Molluscicide screening and identification of novel targets against Pomacea canaliculata.

BACKGROUND: Owing to the nonavailability of any clear targets for molluscicides against Pomacea canaliculata, target-based screening strategy cannot be employed. In this study, the molluscicidal effects of typical pesticides on P. canaliculata were evaluated to obtain the molluscicide target. A series of arylpyrrole compounds were synthesized based on the discovered target, and their structure-activity relationships explored. A preliminary strategy for screening molluscicides based on specific targets was also developed. RESULTS: A laboratory colony of P. canaliculata was developed, which showed no difference in sensitivity to niclosamide compared with the wild group, while exhibiting a higher stability against pesticide response. Mitochondrial adenosine triphosphate (ATP) synthase inhibitors and mitochondrial membrane potential uncouplers were identified and validated as potential targets for molluscicide screening against P. canaliculata. A series of arylpyrrole compounds were designed and synthesized. The median lethal concentration of 4-bromo-2-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile (Compound 102) was 10-fold lower than that of niclosamide. CONCLUSION: New molluscicide targets were discovered and validated, and preliminary strategies were explored for pesticide screening based on these targets. Compound 102 exhibited a high molluscicidal activity and had a great potential value for exploring a molluscicide to control P. canaliculata. © 2024 Society of Chemical Industry.

A configurational analysis on career success of scientific and technological innovation talents in universities.

Introduction: Increasing the career success of scientific and technological innovation talents has become an important means of keeping and using talents in countries around the world. However, the problem has not been solved effectively. Methods: Thirty-five cases were chosen in this study. The combined effects of human capital, psychological capital, micro-social capital, team social capital, and macro-social capital on the career success of scientific and technological innovation talents, as well as relevant influencing mechanisms, were discussed using qualitative comparative analysis (QCA). Results: Results demonstrate that: (a) while a single factor cannot be the only condition for the high career success of scientific and technological innovation talents in universities, increasing macro-social capital plays a relatively universal role in a high career success rate. (b) There are three paths driving the high career success of scientific and technological innovation talents in universities. (c) There are two paths driving the non-high career success of scientific and technological innovation. Both have characteristics of absent psychological capital and micro-social capital. Moreover, the driving mechanism of high career success has an asymmetrical causal relationship. Discussion: Research conclusions are not only conducive to expanding the research perspectives of social capital theory and career success, but also provide valuable insight into how to stimulate the career success of scientific and technological innovation talents in universities.

In vivo efficiency of praziquantel treatment of single-sex Schistosoma japonicum aged three months old in mice.

Schistosomiasis is a major neglected tropical disease mainly caused by Schistosoma haematobium, S. japonicum and S. mansoni, and results in the greatest disease burden. Mass drug administration (MDA) with praziquantel (PZQ), a single drug only available for the disease, has played a vital role in schistosomiasis control. Therefore, any possibility of selection of the parasites for PZQ resistance or low sensitivity may hamper the 2030's target of global disease elimination. We had experimentally demonstrated the long-term survival and reproductive potential of single-sex (of either sex) S. japonicum infections in definitive hosts mice. What has not yet been adequately addressed is whether the long live single-sex schistosomes remain sensitive to PZQ, and what reproduction potential for those schistosomes surviving treatment may have. We therefore performed experimental mice studies to explore the treatment effectiveness of PZQ (at total doses of 200 or 400 mg/kg, corresponding to the sub-standard or standard treatment doses in humans) for single-sex S. japonicum aged three months old. The results showed that no treatment efficiency was observed on female schistosomes, whereas on male schistosomes only at PZQ 400 mg/kg a significant higher efficiency in reducing worm burdens was observed. Moreover, either schistosome males or females surviving PZQ treatment remained their reproduction potential as normal. The results indicate that long (i.e., three months) live single-sex S. japonicum can easily survive the current treatment strategy, and moreover, any schistosomes, if with PZQ resistance or low sensitivity, could be easily transmitted in nature. Therefore, in order to realize the target for the national and the global schistosomiasis elimination, there is undoubtedly a great need for refining PZQ administration and dosage, looking for alternative therapies, and/or developing vaccines against schistosome.

Evaluation of the molluscicidal activities of arylpyrrole on Oncomelania hupensis, the intermediate host of Schistosoma japonicum.

The snail Oncomelania hupensis is the only intermediate host of the highly invasive parasite Schistosoma japonicum. Molluscicide is often used to curb transmission of S. japonicum. Niclosamide, the only World Health Organization (WHO) recognized molluscicide, presents major drawbacks, including high cost and toxicity towards aquatic animals. In the present study, a number of aryl pyrrole derivatives (ADs) were synthesized to serve as potential molluscicides and were tested on O. hupensis. To uncover the underlying mechanisms, adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels were assessed in the soft body of ADs-exposed O. hupensis, using high performance liquid chromatography (HPLC). The effect of C6 on key points of energy metabolism (the activities of complexes I, III, IV and the membrane potential) was determined. We demonstrated that the Compound 6 (C6, 4-bromo-1-(bromomethyl)-2-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile) exerted the strongest molluscicidal activity against adult O. hupensis at LC50 of 0.27, 0.19, and 0.13 mg/L for 24, 48, and 72 h respectively. Moreover, we found that the bromide on the pyrrole ring of C6 was essential for molluscicidal activity. Furthermore, the ATP content reduced from 194.46 to 139.75 µg/g after exposure to 1/2 LC50, and reduced to 93.06 µg/g after exposure to LC50. ADP, on the other hand, remained the same level before and after C6 exposure. We found that C6, at 1/2 LC50, reduced the membrane potential of O. hupensis, while no significant changes were observed in the activities of complexes I, III, and IV. C6 was identified with excellent activities on O. hupensis. The obtained structure-activity relationship and action mechanism study results should be useful for further compound design and development.

Discovery and Validation of a Novel Target of Molluscicides against Oncomelania hupensis, the Intermediate Host of Schistosoma japonicum.

In this study, 196 strains of actinomycetes isolated from marshland soil samples were tested for molluscicidal activity against Oncomelania hupensis. Five strains demonstrated molluscicidal activity, of which the molluscicidal efficiency of Actinomycetes strain A183 was the maximum. After the fermentation supernatant of actinomycetes A183 was extracted with ethyl acetate (EWEA), the LC50 of the EWEA after leaching for 48 h and 72 h were 0.2688 and 0.2195 mg/L, respectively. The effect of EWEA on the key points of energy metabolism was determined. We noted that 1 mg/L of EWEA (A813) significantly reduced the activity of mitochondrial respiratory chain complex I (P < 0.05), while no significant changes were observed in the activities of complexes II, III, and IV. In addition, EWEA (A813) could decrease the membrane potential of O. hupensis purified mitochondria in vitro. The LC50 of the 3 uncoupler (FCCP, DNP, and Tyrphostin A9) after immersion for 24 h were 0.065, 0.135, and 0.110 mg/L, respectively; LC50 after 48 h treatment was 0.064, 0.124, and 0.082 mg/L, respectively; LC50 after 72 h treatment was 0.063, 0.129, and 0.061 mg/L, respectively, and all uncoupler showed strong molluscicidal activities, demonstrating that the mitochondrial membrane potential uncoupling is a potential target for molluscicides against O. hupensis. Moreover, the molluscicidal active substance of strain A183 needs to be further isolated, purified, and structurally characterized considering its promising potential applications.

GWC1 is essential for high grain quality in rice.

Appearance quality is an important determinant of rice quality. Many genes that affect grain appearance quality have been identified, but the regulatory mechanisms that contribute to this trait remain unclear. Here, two grains with chalkiness (gwc1) mutants, gwc1-1 and gwc1-2, were identified from an EMS-mutagenized population of indica rice cultivar Shuhui498 (R498). The gwc1 mutants had poor grain appearance quality consistent with the measured values for the percentage of grains with chalkiness, square of chalky endosperm, the total starch, amylose and sucrose contents. Milling quality and grain size were also affected in the gwc1 mutants. The gwc1-1 and gwc1-2 were found to be loss-of-function allelic mutants. GWC1 was mapped to the long arm of rice chromosome 8 using the MutMap strategy and incorrectly annotated in the reference genome for Nipponbare (MSU). The GWC1 gene corresponds to the WTG1/OsOTUB1 gene, which encodes an otubain-like protease with deubiquitinating activity that is homologous to human OTUB1. GWC1 transcripts accumulated to high levels in early endosperm after fertilization and developing inflorescences, and GWC1-green fluorescent protein (GFP) signal was detected in the nucleus and cytoplasm. GWC1 is likely to regulate grain appearance quality through genes involved in sucrose metabolism and starch biosynthesis. Overall, the present findings reveal that GWC1 is important for grain quality and yield due to its effects on grain chalkiness and size.

Evaluation of protective efficacy induced by different heterologous prime-boost strategies encoding triosephosphate isomerase against Schistosoma japonicum in mice.

BACKGROUND: In China, schistosomiasis japonica is a predominant zoonotic disease, and animal reservoir hosts in the environment largely sustain infections. The development of transmission-blocking veterinary vaccines is urgently needed for the prevention and efficient control of schistosomiasis. Heterologous prime-boost strategy is more effective than traditional vaccination and homologous prime-boost strategies against multiple pathogens infection. In the present study, to further improve protective efficacy, we immunized mice with three types of heterologous prime-boost combinations based on our previously constructed vaccines that encode triosphate isomerase of Schistosoma japonicum, tested the specific immune responses, and evaluated the protective efficacy through challenge infection in mice. METHODS: DNA vaccine (pcDNA3.1-SjTPI.opt), adenoviral vectored vaccine (rAdV-SjTPI.opt), and recombinant protein vaccine (rSjTPI) were prepared and three types of heterologous prime-boost combinations, including DNA i.m. priming-rAdV i.m. boosting, rAdV i.m. priming-rAdV s.c. boosting, and rAdV i.m. priming-rSjTPI boosting strategies, were carried out. The specific immune responses and protective efficacies were evaluated in BALB/c mice RESULTS: Results show that different immune profiles and various levels of protective efficacy were elicited by using different heterologous prime-boost combinations. A synergistic effect was observed using the DNA i.m. priming-rAdV i.m. boosting strategy; however, its protective efficacy was similar to that of rAdV i.m. immunization. Conversely, an antagonistic effect was generated by using the rAd i.m. priming-s.c. boosting strategy. However, the strategy, with rAdV i.m. priming- rSjTPI s.c. boosting, generated the most optimal protective efficacy and worm or egg reduction rate reaching up to 70% in a mouse model. CONCLUSIONS: A suitable immunization strategy, rAdV i.m. priming-rSjTPI boosting strategy, was developed, which elicits a high level of protective efficacy against Schistosoma japonicum infection in mice.

Evaluating the risk of Schistosoma mansoni transmission in mainland China.

Biomphalaria straminea, an intermediate host of Schistosoma mansoni, is predominantly distributed in the South Americas and Caribbean; however, this snail, as an invasive species, was introduced to Shenzhen, southern China, in 1981, and recent epidemiologic surveys demonstrate that the distribution of B. straminea has expanded across the Zhujiang River Basin, South China. In the presence of continuous importation of S. mansoni-infected cases, there is a growing concern about the transmission of S. mansoni in China. To evaluate the risk of S. mansoni transmission in China, we tested the compatibility of B. straminea captured from the snail habitats in southern China with S. mansoni in laboratory. We detected no S. mansoni infections in B. straminea following exposure to the parasite larvae at snail/miracidium ratios of 1:5, 1:10, 1:20, 1:40, and 1:80, while 6.7 to 66.7 % infections occurred in the control Biomphalaria glabrata depending on the ratio. The results of the present study demonstrate that the invasive B. straminea snails seem to be incompatible with S. mansoni, suggesting a low risk of S. mansoni transmission in mainland China.

Resistance to niclosamide in Oncomelania hupensis, the intermediate host of Schistosoma japonicum: should we be worried?

As the currently only available molluscicide, niclosamide has been widely used for snail control for over 2 decades in China. There is therefore a concern about the emergence of niclosamide-resistant snail populations following repeated, extensive use of the chemical. The purpose of this study was to investigate the likelihood of niclosamide resistance in Oncomelania hupensis in China. Active adult O. hupensis snails derived from 20 counties of 10 schistosomiasis-endemic provinces of China, of 10 snails in each drug concentration, were immersed in solutions of 1, 0.5, 0.25, 0.125, 0.063, 0.032, 0.016 and 0.008 mg L-1 of a 50% wettable powder of niclosamide ethanolamine salt (WPN) for 24 and 48 h at 25 °C, and the median lethal concentration (LC50) was estimated. Then, the 24- and 48-h WPN LC50 values were compared with those determined in the same sampling sites in 2002. The results indicated that the 24- and 48-h WPN LC50 values for O. hupensis were not significantly different from those determined in 2002 (P = 0.202 and 0.796, respectively). It is concluded that the current sensitivity of O. hupensis to niclosamide has not changed after more than 2 decades of repeated, extensive application in the main endemic foci of China, and there is no evidence of resistance to niclosamide detected in O. hupensis.

[Cloning and expression of Schistosoma japonicum VCP gene and its mRNA expression levels in different stages].

OBJECTIVE: To prokaryotically express the valosin-containing protein (VCP) of Schistosoma japonicum, and analyze its VCP mRNA expressions in the cercaria, schistosomulum, adult worm (female and male worms) and egg. METHODS: RNA of S. japonicum eggs were extracted, and reversely transcribed into cDNA. The VCP gene of S. japonicum was amplified by using polymerase chain reaction (PCR), and subcloned into the prokaryotically expressed vector pET15b. The recombined plasmid was transformed into BL21 cells, and the expression of the target gene was induced with isopropyl-beta-D-thiogalactopyranoside (IPTG). The recombinant protein was yielded through the purification of inclusion body, and identified by using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The RNA (s) of cercaria, schistosomulum, female adult worm, male adult worm, and egg of S. japonicum were extracted, digested with DNase, purified, and reversely transcribed into cDNA. The mRNA expressions of the VCP gene in various developmental stages of S. japonicum were determined by using fluorescence-based quantitative real-time PCR. RESULTS: The VCP gene of S. japonicum was yielded by PCR amplification, and the recombinant protein was obtained through recombinant plasmid expression and purification of inclusion body. The highest VCP mRNA expression in S. japonicum cercaria was detected by the fluorescence-based quantitative real-time PCR, while low expressions were found in the schistosomulum, egg, female and male adult worms. CONCLUSION: The recombinant protein encoded by the VCP gene of S. japonicum is successfully obtained, and the VCP mRNA expression is determined in various developmental stages of S. japonicum.