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Objective: To assess the expression levels of autoimmune regulator (Aire) and inducible costimulator molecule ligand (ICOSL), as well as T follicular helper (Tfh) cell numbers in rheumatoid arthritis (RA) patients, and to explore their relationship with RA severity. We also aimed to investigate the effect of Aire on arthritis and its underlying mechanisms., Methods: The expression levels of Aire, ICOSL, and Tfh cell numbers were measured in RA patients. The relationship between these factors and the levels of anticyclic citrullinated peptide antibodies (Anti-CCP) as well as the Disease Activity Score in 28 joints (DAS28) was analyzed. To investigate the effect of Aire on arthritis, Aire-overexpressing bone marrow-derived dendritic cells (Aire-BMDCs) and recombinant ICOSL were transferred into collagen-induced arthritis (CIA) mice, the symptoms, clinical scores, anti-collagen type II antibodies (anti-CII Abs), rheumatoid factor (RF), proportions of Tfh cells, and percentages of germinal center (GC) B cells in CIA mice were examined., Results: The results showed that Aire levels were significantly decreased in CD14 + PBMCs from patients with RA, and there were negative correlations between ICOSL expression levels, Tfh cell numbers, and Aire expression. Additionally, these factors were correlated with Anti-CCP levels and DAS28. Aire-BMDCs could influence Tfh differentiation, GC B cell development, as well as the levels of anti-CII Abs and RF, which further alleviate the symptoms and reduce clinical scores partly through ICOSL in CIA mice., Conclusions: The findings suggest that Aire may alleviate rheumatoid arthritis by inhibiting ICOSL, which further inhibits Tfh cell differentiation and autoantibody production., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This work was supported by the following grants: 20230505039ZP from Department of Science and Technology Project, 82471756 from National Natural Science Foundation of China, JJKH20221090KJ from Science and Technology Research Project of Education Department of Jilin Province and 81671548 from National Natural Science Foundation of China., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The diet breadth of generalist herbivores when compared to specialists tends to be associated with greater transcriptional plasticity. Here, we consider whether it may also contribute to variation in host range among two generalists with different levels of polyphagy. We examined two related polyphagous spider mites with different host ranges, Tetranychus urticae (1200 plants) and Tetranychus truncatus (90 plants). Data from multiple populations of both species domesticated on common beans and transferred to new plant hosts (cotton, cucumber, eggplant) were used to investigate transcriptional plasticity relative to population-based variation in gene expression. Compared to T. truncatus, T. urticae exhibited much higher transcriptional plasticity. Populations of this species also showed much more variable expression regulation in response to a plant host, particularly for genes related to detoxification, transport, and transcriptional factors. In response to the different plant hosts, both polyphagous species showed enriched processes of drug/xenobiotics metabolism, with T. urticae orchestrating a relatively broader array of biological pathways. Through co-expression network analysis, we identified gene modules associated with host plant response, revealing shared hub genes primarily involved in detoxification metabolism when both mites fed on the same plants. After silencing a shared hub CYP gene related to eggplant exposure, the performance of both species on the original bean host improved, but the fecundity of T. truncatus decreased when feeding on eggplant. The extensive transcriptomic variation shown by T. urticae might serve as a potential compensatory mechanism for a deficiency of hub genes in this species. This research points to nuanced differences in transcriptomic variability between generalist herbivores., (© 2024 John Wiley & Sons Ltd.)

Despite the rapid advances in sequencing technology, limited genomic resources are currently available for phytophagous spider mites, which include many important agricultural pests. One of these pests is Tetranychus piercei (McGregor), a serious banana pest in East Asia exhibiting remarkable tolerance to high temperature. In this study, we assembled a high-quality genome of T. piercei using a combination of PacBio long reads and Illumina short reads sequencing. With the assistance of chromatin conformation capture technology, 99.9% of the contigs were anchored into three pseudochromosomes with a total size of 86.02 Mb. Repetitive elements, accounting for 14.16% of this genome (12.20 Mb), are predominantly composed of long-terminal repeats (30.7%). By combining evidence of ab initio prediction, transcripts, and homologous proteins, we annotated 11,881 protein-coding genes. Both the genome and proteins have high BUSCO completeness scores (>94%). This high-quality genome, along with reliable annotation, provides a valuable resource for investigating the high-temperature tolerance of this species and exploring the genomic basis that underlies the host range evolution of spider mites., (© 2024. The Author(s).)

Objectives: To elucidate the impact of [ 18 F]FDG positron emission tomography/computed tomography (PET/CT) vs. CT workup on staging and prognostic evaluation of clinical stage (c) I-II NSCLC., Methods: We retrospectively identified 659 cI-II NSCLC who underwent CT (267 patients) or preoperative CT followed by PET/CT (392 patients), followed by curative-intended complete resection in our hospital from January 2008 to December 2013. Differences were assessed between preoperative and postoperative stage. Five-year disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier approach and compared with log-rank test. Impact of preoperative PET/CT on survival was assessed by Cox regression analysis., Results: The study included 659 patients [mean age, 59.5 years ± 10.8 (standard deviation); 379 men]. The PET/CT group was superior over CT group in DFS [12.6 vs. 6.9 years, HR 0.67 (95% CI 0.53-0.84), p < 0.001] and OS [13.9 vs. 10.5 years, HR 0.64 (95% CI 0.50-0.81), p < 0.001]. In CT group, more patients thought to have cN0 migrated to pN1/2 disease as compared with PET/CT group [26.4% (66/250) vs. 19.2% (67/349), p < 0.001], resulting in more stage cI cases being upstaged to pII-IV [24.7% (49/198) vs. 16.1% (47/292), p = 0.02], yet this was not found in cII NSCLC [27.5% (19/69) vs. 27.0% (27/100), p = 0.94]. Cox regression analysis identified preoperative PET/CT as an independent prognostic factor of OS and DFS (p = 0.002, HR = 0.69, 95% CI 0.54-0.88; p = 0.004, HR = 0.72, 95% CI 0.58-0.90)., Conclusion: Addition of preoperative [ 18 F]FDG PET/CT was associated with superior DFS and OS in resectable cI-II NSCLC, which may result from accurate staging and stage-appropriate therapy., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Objectives: To investigate the association between auditory processing and problem behaviors in preschool children, as well as the mediating role of executive function., Methods: A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing, China from June to August 2021. They were evaluated using Preschool Auditory Processing Assessment Scale, Conners Parent Symptom Questionnaire, and Behavior Rating Inventory of Executive Functioning-Preschool version. Children with different demographic features were compared in the scores and the abnormality rates of auditory processing, problem behaviors, and executive function. The influencing factors of the total scores of auditory processing, problem behaviors, and executive function were evaluated using multiple linear regression analysis. Whether executive function was a mediating factor between auditory processing and executive function was examined., Results: Sex and grade were the main influencing factors for the total score of auditory processing ( P <0.05), and sex, grade, parental education level, and family economic status were the main influencing factors for the total scores of problem behaviors and executive function ( P <0.05). The auditory processing score ( r s =0.458, P <0.05) and problem behavior score ( r s =0.185, P <0.05) were significantly positively correlated with the executive function score, and the auditory processing score was significantly positively correlated with the problem behavior score ( r s =0.423, P <0.05). Executive function played a partial mediating role between auditory processing and problem behaviors, and the mediating effect accounted for 33.44% of the total effect., Conclusions: Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function.

L-type lectins (LTLs) contain a carbohydrate recognition domain homologous to leguminous lectins, and have functions in selective protein trafficking, sorting and targeting in the secretory pathway of animals. In this study, a novel LTL, designated as ToERGIC-53, was cloned and identified from obscure puffer Takifugu obscurus. The open reading frame of ToERGIC-53 contained 1554 nucleotides encoding 517 amino acid residues. The deduced ToERGIC-53 protein consisted of a signal peptide, a leguminous lectin domain (LTLD), a coiled-coil region, and a transmembrane region. Quantitative real-time PCR showed that ToERGIC-53 was expressed in all examined tissues, with the highest expression level in the liver. The expression of ToERGIC-53 was significantly upregulated after infection with Vibrio harveyi and Staphylococcus aureus. Recombinant ToERGIC-53-LTLD (rToERGIC-53-LTLD) protein could not only agglutinate and bind to one Gram-positive bacterium (S. aureus) and three Gram-negative bacteria (V. harveyi, V. parahaemolyticus and Aeromonas hydrophila), but also bind to glycoconjugates on the surface of bacteria such as lipopolysaccharide, peptidoglycan, mannose and galactose. In addition, rToERGIC-53-LTLD inhibited the growth of bacteria in vitro. All these results suggested that ToERGIC-53 might be a pattern recognition receptor involved in antibacterial immune response of T. obscurus., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

L-type lectins (LTLs) have leguminous lectin domains that bind to high-mannose-type oligosaccharides. LTLs are involved in glycoprotein secretory pathways and associated with many immune responses. In the present research, three LTL homologs from obscure puffer Takifugu obscurus, designated as ToVIP36-1, ToVIP36-2, and ToVIP36-3, were first cloned and identified. The open reading frames of ToVIP36-1, ToVIP36-2, and ToVIP36-3 were 1068, 1002, and 1086 bp in length, respectively, and encode polypeptides with 355, 333, and 361 amino acids, respectively. Key conserved residues and functional domains, including lectin&#95;leg-like domain (LTLD), transmembrane region, and C-terminal trafficking signal KRFY, were identified in all ToVIP36s. Quantitative real-time PCR analysis showed that the three ToVIP36s were widely expressed in six examined tissues and had relatively high expression levels in the liver and intestine. The expression levels of ToVIP36s were remarkably altered in the liver and kidney after induction by Vibrio harveyi and Staphylococcus aureus. Subsequently, the recombinant LTLDs of ToVIP36s (rToVIP36-LTLDs) were prepared by prokaryotic expression. Three rToVIP36-LTLD proteins agglutinated with S. aureus, V. harveyi, Vibrio parahaemolyticus, and Aeromonas hydrophila in a calcium-dependent manner. In the absence of calcium, rToVIP36-LTLD proteins bound to the bacteria by binding to lipopolysaccharides, peptidoglycans, d-mannose, and d-galactose and inhibited the growth of S. aureus and V. harveyi. Our results indicated that ToVIP36s function as pattern-recognition receptors in T. obscurus immunity, providing insights into the role of LTLs in the antibacterial immunity of fishes., Competing Interests: Declaration of competing interest No potential conflicts of interest were disclosed., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The phytophagous mite Tetranychus truncatus is a serious pest in East Asia but has a relatively narrower host range than the pest mite Tetranychus urticae, which can feed on over 1200 plant species. Here, we generated a high-quality chromosomal level genome of T. truncatus and compared it with that of T. urticae, with an emphasis on the genes related to detoxification and chemoreception, to explore the genomic basis underlying the evolution of host range. We also conducted population genetics analyses (in 86 females from 10 populations) and host transfer experiments (in 4 populations) to investigate transcription changes following transfer to a low-quality host (Solanum melongena, eggplant), and we established possible connections between fitness on eggplant and genes related to detoxification and chemoreception. We found that T. truncatus has fewer genes related to detoxification, transport, and chemoreception than T. urticae, with a particularly strong reduction in gustatory receptor (GR) genes. We also found widespread transcriptional variation among T. truncatus populations, which varied in fitness on eggplant. We characterized selection on detoxification-related genes through ω values and found a negative correlation between expression levels and ω values. Based on the transcription results, as well as the fitness and genetic differences among populations, we identified genes potentially involved in adaptation to eggplant in T. truncatus. Our work provides a genomic resource for this pest mite and new insights into mechanisms underlying the adaptation of herbivorous mites to host plants., (© 2023 Institute of Zoology, Chinese Academy of Sciences.)

Objectives: To investigate the characteristics of auditory processing (AP) in preschool children with attention deficit hyperactivity disorder (ADHD) using Preschool Auditory Processing Assessment Scale (hereafter referred to as "auditory processing scale")., Methods: A total of 41 children with ADHD and 41 typically developing (TD) children were assessed using the auditory processing scale, SNAP-IV rating scale, and Conners' Kiddie Continuous Performance Test (K-CPT). The auditory processing scale score was compared between the TD and ADHD groups. The correlations of the score with SNAP-IV and K-CPT scores were assessed., Results: Compared with the TD group, the ADHD group had significantly higher total score of the auditory processing scale and scores of all dimensions except visual attention ( P <0.05). In the children with ADHD, the attention deficit dimension score of the SNAP-IV rating scale was positively correlated with the total score of the auditory processing scale ( r s30 =0.531, P <0.05; r s27 =0.627, P <0.05) as well as the scores of its subdimensions, including auditory decoding ( r s =0.628, P <0.05), auditory attention ( r s =0.492, P <0.05), and communication ( r s =0.399, P <0.05). The hyperactivity-impulsivity dimension score of the SNAP-IV rating scale was positively correlated with the hyperactivity-impulsivity dimension score of the auditory processing scale ( r s =0.429, P <0.05). In the children with ADHD, the attention deficit dimension score of the K-CPT was positively correlated with the total score ( r s30 =0.574, P <0.05; r s27 =0.485, P <0.05) and the hyperactivity-impulsivity dimension score ( r s =0.602, P <0.05) of the auditory processing scale., Conclusions: Preschool children with ADHD have the risk of AP abnormalities, and the auditory processing scale should be used early for the screening and evaluation of AP abnormalities in children.

Spider mites belonging to the genus Tetranychus infest many important agricultural crops in both fields and greenhouses worldwide and are diversified in their host plant range. How spider mites perceive their suitable host plants remains not completely clear. Here, through two-host-choice designs (bean vs. tomato, and bean vs. eggplant), we tested the efficacies of the olfactory and gustatory systems of five spider mite species ( T. urticae , T. truncatus , T. pueraricola , T. piercei , and T. evansi ), which differ in host plant range in sensing their suitable host plant, by Y-tube olfactometer and two-choice disc experiments. We found that spider mites cannot locate their suitable host plants by volatile odours from a long distance, but they can use olfactory sensation in combination with gustatory sensation to select suitable host plants at a short distance. Highly polyphagous species displayed strong sensitivity in sensing suitable host plants rather than the lowered sensitivity we expected. Intriguingly, our principal component analyses (PCAs) showed that the similarity among five spider mite species in the performance of perceiving suitable host plants was highly correlated with their relative phylogenetic relationships, suggesting a close relationship between the chemosensing system and the speciation of spider mites. Our results highlight the necessity of further work on the chemosensing system in relation to host plant range and speciation of spider mites.

Cabozantinib (XL184) is a small molecule tyrosine kinase receptor inhibitor, which targets c-Met and VEGFR2. Cabozantinib has been approved by the Food and Drug Administration to treat advanced medullary thyroid cancer and renal cell carcinoma. In the present study, we evaluated the ability of cabozantinib to modulate the function of the ATP-binding cassette subfamily G member 2 (ABCG2) by sensitizing cells that are resistant to ABCG2 substrate antineoplastic drugs. We used a drug-selected resistant cell line H460/MX20 and three ABCG2 stable transfected cell lines ABCG2-482-R2, ABCG2-482-G2, and ABCG2-482-T7, which overexpress ABCG2. Cabozantinib, at non-toxic concentrations (3 or 5μM), sensitized the ABCG2-overexpressing cells to mitoxantrone, SN-38, and topotecan. Our results indicate that cabozantinib reverses ABCG2-mediated multidrug resistance by antagonizing the drug efflux function of the ABCG2 transporter instead of downregulating its expression. The molecular docking analysis indicates that cabozantinib binds to the drug-binding site of the ABCG2 transporter. Overall, our findings demonstrate that cabozantinib inhibits the ABCG2 transporter function and consequently enhances the effect of the antineoplastic agents that are substrates of ABCG2. Cabozantinib may be a useful agent in anticancer treatment regimens for patients who are resistant to ABCG2 substrate drugs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)