Straight and curved distributed Bragg reflector design for compact WDM filters.

Grating-assisted contra-directional couplers (CDCs) wavelength selective filters for wavelength division multiplexing (WDM) are designed and experimentally demonstrated. Two configuration setups are designed; a straight-distributed Bragg reflector (SDBR) and curved distributed Bragg reflector (CDBR). The devices are fabricated on a monolithic silicon photonics platform in a GlobalFoundries CMOS foundry. The sidelobe strength of the transmission spectrum is suppressed by controlling the energy exchange between the asymmetric waveguides of the CDC using grating and spacing apodization. The experimental characterization demonstrates a flat-top and low insertion loss (0.43 dB) spectrally stable performance (<0.7 nm spectral shift) across several different wafers. The devices have a compact footprint of only 130µm2/Ch (SDBR) and 3700µm2/Ch (CDBR).

Compact, broadband, and low-loss power splitters using MZI based on Bézier bends.

We experimentally demonstrate wavelength-independent couplers (WICs) based on an asymmetric Mach-Zehnder interferometer (MZI) on a monolithic silicon-photonics platform in a commercial, 300-mm, CMOS foundry. We compare the performance of splitters based on MZIs consisting of circular and 3rd order (cubic) Bézier bends. A semi-analytical model is constructed in order to accurately calculate each device's response based on their specific geometry. The model is successfully tested via 3D-FDTD simulations and experimental characterization. The obtained experimental results demonstrate uniform performance across different wafer sites for various target splitting ratios. We also confirm the superior performance of the Bézier bend-based structure, compared to the circular bend-based structure both in terms of insertion loss (0.14 dB), and performance consistency throughout different wafer dies. The maximum deviation of the optimal device's splitting ratio is 0.6%, over a wavelength span of 100 nm. Moreover, the devices have a compact footprint of 36.3 × 3.8 µ m 2.

Fabrication tolerant and wavelength independent arbitrary power splitters on a monolithic silicon photonics platform.

We experimentally demonstrate wavelength-independent couplers based on an asymmetric Mach-Zehnder interferometer on a monolithic silicon-photonics platform in a state-of-the-art CMOS foundry. The devices are also designed to exhibit fabrication tolerant performance for arbitrary splitting ratios. We have developed a semi-analytical model to optimize the device response and the reliability of the model is benchmarked against 3D-FDTD simulations. Experimental results are consistent with the simulation results obtained by the model and show uniform performance across different wafer sites with a standard deviation for the splitting ratio of only 0.6% at 1310 nm wavelength. The maximum spectral deviation of the splitting ratio (3-dB splitter) is measured to be 1.2% over a wavelength range of at least 80 nm and the insertion loss ranges from 0.08 to 0.38 dB. The wavelength-independent coupler has a compact footprint of 60 × 40 µ m 2.

Red yeast rice for dyslipidaemias and cardiovascular risk reduction: A position paper of the International Lipid Expert Panel.

The risk of atherosclerotic cardiovascular disease (ASCVD) is strongly related to lifetime exposure to low-density lipoprotein (LDL)-cholesterol in longitudinal studies. Lipid-lowering therapy (using statins, ezetimibe and PCSK9 inhibitors) substantially ameliorates the risk and is associated with long-term reduction in cardiovascular (CV) events. The robust evidence supporting these therapies supports their continued (and expanding) role in risk reduction. In addition to these 'conventional' therapeutics, while waiting for other innovative therapies, growing evidence supports the use of a range of 'nutraceuticals' (constituents of food prepared as pharmaceutical formulations) including preparations of red yeast rice (RYR), the product of yeast (Monascus purpureus) grown on rice, which is a constituent of food and is used in traditional Chinese medicine. The major active ingredient, monacolin K, is chemically identical to lovastatin. RYR preparations have been demonstrated to be safe and effective in reducing LDL-C, and CV events. However, surprisingly, RYR has received relatively little attention in international guidelines - and conventional drugs with the strongest evidence for event reduction should always be preferred in clinical practice. Nevertheless, the absence of recommendations relating to RYR may preclude the use of a product which may have clinical utility in particular groups of patients (who may anyway self-prescribe this product), what in the consequence might help to reduce population CV risk. This Position Paper of the International Lipid Expert Panel (ILEP) will use the best available evidence to give advice on the use of red-yeast rice in clinical practice.

Nutraceuticals as Modulators of Autophagy: Relevance in Parkinson's Disease.

Dietary supplements and nutraceuticals have entered the mainstream. Especially in the media, they are strongly advertised as safe and even recommended for certain diseases. Although they may support conventional therapy, sometimes these substances can have unexpected side effects. This review is particularly focused on the modulation of autophagy by selected vitamins and nutraceuticals, and their relevance in the treatment of neurodegenerative diseases, especially Parkinson's disease (PD). Autophagy is crucial in PD; thus, the induction of autophagy may alleviate the course of the disease by reducing the so-called Lewy bodies. Hence, we believe that those substances could be used in prevention and support of conventional therapy of neurodegenerative diseases. This review will shed some light on their ability to modulate the autophagy.

How to Use Respiratory Chain Inhibitors in Toxicology Studies-Whole-Cell Measurements.

Mitochondrial electron transport chain (ETC) inhibition is a phenomenon interesting in itself and serves as a tool for studying various cellular processes. Despite the fact that searching the term "rotenone" in PubMed returns more than 6900 results, there are many discrepancies regarding the directions of changes reported to be caused by this RTC inhibitor in the delicate redox balance of the cell. Here, we performed a multifaceted study of the popular ETC inhibitors rotenone and antimycin A, involving assessment of mitochondrial membrane potential and the production of hydrogen peroxide and superoxide anions at cellular and mitochondrial levels over a wide range of inhibitor concentrations (1 nmol/dm3-100 µmol/dm3). All measurements were performed with whole cells, with accompanying control of ATP levels. Antimycin A was more potent in hindering HepG2 cells' abilities to produce ATP, decreasing ATP levels even at a 1 nmol/dm3 concentration, while in the case of rotenone, a 10,000-times greater concentration was needed to produce a statistically significant decrease. The amount of hydrogen peroxide produced in the course of antimycin A biological activity increased rapidly at low concentrations and decreased below control level at a high concentration of 100 µmol/dm3. While both inhibitors influenced cellular superoxide anion production in a comparable manner, rotenone caused a greater increase in mitochondrial superoxide anions compared to a modest impact for antimycin A. IC50 values for rotenone and antimycin A with respect to HepG2 cell survival were of the same order of magnitude, but the survival curve of cells treated with rotenone was clearly biphasic, suggesting a concentration-dependent mode of biological action. We propose a clear experimental setup allowing for complete and credible analysis of the redox state of cells under stress conditions which allows for better understanding of the effects of ETC inhibition.

Controlling optical return loss in production silicon photonic metamaterial fiber couplers.

A cost-efficient and low-complexity optical input/output (I/O) packaging solution is a substantial challenge for volume production of photonic integrated circuits. To address this, metamaterial fiber couplers are an attractive solution for integrated photonic devices especially for optical I/O, interfacing standard optical fibers to photonic chips. They offer the advantages of refractive index engineering to achieve better mode match as well as higher fabrication tolerances. Metamaterial waveguides, as a fundamental building block of these fiber couplers, have attracted tremendous attention in recent years. Here, we report on effective optical return loss control in Si metamaterial waveguide designs to achieve ultra-low reflection loss in CMOS-compatible silicon photonics implemented in a 300 mm production line. Low backscattering is a substantial consideration for a range of applications. Here, a return loss of better than -30dB is achieved.

Silver Nanoparticles Modulate the Epithelial-to-Mesenchymal Transition in Estrogen-Dependent Breast Cancer Cells In Vitro.

Silver nanoparticles (AgNPs) are frequently detected in many convenience goods, such as cosmetics, that are applied directly to the skin. AgNPs accumulated in cells can modulate a wide range of molecular pathways, causing direct changes in cells. The aim of this study is to assess the capability of AgNPs to modulate the metastasis of breast cancer cells through the induction of epithelial-to-mesenchymal transition (EMT). The effect of the AgNPs on MCF-7 cells was investigated via the sulforhodamine B method, the wound healing test, generation of reactive oxygen species (ROS), the standard cytofluorimetric method of measuring the cell cycle, and the expression of EMT marker proteins and the MTA3 protein via Western blot. To fulfill the results, calcium flux and HDAC activity were measured. Additionally, mitochondrial membrane potential was measured to assess the direct impact of AgNPs on mitochondria. The results indicated that the MCF-7 cells are resistant to the cytotoxic effect of AgNPs and have higher mobility than the control cells. Treatment with AgNPs induced a generation of ROS; however, it did not affect the cell cycle but modulated the expression of EMT marker proteins and the MTA3 protein. Mitochondrial membrane potential and calcium flux were not altered; however, the AgNPs did modulate the total HDAC activity. The presented data support our hypothesis that AgNPs modulate the metastasis of MCF-7 cells through the EMT pathway. These results suggest that AgNPs, by inducing reactive oxygen species generation, alter the metabolism of breast cancer cells and trigger several pathways related to metastasis.

Beam shaping for ultra-compact waveguide crossings on monolithic silicon photonics platform.

A beam shaping approach has been implemented to realize high-performance waveguide crossings based on cosine tapers. Devices with a compact footprint of 4.7µm×4.7µm were fabricated on the GLOBALFOUNDRIES 45 nm monolithic silicon photonics platform (45 CLO technology). Fabricated devices are found to be nearly wavelength independent (±0.035dB for 1260nm≤λ≤1360nm) with low insertion loss (∼0.2dB) and crosstalk (-35dB). The measured response of the devices is consistent with the three-dimensional finite-difference time-domain simulation results. The design stability is validated by measuring the device insertion loss on eight chips, which is found to be 0.197±0.017dB at the designed center wavelength of 1310 nm.

Does Nanosilver Exposure Modulate Steroid Metabolism in the Testes?-A Possible Role of Redox Balance Disruption.

Silver nanoparticles (AgNPs) are a popular engineered nanomaterial widely used in industry. Despite the benefits they bring to society, AgNPs are not neutral to human health. The aim of this study was to evaluate the effects of a single intravenous dose (5 mg/kg body weight) of 20 nm AgNPs on steroid metabolism and redox balance in the testes of adult rats. The effects were evaluated 1 day or 28 days after intervention and compared with saline-treated animals. Decreased aromatase and estrogen receptor α levels (by 21% and 27%, respectively) were observed 1 day after AgNPs administration, while increased testosterone, increased dihydrotestosterone levels, higher androgen receptors and higher aromatase expression in Leydig cells (by 43%, 50%, 20% and 32%, respectively) as well as lower (by 35%) androgen receptor protein levels were observed 28 days after exposure to AgNPs compared to control groups. The AgNPs treatment resulted in decreased superoxide dismutase activity, decreased GSH/GSSG ratio, and increased glutathione reductase activity (by 23%, 63% and 28%, respectively) compared to control animals, irrespective of the time of measurement. Increased (by 28%) intratesticular lipid hydroperoxides level was observed 1 day after AgNPs exposure, while decreased (by 70%) GSH and increased (by 43%) 7-ketocholesterol levels were observed 28 days after treatment compared to control animals. Conclusions: AgNPs exposure caused redox imbalance in the gonads shortly after AgNPs administration, while a longer perspective AgNPs exposure was associated with impaired androgen metabolism, probably due to increased oxidative stress.

Serum anti-inflammatory and inflammatory markers have no causal impact on telomere length: a Mendelian randomization study.

INTRODUCTION: The relationship between inflammatory and anti-inflammatory markers and telomere length (TL), a biological index of aging, is still poorly understood. By applying a 2-sample Mendelian randomization (MR), we investigated the causal associations between adiponectin, bilirubin, C-reactive protein (CRP), leptin, and serum uric acid (SUA) with TL. MATERIAL AND METHODS: MR was implemented by using summary-level data from the largest ever genome-wide association studies (GWAS) conducted on our interested exposure and TL. Inverse variance weighted method (IVW), weighted median (WM)-based method, MR-Egger, MR-Robust Adjusted Profile Score (RAPS), and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were applied. Sensitivity analysis was conducted using the leave-one-out method. RESULTS: With regard to adiponectin, CRP, leptin, and SUA levels, we found no effect on TL for all 4 types of tests (all p > 0.108). Results of the MR-Egger (p = 0.892) and IVW (p = 0.124) showed that bilirubin had no effect on telomere maintenance, whereas the results of the WM (p = 0.030) and RAPS (p = 0.022) were negative, with higher bilirubin concentrations linked to shorter TL. There was a low likelihood of heterogeneity for all the estimations, except for bilirubin (IVW p = 0.026, MR Egger p = 0.018). MR-PRESSO highlighted no outlier. For all the estimations, we observed negligible intercepts that were indicative of low likelihood of the pleiotropy (all p > 0.161). The results of leave-one-out method demonstrated that the links are not driven because of single nucleotide polymorphisms (SNPs). CONCLUSIONS: Our results highlight that neither the anti-inflammatory nor pro-inflammatory markers tested have any significant causal effect on TL. The casual role of bilirubin on TL still needs to be investigated.

[A new occupational and environmental hazard - nanoplastic]. / Nowe zagrozenie zawodowe i srodowiskowe ­ nanoplastik.

Problems arising from the accumulation of plastic waste in the environment have become global. Appeals to stop the usage of disposable drinking straws or plastic cutlery did not come out without reason - 320 million tons of plastic products are produced annually, of which 40% are disposable items. More and more countries and private enterprises are giving up these types of items in favor of their biodegradable substitutes, e.g., cardboard drinking straws. Plastic waste in the environment is subject to a number of physicochemical interactions and biodegradation in which bacteria are involved. By using synthetic waste, they reduce the size of plastic garbage while increasing its dispersion in the environment. Small plastic particles, invisible to the naked eye, are called nanoplastic. Nanoplastic is not inert to living organisms. Due to its size, it is taken up with food by animals and passed on in the trophic chain. The ability to penetrate the body's barriers through nanoplastic leads to the induction of biological effects with various outcomes. Research studies on the interaction of nanoplastic with living organisms are carried out in many laboratories; however, their number is still a drop in the ocean of the data needed to draw clear-cut conclusions about the impact of nanoplastic on living organisms. There is also no data on the direct exposure to nanoplastic contamination at workplaces, schools and public utilities, standards describing the acceptable concentration of nanoplastic in food products and drinking water, and in vitro tests on nanoparticles other than polystyrene nanoparticles. Complementing the existing data will allow assessing the risks arising from the exposure of organisms to nanoplastic. Med Pr. 2020;71(6):743-56.