Research on the Mechanism of Metaldehyde on Pomacea canaliculata.

Golden apple snail (Pomacea canaliculata), a major alien invasive organism in China, affects food production and poses a threat to human health. Metaldehyde is a highly effective, commonly used snail killer with low toxicity. Virulence determination, tissue section, iTRAQ and RNA interference were used to systematically study the toxicity of metaldehyde on P. canaliculata. The molluscicidal activity tests showed that metaldehyde exhibits strong toxicity against P. canaliculata. Physiological and biochemical data indicate that metaldehyde can cause damage to the gills, liver, pancreas, and kidneys of snails, also reduce the oxygen consumption rate and ammonia excretion rate of golden apple snails, and cause neurological diseases. The proteome of the gill region of the golden apple snail after exposure to metaldehyde was analyzed by using iTRAQ technology. A total of 360 differential proteins were identified, and four target proteins were screened, namely, alpha-protein kinase 1 (ALPK1), cubilin (CUBN), sodium- and chloride-dependent GABA transporter 2 (GAT2), and acetylcholinesterase (AChE). RNAi was used to target the four proteins. After the ALPK1 and CUBN protein genes were interfered with by metaldehyde treatment, it was found that the mortality rate of the golden apple snail significantly increased. However, interference of GAT2 and AChE protein genes by metaldehyde led to no significant change in the mortality rates of the snails. The histopathological observation of the gill showed that the rate of cilia shedding in the gill decreased after the interference of ALPK1 and CUBN protein genes.

Mathematical modeling and application of IL-1ß/TNF signaling pathway in regulating chondrocyte apoptosis.

Introduction: Mathematical model can be used to model complex biological processes, and have shown potential in describing apoptosis in chondrocytes. Method: In order to investigate the regulatory mechanisms of TNF signaling pathway in regulating chondrocyte apoptosis, a fractional-order differential equation model is proposed to describe the dynamic behavior and mutual interaction of apoptosis-related genes under the activation of TNF signaling pathway. Compared with the traditional molecular biology techniques, the proposed mathematical modeling has advantages to providing a more comprehensive understanding of the regulatory mechanisms of TNF signaling pathway in chondrocyte apoptosis. Result: In this paper, differentially expressed genes induced by IL-1ß in human chondrocyte apoptosis are screened using high-throughput sequencing. It is found that they were significantly enriched in the TNF signaling pathway. Therefore, a mathematical model of the TNF signaling pathway is built. Using real-time PCR experiments, mRNA data is measured and used to identify the model parameters, as well as the correlation coefficient. Finally, the sensitivity of the model parameters is discussed by using numerical simulation methods, which can be used to predict the effects of different interventions and explore the optimal intervention strategies for regulating chondrocyte apoptosis. Discussion: Therefore, fractional-order differential equation modeling plays an important role in understanding the regulatory mechanisms of TNF signaling pathway in chondrocyte apoptosis and its potential clinical applications.

Fractional differential equation modeling of the HBV infection with time delay and logistic proliferation.

In this article, a fractional-order differential equation model of HBV infection was proposed with a Caputo derivative, delayed immune response, and logistic proliferation. Initially, infection-free and infection equilibriums and the basic reproduction number were computed. Thereafter, the stability of the two equilibriums was analyzed based on the fractional Routh-Hurwitz stability criterion, and the results indicated that the stability will change if the time delay or fractional order changes. In addition, the sensitivity of the basic reproduction number was analyzed to find out the most sensitive parameter. Lastly, the theoretical analysis was verified by numerical simulations. The results showed that the time delay of immune response and fractional order can significantly affect the dynamic behavior in the HBV infection process. Therefore, it is necessary to consider time delay and fractional order in modeling HBV infection and studying its dynamics.

Research on the molluscicidal activity and molecular mechanisms of arecoline against Pomacea canaliculata.

Pomacea canaliculata, as an invasive snail in China, can adversely affect agricultural crop yields, ecological environment, and human health. In this paper, we studied the molluscicidal activity and mechanisms of arecoline against P. canaliculata. The molluscicidal activity tests showed that arecoline exhibits strong toxicity against P. canaliculata, and the LC50 value (72 h) was 1.05 mg/L (15 ± 2 mm shell diameter). Additionally, Molluscicidal toxicity were negatively correlated with the size of snails. Snails (25 ± 2 mm shell diameter) were choosed for mechanisms research and the result of microstructure and biochemistry showed that arecoline (4 mg/L, 20 â„ƒ) had strong toxic effect on the gill, and the main signs were the loss of cilia in the gill filaments. Moreover, arecoline significantly decreased the oxygen consumption rate, ammonia excretion rate and inhibited acetylcholinesterase (AChE). Then, the changes in protein expression were studied by iTRAQ, and 526 downregulated proteins were found. Among these, cilia and flagella-associated 157-like (PcCFP) and rootletin-like (PcRoo) were selected as candidate target proteins through bioinformatics analysis, and then RNA interference (RNAi) was adopted to verify the function of PcCFP and PcRoo. The results showed that after arecoline treated, the mortality and the cilia shedding rate of PcRoo RNAi treated group was significantly lower than control group. The above results indicate that arecoline can bind well with protein PcRoo, and then leads to the drop of gill cilia, affect respiratory metabolism, accelerate its entry into hemolymph, inhibit AChE and finally leads to the death of P. canaliculata.

Identification and functional verification of the target protein of pedunsaponin A in the gills of Pomacea canaliculata.

BACKGROUND: Based on previous research indicating that pedunsaponin A (PA) can destroy the gills of Pomacea canaliculata, we chose the gill as the main research object, and identified the target protein of PA in the gills of P. canaliculata through proteomics and RNA interference (RNAi). RESULTS: Proteomics showed that 180 proteins were downregulated after PA treatment in P. canaliculata. Among them, we chose advillin (PcAdv), receptor type tyrosine protein phosphatase (PcRT) and unconventional myosin heavy chain 6 (PcUM) as candidate target proteins through bioinformatics analysis. The small interfering RNA (siRNA) with the best interference effect was identified through further screening. Gene interference rates were 97%, 98% and 82% for PcAdv, PcRT and PcUM, respectively. The results showed that after RNAi treatment, the mortality of P. canaliculata treated with PcAdv (60.0%) was significantly lower than that for the control (93.3%); histological analysis showed that the structure of the gill was intact, cilia shedding was reduced, and the survival rate of hemocytes had increased. CONCLUSION: These findings indicate that, when the protein was absent or suppressed, the channel for entry of PA into the hemocytes of P. canaliculata was blocked, which reduced PA binding to hemocytes, and that there is a close relationship between shedding of gill cilia and PA entry into hemocytes. PcAdv is thus the key protein in PA destruction of gill cilia. Locating the proteins in gills that interact with drugs and investigating their mode of action is of great importance in the development of new molluscicides to control P. canaliculata populations.

Modeling the COVID-19 Epidemic With Multi-Population and Control Strategies in the United States.

As of January 19, 2021, the cumulative number of people infected with coronavirus disease-2019 (COVID-19) in the United States has reached 24,433,486, and the number is still rising. The outbreak of the COVID-19 epidemic has not only affected the development of the global economy but also seriously threatened the lives and health of human beings around the world. According to the transmission characteristics of COVID-19 in the population, this study established a theoretical differential equation mathematical model, estimated model parameters through epidemiological data, obtained accurate mathematical models, and adopted global sensitivity analysis methods to screen sensitive parameters that significantly affect the development of the epidemic. Based on the established precise mathematical model, we calculate the basic reproductive number of the epidemic, evaluate the transmission capacity of the COVID-19 epidemic, and predict the development trend of the epidemic. By analyzing the sensitivity of parameters and finding sensitive parameters, we can provide effective control strategies for epidemic prevention and control. After appropriate modifications, the model can also be used for mathematical modeling of epidemics in other countries or other infectious diseases.

Analysis of the Relationships between Waste Cooking Oil Qualities and Rejuvenated Asphalt Properties.

Waste cooking oil (WCO), in many cases, can rejuvenate aged asphalt and restore its properties. However, the influence of WCO qualities on rejuvenation behaviors of aged asphalt has not been investigated in detail. The objective of this paper was to evaluate the effects of WCO viscosity and acid value on the basic, rheological, and chemical properties of a typical rejuvenated asphalt. Penetration, ring and ball (R and B) softening point, and ductility were tested to evaluate the influence of WCO qualities on basic properties of rejuvenated asphalts. Then, the rheological properties of rejuvenated asphalt were characterized based on rotational viscometer (RV), dynamic shear rheometer (DSR), and bending beam rheometer (BBR) test results. Further, SARA (saturates, aromatics, resins, and asphaltenes) fraction analysis and Fourier transform infrared spectroscopy (FTIR) tests were performed to investigate the effects of WCO qualities on asphalt chemical composition. Finally, grey correlation coefficients were calculated and the relationships between WCO qualities and rejuvenated asphalt properties were quantitatively evaluated. The experimental results indicated that WCO qualities influence the rejuvenation behaviors of aged asphalt significantly, and the WCO with higher qualities (low acid value and viscosity, as defined in this research) tends to achieve better rejuvenation effects. Based on the results of grey correlation analyses, the acid value is, relatively, a better indicator than viscosity in predicting the rejuvenation efficiency of WCO. The rejuvenation thresholds of WCO are varied with the categories of properties of rejuvenated asphalts, and WCO with an acid value of 0.4-0.7 mg KOH/g, or a viscosity of 140-540 mm²/s, can meet all of the performance requirements for asphalt rejuvenation used in this research.

Biomechanical analysis of optic nerve injury treated by compound light granules and ciliary neurotrophic factor.

In this study, rabbit models of optic nerve injury were reproduced by the clamp method. After modeling, rabbit models were given one injection of 50 ng recombinant human ciliary neurotrophic factor into the vitreous body and/or intragastric injection of 4 g/kg compound light granules containing Radix Angelicae Sinensis and Raidix Paeoniae Alba at 4 days after modeling, once per day for 30 consecutive days. After administration, the animals were sacrificed and the intraorbital optic nerve was harvested. Hematoxylin-eosin staining revealed that the injured optic nerve was thinner and optic nerve fibers were irregular. After treatment with recombinant human ciliary neurotrophic factor, the arrangement of optic nerve fibers was disordered but they were not markedly thinner. After treatment with compound light granules, the arrangement of optic nerve fibers was slightly disordered and their structure was intact. After combined treatment with recombinant human ciliary neurotrophic factor and compound light granules, the arrangement of optic nerve fibers was slightly disordered and the degree of injury was less than after either treatment alone. Results of tensile mechanical testing of the optic nerve showed that the tensile elastic limit strain, elastic limit stress, maximum stress and maximum strain of the injured optic nerve were significantly lower than the normal optic nerve. After treatment with recombinant human ciliary neurotrophic factor and/or compound light granules, the tensile elastic limit strain, elastic limit stress, maximum stress and maximum strain of the injured optic nerve were significantly increased, especially after the combined treatment. These experimental findings indicate that compound light granules and ciliary neurotrophic factor can alleviate optic nerve injury at the histological and biochemical levels, and the combined treatment is more effective than either treatment alone.

Laboratory and field evaluations of rhodojaponin-III against the imported cabbage worm Pieris rapae (L.) (Lepidoptera: Pieridae).

The activity of rhodojaponin-III (R-III), a grayanoid diterpene compound isolated from Rhododendron molle G. Don flowers, was determined under laboratory and field conditions as an antifeedant, stomach poison, contact toxicant and insect growth inhibitor against Pieris rapae (L.) larvae. The median antifeedant concentration (AFC(50)) values in no-choice leaf disc tests were 1.16 and 15.85 mg L(-1) at 24 h after treatment when tested against third and fifth instars respectively. The median lethal concentration (LC(50)) values in leaf disc tests were 2.84 and 9.53 mg L(-1) at 96 h after treatment against third and fifth instars respectively. R-III showed an almost 30 times higher contact toxicity against third instars than for fifth instars, and the median lethal dose (LD(50)) values for topical application were 1.18 and 34.09 mg kg(-1) at 72 h after treatment respectively. R-III disrupted the development of larvae to pupae or adults with median concentration for inhibiting growth (IC(50)) values of only 1.36 mg L(-1) for third instars and 11.28 mg L(-1) for fifth instars. In field trials, a greater than 80% reduction in the adjusted larval numbers was obtained against P. rapae 14 days after treatment when Rhodo 0.1% EC, a commercial botanical insecticide based on R-III, was applied at both 937.5 and 625 mL ha(-1). These results suggest that further research to develop R-III, and extracts from R. molle, as biorational pesticides or as lead compounds for integrated pest management deserve consideration.

Grayanane diterpenoids from the flowers of Rhododendron molle with cytotoxic activity against a Spodoptera frugiperda cell line.

Two new grayanane diterpenoids, rhodomolins A (1) and B (2), together with two known diterpenoids, rhodomolleins I and rhodojaponin III, were isolated from the flowers of Rhododendron molle. The structures of 1 and 2 were elucidated on the basis of interpretation of spectroscopic data. All compounds were evaluated for cytotoxic activity against the Spodoptera frugiperda cell line Sf-9 and gave IC(50) values in the range 12-80 microg/mL.