ALL). Here, we investigated the mechanisms underlying the action of Circ-PRKDC and the microRNA-653-5p/Reelin (miR-653-5p/RELN) axis in T-cell ALL (T-ALL).Clinical specimens were obtained from patients with T-ALL (n = 39) and healthy controls (n = 30). In each specimen, we determined the expression levels of Circ-PRKDC, miR-653-5p, and RELN. Human T-ALL cells (Jurkat) were transfected with Circ-PRKDC- or miR-653-5p-related sequences to investigate cell proliferation, apoptosis, and autophagy. We also determined the levels of Circ-PRKDC, miR-653-5p, RELN, and signaling proteins related to phosphoinositide 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). Finally, we decoded the interactions between Circ-PRKDC, miR-653-5p, and RELN. The expression levels of Circ-PRKDC and RELN were upregulated in T-ALL tissues and cells while the levels of miR-653-5p were downregulated. Thereafter, then silencing of Circ-PRKDC, or the enforced expression of miR-653-5p, repressed the expression of RELN and the activation of the PI3K/AKT/mTOR signaling pathway, thus enhancing cell autophagy and apoptosis, and disrupting cell proliferation. Circ-PRKDC acted a sponge for miR-653-5p while miR-653-5p targeted RELN. The knockdown of miR-653-5p abrogated the silencing of Circ-PRKDC-induced effects in T-ALL cells. The depletion of Circ-PRKDC elevated miR-653-5p to silence RELN-mediated PI3K/AKT/mTOR signaling activation, thereby enhancing autophagy and apoptosis in T-ALL cells.

This study aims to clarify the function of transient receptor potential melastatin 8 (TRPM8) in colon cancer liver metastasis. First, TRPM8 expression was determined by Western blotting in colon cancer patients with/without liver metastasis. Second, colon cancer cells were grouped into Mock, siCON, and siTRPM8 groups. Then, a series of in vitro experiments were conducted. Last, CT26 cells were used to construct colon cancer liver metastasis models on mice in vivo, followed by comparison of liver metastasis and determination of AKT/glycogen synthase kinase-3β (GSK-3β) pathway. Consequently, TRPM8 was upregulated in both colon cancer patients with/without liver metastasis, especially in those with metastasis. Compared with Mock and siCON groups, cells in siTRPM8 group demonstrated significant decreases in clone numbers, cell invasion, and migration; and obvious downregulations of p-AKT/AKT, p-GSK3β/GSK3β, Snail, and Vimentin, with an upregulation of E-cadherin. For in vivo experiments, a sharp decrease was observed in metastatic liver of mice in siTRPM8 group, with significant downregulations of p-AKT/AKT, p-GSK3β/GSK3β, Snail, and Vimentin and an upregulation of E-cadherin, as compared with Mock and siCON groups. Thus, TRPM8 was upregulated in colon cancer patients with liver metastasis, and silencing TRPM8 may suppress the progression and epithelial-mesenchymal transition of colon cancer cells to block its liver metastasis possibly by inhibiting AKT/GSK-3β pathway.

Chronic hepatitis B virus (HBV) infection can lead to fibrosis, liver cirrhosis, and primary hepatocellular carcinoma. Investigating host factors that regulate HBV replication helps to identify antiviral targets. In the current study, we identified Nicotinamide N-Methyltransferase gene (NNMT) as a novel factor that regulates HBV transcription. NNMT is up-regulated at both the mRNA and protein levels in HepG2.2.15 cells compared to HepG2 cells. Overexpression of NNMT reduces HBV replication in several cell models, while knockdown of NNMT enhances HBV DNA levels. Mechanistically, NNMT suppresses HBV DNA replication by inhibiting HBV RNA transcription. The region required for the inhibitory effect of NNMT was narrowed to nt 1672-1708 in enhancer II by luciferase assays. On the other hand, ChIP assays and EMSA results showed that NNMT does not bind to this region substantially, either directly or indirectly. Next, a collection of hepatic nuclear receptor transcription factors was screened to determine whether they were affected by NNMT overexpression. NR5A1, a positive regulator of HBV replication, decreased significantly after NNMT overexpression. Collectively, the findings of this study shed light on the regulation of HBV transcription.

We report a feasibility study of pure leptonic decay $D_s^+\to\mu^+\nu_\mu$ by using a fast simulation software package at STCF. With an expected luminosity of $1~\mathrm{ab}^{-1}$ collected at STCF at a center-of-mass energy of 4.009 GeV, the statistical sensitivity of the branching fraction is determined to be 0.3\%. Combining this result with the $c\rightarrow s$ quark mixing matrix element $|V_{cs}|$ determined from the current global Standard Model fit, the statistical sensitivity of $D_s^+$ decay constant, $f_{D_s^+}$, is estimated to be 0.2\%. Alternatively, combining the current results of $f_{D_s^+}$ calculated by lattice QCD, the statistical sensitivity of $|V_{cs}|$ is determined to be 0.2\%, which helps probe possible new physics beyond. The unprecedented precision to be achieved at STCF will provide a precise calibration of QCD and rigorous test of Standard Model., Comment: 8pages, 7 figures

Motivation MIB2 (metal ion-binding) attempts to overcome the limitation of structure-based prediction approaches, with many proteins lacking a solved structure. MIB2 also offers more accurate prediction performance and more metal ion types. Results MIB2 utilizes both the (PS)2 method and the AlphaFold Protein Structure Database to acquire predicted structures to perform metal ion docking and predict binding residues. MIB2 offers marked improvements over MIB by collecting more MIB residue templates and using the metal ion type-specific scoring function. It offers a total of 18 types of metal ions for binding site predictions. Availability and implementation Freely available on the web at http://bioinfo.cmu.edu.tw/MIB2/. Supplementary information Supplementary data are available at Bioinformatics online.

As a short peptide containing active thiol group, glutathione (GSH) participates in many cellular reactions, so it is of great significance to detect cellular GSH. In this work, amino-rich graphene quantum dots (GQDs) were synthesized, which could coordinate with copper ions (Cu2+) and yield aggregation-induced fluorescence quenching. However, GSH owns stronger coordination ability with Cu2+, so that GSH could promote the dissociation of Cu2+ from the surface of GQDs, and then led to the fluorescence recovery of GQDs. In BR buffer medium at pH 6.8, GSH was able to gradually recover the fluorescence of GQDs (1 μg/mL) that was quenched by Cu2+ (250 μmol/L), which could be finished within 20 min. Additionally, the recovery degree of fluorescence was linear to the concentration of GSH in the range of 20–500 μmol/L with a detection limit of 3.4 μmol/L. This method was applicable to the detection of GSH in cell lysate by the switchable function of Cu2+ to improve the selectivity.

Ribonucleotides are usually functioned as biomarkers to diagnose diseases and monitor the life activities in living organisms, and their discrimination is of great significance but challenging. Taking advantage of the unique characteristics of gold nanorods (AuNRs), herein, a colorimetric sensor array for discrimination of twelve ribonucleotides was developed based on the chemical etching of AuNRs with controllable aspect ratios. During the etching process, AuNRs were preferentially shortened and eventually turned into Au(III) state by Fenton’s reaction. The morphological change of AuNRs led to the significant color change and blue shift in the corresponding extinction spectrum. However, when Fe2+ bound with ribonucleotides, the Fenton’s reaction was prevented and the ability to etch AuNRs was weakened or disappeared. Due to the different structures of nucleotides, the binding ability of them with Fe2+ was distinct, resulting in the discrepancy in the chemical etching of AuNRs, which could be developed for distinguishing ribonucleotides. Moreover, the proposed sensor array was successfully explored to distinguish ribonucleotides in complex human urine samples.

MicroRNAs, as one kind of significant biomarkers, play indispensable roles in the diagnosis and treatment of cancers. Yet, owing to low expression and high sequence homology, high sensitivity and specificity for microRNA detection are greatly challenging. Herein, a sensitive sensing platform with high specificity was developed for microRNA-27a (miRNA-27a) based on the miRNA-27a-triggered chemical etching of gold nanorods to a smaller size, which was accompanied by a significant blue shift and a large decrease of intensity in the localized surface plasmon resonance (LSPR) scattering and remarkable color variability from red to green. When combined with strand displacement reactions as well as liposome signal amplification and transduction, the proposed bioassay presented high selectivity toward miRNA-27a in a dynamic range from 100 fM to 3 pM and a low limit of detection of 16.5 fM (3σ/

Single amino acid variation (SAV) is an amino acid substitution of the protein sequence that can potentially influence the entire protein structure or function, as well as its binding affinity. Protein destabilization is related to diseases, including several cancers, although using traditional experiments to clarify the relationship between SAVs and cancer uses much time and resources. Some SAV prediction methods use computational approaches, with most predicting SAV-induced changes in protein stability. In this investigation, all SAV characteristics generated from protein sequences, structures and the microenvironment were converted into feature vectors and fed into an integrated predicting system using a support vector machine and genetic algorithm. Critical features were used to estimate the relationship between their properties and cancers caused by SAVs. We describe how we developed a prediction system based on protein sequences and structure that is capable of distinguishing if the SAV is related to cancer or not. The five-fold cross-validation performance of our system is 89.73% for the accuracy, 0.74 for the Matthews correlation coefficient, and 0.81 for the F1 score. We have built an online prediction server, CanSavPre (http://bioinfo.cmu.edu.tw/CanSavPre/), which is expected to become a useful, practical tool for cancer research and precision medicine.

Photothermal effects (PTEs) have been greatly concerned with the fast development of new photothermal nanomaterials. Herein we propose a photothermal immunoassay (PTIA) by taking mycotoxins (AFB1) as an example based on the PTEs of plasmonic Cu2–xSe nanocrystals (NCs). By loading plasmonic Cu2–xSe NCs into liposomes to form photothermal soft nanoballs (ptSNBs), on which aptamer of AFB1 previously assembled, a sandwich structure of AFB1 could be formed with the aptamer on ptSNBs and capture antibody. The heat released from the ptSNBs under NIR irradiation, owing to the plasmonic photothermal light-to-heat conversion through photon–electron–phonon coupling, makes the temperature of substrate solution increased, and the increased temperature has a linear relationship with the AFB1 content. Owing to the large amounts of plasmonic Cu2–xSe NCs in the ptSNBs, the PTEs get amplified, making AFB1 higher than 1 ng/mL detectable in food even if with a rough homemade immunothermometer. The proposal of PTIA opens a ne...

A range of circular (Circ) RNAs have been demonstrated to be of therapeutic significance for the treatment of acute lymphoblastic leukemia (ALL). Here, we investigated the mechanisms underlying the action of Circ-PRKDC and the microRNA-653-5p/Reelin (miR-653-5p/RELN) axis in T-cell ALL (T-ALL).Clinical specimens were obtained from patients with T-ALL (n = 39) and healthy controls (n = 30). In each specimen, we determined the expression levels of Circ-PRKDC, miR-653-5p, and RELN. Human T-ALL cells (Jurkat) were transfected with Circ-PRKDC- or miR-653-5p-related sequences to investigate cell proliferation, apoptosis, and autophagy. We also determined the levels of Circ-PRKDC, miR-653-5p, RELN, and signaling proteins related to phosphoinositide 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). Finally, we decoded the interactions between Circ-PRKDC, miR-653-5p, and RELN. The expression levels of Circ-PRKDC and RELN were upregulated in T-ALL tissues and cells while the levels of miR-653-5p were downregulated. Thereafter, then silencing of Circ-PRKDC, or the enforced expression of miR-653-5p, repressed the expression of RELN and the activation of the PI3K/AKT/mTOR signaling pathway, thus enhancing cell autophagy and apoptosis, and disrupting cell proliferation. Circ-PRKDC acted a sponge for miR-653-5p while miR-653-5p targeted RELN. The knockdown of miR-653-5p abrogated the silencing of Circ-PRKDC-induced effects in T-ALL cells. The depletion of Circ-PRKDC elevated miR-653-5p to silence RELN-mediated PI3K/AKT/mTOR signaling activation, thereby enhancing autophagy and apoptosis in T-ALL cells.

As an important biomarker for early diagnosis of cancers, sensitive detection and high-resolution imaging of microRNA-21 in cancer cells have become important and challengeable. In this work, highly sensitive detection and spatial imaging of intracellular microRNA-21 were realized by the reduced signal background through vertical polarization excitation with a polarizer. The lateral local surface plasmon resonance property of gold nanorods (AuNRs) displayed a pronounced green color with low scattering intensity, which was adjusted to red color with strong scattering intensity when the core-satellite gold nanoparticle (AuNP) assembly was constructed on the side of AuNRs through a catalyzed hairpin assembly (CHA) circuit in the presence of microRNA-21. This unique approach allows for effectively reducing the strong background signal to improve the sensitivity of detection. Additionally, the proposed strategy can not only realize the sensitive detection of microRNA-21 with the limit of detection as low as 2 pM (3σ) but also achieve the high spatial imaging of cancer cells, which provided a specific strategy for the construction and imaging of intracellular imaging probes. It is believed that the simple and sensitive approach on the basis of lateral local surface plasmon resonance property of anisotropic AuNRs with excellent sensitivity combined with high spatial imaging holds promising potentials to visualize intracellular microRNAs with low abundance.

Single amino acid variation (SAV) is an amino acid substitution of the protein sequence and might influence the whole protein structure, binding affinity, or functional domain and related to disease, even cancer. However, to clarify the relationship between SAV and cancer using traditional experiments is time and resource consuming. Though there are some SAVs predicted methods using the computational approach, most of them predict the protein stability changed caused by SAV. In this work, all of the SAV characteristics generated from protein sequences, structures, and micro-environment would be converted into feature vectors and fed into an integrated predicting system by using Support Vector Machine and genetic algorithm. The critical features were used to estimate the relationship between their properties and cancer caused by SAVs. In the results, we have developed a prediction system based on protein sequence and structure, which could distinguish the SAV is related to cancer or not, and the accuracy, the Matthews correlation coefficient, and the F1-score yield to 90.88%, 0.77 and 0.83, respectively. Moreover, an online prediction server called CanSavPre was built (http://bioinfo.cmu.edu.tw/CanSavPre/), which will be a useful, practical tool for cancer research and precision medicine.

As a mucopolysaccharide sulfate anticoagulant drug, heparin plays important roles in clinic. In this work, heparin was analyzed based on the nanometal surface energy transfer (NSET) between gold nanorods (AuNRs) and tetrakis (4-sulfophenyl) porphyrin (TPPS4) fluorescent molecules. The results showed that AuNRs could bind TPPS4 by electrostatic interaction and coordination to quench its fluorescence. While heparin was able to bind AuNRs with a stronger electrostatic interaction to compel TPPS4 to leave AuNRs surface, leading to the fluorescence recovery of TPPS4, which was proportional to the concentration of heparin in a range of 0.05∼2 μg/mL with the detection limit as low as 6.7 ng/mL (3σ). Based on this, a NSET platform for the analysis of trace heparin sodium was proposed with fast response, high sensitivity and excellent specificity, which was successfully applied to the detection of heparin in injection with the satisfactory result. Importantly, the NSET mechanism was fully discussed.

As an important biomarker of malignant tumors, spermine is closely related with some diseases. In this work, a nanometal surface energy transfer (NSET) strategy via the positively charged gold nanorods (AuNRs) and the negatively charged tetrakis (4-sulfonatophenyl) porphyrin (TPPS4) was developed to detect spermine in human urine. Under acidic condition, spermine possessed multi-cationic property and a strong affinity towards the anionic phosphate backbone of calf thymus DNA (ctDNA) by electrostatic attraction as well as the groove binding, which enabled to regulate the process of NSET between AuNRs and TPPS4, leading to the fluorescence quenching of TPPS4. Moreover, the quenched fluorescence was proportional to the concentration of spermine, which was applicable to monitor the level of spermine in human urine in the concentration range of 0.5–7.5 μM. The NSET platform for spemine is simple, selective and time-saving, which has great significance in early cancer diagnosis.

As an antibiotic, tetracycline has been widely used against bacterial infection or as feed additives for growth promotion, which may lead to the enrichment of antibiotic residues in animals or their products. Therefore, the detection of tetracycline is closely related to human health. The morphological transformation of CoOOH nanoflakes induced by tetracycline was monitored by scanning electron microscope images, dark-field light scattering images and optical spectra, which found that tetracycline could decompose CoOOH nanoflakes into small nanoparticles with low light scattering signal. As a result, the reduced light scattering of CoOOH nanoflakes was proportional to the increased concentration of tetracycline in the range of 1.0–250 μmol/L, and the limit of determination (LOD) was 0.23 μmol/L (3σ/k). Most foreign substances did not interfere in the analysis of tetracycline. Furthermore, the concentration of tetracycline in different milk samples detected with the standard addition method was so low that it accorded with the safety regulation, which was similar to the detection result with high-performance liquid chromatography (HPLC).

As the main final products of the purine metabolism in human body, uric acid (UA) usually presents in serum and urine. Thus, the level of UA in biology is closely related to human health. In this work, the ultra-small CuS nanoparticles (NPs) were demonstrated to possess intrinsic peroxidase-like activity towards 3,3',5,5'-tetramethylbenzidine (TMB) substrate in the presence of H2O2, which yielded the blue oxidized TMB (oxTMB) with strong absorption at 653 nm. Furthermore, H2O2 could be produced by the enzymatic reaction between UA and uricase to yield the blue oxTMB with the peroxidase mimetics activity of CuS NPs, which provided a sensitive and colorimetric method for UA detection with a linear range from 1.0 × 10−6 M to 1.0 × 10−4 M and a detection limit of 1.0 × 10−7 M. Moreover, the proposed method was successfully applied to the determination of UA in human serum samples, which supplied a similar result to the clinical method.

As a major metabolic product of purine nucleotides, uric acid (UA) usually presents in urine and serum, which is closely related to human health. With the catalysis by uricase, uric acid can yield allantoin, CO2 and H2O2. Then, the produced H2O2 is able to decompose CoOOH nanoflakes into Co2+, resulting in a smaller size with weakened light scattering. This work provides a simple and selective light scattering method for UA analysis with a linear range from 1.0 × 10−5 to 1.0 × 10−3 M and a detection limit of 1.0 × 10−6 M. In addition, this method has been successfully applied to the determination of UA in human serum samples with similar results to clinical methods.

Ricin is an extremely potent ribosome-inactivating protein and serves as a likely food biocontaminant or biological weapon. Thus, simple, sensitive and accurate analytical assays capable of detecting ricin are urgently needed to be established. Herein, we present a novel method for ricin B-chain (RTB) detection by using two materials: (a) a highly efficient hybrid probe that was formed by linking a glucose oxidase (GOD)-encapsulated liposome (GOD-L) to magnetic beads (MBs) through hybridization between an aptamer and a blocker and (b) a new low-background g-C3N4-MnO2 sandwich nanocomposite that exhibits fluorescence resonance energy transfer (FRET) between the g-C3N4 nanosheet and MnO2. In the presence of RTB, the strong binding between RTB and the aptamer can release the blocker-linked liposome from the surface of the MBs. After magnetic separation, the decomposed liposome can release GOD to catalyze the oxidation of glucose, generating a certain amount of H2O2. Then, H2O2 can reduce MnO2 of the g-C3N4-MnO2 nanocomposite to Mn2+, which leads to the elimination of FRET. Thus, the fluorescence of the g-C3N4 nanosheet will be turned on. Because of the excellent signal amplification ability of liposome and the characteristic highly sensitive response of the g-C3N4-MnO2 nanocomposite toward H2O2, RTB could be detected sensitively based on the significantly enhanced fluorescent intensity. The linear range of detection was from 0.25 μg mL-1 to 50 μg mL-1 and the limit of detection (LOD) was 190 ng mL-1. Moreover, the proposed assay was successfully applied in the detection of the entire ricin toxin content in a castor seed.

Plasmonic gold nanorods are promising and sensitive light scattering probes, which can reach the single particle level. Herein, we present the scattering properties of gold nanorods for time-resolved visual detection of heparin based on the rapid etching of gold nanorods under dark-field microscopy.