A study of the attenuation stage of a global infectious disease.

Introduction: Differences in control measures and response speeds between regions may be responsible for the differences in the number of infections of global infectious diseases. Therefore, this article aims to examine the decay stage of global infectious diseases. We demonstrate our method by considering the first wave of the COVID-19 epidemic in 2020. Methods: We introduce the concept of the attenuation rate into the varying coefficient SEIR model to measure the effect of different cities on epidemic control, and make inferences through the integrated adjusted Kalman filter algorithm. Results: We applied the varying coefficient SEIR model to 136 cities in China where the total number of confirmed cases exceeded 20 after the implementation of control measures and analyzed the relationship between the estimated attenuation rate and local factors. Subsequent analysis and inference results show that the attenuation rate is significantly related to the local annual GDP and the longitude and latitude of a city or a region. We also apply the varying coefficient SEIR model to other regions outside China. We find that the fitting curve of the average daily number of new confirmed cases simulated by the variable coefficient SEIR model is consistent with the real data. Discussion: The results show that the cities with better economic development are able to control the epidemic more effectively to a certain extent. On the other hand, geographical location also affected the effectiveness of regional epidemic control. In addition, through the results of attenuation rate analysis, we conclude that China and South Korea have achieved good results in controlling the epidemic in 2020.

Inner-Wall Coated Nanopipette Microextraction for Quantitative Analysis of Per- and Polyfluoroalkyl Substances in Single Cells Using Mass Spectrometry.

Per- and polyfluoroalkyl substances (PFASs) are a series of organic pollutants with potential cytotoxicity and biotoxicity. Accurate and sensitive detection of trace PFASs in single cells can provide insights into investigating their cytotoxicity, carcinogenicity, and mutagenicity. Here we report the development of an inner-wall coated nanopipette microextraction coupled with induced nanoelectrospray ionization mass spectrometry (InESI-MS) method and its application for rapid, sensitive, and accurate analysis of trace PFASs in single cells. A specially designed inner-wall coated nanopipette was prepared for sampling of the cytoplasm from a single cell, and the trace PFASs in the cytoplasm were selectively enriched into the coating via reversed-phase adsorption, ion bonding adsorption, and π-π interaction mechanisms. After the extraction, the cytoplasm was removed, and the enriched PFASs were then desorbed into some organic solvent, applying an alternating current (AC) voltage to the inner-wall coated nanopipette for InESI-MS analysis. The inner-wall coated nanopipette showed an exhaustive extraction to the trace PFASs in one single cell, and thus, the mass of each target analyte in the cytoplasm can be calculated via an internal standard calibration curve method, avoiding the measurement of ultrasmall volume cytoplasm for one single cell. By using the inner-wall coated nanopipette microextraction coupled with InESI-MS method, trace PFASs accumulated in the LO2 cells with pollutant exposure were successfully detected, and the accumulative behaviors and heterogeneities of PFASs in single cells were explored.

Nanospray Laser-Induced Plasma Ionization Mass Spectrometry for Rapid and Sensitive Analysis of Polycyclic Aromatic Hydrocarbons and Halogenated Derivatives.

Polycyclic aromatic hydrocarbons (PAHs) and halogenated derivatives are a series of environmental pollutants with potential toxicity and health risks on biosystems and the ecosystem. Rapid and sensitive analysis of trace PAHs and halogenated PAHs in complex environmental samples is a challenging topic for analytical science. Here we report the development of a nanospray laser-induced plasma ionization MS method for rapid and sensitive analysis of trace PAHs and halogenated PAHs under ambient and open-air conditions. A nanospray tip was applied for loading samples and placed pointing to the MS inlet, being a nanospray emitter with the application of a high voltage. A beam of laser was focused to induce energetic plasma between the nanospray emitter and the MS inlet for ionization of PAHs and halogenated PAHs for mass spectrometric analysis. Meanwhile, an inner-wall naphthyl-coated nanospray emitter was developed and applied as a solid-phase microextraction (SPME) probe for highly selective enrichment of trace PAHs and halogenated PAHs in complex environmental samples, and some organic solvent was applied to desorb the analytes for nanospray laser-induced plasma ionization MS analysis. Satisfactory linearity for each target PAH and halogenated PAH was obtained, with correlation coefficient values (r) no less than 0.9917. The method showed extremely high sensitivity for analysis of trace PAHs and halogenated PAHs in water, with limits of detection (LODs) and quantification (LOQs) of 0.0001-0.02 and 0.0003-0.08 µg/L, respectively. By using the inner-wall naphthyl-coated nanospray laser-induced plasma ionization MS method, sensitive detection of trace PAHs and halogenated PAHs in real sewage and wastewater samples was successfully achieved.

Effects of a chitosan nanoparticles encapsulation on the properties of litchi polyphenols.

Litchi polyphenols have very specific biological activities. Nevertheless, the low and inconsistent oral bioavailability and instability hinder the further application of litchi polyphenols in food systems. This work prepared litchi polyphenols loaded chitosan nanoparticles (LP-CSNPs) by ionic gelation method to enhance the encapsulation on the properties of litchi polyphenols. The optimum conditions of formation via single factors and the Box-Behnken design were chitosan (CS) concentration 1.065 mg/mL, sodium tripolyphosphate (TPP) concentration 0.975 mg/mL, and the mass ratios of polyphenols and CS 1:1 with encapsulation efficiency (EE%) of 45.53%. LP-CSNPs presented the nanosized range of particle size (mean 170 nm), excellent polydispersity index (PDI) (0.156 ± 0.025), and zeta potential values (+ 35.44 ± 0.59). The in vitro release in simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.8) during 100 h was 58.34% and 81.68%, respectively. LP-CSNPs could effectively improve the storage stability and had great antibacterial activity compared with unencapsulated litchi polyphenols.

Exploring the Accumulation Behavior and Heterogeneity of Perfluorooctanesulfonic Acid in Zebrafish Primary Organ Cells by Single-Cell Mass Cytometry.

Perfluorooctanesulfonic acid (PFOS) is a commonly found environmental pollutant with potential toxicity and health risks to biosystems and ecosystems. Study of the accumulation behavior and heterogeneity of PFOS in biological primary organ cells provides us significant insights to explore its cytotoxicity, carcinogenicity, and mutagenicity. Here a single-cell mass cytometry system was established for the high-throughput analysis of trace PFOS and the exploration of its accumulation behavior and heterogeneity in zebrafish primary organ cells. The single-cell mass cytometry system applied a ∼25 µm constant-inner-diameter capillary as the single-cell generation and transportation channel with an etched tip-end of 40 µm as the nanoelectrospray emitter for mass spectrometric analysis. The single-cell mass cytometry system showed satisfactory semiquantitative performance and sensitivity for analysis of PFOS in single cells, with a high detection throughput of ∼35 cells/min. Subsequently, the liver, intestine, heart, and brain from PFOS-exposed zebrafish (100 pg/µL, 28 days) were dissociated and prepared as cell suspensions, and the cell suspensions were introduced into the single-cell mass cytometry system for high-throughput analysis of PFOS in individual primary organ cells. Significant cellular accumulation heterogeneities were observed, with the highest content in liver cells, followed by intestine cells, then heart cells, and the lowest in brain cells. In addition, the dynamics of PFOS in the zebrafish liver, intestine, heart, and brain cells showed typical violin plot distributions and were well-described using a gamma (γ) function.

Synthesis, and biological evaluation of pyrazole matrine derivatives as an insecticide against Spodoptera frugiperda.

As one of the major threats to global food security, Spodoptera frugiperda (S. frugiperda) is highly gaining consideration due to its severe damage. Matrine is a widely and effectively used botanical insecticide in controlling S.frugiperda but lacks a rapidly available effect. To further improved the insecticidal activity of matrine based on combination principles, this work synthesized five new pyrazole matrine derivatives (PMDs) using Michael addition and investigated insecticidal activity against 2nd instar larvae of S. frugiperda(in vivo) and its isolated cell(in vitro). Our result demonstrated that PMDs show higher pesticidal activity than that matrine in both in vitro and in vivo assays. The most toxic derivatives in vitro and in vivo are PMD-3 and PMD-1, with IC50 of 2.49 mM and LC50 of 22.76 mg/L respectively. This research also investigates the anti-proliferation mechanism of PMDs based on isolated cells. PMDs decrease mitochondria membrane potential, arrested cell cycle at the G2/M phase, and upregulated Caspase 3, Caspase 9, and Apaf-1 to induce Caspase-dependent apoptosis. For Caspase-independent apoptosis, AIF and Endo G were found to be upregulated. Besides, pro-apoptotic factors like p53, IBM-1, and anti-apoptotic factors like IAP were upregulated. Moreover, we supposed that there was a linkage between lysosomes and PMD-induced apoptosis according to increased apoptosis rate, activated lysosomes, and upregulated Cathepsin B. This research provides new ideas for the synthesis of matrine derivatives and further demonstrated the anti-proliferation mechanism of PMDs.

The Financial Risk Measurement EVaR Based on DTARCH Models.

The value at risk based on expectile (EVaR) is a very useful method to measure financial risk, especially in measuring extreme financial risk. The double-threshold autoregressive conditional heteroscedastic (DTARCH) model is a valuable tool in assessing the volatility of a financial asset's return. A significant characteristic of DTARCH models is that their conditional mean and conditional variance functions are both piecewise linear, involving double thresholds. This paper proposes the weighted composite expectile regression (WCER) estimation of the DTARCH model based on expectile regression theory. Therefore, we can use EVaR to predict extreme financial risk, especially when the conditional mean and the conditional variance of asset returns are nonlinear. Unlike the existing papers on DTARCH models, we do not assume that the threshold and delay parameters are known. Using simulation studies, it has been demonstrated that the proposed WCER estimation exhibits adequate and promising performance in finite samples. Finally, the proposed approach is used to analyze the daily Hang Seng Index (HSI) and the Standard & Poor's 500 Index (SPI).

Change-Point Detection for Multi-Way Tensor-Based Frameworks.

Graph-based change-point detection methods are often applied due to their advantages for using high-dimensional data. Most applications focus on extracting effective information of objects while ignoring their main features. However, in some applications, one may be interested in detecting objects with different features, such as color. Therefore, we propose a general graph-based change-point detection method under the multi-way tensor framework, aimed at detecting objects with different features that change in the distribution of one or more slices. Furthermore, considering that recorded tensor sequences may be vulnerable to natural disturbances, such as lighting in images or videos, we propose an improved method incorporating histogram equalization techniques to improve detection efficiency. Finally, through simulations and real data analysis, we show that the proposed methods achieve higher efficiency in detecting change-points.

Change-Point Detection in a High-Dimensional Multinomial Sequence Based on Mutual Information.

Time-series data often have an abrupt structure change at an unknown location. This paper proposes a new statistic to test the existence of a change-point in a multinomial sequence, where the number of categories is comparable with the sample size as it tends to infinity. To construct this statistic, the pre-classification is implemented first; then, it is given based on the mutual information between the data and the locations from the pre-classification. Note that this statistic can also be used to estimate the position of the change-point. Under certain conditions, the proposed statistic is asymptotically normally distributed under the null hypothesis and consistent under the alternative hypothesis. Simulation results show the high power of the test based on the proposed statistic and the high accuracy of the estimate. The proposed method is also illustrated with a real example of physical examination data.

A novel group VIF regression for group variable selection with application to multiple change-point detection.

In this paper, we propose a novel group variance inflation factor (VIF) regression model for tackling large data sets where data follows a grouped structure. Unlike classical penalized methods, this approach can perform group variable selection in a sparse model, which is quite different from the classical penalized methods. We further adapt the proposed method associated with a two-stage procedure for detecting multiple change-point in linear models. We carry out extensive simulation studies to show that the proposed group variable selection and change-point detection methods are stable and efficient. Finally, we provide two real data examples, including a body fat data set and an air pollution data set, to illustrate the performance of our algorithms in group selection and change-point detection.

Efficient Aerobic Oxidative Coupling of Methyl Heteroarenes with Indoles.

Direct oxidative coupling of inert C(sp3 )-H bond has been a great challenge. Herein, an environmentally friendly aerobic oxidative coupling of α-methyl substituted N-heteroarenes with indoles is reported. A variety of diheteroaryl ketones were prepared in good yields (up to 72 %). This protocol features simple operation and broad substrates scope (26 examples). Significantly, a plausible mechanism about catalytic cycle was proposed, and two key intermediates were confirmed by high resolution mass spectrometry.

Synthesis of Halopyrazole Matrine Derivatives and Their Insecticidal and Fungicidal Activities.

Matrine is a traditional botanical pesticide with a broad-spectrum biological activity that is widely applied in agriculture. Halopyrazole groups are successfully introduced to the C13 of matrine to synthesize eight new derivatives with a yield of 78-87%. The insecticidal activity results show that the introduction of halopyrazole groups can significantly improve the insecticidal activity of matrine on Plutella xylostella, Mythimna separata and Spodoptera frugiperda with a corrected mortality rate of 100%, which is 25-65% higher than matrine. The fungicidal activity results indicate that derivatives have a high inhibitory effect on Ceratobasidium cornigerum, Cibberella sanbinetti, Gibberrlla zeae and Collectot tichum gloeosporioides. Thereinto, 4-Cl-Pyr-Mat has the best result, with an inhibition rate of 23-33% higher than that of matrine. Therefore, the introduction of halogenated pyrazole groups can improve the agricultural activity of matrine.

The C(sp3)-H bond functionalization of thioethers with styrenes with insight into the mechanism.

A metal-free inactive C(sp3)-H bond functionalization of thioethers with styrenes using TBHP as an initiator and DBU as a base has been developed. This transformation has broken through the low activity of thioethers and realized moderate yields. Herein extended experiments were conducted to confirm the radical relay process, reaction energy and intermediate transformations.

Estimation of the Covariance Matrix in Hierarchical Bayesian Spatio-Temporal Modeling via Dimension Expansion.

Ozone concentrations are key indicators of air quality. Modeling ozone concentrations is challenging because they change both spatially and temporally with complicated structures. Missing data bring even more difficulties. One of our interests in this paper is to model ozone concentrations in a region in the presence of missing data. We propose a method without any assumptions on the correlation structure to estimate the covariance matrix through a dimension expansion method for modeling the semivariograms in nonstationary fields based on the estimations from the hierarchical Bayesian spatio-temporal modeling technique (Le and Zidek). Further, we apply an entropy criterion (Jin et al.) based on a predictive model to decide if new stations need to be added. This entropy criterion helps to solve the environmental network design problem. For demonstration, we apply the method to the ozone concentrations at 25 stations in the Pittsburgh region studied. The comparison of the proposed method and the one is provided through leave-one-out cross-validation, which shows that the proposed method is more general and applicable.

Copper-Catalyzed Aldehyde Exchanged Amidation.

The synthesis of bioactive amides has been the pursuit of chemists. Herein secondary amides incorporated with an aldehyde group were first generated using aldehydes and secondary amines. Various (hetero)aryl aldehydes and even aliphatic aldehydes (>40 examples) were converted into the desired products in moderate to excellent yields (up to 89%). A plausible mechanism involving a Cu(I/II/III) catalytic cycle combined with radical rearrangement was proposed and confirmed with four key intermediates detected by high-resolution mass spectrometry.

An Entropy-Based Approach to Portfolio Optimization.

This paper presents an improved method of applying entropy as a risk in portfolio optimization. A new family of portfolio optimization problems called the return-entropy portfolio optimization (REPO) is introduced that simplifies the computation of portfolio entropy using a combinatorial approach. REPO addresses five main practical concerns with the mean-variance portfolio optimization (MVPO). Pioneered by Harry Markowitz, MVPO revolutionized the financial industry as the first formal mathematical approach to risk-averse investing. REPO uses a mean-entropy objective function instead of the mean-variance objective function used in MVPO. REPO also simplifies the portfolio entropy calculation by utilizing combinatorial generating functions in the optimization objective function. REPO and MVPO were compared by emulating competing portfolios over historical data and REPO significantly outperformed MVPO in a strong majority of cases.

Portfolio Optimization for Binary Options Based on Relative Entropy.

The portfolio optimization problem generally refers to creating an investment portfolio or asset allocation that achieves an optimal balance of expected risk and return. These portfolio returns are traditionally assumed to be continuous random variables. In An Entropy-Based Approach to Portfolio Optimization, we introduced a novel non-parametric optimization method based on Shannon entropy, called return-entropy portfolio optimization (REPO), which offers a simple and fast optimization algorithm for assets with continuous returns. Here, in this paper, we would like to extend the REPO approach to the optimization problem for assets with discrete distributed returns, such as those from a Bernoulli distribution like binary options. Under a discrete probability distribution, portfolios of binary options can be viewed as repeated short-term investments with an optimal buy/sell strategy or general betting strategy. Upon the outcome of each contract, the portfolio incurs a profit (success) or loss (failure). This is similar to a series of gambling wagers. Portfolio selection under this setting can be formulated as a new optimization problem called discrete entropic portfolio optimization (DEPO). DEPO creates optimal portfolios for discrete return assets based on expected growth rate and relative entropy. We show how a portfolio of binary options provides an ideal general setting for this kind of portfolio selection. As an example we apply DEPO to a portfolio of short-term foreign exchange currency pair binary options from the NADEX exchange platform and show how it outperforms leading Kelly criterion strategies. We also provide an additional example of a gambling application using a portfolio of sports bets over the course of an NFL season and present the advantages of DEPO over competing Kelly criterion strategies.

Option Portfolio Selection with Generalized Entropic Portfolio Optimization.

In this third and final paper of our series on the topic of portfolio optimization, we introduce a further generalized portfolio selection method called generalized entropic portfolio optimization (GEPO). GEPO extends discrete entropic portfolio optimization (DEPO) to include intervals of continuous returns, with direct application to a wide range of option strategies. This lays the groundwork for an adaptable optimization framework that can accommodate a wealth of option portfolios, including popular strategies such as covered calls, married puts, credit spreads, straddles, strangles, butterfly spreads, and even iron condors. These option strategies exhibit mixed returns: a combination of discrete and continuous returns with performance best measured by portfolio growth rate, making entropic portfolio optimization an ideal method for option portfolio selection. GEPO provides the mathematical tools to select efficient option portfolios based on their growth rate and relative entropy. We provide an example of GEPO applied to real market option portfolio selection and demonstrate how GEPO outperforms traditional Kelly criterion strategies.

Synthesis, characterization of two matrine derivatives and their cytotoxic effect on Sf9 cell of Spodoptera frugiperda.

The invasion of Spodoptera frugiperda has imposed a serious impact on global food security. Matrine is a botanical pesticide with a broad spectrum of insecticidal activity which was recommended for controlling Spodoptera frugiperda. In order to discover effective insecticide for Spodoptera frugiperda, two matrine derivatives modified with carbon disulfide and nitrogen-containing groups were systhesized. And their inhibition activities on Sf9 cell were evaluated. The structural configuration of compounds were characterized by IR, HPLC, MS, NMR and XRD, with yields of 52% and 65%, respectively. The IC50 of the two newly synthesized compounds on Sf9 cell reduced to 0.648 mmol/L and 1.13 mmol/L, respectively, compared with that of matrine (5.330 mmol/L). In addition, microscopic observation of Sf9 cell treated with the compounds showed that the number of adherent cells decreased, the cells shrunk, vacuolated and apoptotic bodies appeared. The two newly synthesized compounds exhibited better inhibitory effect on Sf9 cell than that of the parent matrine, suggesting that the positive effect of the introduction of 1-pyrrolidinecarbodithioate and diethylcarbamodithioate groups to matrine. The morphological observation of Sf9 cell induced by derivatives indicated that apoptosis induction may be a mechanism that inhibits insect cell proliferation and exerts insecticidal effect.

Semi-synthesis and characterization of some new matrine derivatives as insecticidal agents.

BACKGROUND: Matrine is an important traditional plant-derived insecticide with broad-spectrum activity. However, due to its moderate activity, matrine is mainly applied in combination with other pesticides. In order to discover new potential natural-product-based crop protection agents, a series of matrine derivatives characterized by cyclohexylamine group were synthesized to screen their insecticidal activity against seven typically agricultural pests. RESULTS: The structural configurations of compounds were characterized by IR, 1 H NMR, 13 C NMR, MS and XRD, with the pure yields of 42%, 65% and 71%, respectively. Although all compounds showed poor insecticidal activity against five lepidoptera pests, the compounds 2 and 4 displayed remarkable insecticidal activities against Lipaphis erysimi and Mulberry Root-Knot Nematode with a concentration-dependent manner within 0.5~1.5 mg/ mL. Compared with matrine (60%), compounds 2 and 4 exhibited potent insecticidal activities against L. erysimi, with a corrected mortality of 83.3% and 89.7%, respectively. They also showed excellent control effects on Mulberry Root-Knot Nematode, with corrected mortality as high as 88% and 80%, respectively. CONCLUSION: All four synthesized matrine derivatives showed poor insecticidal activity against five lepidoptera pests, but the compounds 2 and 4 exhibited much stronger insecticidal activities against L. erysimi and Mulberry Root-Knot Nematode than matrine. Combined with the structural characteristics of compounds 1~4, we conclude that 4-methylcyclohexylamine, not the carbon disulfide group or cyclohexylamine group alone, mainly contributed to the improvement of insecticidal activities of matrine derivatives against these two agricultural pests. This work provides a direction and foundation for structural optimization of the matrine pesticides in the future. © 2020 Society of Chemical Industry.