Impact of external carrier noise on the linewidth enhancement factor of a quantum dot distributed feedback laser.

This paper demonstrates that the linewidth enhancement factor of quantum dot lasers is influenced by the external carrier transport issued from different external current sources. A model combining the rate equation and semi-classical carrier noise is used to investigate the different mechanisms leading to the above phenomenon in the context of a quantum dot distributed feedback laser. Meanwhile, the linewidth enhancement factor extracted from the optical phase modulation method shows dramatic differences when the quantum dot laser is driven by different noise-level pumps. Furthermore, the influence of external carrier noise on the frequency noise in the vicinity of the laser's threshold current directly affects the magnitude of the linewidth enhancement factor. Simulations also investigate how the external carrier transport impacts the frequency noise and the spectral linewidth of the QD laser. Overall, we believe that these results are of paramount importance for the development of on-chip integrated ultra-low noise oscillators producing light at or below the shot-noise level.

On prediction of chaotic dynamics in semiconductor lasers by reservoir computing.

Studying the chaotic dynamics of semiconductor lasers is of great importance for their applications in random bit generation and secure communication. While considerable effort has been expended towards investigating these chaotic behaviors through numerical simulations and experiments, the accurate prediction of chaotic dynamics from limited observational data remains a challenge. Recent advancements in machine learning, particularly in reservoir computing, have shown promise in capturing and predicting the complex dynamics of semiconductor lasers. However, existing works on laser chaos predictions often suffer from the need for manual parameter optimization. Moreover, the generalizability of the approach remains to be investigated, i.e., concerning the influences of practical laser inherent noise and measurement noise. To address these challenges, we employ an automated optimization approach, i.e., a genetic algorithm, to select optimal reservoir parameters. This allows efficient training of the reservoir network, enabling the prediction of continuous intensity time series and reconstruction of laser dynamics. Furthermore, the impact of inherent laser noise and measurement noise on the prediction of chaotic dynamics is systematically examined through numerical analysis. Simulation results demonstrate the effectiveness and generalizability of the proposed approach in achieving accurate predictions of chaotic dynamics in semiconductor lasers.

Optical noise characteristics of injection-locked epitaxial quantum dot lasers on silicon.

This work theoretically investigates the relative intensity noise (RIN) and spectral linewidth characteristics of epitaxial quantum dot (QD) lasers on silicon subject to optical injection. The results show that the RIN of QD lasers can be reduced by optical injection, hence a reduction of 10 dB is achieved which leads to a RIN as low as -167.5 dB/Hz in the stable injection-locked area. Furthermore, the spectral linewidth of the QD laser can be greatly improved through the optical injection locked scheme. It is reduced from 556.5 kHz to 9 kHz with injection ratio of -60 dB and can be further reduced down to 1.5 Hz with injection ratio of 0 dB. This work provides an effective method for designing low intensity noise and ultra-narrow linewidth QD laser sources for photonics integrated circuits on silicon.

Targeted metabolomics analysis of serum amino acid profiles in patients with Moyamoya disease.

Amino acids are one of the main metabolites in the body, and provide energy for the body and brain. The purpose of this study is to provide a profile of amino acid changes in the serum of patients with Moyamoya disease (MMD) and identify potential disease biomarkers. In this paper, we quantitatively determined the serum amino acid metabolic profiles of 43 MMD patients and 42 healthy controls (HCs). T test, multivariate statistical analysis, and receiver operating characteristic (ROC) curve analysis were used to identify candidate markers. Thirty-nine amino acids were quantified, and 12 amino acid levels differed significantly between the MMD patients and HCs. Moreover, based on ROC curve analysis, four amino acid (L-methionine, L-glutamic acid, ß-alanine and o-phosphoserine) biomarkers showed high sensitivity and specificity (AUC > 0.90), and showed the best sensitivity and specificity in MetaboAnalyst 5.0 using binary logistic regression analysis. We have provided serum amino acid metabolic profiles of MMD patients, and identified four potential biomarkers which may both provide clinicians with an objective diagnostic method for early detection of MMD and further our understanding of MMD pathogenesis.

Design, semi-synthesis and bioactivity evaluation of novel podophyllotoxin derivatives as potent anti-tumor agents.

In this study, a series of potential candidate molecules with excellent antitumor activity targeting tubulin and PTEN/PI3K/Akt signaling pathway was synthesized by modifying the molecule structure of podophyllotoxin (PPT) at the C-4 position via a structure-guided drug design approach. MTT assay results indicated that compound 12c had stronger anti-proliferative activities against HGC-27, MCF-7 and H460 cell lines than etoposide (VP-16), especially for HGC-27 (12c: IC50 = 0.89 ± 0.023 µM; PPT: IC50 = 6.54 ± 0.69 µM, VP-16: IC50 = 2.66 ± 0.28 µM) with lower affect in healthy human cells (293 T and GES-1). Further pharmacological analysis exhibited that 12c could bind the tubulin at the colchicine site and disrupt the dynamic equilibrium of microtubules. Moreover, 12c also suppressed the expressions/activities of matrix metalloprotease (MMP)-2, vimentin and up-regulation E-cadherin suggesting that 12c could block the epithelial-mesenchymal transition (EMT). The increased cell survival and invasion/migration were associated with the inactivation of PTEN/PI3K/Akt, 12c could regulate this pathway and cascade influence on the mitochondrial pathway, eventually, leading to the cell apoptosis. Thus, 12c may have the potential to become a candidate molecule in gastric cancer clinical treatment.

Systematic impacts of fluoride exposure on the metabolomics of rats.

Fluoride is widely present in the environment. Excessive fluoride exposure leads to fluorosis, which has become a global public health problem and will cause damage to various organs and tissues. Only a few studies focus on serum metabolomics, and there is still a lack of systematic metabolomics associated with fluorosis within the main organs. Therefore, in the current study, a non-targeted metabolomics method using gas chromatography-mass spectrometry (GC-MS) was used to research the effects of fluoride exposure on metabolites in different organs, to uncover potential biomarkers and study whether the affected metabolic pathways are related to the mechanism of fluorosis. Male Sprague-Dawley rats were randomly divided into two groups: a control group and a fluoride exposure group. GC-MS technology was used to identify metabolites. Multivariate statistical analysis identified 16, 24, 20, 20, 24, 13, 7, and 13 differential metabolites in the serum, liver, kidney, heart, hippocampus, cortex, kidney fat, and brown fat, respectively, in the two groups of rats. Fifteen metabolic pathways were affected, involving toxic mechanisms such as oxidative stress, mitochondrial damage, inflammation, and fatty acid, amino acid and energy metabolism disorders. This study provides a new perspective on the understanding of the mechanism of toxicity associated with sodium fluoride, contributing to the prevention and treatment of fluorosis.

Role of the ACE2/Ang-(1-7)/Mas axis in glucose metabolism.

The renin-angiotensin system (RAS) helps to regulate cardiovascular function, the maintenance of electrolyte and fluid balance, and blood pressure. The RAS contains two axes; the angiotensin-converting enzyme/angiotensin II/Ang II type 1 receptors (ACE/Ang II/AT1) classic axis, which has a role in regulating blood pressure, vascular oxidative stress, coagulation, and cellular proliferation. The other is the angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptors (ACE2/Ang-(1-7)/Mas) axis, which can inhibit the former axis, improve fat metabolism, reduce inflammation and oxidative stress, and enhance glucose tolerance and insulin sensitivity. The ACE2/Ang-(1-7)/Mas axis is found in blood vessels, kidneys, liver, pancreas and the brain. It can protect the body from abnormalities in glucose metabolism. The ACE2/Ang-(1-7)/Mas axis can enhance glucose tolerance and improve insulin sensitivity by protecting pancreatic ß cells, increasing insulin secretion, improving glucose metabolism in adipose tissue, enhancing glucose uptake by skeletal muscle, and inhibiting hepatic gluconeogenesis. This article reviews the main characteristics and functions of the ACE2/Ang-(1-7)/Mas axis and its regulation of glucose metabolism in order to demonstrate its potential as a target for the treatment of metabolic diseases such as diabetes.

Design, synthesis and structure-activity relationship studies of novel partial FXR agonists for the treatment of fatty liver.

Nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease, while there is still no medicine available. Farnesoid X receptor (FXR) is considered as a potential target for the treatment of NAFLD, and there are several FXR agonists reached in clinical trials. Based on better safety, industry and academia are pursuing development of the partial FXR agonists. To extend the chemical space of existing partial FXR agonists, we performed a structure-activity relationship study based on previously reported partial agonist 1 by using bioisosteric strategy. All of these efforts resulted in the identification of novel partial FXR agonist 13, which revealed the best agonistic activity in this series. Notably, compound 13 significantly alleviated the hepatic steatosis and hepatic function index in methionine-choline deficient (MCD) induced db/db mice, a classical nonalcoholic steatohepatitis (NASH) model widely used in preclinical evaluation. These results suggested that partial FXR agonist 13 might be a promising lead compound worthy further researches.

Gold nanoparticles coated with a tetramethylammonium lactobionate ionic liquid for enhanced chiral differentiation in open tubular capillary electrochromatography: application to enantioseparation of ß-blockers.

A new bilayer chiral stationary phase for use in open tubular capillary electrochromatography (OT-CEC) system is described. Gold nanoparticles were modified with L-cysteine, with a tetramethylammonium lactobionate ionic liquid that acts as the chiral selector. The gold nanoparticle-coated column provides good enantioseparation and favorable reproducibility. Compared with an uncoated separation system, the column developed displays improved separation of the racemic ß-blockers propranolol, esmolol, bisoprolol and sotalol (resolutions of enotiomers are 6.29, 6.11, 6.12 and 6.02, respectively). The materials and coatings were characterized by scanning electron microscopy and transmission electron microscopy. The main driving forces (CEC and electro-osmotic flow) were studied to evaluate the variation of the immobilized columns. The effects of buffer pH value, concentration of chiral selector, type of organic modifier and applied voltage were optimized. Satisfactory relative standard deviations were achieved in run-to-run, day-to-day and column-to-column experiments. Graphical abstractSchematic preparation of a capillary column with bilayer chiral selectors coated gold nanoparticles. This novel OT-CEC system was applied for separation of four basic racemic ß-blockers.

A novel coating method for CE capillary using carboxymethyl-ß-cyclodextrin-modified magnetic microparticles as stationary for electrochromatography enantioseparation.

Magnetic microparticles (MMPs) have been extensively studied and aroused considerable interest in separation science owing to their superior characteristics. In this paper, a novel coated capillary with carboxymethyl-ß-cyclodextrin-functionalized magnetic microparticles (CD-MMPs) as stationary phase was constructed and then applied to establish an open-tubular capillary electrochromatography enantioseparation system. The preparation of the CD-MMP-coated open-tubular column was very convenient because the coating of the magnetic microparticles onto the capillary column could be easily manipulated by an external magnetic field. The preparation conditions of the coated capillary such as magnetic field intensity and coating time are discussed in detail. The new constructed CD-MMP capillary system was applied to separate enantiomers of several racemic drugs. Compared to the uncoated capillary system, obviously preferable separations of tested enantiomers were obtained. Several important parameters affecting the enantioseparation, such as CM-ß-CD concentration, running buffer pH, organic solvent, and applied voltage, were systematically optimized. Furthermore, satisfactory repeatability and chemical stability of this new CD-MMP capillary system were achieved in the experiment. Graphical abstract ᅟ.

Enantioseparation of propranolol, amlodipine and metoprolol by electrochromatography using an open tubular capillary modified with ß-cyclodextrin and poly(glycidyl methacrylate) nanoparticles.

The inner wall of a capillary was coated with glycidyl methacrylate (GMA) to form tentacle-type coating, and poly(glycidyl methacrylate) nanoparticles (PGMA NPs) were then immobilized on the film. Ethanediamine-ß-cyclodextrin as chiral selector was covalently bonded into the PGMA NPs through the ring-open reaction. The materials were characterized by SEM, TEM and FT-IR. The modified column was applied to the enantioseparation of the racemates of propranolol, amlodipine and metoprolol. Compared to a capillary with a single layer of CD-PGMA (without GMA coating) and to a CD-GMA system (without PGMA nanoparticles), the performance of the capillary is strongly improved. The effects of buffer pH value and applied voltage were optimized. Best resolutions (propranolol: 1.27, metoprolol: 1.01 and amlodipine: 2.93) were obtained when using the PGMA-coated capillary system. The run-to-run, day-to-day and column-to-column reproducibility were tested and found to be highly attractive. The new stationary phase is likely to have a large potential and scope in that it may also be applied to chiral separations of other enantiomers, such as amino acids and biogenic amines. Graphical abstract Schematic presentation of the preparation of a capillary column with glycidyl methacrylate (GMA) coating which was then immobilized with poly(glycidyl methacrylate) nanoparticles and ethanediamine-ß-cyclodextrin. This novel open tubular column was applied to construct capillary electrochromatography system for separation of basic racemic drugs.

A monolithic capillary modified with a copoplymer prepared from the ionic liquid 1-vinyl-3-octylimidazolium bromide and styrene for electrochromatography of alkylbenzenes, polycyclic aromatic hydrocarbons, proteins and amino acids.

A monolithic capillary column was prepared by single-step copolymerization of the ionic liquid 1-vinyl-3-octylimidazolium bromide (VOI) and styrene. The VOI and styrene monomers were introduced to provide multiple interaction sites and increase hydrophobicity and aromaticity of the monolithic column, respectively. The effect of porogen ratio, monomer ratio and reaction temperature on permeability was investigated. The resulting column was characterized by scanning electron microscopy, and the results suggest that the column possesses high porosity and good homogeneity. A relatively strong anodic electroosmotic flow was generated over a wide range of pH values (pH 2.0-10.0), and this facilitates the rapid separation of analytes within 12 min. Alkylbenzenes, polycyclic aromatic hydrocarbons (PAHs), proteins and amino acids were used to evaluate the performance of the monolithic column under capillary electrochromatography mode by UV detection. Mixed-mode retention mechanisms including hydrophobic interaction, π-stacking, ion-exclusion interaction were observed. The monolithic column exhibits high column efficiency (8.72 × 104 plates∙m-1) and satisfying separation capability (the resolution of four alkylbenzenes: 2.54, 2.86 and 4.62, four PAHs: 2.79, 4.83 and 4.77, three proteins: 4.35 and 2.86, two amino acids: 3.34). Graphical abstractSchematic representation of capillary electrochromatography (CEC) systems with ionic liquid and styrene based organic polymer monolithic column for separation of alkylbenzenes, polycyclic aromatic hydrocarbons, proteins and amino acids.

An organic polymer monolith modified with an amino acid ionic liquid and graphene oxide for use in capillary electrochromatography: application to the separation of amino acids, ß-blockers, and nucleotides.

The preparation of an organic polymer monolithic column modified with an amino acid ionic liquid and graphene oxide (AAIL-GO) and its application to capillary electrochromatography (CEC) was described. The AAIL tetramethylammonium-L-arginine was bonded to a monolithic column that was previously modified with graphene oxide by using an hydrochloride/N-hydroxysuccinimide coupling reaction. The morphology of a poly(glycidyl methacrylate-co-ethylene dimethacrylate) monolith was examined by scanning electron microscopy. The incorporation of AAIL and graphene oxide was detected by infrared spectroscopy and elemental analysis. The resulting monolithic column produced a strong and stable electroosmotic flow from the anode to the cathode in the pH range from 3 to 9. Compared with a column modified with AAIL or graphene oxide only, the AAIL-GO-modified column has a better separation ability for amino acids, ß-blockers, and nucleotides (the resolution of three amino acids: 2.231 and 2.036, ß-blockers: 2.779 and 2.470 and nucleotides: 8.345 and 3.321). Molecular modeling was applied to demonstrate the separation mechanism of small molecules which showed a good support for experimental results. Graphical abstract Schematic representation of capillary electrochromatography (CEC) systems with an amino acid ionic liquid-graphene oxide modified organic polymer monolithic column as stationary phases for separation of amino acids, ß-blockers, and nucleotides.

A metal organic framework-functionalized monolithic column for enantioseparation of six basic chiral drugs by capillary electrochromatography.

Poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monoliths were used as a support to grow a zeolitic imidazolate framework-8 (ZIF-8) via layer-by-layer self-assembly. Pepsin, acting as as chiral selector, was covalently linked to the surface of the amino-modified ZIF-8 through the Schiff base method. The material was characterized by scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, Fourier transform infrared spectroscopy and elemental analysis. The pepsin-ZIF-8-poly(GMA-co-EDMA) column was utilized to the enantioseparation of the racemic forms of hydroxychloroquine (HCQ), chloroquine (CHQ), hydroxyzine (HXY), nefopam (NEF), clenbuterol (CLE) and amlodipine (AML). In comparison with a pepsin-poly(GMA-co-EDMA) monolithic column (without self-assembled ZIF-8 nanoparticles), the resolution is strongly enhanced (HCQ: 0.34 → 2.50; CHQ: 0.45 → 1.97; HXY: 0.39 → 1.43; NEF: 0.27 → 0.81; CLE: 0 → 0.81; AML: 0.16 → 0.72). Effects of self-assembly layers of ZIF-8, pepsin concentration, buffer pH values and applied voltage were investigated with hydroxychloroquine as the model analyte. The reproducibility of run-to-run, day-to-day and column-to-column were explored, and found to be satisfactory. Graphical abstractSchematic representation of capillary electrochromatography (CEC) systems with a pepsin-zeolitic imidazolate framework-8 (ZIF-8) modified poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monolithic column as stationary phases for separation of basic racemic drugs. ZIF-8 modified column was prepared via layer-by-layer self-assembly.

Discovery to solve multidrug resistance: Design, synthesis, and biological evaluation of novel agents.

Chemotherapy remains a pillar in the treatment and management of various cancers. However, multidrug resistance (MDR) becomes a severe problem after long-term administration of chemotherapy drugs. Overexpression of P-glycoprotein (P-gp) is a significant cause for tumor MDR. Therefore, P-gp inhibition is considered as an effective strategy to reverse MDR. A third-generation P-gp inhibitor tariquidar was selected as a lead compound, and a new series of triazol-N-ethyl tetrahydroisoquinoline based compounds were designed as novel P-gp inhibitors and synthesized through click chemistry. These compounds presented higher reversal activities than the positive-control verapamil (VRP). Among 18 compounds, compound 11 without cytotoxicity reversed MDR in a dose-dependent manner, with a persistent longer chemosensitizing effect and reversibility compared to others. Mechanism studies discovered that compound 11 could escalate the intracellular accumulation of rhodamine-123 and doxorubicin in K562/A02 cells as well as inhibit their efflux from cells. The results obtained suggest that compound 11 is more potent than VRP administered under the same conditions; it may be a potent and safe candidate for P-gp modulation for further development.

Nonlinearity Correction in OFDR System Using a Zero-Crossing Detection-Based Clock and Self-Reference.

Tuning nonlinearity of the laser is the main source of deterioration of the spatial resolution in optical frequency-domain reflectometry (OFDR) system. In this paper, we develop methods for tuning nonlinearity correction in an OFDR system from the aspect of data acquisition and post-processing. An external clock based on a zero-crossing detection is researched and implemented using a customized circuit. Equal-spacing frequency sampling is, therefore, achieved in real-time. The zero-crossing detection for the beating frequency of 20 MHz is achieved. The maximum sensing distance can reach the same length of the auxiliary interferometer. Moreover, a nonlinearity correction method based on the self-reference method is proposed. The auxiliary interferometer is no longer necessary in this scheme. The tuning information of the laser is extracted by a strong reflectivity point at the end of the measured fiber. The tuning information is then used to resample the raw signal, and the nonlinearity correction can be achieved. The spatial resolution test and the distributed strain measurement test were both performed based on this nonlinearity correction method. The results validated the feasibility of the proposed method. This method reduces the hardware and data burden for the system and has potential value for system integration and miniaturization.

Investigation of the interpolation method to improve the distributed strain measurement accuracy in optical frequency domain reflectometry systems.

We use a spectrum interpolation technique to improve the distributed strain measurement accuracy in a Rayleigh-scatter-based optical frequency domain reflectometry sensing system. We demonstrate that strain accuracy is not limited by the "uncertainty principle" that exists in the time-frequency analysis. Different interpolation methods are investigated and used to improve the accuracy of peak position of the cross-correlation and, therefore, improve the accuracy of the strain. Interpolation implemented by padding zeros on one side of the windowed data in the spatial domain, before the inverse fast Fourier transform, is found to have the best accuracy. Using this method, the strain accuracy and resolution are both improved without decreasing the spatial resolution. The strain of 3 µÏµ within the spatial resolution of 1 cm at the position of 21.4 m is distinguished, and the measurement uncertainty is 3.3 µÏµ.

Effects of AMPD1 gene C34T polymorphism on cardiac index, blood pressure and prognosis in patients with cardiovascular diseases: a meta-analysis.

BACKGROUND: The meta-analysis was aimed to evaluate the effects of AMPD1 gene C34T polymorphism on cardiac function indexes, blood pressure and prognosis in patients with cardiovascular diseases (CVD). METHODS: Eligible studies were retrieved through a comprehensive search of electronic databases and manual search. Then the high-quality studies met the rigorous inclusion and exclusion criteria, as well as related to the subject was selected for the study. Comprehensive data analyses were conducted using STATA software 12.0. RESULTS: The study results revealed that CVD patients with CT + TT genotype of AMPD1 C34T polymorphism presented elevated left ventricular ejection fraction (LVEF) (%) and reduced left ventricular end diastolic dimension (LVEDD) (mm) as compared with CC genotype, moreover, the subgroup analysis found that the LVEF (%) was markedly higher in heart failure (HF) patients carrying CT + TT genotype than CC genotype. Besides, the systolic blood pressure (SBP) (mmHg) in CVD patients with CT + TT genotype was obviously decreased in contrast with the CC genotype. Patients suffered from HF with different genotypes (CT + TT and CC) of AMPD1 C34T polymorphism exhibited no significant differences in total survival rate and cardiac survival rate. CONCLUSIONS: Our current meta-analysis indicated that the T allele of AMPD1 gene C34T polymorphism may be correlated with LVEF, LVEDD and SBP, which plays a protective role in the cardiac functions and blood pressure in CVD patients, but had no effects on total survival rate and cardiac survival rate for HF.

Investigation and development of a high spectral resolution coherent optical spectrum analysis system.

Focusing on high resolution optical spectroscopy, a coherent optical spectrum analysis (COSA) system is investigated in this paper. Principle is built to demonstrate the operation of COSA and its signal processing in both time and frequency domain. According to COSA principle, resolution bandwidth (RBW) filters are found to have significant influence on power accuracy and spectral resolution of the optical spectrum analysis (OSA). Much effort is paid to design RBW filters, including center frequency, bandwidth and type of filters. Two RBW filters are optimized to reduce the power uncertainty of different spectral resolution and satisfy different signal under test. Then, simulations and experiments are conducted to verify COSA principle and results show that the power uncertainty is less than 0.5% and 1.2% for high and medium spectral resolution application, respectively. Finally, experiments on the OSA of actual spectra indicate that COSA system can achieve a 6 MHz spectral resolution and has an excellent capacity in analysis of fine spectrum structures.

Characterization of one novel cry8 gene from Bacillus thuringiensis strain Q52-7.

Bacillus thuringiensis (Bt) is the most widely used insecticidal microbe due to its specific toxicity and safe use with respect to animals and the environment. In this study, we isolated Bt strain Q52-7 from a soil sample collected in the Qian Shan District, Liao Ning Province, China. We observed that the Q52-7 strain produced spherical crystals. The Bt Q52-7 strain had high toxicity against Asian Cockchafer (Holotrichia parallela), exhibiting an LC50 of 3.80 × 10(9) cfu/g, but is not toxic for Anomala corpulenta Motschulsky and Holotrichia oblita. Using general cry8 primers, we amplified a 1.3 kb fragment with the polymerase chain reaction. Specific primers were designed for the amplified fragment to clone the full-length coding region. A novel gene, cry8Na1, had 69 % sequence similarity with cry8Ca1. cry8Na1 gene was successfully expressed in the HD-73(-) acrystalliferous mutant of Bt subsp. Kurstaki HD-73. Bioassays demonstrated that the Cry8Na1 protein is highly toxic for the H. parallela, with a 50 % lethal concentration of 8.18 × 10(10) colony forming units per gram.