The insect ryanodine receptor (RyR) is a novel target of the anthranilic and phthalic insecticides, which have high activity against lepidopteran insects. Several diamide insecticides have been used ...to control pests in orchards in China. To enhance our understanding of the effects of diamides on RyRs, full-length cDNAs were isolated and characterized from the summer fruit tortrix moth, Adoxophyes orana, which is the most severe pest of stone and pome trees worldwide. In addition, the modulation of AoRyR mRNA expression by diamide insecticides was investigated. The AoRyR mRNA obtained had an open reading frame (ORF) of 15 402 bp nucleotides encoding 5 113 amino acids, and shared high and low identity with its orthologs in other insects and mammals of 77–92 and 45–47% identity, respectively. One alternative splice site with two exclusive exons was revealed in AoRyR (a/b). The usage of exon was more frequent in eggs and larvae than in pupae and adults. Quantitative real-time reverse transcription PCR (qRT-PCR) showed that AoRyR mRNA was expressed at all developmental stages, especially in eggs, male pupae and male adults. The expression levels of AoRyR mRNA in the whole body were up-regulated markedly after 3rd instar larvae were treated with chlorantraniliprole at LC10, LC20 and LC50 dosages. The results could provide the basis for further functional studies of AoRyR and for the development of new chemicals with selective activity against insects.
Background
Several studies have shown that scorpion venom peptide BmK AGAP has an analgesic activity. Our previous study also demonstrated that intraplantar injection of BmK AGAP ameliorates ...formalin-induced spontaneous nociceptive behavior. However, the effect of intrathecal injection of BmK AGAP on nociceptive processing is poorly understood.
Methods
We investigated the effects of intrathecal injection of BmK AGAP on spinal nociceptive processing induced by chronic constrictive injury or formalin. Thermal hyperalgesia and mechanical allodynia were measured using radiant heat and the von Frey filaments test. Formalin-induced spontaneous nociceptive behavior was also investigated. C-Fos expression was assessed by immunohistochemistry. Phosphorylated mitogen-activated protein kinase (p-MAPK) expression was monitored by Western blot assay.
Results
Intrathecal injection of BmK AGAP reduced chronic constrictive injury-induced neuropathic pain behavior and pain from formalin-induced inflammation, accompanied by decreased expression of spinal p-MAPKs and c-Fos protein. The results of combining low doses of different MAPK inhibitor (U0126, SP600125, or SB203580; 0.1 µg for each inhibitor) with a low dose of BmK AGAP (0.2 µg) suggested that BmK AGAP could potentiate the effects of MAPK inhibitors on inflammation-associated pain.
Conclusion
Our results demonstrate that intrathecal injection of BmK AGAP produces a sensory-specific analgesic effect via a p-MAPK-dependent mechanism.
Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert ...consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.
Damage to endothelial glycocalyx (EGCX) can lead to coagulation disorders in sepsis. Heat stroke (HS) resembles sepsis in many aspects; however, it is unclear whether EGCX injury is involved in its ...pathophysiology. The purpose of this study was to examine the relationship between the damage of EGCX and the development of coagulation disorders during HS.
We retrospectively collected 159 HS patients and analyzed coagulation characteristics and prognosis of HS patients with or without disseminated intravascular coagulation (DIC). We also replicated a rat HS model and measured coagulation indexes, pulmonary capillary EGCX injury in HS rats. Finally, we evaluated the effect of the antioxidant N-acetylcysteine (NAC) on HS-initiated EGCX injury and coagulation disorders.
Clinical data showed that HS patients complicated with DIC had a higher risk of death than HS patients without DIC. In a rat HS model, we found that rats subjected to heat stress developed hypercoagulability and platelet activation at the core body temperature of 43°C, just before the onset of HS. At 24 h of HS, the rats showed a consumptive hypo-coagulation state. The pulmonary capillary EGCX started to shed at 0 h of HS and became more severe at 24 h of HS. Importantly, pretreatment with NAC substantially alleviated EGCX damage and reversed the hypo-coagulation state in HS rats. Mechanically, HS initiated reactive oxidative species (ROS) generation, while ROS could directly cause EGCX damage. Critically, NAC protected against EGCX injury by attenuating ROS production in heat-stressed or hydrogen peroxide (H
O
)-stimulated endothelial cells.
Our results indicate that the poor prognosis of HS patients correlates with severe coagulation disorders, coagulation abnormalities in HS rats are associated with the damage of EGCX, and NAC improves HS-induced coagulopathy, probably through its protection against EGCX injury by preventing ROS generation.
The costimulatory protein B7-H3 has been shown to play a contributory role in the development and progression of experimental pneumococcal meningitis by augmentation of the innate immunity-associated ...inflammatory response via a TLR2-dependent manner. This study aimed to clarify the component(s) of TLR2-mediated signal transduction pathways responsible for B7-H3-augmented inflammatory response and subsequent brain damage during experimental pneumococcal meningitis. Administration of B7-H3 did not augment expression of TLR2 and other TLR2 upstream components, but led to an enhanced formation of MyD88-IRAK immunocomplex in the brain of S. pneumoniae-infected mice. Furthermore, B7-H3 substantially augmented S. pneumoniae-induced activation of TLR2 downstream NF-κB p65 and MAPK p38 pathways in the brain of S. pneumoniae-infected mice. Notably, blockage of NF-κB p65 and/or MAPK p38 with their specific inhibitors strongly attenuated B7-H3-amplified inflammatory response with significantly reduced proinflammatory cytokine and chemokine production, and markedly ameliorated B7-H3-exacerbated disruption of blood-brain barrier and severity of disease status in S. pneumoniae-infected mice. These results indicate that targeting NF-κB p65 and/or MAPK p38 may represent a promising therapeutic option for amelioration of overwhelming inflammatory response-associated brain injury frequently observed during pneumococcal meningitis.
The purpose of this study was to evaluate the sublethal effects of the beta-cypermethrin on calling behavior and fecundity of a major fruit-boring pest of apple, Carposina sasakii Matsumura. The ...mating rate, fertility (total number of eggs laid per female), and adult longevity of adults were remarkably decreased as compared with that in control when the adults were exposed to 10% lethal concentrations (LC10) of beta-cypermethrin (LC10♀ × LC10♂), and the age-specific survival rate (lx ) was also negatively affected by sublethal beta-cypermethrin especially for the LC10♀× LC10♂ mating combination. However, the age-specific fecundity (mx ) was stimulated particularly in the combination of CK♀× LC10♂. Furthermore, the oviposition period was prolonged and the number of eggs was significantly increased for combinations of CK♀× LC10♂ and LC10♀× CK♂. In the mating experiments, males in control or LC10-beta-cypermethrin treatments preferred to mate with females in control. It might be because of lower calling rate of female survivors treated with sublethal beta-cypermethrin. Our data indicate that treatment of beta-cypermethrin had a sublethal effect on the development and production of C. sasakii, and their mating behavior changes in surviving adults that may contribute to assortative mating.
The Boer goat is one of the top meat breeds in modern animal husbandry and has attracted widespread attention for its unique growth performance. However, the genetic basis of muscle development in ...the Boer goat remains obscure. In this study, we identified specific structural variants in the Boer goat based on genome-wide selection signals and analyzed the basis of the molecular heredity of related candidate genes in muscle development. A total of 9 959 autosomal copy number variations (CNVs) were identified through selection signal analysis in 127 goat genomes. Specifically, we confirmed that the highest signal CNV (HSV) was a chromosomal arrangement containing an approximately 1.11 Mb (CHIR17: 60062304-61171840 bp) duplicated fragment inserted in reverse orientation and a 5 362 bp deleted region (CHIR17:60145940-60151302 bp) with overlapping genes (e.g.,
,
,
,
, and
). The homozygous duplicated HSV genotype (+/+) was found in 96% of Boer goats but was not detected in Eurasian goats and was only detected in 4% of indigenous African goats. The expression network of three candidate genes (
,
, and
) regulating dose transcription was constructed by RNA sequencing. Results indicated that these genes were involved in the proliferation and differentiation of skeletal muscle satellite cells (SMSCs) and their overexpression significantly increased the expression of
. The HSV of the Boer goat contributed to superior skeletal muscle growth via the dose effects of overlapping genes.
The objective of this study was to assess the genetic diversity and population structure of goats in the Yangtze River region using microsatellite and mtDNA to better understand the current status of ...those goat genetic diversity and the effects of natural landscape in fashion of domestic animal genetic diversity. The genetic variability of 16 goat populations in the littoral zone of the Yangtze River was estimated using 21 autosomal microsatellites, which revealed high diversity and genetic population clustering with a dispersed geographical distribution. A phylogenetic analysis of the mitochondrial D‐loop region (482 bp) was conducted in 494 goats from the Yangtze River region. In total, 117 SNPs were reconstructed, and 173 haplotypes were identified, 94.5% of which belonged to lineages A and B. Lineages C, D, and G had lower frequencies (5.2%), and lineage F haplotypes were undetected. Several high‐frequency haplotypes were shared by different ecogeographically distributed populations, and the close phylogenetic relationships among certain low‐frequency haplotypes indicated the historical exchange of genetic material among these populations. In particular, the lineage G haplotype suggests that some west Asian goat genetic material may have been transferred to China via Muslim migration.
In this study, the objective was to assess the genetic diversity and population structure of goats in the Yangtze River region using microsatellite and mtDNA to better understand the current status of those goat genetic diversity and the effects of natural landscape in fashion of domestic animal genetic diversity. The genetic variability of 16 goat populations in the littoral zone of the Yangtze River was estimated using 21 autosomal microsatellites, which revealed high diversity and genetic population clustering with a dispersed geographical distribution. In particular, the lineage G haplotype of D‐loop identified suggests that some west Asian goat genetic material may have been transferred to China via Muslim migration.
Conformational conversion of the normal cellular prion protein, PrP
C
, into the misfolded isoform, PrP
Sc
, is considered to be a central event in the development of fatal neurodegenerative ...diseases. Stabilization of prion protein at the normal cellular form (PrP
C
) with small molecules is a rational and efficient strategy for treatment of prion related diseases. However, few compounds have been identified as potent prion inhibitors by binding to the normal conformation of prion. In this work, to rational screening of inhibitors capable of stabilizing cellular form of prion protein, multiple approaches combining docking-based virtual screening, steady-state fluorescence quenching, surface plasmon resonance and thioflavin T fluorescence assay were used to discover new compounds interrupting PrP
C
to PrP
Sc
conversion. Compound
3253-0207
that can bind to PrP
C
with micromolar affinity and inhibit prion fibrillation was identified from small molecule databases. Molecular dynamics simulation indicated that compound
3253-0207
can bind to the hotspot residues in the binding pocket composed by β1, β2 and α2, which are significant structure moieties in conversion from PrP
C
to PrP
Sc
.
To analyze peripapillary atrophy β/γ zone (PPA-β/γ) and the optic disc ovality index, and to assess their associations with the axial length (AL), refractive error, best corrected visual acuity ...(BCVA), choroidal thickness (CT), and age in highly myopic eyes.
This was a retrospective observational case series. The study included 667 patients consecutively examined for highly myopic eyes spherical equivalent ≤-6.0 diopters (D) and AL≥26 mm with or without myopic retinopathy. Each patient went through a comprehensive ophthalmological examination that included spectral domain optical coherence tomography (SD-OCT) of the macula, A-mode ultrasonography, and a cycloplegic refraction test. The ovality index and PPA-β/γ area were measured from optic disc photographs.
A significant association was seen between PPA-β/γ area and the ovality index (
=0.000,
=-0.232). The PPA-β/γ area increased significantly with a longer AL, older age, worse BCVA, higher refractive error, and thinner choroid (
<0.01). The oval disc was significantly correlated with a longer AL, older age, worse BCVA, higher refractive error, larger PPA-β/γ area, and thinner choroid (
<0.01).
The PPA-β/γ zone and ovality index in highly myopic eyes show distinct associations with the AL, refractive error, BCVA, age, and CT.
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