Plasma metabonomic study on the effect of Para­hydroxybenzaldehyde intervention in a rat model of transient focal cerebral ischemia.

Gastrodia elata Blume has been widely used to treat various central and peripheral nerve diseases, and Para­hydroxybenzaldehyde (PHBA) is one of the indicated components suggested to provide a neuroprotective effect. In our previous, it was shown that PHBA protected mitochondria against cerebral ischemia­reperfusion (I/R) injury in rats. In the present study, how PHBA regulated the metabolic mechanism in blood following cerebral I/R was assessed to identify an effective therapeutic target for the prevention and treatment of ischemic stroke (IS). First, a rat model of cerebral ischemia­reperfusion injury was established via middle cerebral artery occlusion/reperfusion (MCAO/R). The therapeutic effect of PHBA on brain I/R was evaluated by assessing the neurological function score, triphenyl tetrazolium chloride, hematoxylin and eosin, and Nissl staining. Next, a non­targeted metabolomic based on high­performance liquid chromatography quadrupole time­of­flight mass spectrometry was established to identify differential metabolites. Finally, a targeted metabolic spectrum was analyzed and the potential therapeutic targets were verified by Western blotting. The results showed that the neurological function score, cerebral infarction area, hippocampal morphology, and the number of neurons in the PHBA group were significantly improved compared with the model group. Metabonomic analysis showed that 13 different metabolites were identified between the model and PHBA group, which may be involved in the 'tricarboxylic acid cycle', 'glutathione metabolism', and 'mutual transformation of pentose and glucuronates', amongst others. Among these, the levels of the most significant differential metabolite, dGMP, decreased significantly following PHBA treatment. Western blotting was used to verify the expression of membrane­associated guanosine kinase PSD­95 and the subunit of glutamate AMPA receptor GluA1, which significantly increased after PHBA treatment. In addition, it was also found that PHBA increased the expression of the light chain­3 protein and autophagy effector protein 1, whilst the expression of sequestosome­1 decreased, indicating that PHBA promoted autophagy. Similarly, in TUNEL staining and detection of apoptosis­related proteins, it was found that MCAO/R upregulated the expression of Bax and cleaved­caspase­3 whilst downregulating the expression of Bcl­2 and increasing the apoptosis of hippocampal neurons; PHBA reversed this situation. These results suggest that cerebral I/R causes postsynaptic dysfunction by disrupting the interaction between PSD­95 and AMPARs, and the inhibition of the autophagy system eventually leads to the apoptosis of hippocampal neurons.

Larval and/or Adult Exposure to Intraguild Predator Harmonia axyridis Alters Reproductive Allocation Decisions and Offspring Growth in Menochilus sexmaculatus.

Maternal effects can reduce offspring susceptibility to predators by altering resource allocation to young and reproducing larger offspring. While the perception of predation risk can vary according to a prey's life stage, it is unclear whether maternally experienced intraguild predation (IGP) risk during different life stages influences the maternal effects of predatory insects. We investigated the influence of exposure to intraguild predators (Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae)) during the larval and/or adult stages on reproductive decisions and offspring growth in Menochilus sexmaculatus (Fabricius). Independent of the life stage, when M. sexmaculatus females experienced IGP risk, their body weight and fecundity decreased, but the proportion of trophic eggs produced increased. However, egg mass, egg clutch number, and egg clutch size were not influenced by the treatment. Next, when offspring encountered H. axyridis, mothers experiencing IGP risk during the larval and/or adult stages could increase their offspring's weight. Moreover, offspring in IGP environments reached a similar size as those with no-IGP environments when mothers experienced IGP risk during the larval and/or adult stages. Overall, M. sexmaculatus larval and/or adult exposure to IGP risk had no influence on egg size, but increased offspring body size when faced with H. axyridis. Additionally, mothers experiencing IGP risk during different life stages showed increased production of trophic eggs. Because IGP is frequently observed on M. sexmaculatus and favours relatively larger individuals, different stages of M. sexmaculatus express threat-sensitively to IGP risk; inducing maternal effects can be an adaptive survival strategy to defend against H. axyridis.

P­hydroxybenzyl alcohol ameliorates neuronal cerebral ischemia­reperfusion injury by activating mitochondrial autophagy through SIRT1.

Mitochondrial autophagy serves a key role in clearing damaged mitochondria. P­hydroxybenzyl alcohol (pHBA) can improve neuronal injury induced by cerebral ischemia­reperfusion (I/R). However, the mechanism of pHBA improving I/R damage through the mitochondrial pathway remains unclear. A rat model of middle cerebral artery occlusion and reperfusion (MCAO/R) was used in the present study. The rats were treated with sirtuin 1 (SIRT1) inhibitor EX527 and pHBA for 7 days, followed by reperfusion. At 24 h after reperfusion, the infarct size was calculated and the severity of nerve damage was evaluated. Hematoxylin and eosin and Nissl staining revealed cellular changes in the ischemic penumbra. Changes in mitochondrial structure were observed using electron microscopy. Mitochondrial function was evaluated by detecting mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (mPTP) and ATP levels using commercially available kits. In addition, the ischemic penumbra tissues were used for immunofluorescence staining for p62 and LC3 proteins. The expression of SIRT1 and mitochondrial autophagy­related proteins, PTEN­induced kinase 1 (PINK1) and Parkin, were detected by western blotting. Finally, apoptosis was analyzed by TUNEL staining and the expression of apoptosis­related proteins (Bax, Bcl­2 and Caspase­3) by western blotting. The results suggested that postoperative pHBA treatment may reduce the size of cerebral infarction and damage to the nervous system, and may improve cell damage in the ischemic penumbra of MCAO/R rats. Compared with rats in the untreated MCAO/R group, the mitochondrial structure of the pHBA­treated group was improved, the levels of MMP and ATP were increased, and the degree of opening of mPTP was decreased. Simultaneously, immunofluorescence and western blotting results showed that compared with the MCAO/R group, the number of LC3­ and TUNEL­positive cells increased, the number of p62­positive cells decreased, SIRT1 and autophagy protein (PINK1, Parkin and LC3 II/I) expression levels increased and p62 expression decreased in the pHBA group. However, these improvements were blocked by treatment with EX527. In summary, results from the present study suggested that pHBA may improve neuronal injury in the ischemic penumbra of MCAO/R rats through SIRT1­activated mitochondrial autophagy and mitochondrial­mediated neuronal apoptosis.

Effects of mummy consumption on fitness and oviposition site selection on Harmonia axyridis.

Intraguild predation (IGP) has been commonly reported between predators and parasitoids used as biological control agents as predators consuming parasitoids within their hosts. However, the effect of parasitoid-mummy consumption on the fitness of the predator and subsequent oviposition site selection have not been well studied. In our study, we conducted two laboratory experiments to examine the influence of Aphidius gifuensis Ashmead (Hymenoptera: Braconidae) mummies as prey on fitness and subsequently oviposition site selection of Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae). Results indicate that when H. axyridis was reared on A. gifuensis mummies only, its larval development was prolonged, and body weight of the 4th instar larvae and newly emerged adults, and fecundity decreased. Moreover, H. axyridis did not exhibit oviposition preference on plants infested with unparasitized aphids or aphids parasitized for shorter than 9 days. However, compared with plants with mummies (parasitized ≥9 days), H. axyridis laid more eggs on plants with unparasitized aphids. In contrast, H. axyridis previously fed with A. gifuensis mummies did not show a significant oviposition preference between plants with unparasitized aphids and those with mummies (parasitized ≥9 days). Overall, our results suggest that mummy consumption reduced the fitness of H. axyridis. Although H. axyridis avoided laying eggs on plants with A. gifuensis mummies, prior feeding experience on A. gifuensis mummies could alter the oviposition site preference. Thus, in biological control practice, prior feeding experience of H. axyridis should be carefully considered for reduction of IGP and increase of fitness of H. axyridis on A. gifuensis.

Effects of Prey Distribution and Heterospecific Interactions on the Functional Response of Harmonia axyridis and Aphidius gifuensis to Myzus persicae.

Natural enemy guilds normally forage for prey that is patchily distributed simultaneously. Previous studies have investigated the influence of conspecific interactions and prey distribution on the functional response of natural enemies. However, little is known about how prey distribution and heterospecific interactions between natural enemies could affect their foraging efficiency. We examined the effects of prey distribution (aggregate and uniform) and heterospecific interactions on the functional response of a predator, Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae) and a parasitoid, Aphidius gifuensis Ashmead (Hymenoptera: Braconidae) to the green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae). Type II functional responses were observed in all experiments. Functional response curves of single H. axyridis or A. gifuensis were higher in the aggregate treatment than in the uniform treatment when aphid densities were between 40-180 or 70-170, respectively. When comparing between aggregate and uniform treatments with the heterospecific enemy occurrence, no differences were found in the parasitism efficiency of A. gifuensis, while H. axyridis consumed more aphids in the aggregate treatment than in the uniform treatment when aphid densities were between 50-230. The functional response of individual H. axyridis was not affected by A. gifuensis under two aphid distributions. However, the functional response of a single A. gifuensis and the treatment when A. gifuensis concurrently with H. axyridis overlapped in uniform treatment of above approximately 150 aphids. Our results indicate that the predation rate of H. axyridis was affected by aphid distribution, but was not affected by heterospecific interactions. The parasitism rate of A. gifuensis was affected by aphid distribution, and by heterospecific interactions in both the aggregate and uniform treatments. Thus, to optimize the management efficiency of M. persicae, the combined use of H. axyridis and A. gifuensis should be considered when M. persicae is nearly uniformly distributed under relatively high density.

Behavioural patterns and functional responses of a generalist predator revealed using automated video tracking.

BACKGROUND: Tracking predator-prey interactions using automated image recording systems provides insights into novel patterns and mechanisms of predator-prey dynamics, thus these systems have the potential to evaluate biological control agents effectively. Using an automated video tracking system, we aimed to quantify the behavioural patterns of a generalist predator Harmonia axyridis in response to changing prey density. The effect of intraspecific interactions on foraging efficiency was evaluated. In addition, functional response parameters were compared between the observations and model predictions. RESULTS: The associated behavioural component of prey consumption by H. axyridis was modified by prey density, especially for dual predator trials. Both individual and paired H. axyridis exhibited type II functional responses and a consistent cycle of behaviour. Interestingly, intra-specific interference did not affect overall prey consumption. Divergence between estimated and calculated functional response parameters was observed, which might due to the difficulty of separating foraging and non-foraging activity. CONCLUSIONS: Interference interactions between H. axyridis conspecifics might alter their foraging patterns; however, the outcome of prey consumption was not affected by this behaviour. In conclusion, automated video tracking systems may be used to expose the detailed foraging behaviour of predators and could be used to evaluate a wide range of natural enemies. © 2019 Society of Chemical Industry.

Field Testing Integrated Interventions for Schistosomiasis Elimination in the People's Republic of China: Outcomes of a Multifactorial Cluster-Randomized Controlled Trial.

Despite significant progress, China faces the challenge of re-emerging schistosomiasis transmission in currently controlled areas due, in part, to the presence of a range of animal reservoirs, notably water buffalo and cattle, which can harbor Schistosoma japonicum infections. Environmental, ecological and social-demographic changes in China, shown to affect the distribution of oncomelanid snails, can also impact future schistosomiasis transmission. In light of their importance in the S. japonicum, lifecycle, vaccination has been proposed as a means to reduce the excretion of egg from cattle and buffalo, thereby interrupting transmission from these reservoir hosts to snails. A DNA-based vaccine (SjCTPI) our team developed showed encouraging efficacy against S. japonicum in Chinese water buffaloes. Here we report the results of a double-blind cluster randomized trial aimed at determining the impact of a combination of the SjCTPI bovine vaccine (given as a prime-boost regimen), human mass chemotherapy and snail control on the transmission of S. japonicum in 12 selected administrative villages around the Dongting Lake in Hunan province. The trial confirmed human praziquantel treatment is an effective intervention at the population level. Further, mollusciciding had an indirect ~50% efficacy in reducing human infection rates. Serology showed that the SjCTPI vaccine produced an effective antibody response in vaccinated bovines, resulting in a negative correlation with bovine egg counts observed at all post-vaccination time points. Despite these encouraging outcomes, the effect of the vaccine in preventing human infection was inconclusive. This was likely due to activities undertaken by the China National Schistosomiasis Control Program, notably the treatment, sacrifice or removal of bovines from trial villages, over which we had no control; as a result, the trial design was compromised, reducing power and contaminating outcome measures. This highlights the difficulties in undertaking field trials of this nature and magnitude, particularly over a long period, and emphasizes the importance of mathematical modeling in predicting the potential impact of control intervention measures. A transmission blocking vaccine targeting bovines for the prevention of S. japonicum with the required protective efficacy would be invaluable in tandem with other preventive intervention measures if the goal of eliminating schistosomiasis from China is to become a reality.