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In this paper, a complex-valued Zadoff–Chu measurement matrix is proposed and used in an image-based quantized compressive sensing (CS) scheme. The results of theoretical analysis and simulations show that the reconstruction performance generated by the proposed Zadoff–Chu measurement matrix is better than that obtained by commonly used real-valued measurement matrices. We also applied block compressive sensing (BCS) to reduce the computational complexity of CS and analyzed the effect of block size on the reconstruction performance of the method. The results of simulations revealed that an appropriate choice of block size can not only reduce the computational complexity but also improve the accuracy of reconstruction. Moreover, we studied the effect of quantization on the reconstruction performance of image-based BCS through simulations, and the results showed that analog-to-digital converters with medium resolutions are sufficient to implement quantization and achieve comparable reconstruction performance to that obtained at high resolutions, based on which an image-based BCS framework with low power consumption can thus be developed.

To find the predictor of optimal surgical timing for neonatal necrotizing enterocolitis (NEC) patients by analyzing the risk factors of conservative treatment and surgical therapy.Data were collected from 184 NEC patients (Surgery, n=41; conservative treatment, n=143) between the years 2015 and 2019. Data were analyzed by univariate analysis, and multivariate binary logistic regression analysis.Univariate analysis showed that statistically significant differences between the surgery and conservative treatment groups. The results of multivariate Logistic regression analysis indicated intestinal wall thickening by B-ultrasound and gestational age were independent factors to predict early surgical indications of NEC (p0.05). The true positive rate, false positive rate, true negative rate and false negative rate in the diagnosis of necrotic bowel perforation guided by DAAS (Duke abdominal X-ray score) ≥7 and MD7 (seven clinical metrics of metabolic derangement) ≥3 were 12.8%, 0.0%, 100.0% and 87.2%, respectively.In summary, the ultrasound examination in NEC children showing thickening intestinal wall and poor intestinal peristalsis indicated for early operation.

Background: Biogenic amines are harmful to human health at a certain extent. As a kind of biogenic amine oxidase, multicopper oxidase can be used to degrade them. Currently, the literature about enzyme from Enterococcus spp. are limited, and recombinant multicopper oxidase might be an effective way to degrade biogenic amines. Objective: (i) Select and identify strains that can degrade biogenic amines, (ii) overexpress enzyme from Enterococcus spp., (iii) measure gene expression and probe amine-degradation differences among strains (native, E. coli DH5α, and L. delbruckii), and (iv) examine the biochemical properties of recombinant multicopper oxidase, (v) apply the recombinant enzyme into smoked horsemeat sausage. Methods: Reverse transcription PCR and high-performance liquid chromatography were performed to examine gene expression and amine degradation rate. Results: The results demonstrated that target enzymes were successfully overexpressed, accompanied by increased amine-degrading activity (P Conclusion: In this work, gene expression levels were higher in recombinant M5B than recombinant M2B, regardless of host. E. coli is more stable to express multicopper oxidase. Besides, the amine-degrading ability was markedly increased in the two recombinant strains. After prolonged incubation, the recombinant enzyme could degrade three amines, and it displayed high alkali resistance and thermostability.

With the sustained evolution and expeditious popularization of cloud computing, an ever-increasing number of individuals and enterprises are encouraged to outsource data to cloud servers for reducing management overhead and ease of access. Privacy requirements demand encryption of sensitive information before outsourcing, which, on the other hand, diminishes the usability of data and makes considerable efficient keyword search techniques used on plaintext inapplicable. In this paper, we propose a secure multi-keyword ranked search scheme based on document similarity to work out the problem. In order to achieve the goals of multi-keyword search and ranking search results, we adopt the vector space model and TF-IDF model to generate index and query vectors. By introducing the secure kNN computation, index and query vectors can be encrypted to prevent cloud servers from obtaining sensitive frequency information. For the need of efficiency advancement, we adopt the $B^{+}$ -tree as the basic structure to build the index and construct a similar document collection for each document. Due to the use of our unique index structure, compared to linear search, the search efficiency is more exceptional. Extensive experiments on the real-world document collection are conducted to demonstrate the feasibility and efficiency of the proposed solution.

With the sustained evolution and expeditious popularization of cloud computing, an ever-increasing number of individuals and enterprises are encouraged to outsource data to cloud servers for reducing management overhead and ease of access. Privacy requirements demand encryption of sensitive information before outsourcing, which, on the other hand, diminishes the usability of data and makes considerable efficient keyword search techniques used on plaintext inapplicable. In this paper, we propose a secure multi-keyword ranked search scheme based on document similarity to work out the problem. In order to achieve the goals of multi-keyword search and ranking search results, we adopt the vector space model and TF-IDF model to generate index and query vectors. By introducing the secure kNN computation, index and query vectors can be encrypted to prevent cloud servers from obtaining sensitive frequency information. For the need of efficiency advancement, we adopt the $B^{+}$ -tree as the basic structure to build the index and construct a similar document collection for each document. Due to the use of our unique index structure, compared to linear search, the search efficiency is more exceptional. Extensive experiments on the real-world document collection are conducted to demonstrate the feasibility and efficiency of the proposed solution.

Eight new flavonoids, including two β-hydroxy/methoxychalcones, velutones A and B (1 and 2), two 1,3-diarylpropan-1-ols, velutols C and D (3 and 4), a dihydroxychalcone, velutone E (5), a chalcone, velutone F (6), a furanoflavanone, velutone G (7), and a furanoflavonol, velutone H (8), and 14 known compounds were isolated from Millettia velutina. Their structures were determined by high-resolution electrospray ionisation mass spectrometry (HR-ESIMS) and spectroscopic data analyses and time-dependent density functional theory electronic circular dichroism (TD-DFT-ECD) calculations. Among the isolated constituents, compound 6 exhibited the most potent inhibitory effect (IC50: 1.3 μM) against nigericin-induced IL-1β release in THP-1 cells. The initial mechanism of action study revealed that compound 6 suppressed NLRP3 inflammasome activation via blocking ASC oligomerization without affecting the priming step, which subsequently inhibited caspase-1 activation and IL-1β secretion. Most importantly, compound 6 exerted potent protective effects in the LPS-induced septic shock mice model by improving the survival rate of mice and suppressing serum IL-1β release. These results demonstrated that compound 6 had the potential to be developed as a broad-spectrum NLRP3 inflammasome inhibitor for the treatment of NLRP3-related disease.

Black pepper (Piper nigrum L.) has been commonly utilized in food preparation and traditional medicine in several countries. Seven new amide alkaloids, pipernigramides A-G (3, 10, 38, and 41-44), a new piperic ester, pipernigrester A (48), along with 47 known compounds were isolated from the EtOH extract of P. nigrum. The inhibitory effects on nitric oxide (NO) of all compounds were then evaluated. Among the tested compounds, three of them (42-44) significantly inhibited inducible nitric oxide synthase (iNOS)-mediated NO (IC50 = 4.74 ± 0.18, 4.08 ± 0.19, and 3.71 ± 0.32 μM, respectively), and IL-1β, IL-6, TNF-α, and PGE2 release in RAW 264.7 cells stimulated by lipopolysaccharide. Moreover, 42-44 suppressed IκB degradation and further inhibited the cytosol-nucleus translocation of the p65 subunit by targeting IKK-β. In the carrageenan-induced paw edema test, 42-44 demonstrated anti-inflammatory effects as well. These results indicate that all three compounds from P.nigrum have the potential anti-inflammatory effects.

The bit error rate (BER) formula of the M-QAM system is derived under nonequally likely condition of the constellation points, from which improving the BER performance of the M-QAM system by optimizing the probability distribution of constellation points is identified. Based on the analysis, the bit-level XOR method is employed to encrypt the image data and modify the probability distribution of the constellation points. The simulation results show that bit-level XOR is helpful to obtain a better probability distribution of the 16-QAM system compared to that without bit XOR and hence can improve the BER performance of the proposed OFDM transmission system. Simulation results based on test images over the AWGN channel further confirm that the reliability of the OFDM transmission system and the reconstructed quality of the compressed image are both significantly enhanced using bit-level XOR operation.

Searching the targets of natural products is very important for drug discovery and elucidating the mechanism of drug action and disease. Honokiol (HK), as the major active component of Magnolia officinalis RehderE.H.Wilson, has been widely used in medicine and cosmetics. Among its bioactivities, its anti-inflammatory activity is particularly impressive. However, the target protein of HK in anti-inflammatory action and its regulatory mechanism are unclear.Here, we identified the target protein and molecular mechanism of the anti- inflammatory action of HK.First, an LPS-induced septic shock model and DSS-induced ulcerative colitis model were used to assess the anti-inflammatory efficacy of HK. Second, the drug affinity responsive target stability, proteomics analysis, thermal shift assays and cellular thermal shift assays were used to identify and validate the target of HK. Finally, western blot, ELISA, LDH immunofluorescence staining, shRNA and LC/MS for L-leucine analysis were performed to determine the mechanism of the anti-inflammatory action of HK.This study revealed that HK significantly alleviated LPS-induced septic shock and DSS-induced ulcerative colitis in vivo, suggesting that HK has significant anti-inflammatory activity. HK treatment dramatically reduced IL-1β release and caspase-1 activation at different time points, showing that HK could inhibit both NLRP3 inflammasome priming and activation processes in cells. HK also suppressed adaptor apoptosis speck-like protein oligomerization. Mechanistically, SLC3A2 was identified as a direct target of HK in THP-1 cells. HK downregulated SLC3A2 expression by promoting its degradation via proteasome-mediated proteolysis. Further study demonstrated that HK triggered SLC3A2 to suppress NLRP3 inflammasome activation by significantly reducing the content of L-leucine transported into cells and lysosomes to block the mTORC1 pathway.Our work identified HK as a promising anti-inflammatory drug candidate through the SLC3A2/L-leucine/mTORC1/NLRP3 pathways.

During the development of tumors, tumors “educate” platelets causing changes in their mRNAs expression profiles and phenotypes, thereby, tumor-educated platelet (TEP) mRNA profile has the potential to diagnose lung cancer. The current study aimed to examine whether TEPs might be a potential biomarker for lung cancer diagnostics. Platelet precipitation was obtained by low-speed centrifugation and subjected to Trizol for total RNA extraction. Platelet MAX, MTURN, and HLA-B mRNA were selected by microarray, validated by qPCR, and analyzed combined with related clinical factors. Our results showed that a three-platelet mRNA set: MAX, MTURN, and HLA-B was significantly up-regulated in lung cancer patients as well as in early-stage lung cancer patients compared with those from healthy donors, the area under the curve (AUC) was 0.734, 0.787, respectively, among which platelet MTURN mRNA processed a dramatically high diagnostic efficiency in female patients with lung cancer, its AUC for female was 0.825. More importantly, the three-platelet mRNA set: MAX, MTURN, and HLA-B was associated with chemotherapeutic effect, low mRNA expression of this three-platelet set was correlated with “favorable” first chemotherapy response. A three-platelet mRNA set: MAX, MTURN and HLA-B enables blood-based lung cancer diagnosis and chemotherapy response prediction.

Graphical abstract, Highlights • Six new natural compounds were isolated from Millettia pachyloba Drake. • The cytotoxic activities of these new compounds were evaluated. • Ten (3–5, 9, 12, 17–19, 24, and 25) of 28 isolated compounds showed cytotoxicity. • The ten cytotoxic compounds induced autophagy in cancer cells. • Compound 9 induced apoptosis and autophagy, suggesting it could be a potential anticancer drug candidate., In this study, systematic separation and subsequent pharmacological activity studies were carried out to identify cytotoxic natural products from the dried stems of Millettia pachyloba Drake. Five previously undescribed isoflavones, pachyvones A–E; one previously undescribed xanthone, pachythone A; and twenty-two known compounds were obtained. The structures of these compounds were assigned on the basis of 1D/2D NMR data and high-resolution electrospray ionization mass spectroscopy analysis. Preliminary activity screening with HeLa and MCF-7 cells showed that ten compounds (3–5, 9, 12, 17–19, 24, and 25) had potential cytotoxicity. Further in-depth activity studies with five cancer cell lines (HeLa, HepG2, MCF-7, Hct116, and MDA-MB-231) and one normal cell line (HUVEC) revealed that these ten compounds showed specific cytotoxicity in cancer cells, with IC50 values ranging from 5 to 40 μM, while they had no effect on normal cell lines. To investigate whether the cytotoxicity of these ten compounds was associated with autophagy, their autophagic effects were evaluated in GFP-LC3-HeLa cells. The results demonstrated that compound 9 (durmillone) significantly induced autophagy in a concentration-dependent manner and had the best activity as an autophagy inducer among all of the compounds. Therefore, compound 9 was selected for further study. The PI/Annexin V double staining assay and Western blotting results revealed that compound 9 also induced obvious apoptosis in HeLa and MCF-7 cells, which suggests that it mediates cytotoxic activity through activation of both apoptosis and autophagy. Taken together, this study identified ten natural cytotoxic products from the dried stems of Millettia pachyloba Drake, of which compound 9 induced apoptosis and autophagy and could be an anticancer drug candidate.

To develop highly efficient non-noble-metal electrocatalysts for oxygen evolution reaction is still a great challenge. Herein, cobalt and iron oxide with hollow structure has been fabricated using ZIF-67 as template, via reflux process followed by calcination. The simultaneous structural and electronic modulation are achieved due to the homogenous Fe incorporation. The Co sites in higher oxidation states and Fe sites with higher electron density can enhance the adsorption of H2O molecules and OOH species, and thus promote the water oxidation. The unique hollow structure also facilitates the mass transfer at the interface of electrolyte and active atoms. The optimal cobalt and iron oxide hollow nanocages exhibit superior OER performance, delivering an ultralow overpotential of 274 mV at 10 mA cm−2 and a very small Tafel slope of 31 mV dec−1 in alkaline media, which outperform the state-of-the-art RuO2. This work provides an efficient approach to design and explore non-precious electrocatalysts for electrochemical energy conversion and storage.

Safe and reliable operation of mechanical equipment depends on timely and accurate fault diagnosis. When the actual working conditions are complex and variable and the available sample data set is small, recognition accuracy of the rolling bearing fault diagnosis model is low. To solve this problem, a novel method based on Markov transition field (MTF) and multi-dimension convolutional neural network (MDCNN) is proposed in this paper. Firstly, the original vibration signals are converted into two-dimensional images containing temporal correlation by MTF. Then, a neural network model is constructed by using multi-dimension attention and E-rectified linear units (E-Relu) activation function to fully extract fault feature information. Finally, the MTF images are input into the model and the data is normalized using the group normalization method. The MDCNN model is validated on two different data sets, and the results show that compared with other intelligent fault diagnosis methods, the MDCNN has higher fault diagnosis accuracy and stronger robustness under both variable working conditions and small sample data sets conditions.

We propose the fractional-order total variation (TV) algorithm with nonlocal self-similarity for image reconstruction in compressed sensing to alleviate texture details deterioration and eliminate staircase artifacts, which results from the TV algorithms. The Grunwald–Letnikov fractional-order differential operators, which consider more neighboring image pixels and use four different directions to handle fractional-order gradients, are used to replace the integer-order differential operators. To suppress the staircase artifacts, modified nonlocal means operators are introduced into our method, which can contain prior image structural information and update the Lagrangian multipliers. An efficient augmented Lagrangian algorithm is used to solve the TV problem. Numerical results show that the algorithm achieves remarkable performance improvements at various sampling ratios. Compared with fractional-order TV-based projections onto convex sets, the maximum gains of peak signal-to-noise ratio and structural similarity index with all images are up to 2.52 dB and 0.0178, respectively, and the algorithm performs the better for preserving details and eliminating the staircase effect at the cost of taking more time.

We propose an all-fiber broadband circular polarizer based on leaky mode coupling and a phase-matched turning point (PMTP) in a chirped, double-helix, chiral, long-period, fiber grating (CLPG). The CLPG was coated with a material in which the refractive index was higher than that of the fiber cladding, enabling the coupling of the core mode to leaky modes to achieve a desired extinction ratio. The complex coupled-mode theory was employed to investigate the coupling mechanism and conditions under which the desired coupling efficiency could be achieved. Moreover, the PMTP in phase-matched curves, which resolved the conflict between the operating bandwidth and the grating pitch range of the CLPG and made a large bandwidth with a small grating pitch possible, was used in the design to achieve a compact structure. Finally, two broadband circular polarizers with an extinction ratio above 25 dB were simulated; one had a bandwidth of over 120 nm and a length of 3.5 cm, and the other had a bandwidth of over 300 nm and a length of 8 cm.

Magnolol and honokiol are the two major active ingredients with similar structure and anticancer activity from traditional Chinese medicine Magnolia officinalis, and honokiol is now in a phase I clinical trial (CTR20170822) for advanced non-small cell lung cancer (NSCLC). In search of potent lead compounds with better activity, our previous study has demonstrated that magnolol derivative C2, 3-(4-aminopiperidin-1-yl)methyl magnolol, has better activity than honokiol. Here, based on the core of 3-(4-aminopiperidin-1-yl)methyl magnolol, we synthesized fifty-one magnolol derivatives. Among them, compound 30 exhibited the most potent antiproliferative activities on H460, HCC827, H1975 cell lines with the IC50 values of 0.63–0.93 μM, which were approximately 10- and 100-fold more potent than those of C2 and magnolol, respectively. Besides, oral administration of 30 and C2 on an H460 xenograft model also demonstrated that 30 has better activity than C2. Mechanism study revealed that 30 induced G0/G1 phase cell cycle arrest, apoptosis and autophagy in cancer cells. Moreover, blocking autophagy by the autophagic inhibitor enhanced the anticancer activity of 30 in vitro and in vivo, suggesting autophagy played a cytoprotective role on 30-induced cancer cell death. Taken together, our study implied that compound 30 combined with autophagic inhibitor could be another choice for NSCLC treatment in further investigation.

Background Small nuclear RNA (snRNA) levels are extremely variable across a wide range of biological conditions. SnRNAs could potentially regulate alternative splicing to drive genetic, dysplastic and neoplastic disease, which might be the main reason for mRNA profile alteration in tumor educated platelets (TEPs). Methods Platelets were isolated from the plasma of lung cancer patients and healthy donors by low-speed centrifugation and subjected to RNA isolation. SnRNA U1, U2, U5 levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated by ultracentrifugation and identified by qNano. Results TEP U1, U2, U5 levels were significantly decreased in patients with lung cancer as well as with early stage patients, their downregulation was correlated with lung cancer progression, possessing favorable diagnostic efficiency. More importantly, TEP U1, U2 and U5 levels were closely correlated between paired exosomes and TEP from treated patients but not from untreated ones, and U1, U5 but not U2 in platelets were elevated by apo-exosomes. Conclusion Tumor educated platelet small nuclear RNAs are downregulated and act as promising biomarkers in lung cancer.

Biogenic amines are harmful to human health at a certain extent. As a kind of biogenic amine oxidase, multicopper oxidase can be used to degrade them. Currently, the literature about enzyme from Enterococcus spp. are limited, and recombinant multicopper oxidase might be an effective way to degrade biogenic amines.(i) Select and identify strains that can degrade biogenic amines, (ii) overexpress enzyme from Enterococcus spp., (iii) measure gene expression and probe amine-degradation differences among strains (native, E. coli DH5α, and L. delbruckii), and (iv) examine the biochemical properties of recombinant multicopper oxidase, (v) apply the recombinant enzyme into smoked horsemeat sausage.Reverse transcription PCR and high-performance liquid chromatography were performed to examine gene expression and amine degradation rate.The results demonstrated that target enzymes were successfully overexpressed, accompanied by increased amine-degrading activity (P0.05). Gene from E. faecalis M5B was expressed in L. delbrueckii resulted in degradation rates for phenylethylamine, putrescine, histamine and tyramine of 54%, 52%, 70% and 40%, respectively, significantly higher than achieved by other recombinant strains.In this work, gene expression levels were higher in recombinant M5B than recombinant M2B, regardless of host. E. coli is more stable to express multicopper oxidase. Besides, the amine-degrading ability was markedly increased in the two recombinant strains. After prolonged incubation, the recombinant enzyme could degrade three amines, and it displayed high alkali resistance and thermostability.

Black pepper (

Millettia pulchra is a renowned anti-inflammatory herbal medicine in southeast provinces of China. However, the underlying anti-inflammation mechanism remained incompletely understood. Herein, four new isoflavones, pulvones A-D and eleven reported constituents were isolated from the stems of Millettia pulchra with their structures being elucidated by HRMS and NMR analysis. The anti-inflammatory activities of pulvones A and C were further evaluated due to the better inhibitory activity on nitric oxide production in LPS-stimulated RAW264.7 cells and no obvious cytotoxicity to RAW264.7 cells. Western blot showed that pulvones A significantly decreased the levels of iNOS and COX-2 proteins and pulvones C only decreased the level of iNOS protein. ELISA analysis demonstrated that pulvones A inhibited the production of both interleukin-6 (IL-6) and IL-1β while pulvones C showed better suppression effect on IL-1β production in LPS-stimulated RAW264.7 cells. Then, their potential inhibitory effects on NF-κB pathway were tested in LPS-stimulated RAW264.7 cells. Immunofluorescence and western blot assay showed that pulvones A and C reduced the nuclear translocation of NF-κB(p65) and interrupted IκB phosphorylation. The ADP-Glo™ kinase assay showed pulvones A and C could directedly inhibit the IKKβ kinase activity with the inhibitory rate of 40%, which were also verified by docking study. Collectively, these results suggested that pulvones A and C's anti-inflammatory effects were relevant to the interruption of NF-κB activation by inhibiting IKKβ kinase.

Parkinson’s disease (PD) is a slowly progressive and complex neurodegenerative disorder. Up to date, there are no approved drugs that could slow or reverse the neurodegenerative process of PD. Here, we reported the synthesis of series of piperine analogues and the evaluation of their neuroprotective effects against hydrogen peroxide (H2O2) induced damage in the neuron-like PC12 cells. Among these analogues, 3b exhibited the most potent protection effect and its underlying mechanism was further investigated. Further results indicated that the ROS scavenging and cytoprotection effect of 3b might be related to the Nrf2 activation and upregulation of related phase II antioxidant enzymes, such as HO-1 and NQO1. In in vivo study, oral administration (100 mg/kg) of 3b significantly attenuated PD-associated behavioral deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and protected tyrosine hydroxylase-immunopositive dopaminergic neurons. Our results provided evidence that 3b might be a promising candidate for Parkinson’s disease treatment.

Accumulating evidence supports a role for exosomal protein in diagnosis. The purpose of this study was to identify the tumor‐derived exosomal biomarkers in the serum that improve the diagnostic value in Chinese non‐small cell lung cancer (NSCLC) patients. Serum exosomes were isolated from healthy donors (n = 46) and NSCLC patients (n = 125) by ultracentrifugation and were characterized using transmission electron microscopy, qNano, and immunoblotting. Proteomic profiles (by mass spectrometry) revealed multiple differentially expressed proteins in the healthy and NSCLC groups. The exosomal expression levels of alpha‐2‐HS‐glycoprotein (AHSG) and extracellular matrix protein 1 (ECM1) increased significantly in the NSCLC patients compared to the healthy group. Alpha‐2‐HS‐glycoprotein showed diagnostic values with a maximum area under the receiver operating characteristic curve (AUC) as 0.736 for NSCLC vs healthy individuals (P

Two new triterpenoids, named as 3β-(E)-p-caffeoylnepeticin (1) and 3β-(E)-3,4-dimethoxycinnamate-20(S)-dammarenediol II (2), along with three known compounds 3, 4 and 5 were isolated from the stems of Celastrus orbiculatus Thunb. The structures of these compounds were elucidated by spectroscopic methods including IR, 1D and 2D NMR as well as by high-resolution mass spectrometric analysis. The anti-inflammatory activities and the cytotoxic effects were evaluated on lipopolysaccharide induced nitric oxide production in RAW 264.7 cells and two tumor cell lines (MCF-7 and A2780s), respectively. Results showed that compounds 1 and 3 exhibited weak anti-inflammatory activity with the IC50 value of 18.50 and 10.51 μM respectively, while all compounds were inactive in both cell lines (IC50 > 20 μM).

Background and objective During the occurring and developing of tumor, tumor-educated platelets mRNA profiles were altered. Since platelets are anuclear, the level of mRNAs is probably post-transcriptional regulated by the splicing maturation of pre-mRNA and alternative splicing. Apoptotic chromatin condensation inducer 1 (ACIN1) has been shown to be a component of a splicing-dependent multiprotein exon junction complex (EJC) and was involved in mRNA metabolism associated with splicing. This study analyzed the expression of ACIN1 mRNA in platelets, and explored its potential as a biomarker of lung cancer. Methods 156 patients with lung cancer and 58 healthy controls in Shandong Cancer Hospital were collected. We isolated platelet pellets by low-speed centrifugation and extracted total RNA. The expression of ACIN1 mRNA in platelets was detected by RT-PCR, the results were analyzed statistically. And the relationship between expression of ACIN1 mRNA and clinical factors were also analyzed. Results The expression level of ACIN1 mRNA in platelets of patients with lung cancer was significantly higher than that in platelets of healthy controls (P=0.015). The ROC curve showed that the area under the curve of ACIN1 mRNA for detecting lung cancer were 0.608. The expression of ACIN1 mRNA in platelets of lung cancer has no significant relationship with age, gender, pathological type and metastasis or not (P>0.05). Conclusion ACIN1 mRNA was highly expressed in platelets of lung cancer patients, and the detection of its expression level might have potential clinical value for the diagnosis of lung cancer.

Aim: We investigated HSP90α as screening biomarker for early colorectal cancer (CRC). Methods & results: Seventy-seven CRC patients and 78 healthy controls were enrolled. Plasma HSP90α was significantly higher in CRC patients than in healthy controls (p

EGFR T790 M accounts for 50% to 60% of cases of non-small-cell lung carcinoma (NSCLC) resistance to the first-generation EGFR tyrosine kinase inhibitors (TKIs). Hence, identifying novel compounds with activity against TKIs resistant is of great value. In this study, twenty honokiol and magnolol derivatives were isolated from the EtOH extract of Magnolia officinalis and the antiproliferative activity was evaluated on HCC827 (19del EGFR mutation), H1975 (L858 R/T790 M EGFR mutation), and H460 (KRAS mutation) cell lines. Among the isolated compounds, piperitylmagnolol (a 3-substituted magnolol derivative) showed the best antiproliferative activity against those three cell lines with the IC50 values of 15.85, 15.60 and 18.60 μM, respectively, which provided a direction for the structural modification of magnolol. Further structural modification led to the synthesis of thirty-one magnolol derivatives, and compounds A13, C1, and C2 exhibited significant and broad-spectrum antiproliferative activity with the IC50 values ranging from 4.81 to 13.54 μM, which were approximately 4- and 8-fold more potent than those of honokiol and magnolol, respectively. Moreover, their aqueous solubility was remarkably improved with 12-, 400- and 105 fold greater than those of honokiol and magnolol. Anti-tumor mechanism research revealed that these three compounds were able to induce cell cycle arrest at G0/G1 phase, cause efficient apoptosis in H1975 cells, and also prevent the migration of HUVECs in a dose-dependent manner through Cdk2, Cdk4, Cyclin E, and Cyclin D1 inhibition as well as up-regulation of cleaved-PARP and cleaved-caspase 3 levels. In in vivo antitumor activity, C2 (10, 30 and 100 mg/kg, po) dose-dependently inhibited the tumor growth in H1975 xenograft model with the tumor inhibition rate of 46.3%, 59.3% and 61.2% respectively, suggesting that C2 is a potential oral anticancer agent deserving further investigation.

Inhibitors that bind to the paclitaxel- or vinblastine-binding sites of tubulin have been part of the pharmacopoeia of anticancer therapy for decades. However, tubulin inhibitors that bind to the colchicine-binding site are not used in clinical cancer therapy, because of their low therapeutic index. To address multidrug resistance to many conventional tubulin-binding agents, numerous efforts have attempted to clinically develop inhibitors that bind the colchicine-binding site. Previously, we have found that millepachine (MIL), a natural chalcone-type small molecule extracted from the plant Millettia pachycarpa, and its two derivatives (MDs) SKLB028 and SKLB050 have potential antitumor activities both in vitro and in vivo. However, their cellular targets and mechanisms are unclear. Here, biochemical and cellular experiments revealed that the MDs directly and irreversibly bind β-tubulin. X-ray crystallography of the tubulin–MD structures disclosed that the MDs bind at the tubulin intradimer interface and to the same site as colchicine and that their binding mode is similar to that of colchicine. Of note, MDs inhibited tubulin polymerization and caused G(2)/M cell-cycle arrest. Comprehensive analysis further revealed that free MIL exhibits an s-cis conformation, whereas MIL in the colchicine-binding site in tubulin adopts an s-trans conformation. Moreover, introducing an α-methyl to MDs to increase the proportion of s-trans conformations augmented MDs' tubulin inhibition activity. Our study uncovers a new class of chalcone-type tubulin inhibitors that bind the colchicine-binding site in β-tubulin and suggests that the s-trans conformation of these compounds may make them more active anticancer agents.

Two new lignan derivatives and nine known compounds were isolated from the EtOAc and n-BuOH extracts of Millettia dorwardi Coll. Et. Hemsl. The structures of the compounds were determined by 1D and 2D NMR, CD and HRMS. Then, cytotoxic effects of these compounds were evaluated against five cancer cell lines (HepG2, HCT116, MCF7, Raji and KG-1). Results showed the isolated compounds have no obvious cytotoxic activity, but millepurpan (5) showed moderate growth inhibitory activity against Raij and KG-1 cells, with IC50 values of 36.13 and 30.11 μM, respectively. Further activity evaluation revealed that millepurpan (5) could induce G1 arrest and apoptosis in KG-1 cells. The lignan skeleton was isolated from Millettia genus for the first time and all compounds were firstly reported from Millettia dorwardi Coll. Et.

In the present study, a new Lieb lattice with five points(hereinafter referred to as Lieb-5 lattice) in the minimum periodic unit is used as a platform. The sites of Lieb-5 lattices are classified into two categories according to their spatial position, respectively, the center lattice and the edge lattices. We investigate the effect of two categories lattices with different intensity on the propagation of the out-of-phase octupole beam. According to simulation results, when the intensity of the center lattice is less than that of the edge lattices(the ratio of two lattice intensities is 2:3), eight-peak shape is always maintained during beam propagation, presenting “strong localization”. Otherwise, the energy between incident lattices is periodically coupled with the increase of propagation distance, presenting “weak localization.”

A novel highly sensitive intensity detection method has been proposed based on a self-interference ring resonator, where it is obtained by introducing an additional interference sensing arm between two coupling regions in the conventional planar add-drop micro-ring resonator. By means of dissipative and dispersive coupling mechanisms, optical path length changes of sensing arm not only bring the shift in a resonant wavelength, but also result in the variation of the linewidth and extinction of the spectrum. Using the analytical expression of the transmittance, it is proved that this sensor can monitor optical path length changes of sensing arm with a theoretical detection limit ( $5.6\times 10^{-3}$ nm) by measuring intensity variations at a certain transmission valley.

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening and interstitial lung disease with the median survival of only 3-5 years. However, due to the unclear etiology and problems in accurate diagnosis, up to now only two drugs were approved by FDA for the treatment of IPF and their outcome responses are limited. Numerous studies have shown that TGF-β is the most important cytokine in the development of pulmonary fibrosis and plays a role through its downstream signaling molecule TGF-binding receptor Smads protein. In this paper, compounds bearing 2(1H)-quinolone scaffold were designed and their anti-fibrosis effects were evaluated. Of these compounds, 20f was identified as the most active one and could inhibit TGF-β-induced collagen deposition of NRK-49F cells and mouse fibroblasts migration with comparable activity and lower cytotoxicity than nintedanib in vitro. Further mechanism studies indicated that 20f reduced the expression of fibrogenic phenotypic protein α-SMA and collagen Ⅰ by inhibiting the TGF-β/Smad dependent pathways and ERK1/2 and p38 pathways. Moreover, compared with the nintedanib, 20f (100 mg/kg/day, p.o) more effectively alleviated collagen deposition in lung tissue and delayed the destruction of lung tissue structure both in bleomycin-induced prevention and treatment mice pulmonary fibrosis models. The immunohistochemical experiments further showed that 20f could block the expression level of phosphorylated Smad3 in the lung tissue cells, which resulted in its anti-fibrosis effects in vivo. In addition, 20f demonstrated good bioavailability (F = 41.55% vs 12%, compare with nintedanib) and an appropriate elimination half-life (T1/2 = 3.5 h), suggesting that 20f may be a potential drug candidate for the treatment of pulmonary fibrosis.

Idiopathic pulmonary fibrosis, characterized by excess accumulation of extracellular matrix, involved in many chronic diseases or injuries, threatens human health greatly. We have reported a series of compounds bearing coumarin scaffold which potently inhibited TGF-β-induced total collagen accumulation in NRK-49F cell line and migration of macrophages. Compound 9d also suppressed the TGF-β-induced protein expression of COL1A1, α-SMA, and p-Smad3 in vitro. Meanwhile, 9d at a dose of 100 mg/kg/day through oral administrations for 4 weeks effectively alleviated infiltration of inflammatory cells in lung tissue and fibrotic degree in bleomycin-induced pulmonary fibrosis model, which may related to its inhibition of TGF-β/Smad3 pathway and anti-inflammation efficacy. In addition, 9d demonstrated decent bioavailability (F = 39.88%) and suitable eliminated half-life time (T1/2 = 13.09 h), suggesting that 9d could be a potential drug candidate for the treatment of fibrotic diseases.

Background Platelets have emerged as key players in tumorigenesis and tumor progression. Tumor-educated platelet (TEP) RNA profile has the potential to diagnose non-small-cell lung cancer (NSCLC). The objective of this study was to identify potential TEP RNA biomarkers for the diagnosis of NSCLC and to explore the mechanisms in alternations of TEP RNA profile. Methods The RNA-seq datasets GSE68086 and GSE89843 were downloaded from Gene Expression Omnibus DataSets (GEO DataSets). Then, the functional enrichment of the differentially expressed mRNAs was analyzed by the Database for Annotation Visualization and Integrated Discovery (DAVID). The miRNAs which regulated the differential mRNAs and the target mRNAs of miRNAs were identified by miRanda and miRDB. Then, the miRNA-mRNA regulatory network was visualized via Cytoscape software. Results Twenty consistently altered mRNAs (2 up-regulated and 18 down-regulated) were identified from the two GSE datasets, and they were significantly enriched in several biological processes, including transport and establishment of localization. Twenty identical miRNAs were found between exosomal miRNA-seq dataset and 229 miRNAs that regulated 20 consistently differential mRNAs in platelets. We also analyzed 13 spliceosomal mRNAs and their miRNA predictions; there were 27 common miRNAs between 206 differential exosomal miRNAs and 338 miRNAs that regulated 13 distinct spliceosomal mRNAs. Conclusion This study identified 20 potential TEP RNA biomarkers in NSCLC for diagnosis by integrated bioinformatical analysis, and alternations in TEP RNA profile may be related to the post-transcriptional regulation and the splicing metabolisms of spliceosome.

Natural products and their derivatives have historically been invaluable as a source of therapeutic agents. Honokiol, as a well-known natural product in Chinese herbal medicine Houpu, is finally being studied in a Phase I clinical trial (CTR20170822) in patients with Advanced Non-Small Cell Lung Cancer (NSCLS) in China this year. During the honokiol liposome formulation process, five major impurities were present in the range of 0.05–0.1% based on the HPLC analysis. These five major impurities were obtained from the forced degradation product of honokiol through countercurrent chromatography and prep-HPLC. The structure were elucidated with 1H NMR, 13C NMR, 2D NMR and MS spectral data. The proposed HPLC method was validated for specificity, linearity (concentration range 0.01–1.62, 0.003–0.96, 0.05–7.98, 0.04–6.52, 0.03–5.18 μg/ml for impurities I–V respectively, R2 > 0.9988), accuracy (99.11–100.67%), precision (CV

A liquid level sensing scheme based on leaky mode attenuation and a corresponding liquid level sensor based on a guided-mode–leaky-mode–guided-mode (GLG) fiber structure are proposed, which aim at the liquid whose refractive index (RI) is higher than that of the silica fiber. With mode expansion in terms of guided modes and leaky modes, theoretical analysis and simulations on the sensor are presented. The results, which are then verified by our experiments, indicate that the sensor offers not only an excellent linear response to the liquid level, but also a capability of discriminating the RI of the liquid.

We present a fiber sensing for temperature with two different mode interferences. The sensor consists of a single mode-multimode-single mode (SMS) fiber with a specifically designed and synthesized thermo-optic polymer cladding, forming a leaky mode fiber interferometer and a guided one at different temperatures. A maximum temperature sensitivity of 1.4 dB/°C below 61°C and of 15 nm/°C above 72°C have been achieved. The high temperature sensitivity is mainly attributed to the high thermo-optic coefficient of the polymer cladding. The phenomenon of the fiber temperature sensing around the transformation point can be observed and studied using the proposed fiber sample. It is found that the SMS fiber sensor is more sensitive to temperature for both of the mode interferences when the refractive index (RI) of the polymer is closer to that of the multimode fiber core, and the measurement range is relatively wide.

We analyze the evolution of transverse acceleration two-dimensional (2D) Airy beams propagating in Lieb photonic lattices with different photorefractive self-focusing nonlinearity. Numerical simulation shows that a decreased transverse acceleration of Airy beam and even a completely stopped state, the energy localized at the main lobe position, can be reached while the Airy beam is launched into the on-site/off-site of the Lieb photonic lattices by varying the medium nonlinearity. We discover that the transverse acceleration when the main lobe of Airy beam incident to off-site of the Lieb photonic lattice can be suppressed, which need a bias voltage larger than the on-site case when the main lobe of Airy beam incident to off-site of the Lieb photonic lattice. Additionally, the main lobe energy of the Airy beam still converges at the attractive defect lattice sites and spreads out to surrounding lattice sites due to the existence of repulsive defects under saturable nonlinearity.

A capillary electrophoresis coupled with electrochemiluminescent detection system (CE-ECL) was developed for the detection of polymerase chain reaction (PCR) amplicons. The ECL luminophore, tris(1,10-phenanthroline) ruthenium(II) (Ru(phen)(3)(2+)), was labeled to the PCR primers before amplification. Ru(phen)(3)(2+) was then introduced to PCR amplicons by PCR amplification. Eventually, the PCR amplicons were separated and detected by the homemade CE-ECL system. The detection of a typical genetically modified organism (GMO), Roundup Ready Soy (RRS), was shown as an example to demonstrate the reliability of the proposed approach. Four pairs of primers were amplified by multiple PCR (MPCR) simultaneously, three of which were targeted on the specific sequence of exogenous genes of RRS, and another was targeted on the endogenous reference gene of soybean. Both the conditions for PCR amplification and CE-ECL separation and detection were investigated in detail. Results showed that, under the optimal conditions, the proposed method can accurately identifying RRS. The corresponding limit of detection (LOD) was below 0.01% with 35 PCR cycles.

A liquid level sensor based on single leaky mode attenuation in a single-mode-multimode-single-mode (SMS) fiber structure is proposed and demonstrated, which aims at the liquid whose refractive index is higher than that of the silica fiber. Its operating principle is investigated theoretically by using the mode expansion method, and a monotonic and linear sensing response is obtained. Experiments are then carried out to verify the theoretical analysis.

The accurate node location is necessary for wireless sensor network applications in both the military and civilian areas. In this paper, we use the Cramer-Rao Bound (CRB) to verify that node localization algorithms based on received signal strength (RSS) and time of arrival (TOA) are both reasonable. The varying number of blindfolded nodes as well as the hybrid of RSS and TOA ranging methods are used to investigate the localization effect. Meanwhile, the maximum likelihood estimation (MLE) is applied to estimate the location accuracy. Simulation results demonstrate that both the localization algorithms based on RSS and TOA are absolutely effective, and the localization are much more accurate with either increasing blindfolded nodes or decreasing the certain parameters value. The node localization based on hybrid RSS/TOA ranging method results in 0.846m average RMS error and 0.229m average RMS CRB, which illustrates that it is much more accurate than the node locating based on RSS and TOA individually.

A simple temperature sensor based on a bent singlemode–multimode–singlemode (SMS) fiber structure fastened on a polymer base plate is proposed and experimentally investigated. The surrounding refractive index (RI) is higher than that of the silica fiber and RI changes with temperature will not lead to wavelength shift. This SMS fiber structure utilizes changing of temperature to control the curvature of SMS fiber which is induced by expanding of polymer base plate. The shifts of central wavelength are measured at temperature range from 59 to 82 °C. The proposed temperature sensor offers sensitivity of 3.9 nm/°C, which is significantly higher than that of a normal straight SMS structure or a grating-based fiber structure.

In this article, a CE with a new electrochemiluminescent (ECL) detection system was developed. A microfluidic ECL detection cell with less than 0.5 microL dead volumes was developed and used as detector for this system. A hydrofluoric acid-etched porous joint was made at 8 mm from the outlet of the separation capillary to isolate the CE high voltage from ECL detection. The proposed CE-ECL system was applied for separation and detection of some proteins labeled with tris(1,10-phenanthroline) ruthenium(II). High efficiency ECL-enhanced reagent, tripropylamine, was infused to the detection cell as coreactant by a micro-infusion system to obtain maximum and stable ECL signal. The performance of this setup was illustrated by the analysis of tris(1,10-phenanthroline) ruthenium(II)-labeled proteins. The background electrolyte for protein detection was 20 mM Tris-CH3COOH with 2.0% m/m PVP at pH 4.0. Under the optimal conditions, the corresponding LOD were 2.2 x 10(-10) M for HSA, 4.4 x 10(-10) M for casein (alpha-S1) and 5.1 x 10(-10) M for cytochrome c. The proposed method was also successfully used for the trace analysis of albumin in human urine without any pretreatment.

We propose a novel iteration-free blind phase noise estimation scheme for coherent optical orthogonal frequency division multiplexing (CO-OFDM) systems. In the new algorithm, the cost function is selected as the similar expression with real and imaginary parts as that in the modified constant modulus algorithm, and the new cost function is derived under some assumptions, where it is infinitely approximated by the sine and cosine functions. By means of the analytical formula of the cost function, the initial coarse common phase error can be obtained with only some samples, where the algorithm avoids computational complexity of conventional blind phase noise compensation scheme. In CO-OFDM systems with high-order modulation format (32 quadrature amplitude modulation) and narrow linewidth lasers, it is proved by the simulation results that the phase noise can be effectively compensated with the proposed blind estimation method.