Chromones and biflavonoids from Garcinia pedunculata and Garcinia nujiangensis and their anti-inflammatory activity.

Plants of the Garcinia genus were rich in structurally diverse and naturally bioactive components, while limited studies have been reported for Garcinia pedunculata Roxb. and G. nujiangensis C. Y. Wu & Y. H. Li. Four previously undescribed compounds including three chromones, garpedunchromones A-C (1-3), and one biflavonoid, nujiangbiflavone A (14), along with fifteen known analogs (4-13, 15-19) were isolated from G. pedunculata and G. nujiangensis. The structures of the isolated compounds were determined based on their HRESIMS data, extensive NMR spectroscopic analyses, and ECD calculations. The chromone derivatives were isolated from Garcinia for the first time. Compound 14 was a rare biflavonoid with C-3─C-6″ linkage. The biological evaluation of these isolates against NO production was conducted in the LPS-induced RAW 264.7 cells, resulting in the identification of a series of potent NO inhibitors, of which garpedunchromone B (2) was the most active with an IC50 value of 18.11 ± 0.96 µM. In the network pharmacology studies, the potential targets of compounds and inflammation were obtained from PharmMapper and GeneCards database. GO and KEGG enrichment analysis revealed that the overlapped targets were closely related to the major pathogenic processes linked to inflammation. Garpedunchromone B and proteins binding sites were being predicted.

Photonic-assisted multi-format dual-band microwave signal generator without background noise.

We report a photonic approach to generate background-free multi-format dual-band microwave signals based on a single modulator, which is suitable for high-precision and fast detection of radars in complex electromagnetic environments. By applying different radio-frequency signals and electrical coding signals to the polarization-division multiplexing Mach-Zehnder modulator (PDM-MZM), the generation of dual-band dual-chirp signals or dual-band phase-coded pulse signals centered at 10 and 15.5 GHz is experimentally demonstrated. Furthermore, by choosing an appropriate fiber length, we verified that the generated dual-band dual-chirp signals are not affected by chromatic-dispersion induced-power fading (CDIP); meanwhile, by autocorrelation calculations, we got high pulse compression ratios (PCRs) of 13 of the generated dual-band phase-encoded signals, showing that the generated phase-encoded signals can be emitted directly without extra pulse truncation operation. The proposed system features a compact structure, reconfigurability and polarization independence, which is promising for multi-functional dual-band radar systems.

Cytotoxicity, endocrine disrupting activity, and chemical analysis of 42 food contact silicone rubber products.

After migration in 95 % ethanol (food simulant) at 70 °C for 2 h (accelerated conditions), the cytotoxicity and endocrine-disruption activity of 42 food contact silicone products (FCSPs) obtained from the Chinese market were studied. Of 31 kitchenwares, 96 % showed mild or above cytotoxicity (relative growth rate < 80 %) using the HeLa neutral red uptake test; and 84 % showed estrogenic (64 %), anti-estrogenic (19 %), androgenic (42 %), and anti-androgenic (39 %) activities by the Dual-luciferase reporter gene assay. The mold sample induced late phase HeLa apoptosis as detected by Annexin V-FITC/PI double staining flow cytometry, in addition, the migration of mold sample has a higher risk of endocrine disruption at high temperature usage. Encouragingly, 11 bottle nipples had neither cytotoxic nor hormonal activity. Utilizing multiple mass spectrometry techniques, non-intentionally added substances (NIASs) in 31 kitchenwares were analyzed, and the migration levels of 26 organic compounds and 21 metals were quantified, furthermore, the safe risk of single migrant was evaluated through their special migration limit (SML) or threshold of toxicological concern (TTC). Using "nchoosek" statement and Spearman's correlation analysis in MATLAB, the migration of 38 compounds or combinations including metals, plasticizers, methylsiloxanes, and lubricants, had strong correlation with cytotoxicity or hormonal activity. The coexistence of various chemical substances in migrants leads to complex biological toxicity of FCSPs, so it is very important to detect the toxicity of the final products. The combination of bioassays and chemical analyses are valuable tools to facilitate the identification and analyses of FCSPs and migrants that have potential safety risks.

Triterpene Derivatives from Garcinia oligantha and Their Anti-Cancer Activity.

Phytochemical investigations of leaves and twigs from Garcinia oligantha Merr. resulted in the isolation of five undescribed triterpene derivatives (1-5) and six known analogs (6-11). Their structures were determined based on extensive spectroscopic data and high-resolution mass spectra analyses. Compounds 1-11 were tested for their in vitro cytotoxicity against three human cancer cell lines (HeLa, HepG-2, and MCF-7). Compounds 1, 2, 8, and 11 exhibited broad and significant cytotoxicity against the tested cell lines with IC50 values ranging from 5.04 to 21.55 µM. Compounds 5 and 9 showed cytotoxicity against HeLa and MCF-7 with IC50 values ranging from 13.22 to 19.62 µM. The preliminary structure-activity relationship for the 11 isolated compounds is also discussed.

Photonic-assisted frequency downconverter with self-interference cancellation and fiber dispersion elimination based on stimulated Brillouin scattering.

A photonic-assisted frequency downconverter with self-interference cancellation and fiber dispersion elimination is proposed for in-band full-duplex (IBFD) radio-over-fiber (ROF) systems based on stimulated Brillouin scattering. In this work, a dual-polarization Mach-Zehnder modulator (DPol-MZM) is employed to cancel the self-interference signal in the optical domain, thus the proposed system has a large operation bandwidth without the limitation of the electrical bottleneck. Meanwhile, a widely tunable microwave photonic filter (MPF) based on stimulated Brillouin scattering (SBS) is constructed to perform carrier-suppressed single-sideband modulation of LO. Therefore, the proposed photonic frequency downconverter is naturally free from fiber dispersion. Furthermore, thanks to the characteristics of the SBS-based MPF, such as large out-of-band rejection ratio, high resolution and wideband tunability, the proposed system has a high flexibility and downconversion efficiency, which is of great significance for IBFD ROF systems.

Cephaloliverols A and B, two sterol-hybrid meroterpenoids from Cephalotaxus oliveri.

Cephaloliverols A (1) and B (2), two meroterpenoids based on a sterol and an abietane diterpene possessing a dioxane ring, were isolated from the twigs and leaves of Cephalotaxus oliveri. Their structures were established by spectroscopic analysis and quantum chemical calculation. 1 and 2 represent the first sterol-hybrid meroditerpenoids. The two compounds and their precursors decreased NO production in a dose-dependent manner in LPS-stimulated RAW 264.7 macrophages.

Optimization of cationic polymer-mediated transfection for RNA interference.

Transfection efficiency was estimated to optimize the conditions for RNA interference (RNAi), including transfection time, validity, and nucleic acid concentration and type, using the EZ Trans Cell Reagent, a cationic polymer. An shRNA against GFP was designed and transfected into cells using the EZ transfection reagent. The shRNA significantly decreased the expression of GFP. In addition, pre-diluted transfection reagent at room temperature and small nucleic acids increased the transfection efficiency, which peaked at 24 h. Compared with circular nucleic acids, linear nucleic acids showed higher transfection efficiency and a higher genome integration rate. We optimized cationic polymer-mediated RNAi conditions, and our data will be useful for future RNAi studies.

Identification, migration, and childhood exposure of methylsiloxanes in silicone infant bottle nipples marketed in China.

The analysis, migration, and childhood exposure of methylsiloxanes (MSs) in 32 silicone infant bottle nipples marketed in China were studied. Thirty types of MSs in two families, which included 11 linear MSs (LMSs, L4-L14) and 19 cyclic MSs (CMSs, D4-D22), were identified using gas chromatography-mass spectrometry (GC-MS) associated with standards, retention index, and carbon number rule. In 32 nipples, MSs with molecular weight < 1000 Da and CMSs were predominant. Considering the actual daily use of bottle nipples, the migration tests of MSs from nipples to artificial saliva and reconstituted powdered formula were performed. In particular, the orthogonal test design-QuEChERS-GC/MS was employed to detect MSs in formula. The median migration level of ΣMSs (MW < 1000 Da) in formula was 950.9 ng/mL, which was much higher than that in artificial saliva (98.1 ng/mL). If formula is fed to children aged 3-36 months using bottle nipples according to product instructions, the daily oral exposure to ΣMSs (MW < 1000) for children ranged from 52 to 146 µg/kg bw-day, which were two to five orders of magnitude higher than those of other exposure pathways. In sum, oral intake (especially through formula) may be the predominant pathway of exposure of MSs in children. This research enhances our understanding of the oral exposure risks of MSs and provides useful information that could aid the development of risk management strategies.

Alternative Lengthening of Telomeres Phenotype Predicts Progression Risk in Noninsulinomas in a Chinese Cohort.

INTRODUCTION: Recent studies have suggested that alternative lengthening of telomeres (ALT) is associated with metastasis and poor survival in pancreatic neuroendocrine tumors (PanNETs). This study evaluated whether this association is applicable to Chinese patients as well as the potential somatic mutations associated with ALT. METHODS: We assessed the prevalence of ALT by performing telomere-specific fluorescence in situ hybridization and analyzed DAXX/ATRX expression using immunohistochemistry in 112 Chinese patients with PanNETs to evaluate the association between ALT and clinical outcomes. A subset of the noninsulinoma samples (28/60) was subjected to Sanger sequencing and targeted sequencing. RESULTS: The ALT-positive phenotype was identified in 23.2% (26/112) of the samples. The clinicopathologic factors significantly associated with progression in the noninsulinoma (n = 60) cohort were the female sex (p = 0.006), Ki-67 index (p < 0.001), World Health Organization grade (p = 0.031), and ALT positivity (p = 0.013). Patients with ALT-positive PanNETs had significantly shorter progression-free survival than those with ALT-negative PanNETs in the entire cohort (p < 0.001), noninsulinoma subgroup (p = 0.01), and G2 subgroup (p = 0.001). ALT-positive samples frequently harbored somatic mutations in DAXX, ATRX, MEN1, SETBP1, PRKDC, and GNAS. CONCLUSIONS: We confirmed that ALT positivity is an effective risk predictor, especially in the noninsulinoma and G2 subgroups. ALT is also related to somatic mutations in MEN1, SETBP1, PRKDC, and GNAS, in addition to DAXX and ATRX.

Issues related to the health status, work pressure and occupational environments of medical staff at level A tertiary public hospitals in Shanghai.

BACKGROUND: Medical staff is the main force behind the construction of a healthy China. As a result of increasing social pressure, doctors are at high risk for diseases such as "sudden death" and "overwork death". It is essential that the physical and mental health of medical staff be assessed and long-term mechanisms be introduced to care for medical staff. This study sought to investigate the health status, work pressure, and occupational environments of medical staff at level A tertiary public hospitals in Shanghai to provide a basis for exploring the establishment of long-term mechanisms for the exquisite and precise care of medical staff. METHODS: A questionnaire was administered to employees at 10 level A tertiary public hospitals in Shanghai using a random sampling method; 50 medical staff were surveyed at each hospital. A descriptive analysis of the data was conducted using R language. RESULTS: A total of 478 questionnaires were collected; thus, the recovery rate was 95.6%. The analysis revealed that 61% of the medical staff surveyed believed that their health was "good," and 57% believed that they were under high pressure. Over 50% of medical staff were moderately satisfied with their practice environment and salary; however, staff's satisfaction evaluations were affected by their academic qualifications (degrees), work positions, and other factors. Reasonable salary is the primary motivating and demotivating factor. CONCLUSIONS: The party organization can play a leading role in contacting and serving employees. Further, 4 caring systems for health protection, welfare benefits, safety protection, and career planning should be offered to medical staff to ensure they are cared for with elaboration and precision.

Deep Learning on MRI Images for Diagnosis of Lung Cancer Spinal Bone Metastasis.

This paper aimed to explore the adoption of deep learning algorithms in lung cancer spinal bone metastasis diagnosis. Comprehensive analysis was carried out with the aid of AdaBoost algorithm and Chan-Vese (CV) algorithm. 87 patients with lung cancer spinal bone metastasis were taken as research subjects, and comprehensive evaluation was made in terms of preliminary classification of images, segmentation results, Dice index, and Jaccard coefficient. After the case of misjudgment on whether there was hot spot was excluded, the initial classification accuracy of the AdaBoost algorithm can reach 96.55%. True positive rate (TPR) was 2.3%, and false negative rate (FNR) was 1.15%. 45 MRI images with hot spots were utilized as test set to detect the segmentation accuracy of CV, maximum between-cluster variance method (OTSU), and region growing algorithm. The results showed that the Dice index and Jaccard coefficient of the CV algorithm were 0.8591 and 0.8002, respectively, which were considerably superior to OTSU (0.6125 and 0.5541) and region growing algorithm (0.7293 and 0.6598). In summary, the AdaBoost algorithm was adopted for image preliminary classification, and CV algorithm for image segmentation was ideal for the diagnosis of lung cancer spinal bone metastasis and it was worthy of clinical promotion.

Improving the adaptability of the optical performance monitor by transfer learning.

Owing to their mighty fitting ability, the supervised learning-based deep-learning (DL) models have been widely used in the area of optical performance monitoring (OPM) to improve the optical monitors' performance. However, the supervised learning-based DL models used in OPM are based on two important premises. The first premise is enough training data with labels; the second premise is the same distribution of the training and test data. Nevertheless, it is hard to meet the two premises in the real-world environment where the optical performance monitors are deployed, since the data are unlabeled and the optical network environment is dynamic (such as component aging caused by slow parameter variation), causing the degradation of the monitoring performance. This is because the supervised learning-based DL models lack the adaptability of the dynamic environment. For the purpose of improving the optical performance monitors' adaptability, we propose a transfer-learning-based convolutional neural network model to maintain the monitoring performance in the dynamic optical network environment. The transfer-learning method can transfer the learned knowledge from the labeled data under an invariant optical network environment to the unlabeled data under a dynamic optical network environment. During the training phase, the maximum mean discrepancy (MMD) is applied to match the features extracted from the source and the target domains. When the trained model is deployed in the OPM monitor, the robustness of the system to the dynamic environment would be enhanced. Four signals (60/100 Gbps 16/64 QAM) under different working environments are used to verify the adaptability of the method. The influence of the MMD's weight rates, batch size, and weight parameters confirmed the effectiveness of our method.

Upregulated MicroRNA-483-3p is an Early Event in Pancreatic Ductal Adenocarcinoma (PDAC) and as a Powerful Liquid Biopsy Biomarker in PDAC.

BACKGROUND: There is an urgent need for the development of effective noninvasive biomarkers for early pancreatic cancer diagnosis. MicroRNAs (miRNAs) are promising candidates that can be identified in peripheral blood and can act as "liquid biopsy" biomarkers. miR-483-3p is overexpressed in the tumor tissue of pancreatic duct adenocarcinoma, but its potential as noninvasive biomarker remains unknown. METHODS: We conducted locked nucleic acid in situ hybridization (LNA-ISH) for miR-483-3p in archival tissues of 107 patients with PDAC. We also used immunohistochemistry to evaluate SMAD4 expression, the putative miR-483-3p target gene. miR-483-3p expression level was also assessed using quantitative real-time PCR (qRT-PCR) in serum and serum exosome samples from 63 patients with PDAC and 22 healthy individuals. RESULTS: LNA-ISH showed that miR-483-3p was overexpressed in PDAC and PanIN tissues compared to normal pancreatic duct cells. miR-483-3p expression levels correlated with increases in PanIN lesion grade. miR-483-3p expression negatively correlated with Smad4 expression (γ=-0.770, p<0.0001) in PDAC and PanIN tissues. Circulating miR-483-3p levels were significantly elevated in the serum and serum exosomes of PDAC patients compared to healthy controls (p<0.0001 and p<0.01, respectively). Specifically, serum miR-483-3p levels were able to distinguish patients with early stage (≤2cm) PDAC from healthy controls with an AUC of 0.83 [95% CI, 0.70-0.96]. Higher serum exosomal miR-483-3p levels predicted worse survival in PDAC patients and serum exosomal miR-483-3p also proved to be an independent prognostic factor for PDAC (hazard ratio = 3.307; 95% CI=1.104 to 9.903; p=0.033). In vitro studies also showed that miR-483-3p promoted pancreatic cancer cell migration and invasion. CONCLUSION: miR-483-3p overexpression occurs early in PDAC development and is present in premalignant PanIN lesions. Serum miR-483-3p may act as an early PDAC diagnostic biomarker and serum exosomal miR-483-3p may be a PDAC prognostic biomarker.

Photonic generation of quadruple bandwidth dual-band dual-chirp microwave waveforms with immunity to power fading.

A photonic method to generate and transmit quadruple bandwidth dual-band dual-chirp microwave waveforms with immunity to fiber chromatic dispersion induced power fading is proposed and experimentally demonstrated, which is suitable for Doppler blind-speed elimination, small target detection, and multiband detection in multiband radar systems. A dual-polarization dual-parallel Mach-Zehnder modulator is utilized to realize carrier-suppressed harmonic single-sideband modulation of a radio frequency carrier and carrier-suppressed DSB modulation of a baseband single-chirped waveform at two orthogonal polarization states. After photoelectronic conversion, dual-band bandwidth-quadrupling dual-chirp waveforms are generated. Moreover, different from traditional DSB-based dual-chirp signal generation, the generated dual-chirp microwave waveforms can be transmitted over fiber without power fading, which is significant in dual-band radars for one to multiple base station transmissions.

ZEB1-Mediated Transcriptional Upregulation of circWWC3 Promotes Breast Cancer Progression through Activating Ras Signaling Pathway.

Zinc finger E-box binding homeobox 1 (ZEB1) has been widely recognized as an important driver of tumor growth and metastasis. However, nothing is known about ZEB1-regulated circular (circ)RNAs in cancer. In the current study, we evaluated the function of a novel ZEB1-regulated circRNA derived from the WWC3 gene locus, circWWC3 in breast cancer progression. We found that ZEB1 upregulated circWWC3 expression but not the linear WWC3 mRNA expression. circWWC3 is highly expressed in breast cancer tissues and is associated with the poor prognosis of breast cancer patients. Silencing of circWWC3 significantly suppresses the proliferation, migration, and invasion of breast cancer cells. Mechanically, circWWC3 upregulates multiple oncogenes' expression of the Ras signaling pathway through acting as the sponge of microRNA (miR)-26b-3p and miR-660-3p. Moreover, short hairpin (sh)RNA-mediated knockdown of circWWC3 partially antagonized ZEB1-mediated breast cancer growth and metastasis in vivo. Our findings reveal that ZEB1-mediated upregulation of circWWC3 promotes breast cancer progression through activating Ras signaling pathway, which provides a potential therapeutic target and prognostic biomarker for breast cancer.

Microwave photonic frequency down-conversion and channel switching for satellite communication.

We present a photonic approach to realize radio frequency (RF) down-conversion and intermediate frequency (IF) channel switching for satellite communication. Conventionally, photonic RF mixers always suffer from limitations of one operational state and one IF channel. We proposed a photonic repeater that can realize multiple frequency down-conversion states and different IF channel switching. Two separated RF ports and two independent local oscillator ports ensure the repeater can down-convert RF signals in different bands simultaneously. Based on the characteristic that orthogonally polarized optical signals cannot beat with each other, the crosstalk between different channels is alleviated. Since no optical filters are involved, the repeater can process broadband RF signals down-conversion and broadband IF signals channel switching. The proposed photonic repeater features compact structure, broad and different bands of operation, and no physical optical splitting, which is promising for a satellite payload.

Dual-chirp microwave waveform transmitter with elimination of power fading for one-to-multibase station fiber transmission.

We present a photonic approach to generate and transmit a dual-chirp microwave waveform with antidispersion performance. Traditionally, the microwave signal generated based on double-sideband (DSB) modulation suffers from power fading significantly. We propose a DSB-based dual-chirp microwave waveform transmitter that can eliminate the chromatic dispersion-induced power fading (CDIP) over fiber transmission. The CDIP elimination, rather than compensation, ensures that the working bandwidth of the dual-chirp waveform is not limited by the periodical power fading. The proposed signal modulation scheme makes the signal transmitter free from the direct current bias drifting of the modulator. Moreover, thanks to the phase modulation, the generated waveform is background-free. The proposed dual-chirp waveform transmitter features a compact structure, polarization independence, and CDIP elimination, which has great potential in radars for one-to-multibase station fiber transmission.

Comparison detection methods for EGFR in formalin-fixed paraffin-embedded tissues of patients with NSCLC.

Epidermal growth factor receptor (EGFR) is an important gene in the development of lung cancer. Non-small cell lung cancer (NSCLC) is the most common lung cancer. In the present study, the expression of EGFR in 717 patients with NSCLC was detected by Ventana automatic immunohistochemical technique, and the samples was verified by Real-time PCR, and then the results were compared with the data acquired by next-generation sequencing technology (NGS), which is the high throughput, multiple sites for EGFR gene mutation testing. The expression of Ventana EGFR in 717 cases of NSCLC was detected by immunohistochemistry, and the positive rate was 60.70 % (435 / 717). The mutation rate of EGFR was 57.60 % (413/717). The coincidence rate of Ventana EGFR immunohistochemical assay and Real-time PCR assay reached 94.94 %, and the two had high consistency. The coincidence rate of Ventana EGFR immunohistochemical assay and NGS were high correlation. Based on these results, Ventana EGFR automatic immunohistochemical detection has high accuracy, simple operation process, low price and easy interpretation. It can be used as the preferred method for EGFR detection.

FCC-compliant millimeter-wave ultra-wideband pulse generator based on optoelectronic oscillation.

We report a photonic scheme to generate a millimeter-wave ultra-wideband (MMW-UWB) pulse based on optoelectronic oscillation (OEO). Normally, a millimeter-wave signal source is essential for the generation of a MMW-UWB pulse. The key novelty of our work is that no millimeter-wave signal source is required. The MMW-UWB pulses are directly generated by truncating an OEO signal into pulses. The principle behind the proposed scheme is analyzed in detail. A proof-of-concept experiment shows that the generated MMW-UWB pulses fit the Federal Communications Commission (FCC) spectral mask very well.

Expression of PD-L1 in triple negative breast cancer tissues and its relationship with angiogenesis / 中国肿瘤生物治疗杂志

@# Objective: To investigate the expressions of programmed death ligand 1（PD-L1）in triple-negative breast cancer (TNBC) and its correlation with angiogenesis. Methods: 120 cases of TNBC patients who underwent surgery in the Fourth Hospital of Hebei Medical University from March 1, 2011 to June 1, 2012 were collected. The tumor tissues of patients were surgically resected and confirmed by pathology. PD-L1 protein expression in TNBC tissues of 120 patients was detected by tissue microarray combined with immunohistochemistry, and its relationship with various clinical indicators was analyzed. Blood vessels and lymphatic vessels were labeled withCD34andD2-40todetectmicrovesseldensity(MVD)andlymphaticvesseldensity(LVD)inTNBC.Results:Thepositiveexpression rate of PD-L1 in the tumor cells and interstitial infiltrating lymphocytes fromTNBC was 56.7% (68/120); No correlation was found between PD-L1 protein expression and the gender, age, histological grade, clinical stage, or tumor size of patients with TNBC (P>0.05), but related to the lymph node metastasis (P<0.05) and vascular thrombus (P<0.05). TNBC with high PD-L1 expression exhibited high incidence of lymph node metastasis and formation of vascular thrombus, and the expression of PD-L1 was positively correlated with MVD (r=0.500, P=0.02) as well as LVD (r=0.662, P=0.01). Log-Rank test showed that the survival time of TNBC patients with positive PD-L1 protein expression was significantly shorter than that of patients with negative expression (P<0.05). Cox multivariate analysis suggested that PD-L1 protein expression could be an independent prognostic factor for TNBC overall survival. Conclusion: PD-L1 plays an important role in TNBC angiogenesis and lymphangiogenesis, and is closely related to TNBC invasion and metastasis; blocking PD1/PD-L1 signal pathway is expected to be an effective new strategy for TNBC treatment.