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Toxoplasma gondii (T. gondii) is an important pathogen that can cause serious public health problems. Currently, therapeutic drugs for toxoplasmosis present serious side effects, researches on more effective and novel substances with relatively low toxicity are urgently needed. Spider venoms comprise diverse novel pharmacological compounds. However, the anti- T. gondii activity of spider venoms remains largely unknown. This study was carried out to evaluate the anti-parasitic effect of spider venoms from Ornitoctonus huwena (HWVM) and Chilobrachys jingzhao (JZVM) against T. gondii tachyzoites in vitro and in vivo. Cytotoxic activity of HWVM and JZVM to HeLa cells was determined by MTT cell viability assays. Low doses (3.125, 6.25 and 12.5 μg/mL) of HWVM and JZVM displayed low toxicity to HeLa cells. Trypan blue exclusion assay indicated that either of HWVM and JZVM affected the viability of tachyzoites in a time-dependent manner. Both spider venoms inhibited the invasion and proliferation of tachyzoites in vitro (p < 0.05). Moreover, Mice treated with HWVM after infection with 2 × 103 T. gondii tachyzoites showed a better survival rate than mice treated with saline alone (p < 0.05), while mice treated with JZVM did not. Our findings indicate that HWVM is a promising agent for the treatment of toxoplasmosis. • In vitro, HWVM or JZVM can effectively inhibit the invasion and proliferation of T. gondii. • In vivo, HWVM can significantly prolong the survival time of mice infected with T. gondii. • HWVM is a promising agent for the treatment of toxoplasmosis. [ABSTRACT FROM AUTHOR]

Abstract Toxoplasmosis is a widely distributed parasitic protozoan disease, caused by Toxoplasma gondii (T. gondii). High prevalence of toxoplasmosis and limitations of conventional treatments lead to a search for new therapeutic drugs. Lycosin-I is a linear peptide, derived from the venom of the spider Lycosa singoriensis. The aim of the present study was to determine the anti-parasitic effect of lycosin-Ι against T. gondii. In vitro, the anti- T. gondii activities of lycosin-Ι were evaluated by MTT assay, trypan blue exclusion assay, cell counting assay and plaque assay. Cytokines of IL-6 and IL-8 were measured by quantitative PCR. In addition, the structures of tachyzoites treated with lycosin-Ι were also observed by scanning and transmission electron microscopy. In vivo, mice were challenged with parasites treated by lycosin-I. The results revealed that lycosin-Ι had shown a significant ability to inhibit T. gondii invasion and proliferation. Cytokines of IL-6 and IL-8 were reduced by lycosin-Ι at transcription level in human foreskin fibroblast (HFF) cells infected with T. gondii tachyzoites, but they were increased compared to non-infected cells. For tachyzoites, lycosin-Ι induced their cell membrane alterations with formation of invaginations, some of them appeared to be vacuolated in their cytoplasm. Moreover, lycosin-Ι had prolonged the survival time of mice by controlling T. gondii proliferation. In conclusion, our present study provides the first evidence for anti- T. gondii by using the spider peptide lycosin-Ι. These findings suggest that lycosin-Ι is a potential alternative agent for the treatment of toxoplasmosis. Graphical abstract Image 105265 Highlights • Lycosin-I had shown a significant ability to inhibit Toxoplasma gondii invasion and proliferation. • Lycosin-Ι induced tachyzoites' cell membrane alterations with formation of invaginations. • Lycosin-I decreased IL-6 and IL-8 cytokine levels of infected cells in transcription. [ABSTRACT FROM AUTHOR]

Abstract: A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for simultaneous determination of three representative phytohormones in plant samples: gibberellic acid (GA3), indole-3-acetic acid (IAA) and abscisic acid (ABA). A solid-phase extraction (SPE) pretreatment method was used to concentrate and purify the three phytohormones of different groups from plant samples. The separation was carried out on a C18 reversed-phase column, using methanol/water containing 0.2% formic acid (50:50, v/v) as the isocratic mobile phase at the flow-rate of 1.0mLmin−1, and the three phytohormones were eluted within 7min. A linear ion trap mass spectrometer equipped with electrospray ionization source was operated in negative ion mode. Selective reaction monitoring (SRM) was employed for quantitative measurement. The SRM transitions monitored were as 345→239, 301 for GA3, 174→130 for IAA and 263→153, 219 for ABA. Good linearities were found within the ranges of 5–200μgmL−1 for IAA and 0.005–10μgmL−1 for ABA and GA3. Their detection limits based on a signal-to-noise ratio of three were 0.005μgmL−1, 2.2μgmL−1 and 0.003μgmL−1 for GA3, IAA and ABA, respectively. Good recoveries from 95.5% to 102.4% for the three phytohormones were obtained. The results demonstrated that the SPE-LC–MS/MS method developed is highly effective for analyzing trace amounts of the three phytohormones in plant samples. [Copyright &y& Elsevier]

Abstract: A reversed-phase ion-pair high-performance liquid chromatographic method, using tetrabutylammonium bromide (TBABr) as ion-pair reagent, has been developed for the simultaneous analysis of silicon (Si) and phosphorus (P) as heteropoly acids in soil and plant samples. The effect of the concentrations of ion-pair reagent, acetate buffer and organic modifier as well as the pH of buffer on separation was made clear. The reaction conditions and stability of heteropoly acids were investigated. Furthermore, the phenomenon occurred in the optimized process was also further researched. The separation was performed on a reversed-phase C18 column within 11min with 40:60 (v/v) 0.1M acetate buffer (pH 3.9)–acetonitrile (ACN) containing 0.8mM TBABr as a mobile phase. The linear ranges of the peak area calibration curves for Si and P were 0.08–50mg/L and 0.40–50mg/L, respectively. The detection limits calculated at S/N=3 were 0.0057mg/L and 0.0280mg/L for Si and P, respectively. The method was successfully applied to the analysis of soluble and total contents of Si and P in soil and plant samples. [Copyright &y& Elsevier]

A simple, rapid and accurate ion-exclusion chromatographic method coupled with a UV detector for the determination of uric acid in human urine samples has been developed. The separation was carried out on an ion-exclusion column using only pure water as mobile phase. The detection wavelength was 254 nm and urine sample was injected directly without any pretreatment. Furthermore, the retention behavior of uric acid on the ion-exclusion column was researched when pure water and 1 mmol·L−1 HCl were used as mobile phase, respectively. The stability of uric acid was also further investigated within 28 days. In this method, the linear range of the calibration curve for uric acid was 0.25-100 mg·L−1, and the detection limit calculated at S/N=3 was 0.02 mg·L−1. The proposed ion-exclusion chromatographic method has been used for the determination of uric acid in human urine. [ABSTRACT FROM AUTHOR]

Synapse loss is one of the most critical features in Alzheimer's disease (AD) and correlates with cognitive decline. Astrocytes mediate synapse elimination through multiple EGF-like domains 10 (MEGF10) pathways in the developing and adult brain to build the precise neural connectivity. However, whether and how astrocytes mediate synapse loss in AD remains unknown. We here find that the phagocytic receptor MEGF10 of astrocytes is significantly increased in vivo and in vitro, which results in excessive engulfment of synapses by astrocytes in APP/PS1 mice. We also observe that the astrocytic lysosomal-associated membrane protein 1 (LAMP1) is significantly elevated, colocalized with the engulfed synaptic puncta in APP/PS1 mice, and astrocytic lysosomes contain more engulfed synaptic puncta in APP/PS1 mice relative to wild type mice. Together, our data provide evidence that astrocytes excessively engulf synapses in APP/PS1 mice, which is mediated by increased MEGF10 and activated lysosomes. The approach targeting synapse engulfment pathway in astrocytes would be a potent therapy for AD. [ABSTRACT FROM AUTHOR]

We analyzed 13C characteristics in samples of bird bones, feathers, eggshell carbonate and membrane from modern specimens of red-footed booby (Sula sula) as well as fish muscle, scales, and bones from its predominant food source, flying fish (Exocoetus volitans), and muscle from its secondary food source squid (Loligo chinensis), as well as in ancient sub-fossil samples of seabird and flying fish at the Xisha Islands, South China Sea. δ13C is tissue-specific in both seabirds and flying fish due to the variance in turn-over among the tissues and differences in the type and content of amino acids across a diverse range of tissues. The δ13C discrimination factors also differed significantly among the various tissues between tropical seabirds and their prey. A Suess effect, caused by fossil fuel combustion and the emission of carbon with fewer 13C isotopes, was observed in the bird and fish tissue from ancient to modern time. Our study provides a multiple variability index for δ13C in organisms along a food chain, and verifies that tissue-specific 13C analysis is essential to identify diet and species and thus is a valuable tool for research on tropical seabird ecology. [ABSTRACT FROM AUTHOR]

To understand the aerosol characteristics in a regional background environment, fine-particle (PM2.5, n = 228) samples were collected over a one-year period at the Shangdianzi (SDZ) station, which is a Global Atmospheric Watch regional background station in North China. The chemical and optical characteristics of PM2.5 were analyzed, including organic carbon, elemental carbon, water-soluble organic carbon, water-soluble inorganic ions, and fluorescent components of water-soluble organic matter. The source factors of major aerosol components are apportioned, and the sources of the fluorescent chromophores are further analyzed. The major chemical components of PM2.5 at SDZ were NO3−, organic matter, SO42−, and NH4+. Annually, water-soluble organic carbon contributed 48% ± 15% to the total organic carbon. Secondary formation (52%) and fossil fuel combustion (63%) are the largest sources of water-soluble organic matter and water-insoluble organic matter, respectively. In addition, three humic-like and one protein-like matter were identified via parallel factor analysis for excitation—emission matrices. The fluorescence intensities of the components were highest in winter and lowest in summer, indicating the main impact of burning sources. This study contributes to understanding the chemical and optical characteristics of ambient aerosols in the background atmosphere. [ABSTRACT FROM AUTHOR]

Random beacons play a crucial role in blockchains. Most random beacons in a blockchain are performed in a distributed approach to secure the generation of random numbers. However, blockchain nodes are in an open environment and are vulnerable to adversary reboot attacks. After such an attack, the number of members involved in a random number generation decreases. The random numbers generated by the system become insecure. To solve this problem while guaranteeing fast recovery of capabilities, we designed a threshold signature scheme based on share recovery. A bivariate polynomial was generated among the participants in the distributed key generation phase. While preserving the threshold signature key share, it can also help participants who lost their shares to recover. The same threshold setting for signing and recovery guarantees the security of the system. The results of our scheme show that we take an acceptable time overhead in distributed key generation and simultaneously enrich the share recovery functionality for the threshold signature-based random number generation scheme. [ABSTRACT FROM AUTHOR]

With the increasing demand for privacy protection in the blockchain, the universal zero-knowledge proof protocol has been developed and widely used. Because hash function is an important cryptographic primitive in a blockchain, the zero-knowledge proof of hash preimage has a wide range of application scenarios. However, it is hard to implement it due to the transformation of efficiency and execution complexity. Currently, there are only zero-knowledge proof circuits of some widely used hash functions that have been implemented, such as SHA256. SM3 is a Chinese hash function standard published by the Chinese Commercial Cryptography Administration Office for the use of electronic authentication service systems, and hence might be used in several cryptographic applications in China. As the national cryptographic hash function standard, the zero-knowledge proof circuit of SM3 (Chinese Commercial Cryptography) has not been implemented. Therefore, this paper analyzed the SM3 algorithm process, designed a new layered circuit structure, and implemented the SM3 hash preimage zero-knowledge proof circuit with a circuit size reduced by half compared to the automatic generator. Moreover, we proposed several extended practical protocols based on the SM3 zero-knowledge proof circuit, which is widely used in blockchain. [ABSTRACT FROM AUTHOR]

Due to numerous side effects of traditional treatments for toxoplasmosis, it is urgent to develop new anti- Toxoplasma agents with high efficiency and low toxicity. In this study, using drug-food-homologous chalcone skeleton as a leading compound, 6 series of chalcone derivatives were designed, synthesized, and almost 1/2 compounds have good anti- Toxoplasma activity in vitro. The quantitative structure-activity relationship model of the anti- Toxoplasma activity of the second batch of compounds was established by random forest method (R2 = 0.9407). The Michael receptor in the molecular skeleton of chalcones plays an important role in improving the activity. Among these compounds, four chalcone derivatives exhibited potent anti - T. gondii activity and low cytotoxicity in vitro. Specifically, three of them (4a , 4c and 5e) effectively inhibited the proliferation of Toxoplasma tachyzoites in vivo. Liver and spleen index and biochemical parameters, such as alanine aminotransferase, aspartate aminotransferase and malondialdehyde were significantly decreased by the three chalcone derivatives, suggesting that they have protective effects on the liver of mice infected with Toxoplasma tachyzoites. Overall, this article provides a series of promising compounds for the development of anti- Toxoplasma agents. [Display omitted] • Novel chalcone derivatives 4a , 4c and 5e showed potent anti- Toxoplasma gondii effects at low concentration with low cytotoxicity in vitro and in vivo. • The anti - T. gondii activity and liver-protective effects of 4a , 4c and 5e were comprehensively evaluated by biochemical parameters. • Novel chalcone derivatives 4a , 4c and 5e are promising for the treatment of toxoplasmosis. [ABSTRACT FROM AUTHOR]

The nitrogen (N) utilization strategy of plants has become a topic of interest within the field of phytoecology. However, few studies have considered N cycling on coral island ecosystems from the perspective of their evolution. The aim of this study was to test the impacts of biological transport by seabirds, on the sources and uses of N by plants, and pathways of N cycling in soil–plant ecosystems on coral islands. A series of eight coral islands were investigated, five of which were affected to a varying extent by seabirds. The total phosphorus (TP) concentration from avian sources and the δ 15 N values of total nitrogen (TN) and inorganic nitrogen (IN: NH 4 + -N, and NO 3 − -N), δ 18 O of NO 3 − -O, in soils were determined, as well as proxies in plant leaves of two dominant plant species, including TN, the carbon/nitrogen ratio (C/N), and δ 13 C and δ 15 N values. The results show that, with an increase of TP, the TN and IN content, and δ 15 N values in soils all increased. Plant C/N and δ 15 N values decreased and increased, respectively, as the soil N content increased. When the TN content of the soil was low, the δ 15 N value in plant leaves was similar to that in soil NO 3 − , but was much lower than that in soil NH 4 + . When the soil TN content was high, the δ 15 N values were similar. Both plants and soil were probably N-limited prior to seabird colonization, with the N source on the barren coral islands originating primarily from atmospheric deposition. With seabird guano input and subsequent pedogenesis, the source of N switched to guano. Under these conditions, most of the N utilized by plants originated from NH 4 + , while nitrate is dominant for non-seabirds islands. Seabird activities have played a key role in the N dynamics of soil–plant ecosystems at coral islands. [ABSTRACT FROM AUTHOR]

Objective: The peptide lycosin-I has anti-bacterial and anti-cancer capacities. However, the anti-inflammatory activity of lycosin-I remains unknown. We investigated whether lycosin-I could attenuate inflammation.Materials and methods: Human umbilical vein endothelial cells (HUVECs) were treated with lycosin-I before exposure to tumor necrosis factor-α (TNF-α). The expression of intercellular cell adhesion molecule-1 (ICAM-1), nuclear transcription factor-kappa B (NF-κB) p65 and inhibitory subunit of NF-κB alpha (IκBα) was evaluated by western blot. The expression of interleukin-6 (IL-6) and interleukin-8 (IL-8) was detected by quantitative RT-PCR or ELISA. Immunofluorescence analysis was used to determine the impact of lycosin-I on NF-κB pathway. C57BL/6 mice were pretreated with lycosin-I before exposure with lipopolysaccharide (LPS).Results: Lycosin-I significantly reduced the TNF-α-enhanced expression of IL-6, IL-8 and ICAM-1. Lycosin-I also inhibited the human monocyte cells adhesion to HUVECs. We further demonstrated that lycosin-I could effectively suppress the reaction of endothelial cells to TNF-α by inhibiting IκBα degradation. Subsequently, the phosphorylation and translocation of NF-κB p65 could also be attenuated. Furthermore, lycosin-I exhibited a significant protection of C57BL/6 mice against LPS-induced death.Conclusions: Our results suggested that the anti-inflammatory activity of lycosin-I was associated with NF-κB activation and lycosin-I had potential to be a novel therapeutic candidate for inflammatory diseases. [ABSTRACT FROM AUTHOR]

Water-soluble organic aerosol (WSOA) constitutes a large fraction of OA and plays an important role in formation of secondary OA (SOA). Here we characterized the sources and molecular composition of WSOA in summer in Beijing using high-resolution aerosol mass spectrometer and orbitrap mass spectrometer equipped with electrospray ionization. Our results showed that WSOA was the major fraction of OA on average accounting for 69% in summer, which is much higher than that (47%) in winter. However, the oxidation degree of WSOA was comparable between summer and winter (O/C = 0.62 vs. 0.63). Positive matrix factorization analysis showed that SOA contributed dominantly to WSOA (72%) indicating that WSOA was mainly from secondary formation. The two water-soluble SOA factors that are associated with regional processing (OOA-1) and photochemical production (OOA-2), respectively, showed very different behaviors throughout the study. OOA-2 showed much enhanced contribution during polluted periods with low relative humidity (RH), while OOA-1 played a more important role during high RH periods. Molecular composition analysis of WSOA revealed a high diversity of CHO (compounds only containing carbon, hydrogen and oxygen) and CHOS (sulfur-containing organics) in WSOA in summer. Particularly, the relative intensity fraction of CHOS- compounds was increased by 42% from clean to polluted days which was associated with large increases (20%) in organosulfates (OSs) with lower O∗/C (0.1–0.4), and OOA-1. These results suggest the formation of more unsaturated OSs in OOA-1 during polluted days in summer. Comparatively, the biogenic-derived OSs remained relatively stable (24–31%) for the entire study highlighting the ubiquitous importance of biogenic SOA in summer. Image 1 • Water-soluble organic aerosol was the major fraction of OA in summer in Beijing. • SOA from regional and photochemical processing contributed dominantly to WSOA. • A high diversity of CHO and CHOS molecular compounds in WSOA was observed. • Formation of more organosulfates during polluted days than clean days in summer. [ABSTRACT FROM AUTHOR]