Thrombomodulin reduces α-synuclein generation and ameliorates neuropathology in a mouse model of Parkinson's disease.

The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson's disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD. Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1ß, which is subsequently secreted into the extracellular space. This secreted IL-1ß then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw.

Mouse serum albumin induces neuronal apoptosis and tauopathies.

The elderly frequently present impaired blood-brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders.

Seasonal characterization of chemical and optical properties of water-soluble organic aerosol in Beijing.

Water-soluble organic aerosol (WSOA) plays a crucial role in altering radiative forcing and impacting human health. However, our understanding of the seasonal variations of WSOA in Chinese megacities after the three-year clean air action plan is limited. In this study, we analyzed PM2.5 filter samples collected over one year (2020-2021) in Beijing to characterize the seasonal changes in the chemical and optical properties of WSOA using an offline aerosol mass spectrometer along with spectroscopy techniques. The mean mass concentration of WSOA during the observation period was 8.84 ± 7.12 µg m-3, constituting approximately 64-67 % of OA. Our results indicate the contribution of secondary OA (SOA) increased by 13-28 % due to a substantial reduction in primary emissions after the clean air action plan. The composition of WSOA exhibited pronounced seasonal variations, with a predominant contribution from less oxidized SOA in summer (61 %) and primary OA originating from coal combustion and biomass burning during the heating season (34 %). The mass absorption efficiency of WSOA at 365 nm in winter was nearly twice that in summer, suggesting that WSOA from primary emissions possesses a stronger light-absorbing capability than SOA. On average, water-soluble brown carbon accounted for 33-48 % of total brown carbon absorption. Fluorescence analysis revealed humic-like substances as the most significant fluorescence component of WSOA, constituting 82 %. Furthermore, both absorption and fluorescence chromophores were associated with nitrogen-containing compounds, highlighting the role of nitrogen-containing species in influencing the optical properties of WSOA. The results are important for chemical transport models to accurately simulate the WSOA and its climate effects.

Astrocytes Excessively Engulf Synapses in a Mouse Model of Alzheimer's Disease.

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.

ArhGAP11A mediates amyloid-ß generation and neuropathology in an Alzheimer's disease-like mouse model.

Amyloid-ß (Aß) plays an important role in the neuropathology of Alzheimer's disease (AD), but some factors promoting Aß generation and Aß oligomer (Aßo) neurotoxicity remain unclear. We here find that the levels of ArhGAP11A, a Ras homology GTPase-activating protein, significantly increase in patients with AD and amyloid precursor protein (APP)/presenilin-1 (PS1) mice. Reducing the ArhGAP11A level in neurons not only inhibits Aß generation by decreasing the expression of APP, PS1, and ß-secretase (BACE1) through the RhoA/ROCK/Erk signaling pathway but also reduces Aßo neurotoxicity by decreasing the expressions of apoptosis-related p53 target genes. In APP/PS1 mice, specific reduction of the ArhGAP11A level in neurons significantly reduces Aß production and plaque deposition and ameliorates neuronal damage, neuroinflammation, and cognitive deficits. Moreover, Aßos enhance ArhGAP11A expression in neurons by activating E2F1, which thus forms a deleterious cycle. Our results demonstrate that ArhGAP11A may be involved in AD pathogenesis and that decreasing ArhGAP11A expression may be a promising therapeutic strategy for AD treatment.

Size distributions of molecular markers for biogenic secondary organic aerosol in urban Beijing.

To understand the source, formation, and seasonality of biogenic secondary organic aerosol (BSOA), a nine-stage cascade impactor was utilized to collect size-segregated particulate samples from April 2017 to January 2018 in Beijing, China. BSOA tracers derived from isoprene, monoterpene, and sesquiterpene were measured with gas chromatography-mass spectrometry. Isoprene and monoterpene SOA tracers exhibited significant seasonal variations, with a summer maximum and a winter minimum. Dominance of 2-methyltetrols (isoprene SOA tracers) with a good correlation with levoglucosan (a biomass burning tracer), which was combined with the detection of methyltartaric acids (possible indicators for aged isoprene) in summer, implies possible biomass burning and long-range transport. In contrast, sesquiterpene SOA tracer (ß-caryophyllinic acid) was dominant in winter and was probably associated with the local burning of biomass. Bimodal size distributions were observed for most isoprene SOA tracers, consistent with previous laboratory experiments and field studies showing that they can be formed not only in the aerosol phase but also in the gas phase. Monoterpene SOA tracers cis-pinonic acid and pinic acid showed a coarse-mode peak (5.8-9.0 µm) in four seasons due to their volatile nature. Sesquiterpene SOA tracer ß-caryophyllinic acid showed a unimodal pattern with a major fine-mode peak (1.1-2.1 µm), which is linked to local biomass burning. The tracer-yield method was used to quantify the contributions of isoprene, monoterpene, and sesquiterpene to secondary organic carbon (SOC) and SOA. The highest isoprene SOC and SOA concentrations occurred in summer (2.00 µgC m-3 and 4.93 µg m-3, respectively), contributing to 1.61% of OC and 5.22% of PM2.5, respectively. These results suggest that BSOA tracers are promising tracers for understanding the source, formation, and seasonality of BSOA.

Implementation and Optimization of Zero-Knowledge Proof Circuit Based on Hash Function SM3.

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.

Distributed Random Beacon for Blockchain Based on Share Recovery Threshold Signature.

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.

Efficient Immunotherapy of Drug-Free Layered Double Hydroxide Nanoparticles via Neutralizing Excess Acid and Blocking Tumor Cell Autophagy.

Cancer immunotherapy efficacy is largely limited by the suppressive tumor immune microenvironment (TIME) where antitumor immune cells are inhibited and tumor antigens continue to mutate or be lost. To remodel the TIME, we here applied weakly alkaline layered double hydroxide nanoparticles (LDH NPs) to neutralize the excess acid and block autophagy of tumor cells for neoadjuvant cancer immunotherapy. Peritumoral injection of LDH NPs provided a long-term and efficient acid-neutralization in the TIME, blocked the lysosome-mediated autophagy pathway in tumor cells, and increased the levels of antitumor tumor-associated macrophages and T cells. These LDH NPs captured tumor antigens released in the tumor tissues and effectively inhibited the growth of both melanoma and colon tumors in vivo. These findings indicate that LDH NPs, as an immunomodulator and adjuvant, successfully "awaken" and promote the host innate and adaptive immune systems, showing promising potential for solid tumor immunotherapy.

Correction: Liu et al. Anti-Toxoplasma gondii Effects of a Novel Spider Peptide XYP1 In Vitro and In Vivo. Biomedicines 2021, 9, 934.

In the original publication, there were mistakes in Figure 3C, Figure 6B and Figure S2A,B as published [...].

Discovery and evaluation of chalcone derivatives as novel potential anti-Toxoplasma gondii agents.

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.

Anti-Toxoplasma gondii Effects of a Novel Spider Peptide XYP1 In Vitro and In Vivo.

Toxoplasmosis, caused by an obligate intracellular parasite Toxoplasma gondii, is one of the most prevalent zoonoses worldwide. Treatments for this disease by traditional drugs have shown numerous side effects, thus effective alternative anti-Toxoplasma strategies or drugs are urgently needed. In this study, a novel spider peptide, XYP1, was identified from the cDNA library of the venom gland of the spider Lycosa coelestis. Our results showed that XYP1 has potent anti-Toxoplasma activity in vitro and in vivo. Specifically, treatment with XYP1 significantly inhibited the viability, invasion and proliferation of tachyzoites with low cytotoxicity (IC50 = 38.79 µΜ) on human host cells, and increased the survival rate of mice acutely infected with T. gondii. Next, scanning electron microscopy, transmission electron microscopy and RNA sequencing were employed to further explore the functional mechanism of XYP1, and the results indicated that XYP1 causes membrane perforation, swelling and disruption of tachyzoites, which could be closely associated with differential expression of several membrane-associated proteins including HSP29. In conclusion, XYP1 may be a promising new drug candidate for the treatment of toxoplasmosis.

Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer's disease.

BACKGROUND: Tau pathology is a hallmark of Alzheimer's disease (AD) and other tauopathies. During disease progression, abnormally phosphorylated forms of tau aggregate and accumulate into neurofibrillary tangles, leading to synapse loss, neuroinflammation, and neurodegeneration. Thus, targeting of tau pathology is expected to be a promising strategy for AD treatment. METHODS: The effect of rutin on tau aggregation was detected by thioflavin T fluorescence and transmission electron microscope imaging. The effect of rutin on tau oligomer-induced cytotoxicity was assessed by MTT assay. The effect of rutin on tau oligomer-mediated the production of IL-1ß and TNF-α in vitro was measured by ELISA. The uptake of extracellular tau by microglia was determined by immunocytochemistry. Six-month-old male Tau-P301S mice were treated with rutin or vehicle by oral administration daily for 30 days. The cognitive performance was determined using the Morris water maze test, Y-maze test, and novel object recognition test. The levels of pathological tau, gliosis, NF-kB activation, proinflammatory cytokines such as IL-1ß and TNF-α, and synaptic proteins including synaptophysin and PSD95 in the brains of the mice were evaluated by immunolabeling, immunoblotting, or ELISA. RESULTS: We showed that rutin, a natural flavonoid glycoside, inhibited tau aggregation and tau oligomer-induced cytotoxicity, lowered the production of proinflammatory cytokines, protected neuronal morphology from toxic tau oligomers, and promoted microglial uptake of extracellular tau oligomers in vitro. When applied to Tau-P301S mouse model of tauopathy, rutin reduced pathological tau levels, regulated tau hyperphosphorylation by increasing PP2A level, suppressed gliosis and neuroinflammation by downregulating NF-kB pathway, prevented microglial synapse engulfment, and rescued synapse loss in mouse brains, resulting in a significant improvement of cognition. CONCLUSION: In combination with the previously reported therapeutic effects of rutin on Aß pathology, rutin is a promising drug candidate for AD treatment based its combinatorial targeting of tau and Aß.

The immunodominant and neutralization linear epitopes for SARS-CoV-2.

Although vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulate the 3D structures and predict the B cell epitopes on the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches and validate epitope immunogenicity by immunizing mice. Almost all 33 predicted epitopes effectively induce antibody production, six of these are immunodominant epitopes in individuals, and 23 are conserved within SARS-CoV-2, SARS-CoV, and bat coronavirus RaTG13. We find that the immunodominant epitopes of individuals with domestic (China) SARS-CoV-2 are different from those of individuals with imported (Europe) SARS-CoV-2, which may be caused by mutations on the S (G614D) and N proteins. Importantly, we find several epitopes on the S protein that elicit neutralizing antibodies against D614 and G614 SARS-CoV-2, which can contribute to vaccine design against coronaviruses.

Molecular composition and sources of water-soluble organic aerosol in summer in Beijing.

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.

Anti-Toxoplasma gondii effect of two spider venoms in vitro and in vivo.

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 × 103T. 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.

Anti-parasitic effect on Toxoplasma gondii induced by a spider peptide lycosin-I.

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.

Tissue-specific δ13C in ancient and modern tropical seabirds and flying fish in the Xisha Islands, South China Sea.

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.

The peptide lycosin-I attenuates TNF-α-induced inflammation in human umbilical vein endothelial cells via IκB/NF-κB signaling pathway.

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.

Nitrogen cycling in the soil-plant system along a series of coral islands affected by seabirds in the South China Sea.

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 δ15N values of total nitrogen (TN) and inorganic nitrogen (IN: NH4+-N, and NO3--N), δ18O of NO3--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 δ13C and δ15N values. The results show that, with an increase of TP, the TN and IN content, and δ15N values in soils all increased. Plant C/N and δ15N values decreased and increased, respectively, as the soil N content increased. When the TN content of the soil was low, the δ15N value in plant leaves was similar to that in soil NO3-, but was much lower than that in soil NH4+. When the soil TN content was high, the δ15N 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 NH4+, 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.