Increased expression of NLRP3 associated with elevated levels of HMGB1 in children with febrile seizures: a case-control study.

BACKGROUND: High mobility group box-1 (HMGB1) is an endogenous danger signal that mediates activation of the innate immune response including NLR pyrin domain containing 3 (NLRP3) inflammasome activation and proinflammatory cytokine release. Although HMGB1 and NLRP3 have been implicated in the pathophysiology of seizures, the correlation between HMGB1 and NLRP3 expression has not been determined in children with febrile seizures (FS). To explore the relationship between extra-cellular HMGB1 and NLRP3 in children with FS, we analyzed serum HMGB1, NLRP3, caspase-1, and proinflammatory cytokines in patients with FS. METHODS: Thirty children with FS and thirty age-matched febrile controls were included in this study. Blood was obtained from the children with FS within 1 h of the time of the seizure; subsequently, the serum contents of HMGB1, NLRP3, caspase-1, interleukin (IL)-1ß, interleukin (IL)-6, and tumour necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. The Mann‒Whitney U test was used to compare serum cytokine levels between FS patients and controls. Spearman's rank correlation coefficient was calculated to detect significant correlations between cytokine levels. RESULTS: Serum levels of HMGB1, NLRP3, caspase-1, IL-1ß, IL-6, and TNF-α were significantly higher in FS patients than in febrile controls (p < 0.05). Serum levels of HMGB1 were significantly correlated with levels of NLRP3 and caspase-1 (both, p < 0.05). Serum levels of caspase-1 were significantly correlated with levels of IL-1ß (p < 0.05). Serum levels of IL-1ß were significantly correlated with levels of IL-6 and TNF-α (p < 0.05). CONCLUSIONS: HMGB1 is up-regulated in the peripheral serum of FS patients, which may be responsible, at least in part, for the increased expression of NLRP3 and Caspase-1. Increased expression of caspase-1 was significantly associated with elevated serum levels of IL-1ß. Given that activated Caspase-1 directly regulates the expression of mature IL-1ß and positively correlates with activation of the NLRP3 inflammasome, our data suggest that increased levels of peripheral HMGB1 possibly mediate IL-1ß secretion through the activation of the NLRP3 inflammasome in children with FS. Thus, both HMGB1 and NLRP3 might be potential targets for preventing or limiting FS.

Biallelic ADGRV1 variants are associated with Rolandic epilepsy.

OBJECTIVE: Rolandic epilepsy (RE) is among the most common focal epilepsies in childhood. For the majority of patients with RE and atypical RE (ARE), the etiology remains elusive. We thus screened patients with RE/ARE in order to detect disease-causing variants.. METHODS: A trios-based whole-exome sequencing approach was performed in a cohort of 28 patients with RE/ARE. Clinical data and EEGs were reviewed. Variants were validated by Sanger sequencing. RESULTS: Two compound heterozygous missense variants p.Val272Ile/p.Asn3028Ser and p.Ala3657Val/p.Met4419Val of ADGRV1 were identified in two unrelated familial cases of RE/ARE. All the variants were in the calcium exchanger ß domain and were suggested to be damaging by at least one web-based prediction tool. These variants are not present or are present at a very low minor allele frequency in the gnomAD database. Previously, biallelic ADGRV1 variants (p.Gly2756Arg and p.Glu4410Lys) have been observed in RE, consistent with the observation in this study and supporting the association between ADGRV1 variants and RE. Additionally, a de novo mutation, p.Asp668Asn, in GRIN2B was identified in a sporadic case of ARE, and a missense variant, p.Asn1551Ser, in RyR2 was identified in a family with RE with incomplete penetrance. These genes are all calcium homeostasis associated genes, suggesting the potential effect of calcium homeostasis in RE/ARE. CONCLUSIONS: The results from the present study suggest that the genes ADGRV1, GRIN2B, and RyR2 are associated with RE/ARE. These data link defects in neuronal intracellular calcium homeostasis to RE/ARE pathogenesis implicating that these defects plays an important role in the development of these conditions.

[Multi-objective Identification Method for Influencing Factors of Soil Heavy Metal Content Change].

Identifying the influencing factors of soil heavy metal content changes is the basis for reducing or preventing soil heavy metal pollution. Taking an agricultural experimental field in Changping District of Beijing as an example, the heavy metal content changes in As, Cr, Cu, Ni, Pb, and Zn from 2012 to 2022 were firstly analyzed. Secondly, the influencing factors of the heavy metal content changes were detected based on the geographical detector at the single-target and multi-target levels, respectively. Finally, comparative experiments with the correlation analysis method and existing studies were set up to evaluate the effectiveness of the identification method of influencing factors developed in this study. The results showed that human activity factors have exacerbated the changes in soil heavy metal content in the study area as follows： ① At the single-target level, the land use type was the main influencing factor on the changes in Cr, Cu, and Zn contents, and the annual deposition flux influenced the changes in As. The results of the interaction detection showed that there was an enhancement effect among the factors, and the interaction of the human activity factors dominated for the factor identification. ② The results of the multi-target level detection covered the results of the single-target level detection, which could identify more influencing factors. The land use type affected the changes in Cu, Zn, Cr, Ni, and As, and the changes in As and Zn were influenced by the annual deposition fluxes. ③ The multi-target identification method coupled with geographical detector and principal component analysis could effectively identify the influencing factors of soil heavy metal content changes, which was much more effective than the single soil heavy metal correlation method. The developed multi-target identification method for influencing factors of heavy metal content changes can provide technical support for the regional pollution monitoring and macro-management of soil heavy metals.

Visual event-related potentials reveal the early whole-word lexical processing of Chinese two-character words.

Morphologically complex words are common across different languages, especially in Chinese, because more than 90% of common modern Chinese words are complex words. Many behavioral studies have suggested the whole-word processing of Chinese complex words, but the neural correlates of whole-word processing remain unclear. Previous electrophysiological studies revealed automatic and early (∼250 ms) access to the orthographic forms of monomorphic words in the ventral occipitotemporal area. In this study, we investigated whether there is also automatic and early orthographic recognition of Chinese complex words (as whole units) by recording event-related potentials (ERPs). A total of 150 two-character words and 150 two-character pseudowords composed of the same 300 characters (morphemes) were pseudorandomly presented to proficient Chinese readers. Participants were required to determine the color of each stimulus in the color decision task and to determine whether each stimulus was a word in the lexical decision task. The two constituent characters of each stimulus were horizontally arranged in Experiment 1 and vertically arranged in Experiment 2. The results revealed a significant early ERP difference between words and pseudowords approximately 250-300 ms after stimulus onset in the parieto-occipital scalp region. The early ERP difference was more prominent in the color decision task than in the lexical decision task, more prominent in Experiment 1 than in Experiment 2, and more prominent in the left parieto-occipital scalp region than in the right. Source analysis results showed that the early ERP difference originated from the left ventral occipitotemporal cortex. These results reflected early and automatic access to whole-word orthographic representations of Chinese complex words in the left ventral occipitotemporal cortex.

Stable and Efficient Agrobacterium-Mediated Genetic Transformation of Larch Using Embryogenic Callus.

Larix olgensis or larch is an economically important coniferous tree species with rapid growth in the early stages, strong adaptability, and a short time to harvest. The genetic improvement of larch has garnered considerable attention in recent years for reclaiming timber forests. However, traditional breeding methods are largely ineffective for achieving rapid genetic improvement of L. olgensis. Studies show that the efficiency of plant regeneration can be improved by optimizing somatic embryogenesis. On this basis, we devised a stable, fast and efficient Agrobacterium-mediated genetic transformation method using suspended embryogenic calluses as explants and ß-glucuronidase as the reporter. We evaluated the effects of the Agrobacterium load, co-culture period, and addition of acetosyringone and transformant screening antibiotic on the transformation efficiency. In addition, we tested the pCAMBIA 1300-PtHCA 2-1 promoter-GUS binary expression vector, which contains the GUS gene ORF under the control of Populus trichocarpa high cambial activity PtHCA 2-1 promoter, and observed the tissue-specific expression of the GUS gene in the somatic embryos of transgenic larch. This novel technique can not only accelerate the generation of superior transgenic strains of L. olgensis but also aid in future gene functional studies.

Surface acidity effects of Al-SBA-15 mesoporous materials on adsorptive desulfurization.

SBA-15 and Aluminum-substituted SBA-15 with Si/Al molar ratio 10 (Al-SBA-15(10)) mesoporous materials were directly synthesized by a hydrolysis approach and characterized by a powder X-ray diffraction (XRD), N2 physisorption analysis and Fourier transform infrared (FTIR) etc. The relative number of hydroxyl groups was investigated by in situ FTIR systematically. The acid type and acid strength of the adsorbents were monitord by FTIR at 423 K and 673 K, respectively, utilizing pyridine as a probe. Desulfurization performances of the adsorbents were investigated via static adsorption experiment. Gas chromatography-sulfur chemiluminescence detector (GC-SCD) was employed to detect the sulfur compounds in model fuels before and after treated by the adsorbents. The calcined Al-SBA-15(10) material shows well-ordered hexagonal mesostructure and strong Lewis acid sites (L acid) and weak Brönsted acid sites (B acid). The number of hydroxy on the surface of the Al-SBA-15(10) is more than that of SBA-15, which is beneficial to further modifications such as spontaneous monolayer dispersion. Desulfurization performance of the adsorbents is affected by surface acidity of adsorbents and the constituent of model fuels (olefins, arene, etc.). The thiophene and olefins adsorbed on the B acid site of the adsorbent may occur subsequently alkylation reactions, which may block the pores of the adsorbents and thus cause the reduction of desulfurization capacity.

Analysis of epitopes in the capsid protein of avian hepatitis E virus by using monoclonal antibodies.

Avian hepatitis E virus (HEV) is related genetically and antigenically to human and swine HEVs and capsid protein of avian HEV shares approximately 48-49% amino acid sequence identities with those of human and swine HEVs. Six monoclonal antibodies (MAbs) were produced and used to locate different epitopes in the ORF2 region of aa 339-570 of avian HEV Chinese isolate. The results showed that five epitopes were located in the aa 339-414 region and one in the aa 510-515 region. Two epitopes located in aa 339-355 and aa 384-414 regions are the immunodominant epitopes on the surface of the avian HEV particles as demonstrated by immune capture of viral particles and immunohistochemical detection of the ORF2 antigens with two MAbs.