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Epoxyoctadecamonoenoic acids (EpOMEs) are produced from linoleic acid by a cytochrome P450 monooxygenase (CYP) and play a crucial role in terminating excessive and unnecessary immune responses during the late infection stage in insects. This suggests that an increase in the EpOME level may enhance the virulence of insect pathogens against pests. This study tested this hypothesis using a specific inhibitor against soluble epoxide hydrolase (sEH) to degrade EpOMEs, which leads to elevated endogenous EpOME levels. A baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), was used to infect three different lepidopteran insects (Spodoptera exigua, Maruca vitrata, and Plutella xylostella) by oral feeding or hemocoelic injection treatments. Within one hour, the viral infection induced the expression of three different phospholipase A 2 (PLA 2 ) genes and, after 12 h, up-regulated the expressions of CYP and sEH genes in Spodopera exigua. As expected, AcMNPV virulence was suppressed by the addition of arachidonic acid (a catalytic product of PLA 2 ) but was enhanced by the addition of either of the EpOME regioisomers. In addition, treatment with a specific sEH inhibitor (AUDA) increased AcMNPV virulence against three different lepidopteran insects, presumably by increasing endogenous EpOME levels. This enhanced effect of EpOMEs on virulence was further supported by specific RNA interference (RNAi), in which RNAi specific to CYP expression decreased AcMNPV virulence while a specific RNAi against sEH expression significantly enhanced virulence. In response to AcMNPV infection, TUNEL assay results showed that S. exigua larvae exhibited apoptosis in the midgut, fat body, and epidermis. Inhibition of apoptosis by a pan-caspase inhibitor, Z-VAD-FMK, significantly increased virulence. Similarly, the addition of AUDA to the viral treatment suppressed the gene expression of five inducible caspases and cytochrome C to suppress apoptosis, which led to a significant increase in the tissue viral titers. These results indicate that EpOMEs play a role in terminating excessive and unnecessary immune responses against viral infection during the late stage by down-regulating antiviral apoptosis in lepidopteran insects., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The tomato spotted wilt virus (TSWV) is a member of the Tospoviridae family and has an negative/ambisense single-stranded RNA genome. Frankliniella occidentalis and F. intonsa are known to be dominant pests in Capsicum annuum (hot pepper) and can cause damage to the plant either directly by feeding, or indirectly by transmitting TSWV in a persistent and propagative manner, resulting in serious economic damage. This study compared the immune responses of two different thrips species against TSWV infection by transcriptome analysis, which then allowed the assessment of antiviral responses using RNA interference (RNAi). Both adult thrips shared about 90 % of the transcripts in non-viruliferous conditions. Most signal components of the immune pathways were shared by these two thrips species, and their expression levels fluctuated differentially in response to TSWV infection at early immature stages. The functional assays using RNAi treatments indicated that the Toll and JAK/STAT pathways were associated with the antiviral responses, but the IMD pathway was not. The upregulation of dorsal switch protein one supported its physiological role in recognizing TSWV infection and triggering the eicosanoid biosynthetic pathway, which mediates melanization and apoptosis in thrips. In addition, the signal components of the RNAi pathways fluctuated highly after TSWV infection. Individual RNAi treatments specific to the antiviral signalling and response components led to significant increases in the TSWV amount in the thrips, causing virus-induced mortality. These findings suggest that immune signalling pathways leading to antiviral responses are operating in the thrips to regulate TSWV litres to prevent a fatal viral overload. This study also indicates the differential antiviral responses between the TSWV-transmitting F. occidentalis and F. intonsa .

Honeybees require an efficient immune system to defend against microbial pathogens. The American foulbrood pathogen, Paenibacillus larvae, is lethal to honeybees and one of the main causes of colony collapse. This study investigated the immune responses of Apis mellifera and Apis cerana honeybees against the bacterial pathogen P. larvae. Both species of honeybee larvae exhibited significant mortality even at 102 103 cfu/mL of P. larvae by diet-feeding, although A. mellifera appeared to be more tolerant to the bacterial pathogen than A. cerana. Upon bacterial infection, the two honeybee species expressed both cellular and humoral immune responses. Hemocytes of both species exhibited characteristic spreading behaviors, accompanied by cytoskeletal extension along with F-actin growth, and formed nodules. Larvae of both species also expressed an antimicrobial peptide called apolipophorin III (ApoLpIII) in response to bacterial infection. However, these immune responses were significantly suppressed by a specific inhibitor to phospholipase A2 (PLA2). Each honeybee genome encodes four PLA2 genes (PLA2A ~ PLA2D), representing four orthologous combinations between the two species. In response to P. larvae infection, both species significantly up-regulated PLA2 enzyme activities and the expression of all four PLA2 genes. To determine the roles of the four PLA2s in the immune responses, RNA interference (RNAi) was performed by injecting gene-specific double stranded RNAs (dsRNAs). All four RNAi treatments significantly suppressed the immune responses, and specific inhibition of the two secretory PLA2s (PLA2A and PLA2B) potently suppressed nodule formation and ApoLpIII expression. These results demonstrate the cellular and humoral immune responses of A. mellifera and A. cerana against P. larvae. This study suggests that eicosanoids play a crucial role in mediating common immune responses in two closely related honeybees., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Mesenchymal-epidermal transition factor gene amplification ( MET amp) is being investigated as a therapeutic target in advanced non-small cell lung cancer (NSCLC). We reviewed the epidemiology and disease characteristics associated with primary and secondary MET amp, as well as the testing procedures used to identify MET amp, in advanced NSCLC. Economic and humanistic burdens, and the practice patterns and treatments under investigation for MET amp were also examined., Methods: Embase and Medline (via ProQuest), ClinicalTrials.gov, and Cochrane Controlled Register of Trials (2015-2022) were systematically searched. Conference abstracts were searched via Embase and conference proceedings websites (2020-2022). The review focused on evidence from the United States; global evidence was included for identified evidence gaps., Results: The median rate of primary MET amp in NSCLC across the references was 4.8% (n=4 studies) and of secondary MET amp (epidermal growth factor receptor [ EGFR ]-mutant NSCLC) was 15% (n=10). Next-generation sequencing (NGS; n=12) and/or fluorescence in situ hybridization (FISH; n=11) were most frequently used in real-world studies and FISH testing most frequently used in clinical trials (n=9/10). MET amp definitions varied among clinical trials using ISH/FISH testing (MET to chromosome 7 centromere ratio of ≥1.8 to ≥3.0; or gene copy number [GCN] ≥5 to ≥10) and among trials using NGS (tissue testing: GCN ≥6; liquid biopsy: MET copy number ≥2.1 to >5). Limited to no data were identified on the economic and humanistic burdens, and real-world treatment of MET amp NSCLC. Promising preliminary results from trials enrolling patients with EGFR -mutated, MET amp advanced NSCLC progressing on an EGFR-tyrosine kinase inhibitor (TKI) were observed with MET-TKIs (i.e., tepotinib, savolitinib, and capmatinib) in combination with EGFR-TKIs (i.e., gefitinib and osimertinib). For metastatic NSCLC and high-level MET amp, monotherapy with capmatinib, crizotinib, and tepotinib are recommended in the 2022 published NSCLC NCCN Guidelines., Conclusion: Primary MET amp occurs in approximately 5% of NSCLC cases, and secondary MET amp in approximately 15% of cases previously treated with an EGFR inhibitor. Variability in testing methods (including ISH/FISH and NGS) and definitions were observed. Several treatments are promising in treating MET amp NSCLC. Additional studies evaluating the clinical, economic, and humanistic burdens are needed., Competing Interests: Authors MY, FL, and RH were employed by the company EMD Serono, Inc., Rockland, MA, USA, an affiliate of Merck KGaA, at the time of the study. Authors EM and BL were employed by the company OPEN Health at the time of this study, which was the recipient of consulting fees from EMD Serono, Inc., Rockland, MA, USA, an affiliate of Merck KGaA. Author RS received honoraria from AstraZeneca, and Amgen; attended advisory boards and provided consulting for AstraZeneca, EMD Serono, Inc., Rockland, MA, USA, an affiliate of Merck KGaA, Daiichi Sankyo, Lilly, Janssen Oncology, Macrogenics, Sanofi/Aventis, Regeneron, Mirati Therapeutics, and GlaxoSmithKline; received research funding from Merck, AstraZeneca Investigator-sponsored trials, and BMS Institution research funding., (Copyright © 2024 Yang, Mandal, Liu, O’Hara, Lesher and Sanborn.)

Background: The relation between shyness and self-esteem in women has not been fully elucidated. Shyness is a source of many problems in social interactions, although it may be positively evaluated by women as a stereotypically female trait. The aim of the study was to examine relations between shyness, self-esteem, its dimensions, and contingencies of self-worth in women. It also compared the self-esteem and contingencies of self-worth in shy and bold women., Participants and Procedure: The study was conducted in a sample of 1020 Polish women, aged 18-73. The Revised Cheek and Buss Shyness Scale, the Multidimensional Self-Esteem Inventory, and the Contingencies of Self-Worth Scale were used., Results: The results of linear multiple regression showed that predictors of shyness were dimensions of self-esteem related to likeability, personal power, lovability, body functioning, academic/professional competences, and self-worth conditioned by others' approval and God's love. Shy women had significantly lower global self-esteem in comparison to bold women. Shy women evaluated themselves lower than bold women did, in all the dimensions of self-esteem. Both shy and bold women find family support and academic/professional competencies the main contingencies of self-worth, and God's love was indicated the least., Conclusions: The results illustrated the importance of shyness for women's self-esteem, and also have implications for understanding how shy and bold women may express themselves in social life., Competing Interests: The author declares no conflict of interest., (Copyright © Institute of Psychology, University of Gdansk.)

Background: Mindfulness is a specific state of attention which involves a constant focus on what is happening at the present time in a way that is neither judgmental nor evaluative. The aim of this study was to investigate the importance of mindfulness for relationship quality and conflict resolution strategies in close relationships. Five components of mindfulness were examined: observing, describing, acting with awareness, nonjudging, and nonreactivity., Participants and Procedure: The study included 153 participants (79 women, 74 men; aged 19-60 years). 39.2% of the respondents were married, 20.9% were engaged, 39.9 were in romantic relationships. The mean duration of the close relationship was 6.25 years. The following measures were used: the Five Facet Mindfulness Questionnaire, the Patterns of Problem Solving Questionnaire, and the Dyadic Adaptation Scale., Results: Acting with awareness, dialogue and avoiding conflict escalation strategy were predictors of relationship quality. The relationship status (marriage and engagement) was also a predictor of relationship quality. Gender, age, and duration of the relationship were not predictors of relationship quality. The results showed correlation between mindfulness and relationship quality ( r = .28). There was a positive correlation between nonjudging and satisfaction in the relationship and between describing and emotional expression. Also, there was a negative correlation between nonreactivity and compatibility. Mindfulness was positively correlated with dialogue and negatively correlated with escalation of and withdrawal from a conflict., Conclusions: Mindfulness is important to the relationship's quality and conflict resolution strategies. Among the components of mindfulness, especially acting with awareness is important to relationship quality., (Copyright © Institute of Psychology, University of Gdansk.)

Objective: Describe patients born with unilateral cleft lip with or without cleft alveolus (CL±A) in relation to cleft severity and laterality, gender, associated anomalies and syndromes, number and type of lip- and nose operations, and time of alveolar bone graft (ABG) treatment in relation to dental status in cleft area., Materials and Methods: Patients included 220 children born with unilateral CL±A, born between 1988 and 1997 referred to the Oslo Cleft Lip and Palate Team. The data were collected retrospectively. All patients were followed up until 18 years of age., Results: Among all CL±A, 3.6% had recognized syndromes, 6.8% had associated anomalies, and in 89.6% CL±A was the only malformation. CL±A was more common, but not more severe, on the left side. Among the 160 individuals with CL±A without syndromes and associated anomalies, 66.9% had an isolated soft tissue CL, and 33.1% were diagnosed with a CL alveolus (CL+A). Male predominance was observed. Children with CL+A had more severe soft tissue clefts of the lip and underwent more lip and nose surgeries than children born with CL. The time of ABG was found to be at a younger age when the patient had a lateral incisor in the cleft area than when this tooth was missing., Conclusion: Findings provide a reference for morphologic variations in CL±A, and insight into the surgical burden of care until the age of 18 years.

Objectives: The objective of the study was to examine the repertoire and intensity of manipulation tactics of neurotic patients in everyday life and during therapy, as well as diagnosing the intensity of Machiavellianism in neurotic patients., Methods: There were 111 study subjects: 44 patients with diagnosed neurotic disorders, 44 people from the control group and 23 therapists. The manipulation tactics were measured by means of survey methods of E. Mandal and D. Kocur and Machiavellianism was measured using the MACH-IV scale of M. Christi and F. Geis., Results: In comparison to people from the control group, the patients were more willing to use manipulation tactics such as guilt induction, threatening to break up the relationship, and self-mutilation but less willing to use supplication/begging. The intensity of tendency to undertake manipulation was higher in everyday life than during therapy. The Machiavellianism of patients was positively correlated with the tendency to employ manipulation tactics. Differences within the scope of general Machiavellianism between the patients and the control group were not noted., Conclusions: The manipulation tactics of neurotic patients are of morbid nature. They are related to anxiety, feeling of guilt and hostility. The tendency to manipulate correlates with Machiavellianism.