TRANSPARENT TESTA GLABRA1 Regulates High-Intensity Blue Light-Induced Phototropism by Reducing CRYPTOCHROME1 Levels.

The asymmetrical distribution of auxin supports high intensity blue light (HBL)-mediated phototropism. Flavonoids, secondary metabolites induced by blue light and TRANSPARENT TESTA GLABRA1 (TTG1), alter auxin transport. However, the role of TTG1 in HBL-induced phototropism in Arabidopsis (Arabidopsis thaliana) remains unclear. We found that TTG1 regulates HBL-mediated phototropism. HBL-induced degradation of CRYPTOCHROME 1 (CRY1) was repressed in ttg1-1, and depletion of CRY1 rescued the phototropic defects of the ttg1-1 mutant. Moreover, overexpression of CRY1 in a cry1 mutant background led to phototropic defects in response to HBL. These results indicated that CRY1 is involved in the regulation of TTG1-mediated phototropism in response to HBL. Further investigation showed that TTG1 physically interacts with CRY1 via its N-terminus and that the added TTG1 promotes the dimerization of CRY1. The interaction between TTG1 and CRY1 may promote HBL-mediated degradation of CRY1. TTG1 also physically interacted with blue light inhibitor of cryptochrome 1 (BIC1) and Light-Response Bric-a-Brack/Tramtrack/Broad 2 (LRB2), and these interactions either inhibited or promoted their interaction with CRY1. Exogenous gibberellins (GA) and auxins, two key plant hormones that crosstalk with CRY1, may confer the recovery of phototropic defects in the ttg1-1 mutant and CRY1-overexpressing plants. Our results revealed that TTG1 participates in the regulation of HBL-induced phototropism by modulating CRY1 levels, which are coordinated with GA or IAA signaling.

Boosted Mg-CO2 Batteries by Amine-Mediated CO2 Capture Chemistry and Mg2+ -Conducting Solid-electrolyte Interphases.

Mg-CO2 battery has been considered as an ideal system for energy conversion and CO2 fixation. However, its practical application is significantly limited by the poor reversibility and sluggish kinetics of CO2 cathode and Mg anode. Here, a new amine mediated chemistry strategy is proposed to realize a highly reversible and high-rate Mg-CO2 battery in conventional electrolyte. Judiciously combined experimental characterization and theoretical computation unveiled that the introduced amine could simultaneously modify the reactant state of CO2 and Mg2+ to accelerate CO2 cathodic reactions on the thermodynamic-kinetic levels and facilitate the formation of Mg2+ -conductive solid-electrolyte interphase (SEI) to enable highly reversible Mg anode. As a result, the Mg-CO2 battery exhibits boosted stable cyclability (70 cycles, more than 400 h at 200 mA g-1 ) and high-rate capability (from 100 to 2000 mA g-1 with 1.5 V overpotential) even at -15 °C. This work opens a newly promising avenue for advanced metal-CO2 batteries.

An Image-Based Quantized Compressive Sensing Scheme Using Zadoff-Chu Measurement Matrix.

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.

A Novel Complex-Valued Gaussian Measurement Matrix for Image Compressed Sensing.

The measurement matrix used influences the performance of image reconstruction in compressed sensing. To enhance the performance of image reconstruction in compressed sensing, two different Gaussian random matrices were orthogonalized via Gram-Schmidt orthogonalization, respectively. Then, one was used as the real part and the other as the imaginary part to construct a complex-valued Gaussian matrix. Furthermore, we sparsified the proposed measurement matrix to reduce the storage space and computation. The experimental results show that the complex-valued Gaussian matrix after orthogonalization has better image reconstruction performance, and the peak signal-to-noise ratio and structural similarity under different compression ratios are better than the real-valued measurement matrix. Moreover, the sparse measurement matrix can effectively reduce the amount of calculation.

Flavonoids with Inhibitory Effects on NLRP3 Inflammasome Activation from Millettia velutina.

Eight new flavonoids, including two ß-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-1ß 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-1ß 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-1ß 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.

Modulation of LPS-induced inflammation in RAW264.7 murine cells by novel isoflavonoids from Millettia pulchra.

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-1ß while pulvones C showed better suppression effect on IL-1ß 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 IKKß 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 IKKß kinase.

The compound millepachine and its derivatives inhibit tubulin polymerization by irreversibly binding to the colchicine-binding site in ß-tubulin.

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 ß-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 G2/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 ß-tubulin and suggests that the s-trans conformation of these compounds may make them more active anticancer agents.

Tumor-derived exosomal proteins as diagnostic biomarkers in non-small cell lung cancer.

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 < .0001) and 0.682 for early stage NSCLC vs healthy individuals (P < .01). Extracellular matrix protein 1 showed the diagnostic capacity with AUC values of 0.683 (P < .001) and 0.656 (P < .05) in cancer and early stage NSCLC compared to healthy individuals. When AHSG was combined with ECM1, the AUCs were 0.795 and 0.739 in NSCLC and early stage patients, respectively. Taken together, the combination of AHSG, ECM1, and carcinoembryonic antigen improved the diagnostic potential of NSCLC. The diagnosis values were AUC of 0.938 for NSCLC and 0.911 for early stage NSCLC vs healthy individuals. Our results suggest that novel proteomic signatures found in serum exosomes of NSCLC patients show potential usefulness as diagnostic tools.

Identification of potential tumor-educated platelets RNA biomarkers in non-small-cell lung cancer by integrated bioinformatical analysis.

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.

Identification of tryptophan metabolism- and immune-related genes signature and prediction of immune infiltration landscape in bladder urothelial carcinoma.

Introduction: Tryptophan metabolism is indirectly involved in immune tolerance and promotes response to anticancer drugs. However, the mechanisms underlying tryptophan metabolism and immune landscape in bladder urothelial carcinoma (BLCA) are not fully understood. Methods: A BLCA dataset containing 406 tumor samples with clinical survival information and 19 normal samples were obtained from the Cancer Genome Atlas database. The validation set, GSE32894, contained 223 BLCA tumor samples with survival information, and the single-cell dataset, GSE135337, included seven BLCA tumor samples; both were obtained from the gene expression omnibus database. Univariate and multivariate Cox regression analyses were conducted to evaluate clinical parameters and risk scores. Immune infiltration and checkpoint analyses were performed to explore the immune landscape of BLCA. Single-cell analysis was conducted to further identify the roles of model genes in BLCA. Finally, NAMPT expression in BLCA and adjacent tissues was detected using RT-qPCR, CCK-8 and Transwell assays were conducted to determine the role of NAMPT in BLCA cells. Results: Six crossover genes (TDO2, ACAT1, IDO1, KMO, KYNU, and NAMPT) were identified by overlap analysis of tryptophan metabolism-related genes, immune-related genes, and differentially expressed genes (DEGs). Three biomarkers, NAMPT, IDO1, and ACAT1, were identified using Cox regression analysis. Accordingly, a tryptophan metabolism- and immune-related gene risk model was constructed, and the patients were divided into high- and low-risk groups. There were significant differences in the clinical parameters, prognosis, immune infiltration, and immunotherapy response between the risk groups. RT-qPCR revealed that NAMPT was upregulated in BLCA samples. Knocking down NAMPT significantly inhibited BLCA cell proliferation, migration, and invasion. Discussion: In our study, we constructed a tryptophan metabolism- and immune-related gene risk model based on three biomarkers, namely NAMPT, IDO1, and ACAT1, that were significantly associated with the progression and immune landscape of BLCA. The risk model could effectively predict patient prognosis and immunotherapy response and can guide individualized immunotherapy.

Identification of the target protein and molecular mechanism of honokiol in anti-inflammatory action.

BACKGROUND: 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 Rehder & E.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. PURPOSE: Here, we identified the target protein and molecular mechanism of the anti- inflammatory action of HK. METHODS: 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. RESULTS: 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-1ß 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. CONCLUSIONS: Our work identified HK as a promising anti-inflammatory drug candidate through the SLC3A2/L-leucine/mTORC1/NLRP3 pathways.

Guided-mode-leaky-mode-guided-mode fiber structure and its application to high refractive index sensing.

We propose a fiber structure based on a single-mode-multimode-single-mode one. A theoretical analysis model based on leaky mode expansion along with a new concept of leaky mode interference is presented to facilitate and enlighten the analysis for the leaky structure. Then we focus on transmission characteristics of the structure in response to surrounding refractive indices (RI) that are higher than that of the silica fiber. In our simulation, output intensity of the structure increases monotonically for RI from 1.46 to 1.55, and changes over 2.0 dB for a change of 0.01 in RI range from 1.46 to 1.48, which is well verified by the following experiments.

Broadband Circular Polarizer Based on Chirped Double-Helix Chiral Fiber Grating.

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.

Imaging manifestations of neonatal necrotizing enterocolitis to predict timing of surgery.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (p < 0.05). 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. CONCLUSIONS: In summary, the ultrasound examination in NEC children showing thickening intestinal wall and poor intestinal peristalsis indicated for early operation.

The ethanolic extract of Artemisia anomala exerts anti-inflammatory effects via inhibition of NLRP3 inflammasome.

BACKGROUND: Artemisia anomala S. Moore (Compositae), known as "Nan-Liu-Ji-Nu" in traditional Chinese medicine (TCM), has been used to treat many inflammatory diseases, including enteritis, acute icteric hepatitis, rheumatism, toothache, tonsillitis, and chronic bronchitis, for centuries. Our preliminary studies have demonstrated that the ethanolic extract of A. anomala (EAA) might be with the potential of inhibiting the activation of the NLRP3 inflammasome. However, the anti-inflammatory activity of EAA based on NLRP3 inflammasome inhibition is still unclear. PURPOSE: This work aimed to elucidate the anti-inflammatory mechanism of EAA by inhibiting NLRP3 inflammasome activation. METHODS: Lipopolysaccharide (LPS)-primed bone marrow-derived macrophages (BMDMs) were used to evaluate the inhibitory effects on NLRP3 inflammasome activation. The level of IL-1ß was determined by ELISA. The expression levels of IL-1ß, caspase-1, NLRP3, and ASC were assayed using western blot analysis. ASC oligomerization and speck formation were detected by immunofluorescence microscopy. The measurements of intracellular chloride and potassium were conducted using N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) probe assay and inductively coupled plasma-optical emission spectrometry (ICP-OES), respectively. Mitochondrial reactive oxygen species (mtROS) were examined using the MitoSOX method. Acridine orange (AO) staining was used to detect the permeability of the lysosomal membrane. A DSS-induced ulcerative colitis model was established to evaluate the anti-inflammatory effects of EAA in vivo. Finally, high-performance liquid chromatography (HPLC) was employed to identify and quantify the major constituents of EAA. RESULTS: In BMDMs, EAA significantly inhibited the release of IL-1ß induced by LPS. The mechanistic study revealed that EAA inhibited NLRP3 inflammasome activation by blocking the oligomerization of ASC and suppressed the LPS-induced priming step. Furthermore, EAA protected lysosomes by inhibiting the TAK1-JNK pathway, thereby inhibiting the assembly of downstream NLRP3 inflammasome and the production of IL-1ß. In addition, EAA exerted potent protective effects in an ulcerative colitis model by decreasing the content of colonic IL-1ß and alleviating the process of ulcerative colitis. HPLC analysis identified eight main components of EAA, including isofraxidin (1), quercetin-7-O-ß-D-glucopyranoside (2), apigenin-7-O-ß-D-glucopyranoside (3), 7-methoxycoumarin (4), quercetin (5), luteolin (6), kaempferol (7), and eupatorin (8), Of these compounds, quercetin and kaempferol were found to be the most potent ingredients. CONCLUSION: These findings collectively reveal that EAA exerts anti-inflammatory effects by both suppressing the NLRP3 priming step and protecting lysosomes to inhibit NLRP3 inflammasome activation, suggesting that this traditional herbal medicine might be used to treat NLRP3-driven inflammatory diseases.

Adiabatic circular polarizer based on chiral fiber grating.

Based on the adiabatic coupling principle, a new scheme of a broadband circular polarizer formed by twisting a high-birefringence (Hi-Bi) fiber with a slowly varying twist rate is proposed. The conditions of adiabatic coupling for the adiabatic polarizer are first identified through analytical derivations. These conditions are easily realized by choosing a reasonable variation of the twist rate. Moreover, the bandwidth of the polarizer is able to be directly determined by the twist rates at the two ends. Finally, the broadband characteristics of the polarizer are demonstrated by simulations. It is also shown that the performance of the polarizer can be remarkably improved by accomplishing a multi-mode phase-matching along the grating or by using of the couplings of the core mode to lossy modes.

Heterologous Expression and Application of Multicopper Oxidases from Enterococcus spp. for Degradation of Biogenic Amines.

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 <0.05). 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. 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.

Synthesis and evaluation of new compounds bearing 3-(4-aminopiperidin-1-yl)methyl magnolol scaffold as anticancer agents for the treatment of non-small cell lung cancer via targeting autophagy.

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 30in 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.

New insight into quasi leaky mode approximations for unified coupled-mode analysis.

To facilitate the analysis of radiation mode couplings, quasi leaky mode approximations were utilized in coupled-mode analysis. The key to effectively and accurately apply this approach is how to well approximate radiation modes by the quasi leaky modes in an equivalent closed waveguide model. In this paper, the principle, applicability and accuracy of the approximations are demonstrated, and the detailed implementation is also suggested by applying a unified coupled-mode analysis to fiber gratings. First of all, based on a thorough study on the characteristics of the complex modes, for the first time, quasi leaky modes are classified into guided-mode-like inner-cladding and radiation-mode-like outer-cladding leaky modes so as to explicitly establish equivalence relationships between the discrete leaky modes and the continuous radiation modes. With this new insight, the whole analysis process especially for some of the practically tricky issues such as the criteria for developing the proper equivalent waveguide model and the subsequent mode expansion basis are better understood and easier to be dealt with for different problems where radiation modes come into play. Moreover, as essential preconditions to extend the conventional coupled mode analysis to the present unified one, the couplings between the guided core mode and a leaky mode are studied in a systematic and consistent manner. An intuitive and then a deep understanding on the roles of complex modes on mode coupling and power exchanging are thus gained for further simulations. Lastly, the transmission spectra of fiber gratings with different surrounding indices are simulated. The simulated results agree well with those obtained theoretically and experimentally in the literatures, which strongly validate the principle of quasi leaky mode approximations and its implementation on the unified coupled-mode analysis expounded in this paper.

Small Nuclear RNAs (U1, U2, U5) in Tumor-Educated Platelets Are Downregulated and Act as Promising Biomarkers in Lung Cancer.

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.