IL4I1: a novel molecular biomarker represents an inflamed tumor microenvironment and precisely predicts the molecular subtype and immunotherapy response of bladder cancer.

Introduction: IL4I1, also known as Interleukin-4-induced gene 1, is an enzyme that can modulate the immune system by acting as a L-amino acid oxidase. Nevertheless, a precise understanding of the correlation of IL4I1 with immunological features and immunotherapy efficacy in bladder cancer (BLCA) remains incomplete. Methods: We analyzed RNA sequencing data from the Cancer Genome Atlas (TCGA) to investigate the immune function and prognostic importance of IL4I1 across different cancer types. We further examined the TCGA-BLCA cohort for correlations between IL4I1 and various immunological characteristics of tumor microenvironment (TME), such as cancer immune cycle, immune cell infiltration, immune checkpoint expression and T cell inflamed score. Validation was conducted using two independent cohort, GSE48075 and E-MTAB-4321. Finally, RNA sequencing data from the IMvigor210 cohort and immunohistochemistry assays were employed to validate the predictive value of IL4I1 for the TME and immunotherapy efficacy. Results: In our findings, a positive correlation was observed between IL4I1 expression and immunomodulators expression, immune cell infiltration, the cancer immune cycle, and T cell inflamed score in BLCA, suggesting a significant link to the inflamed TME. In addition, studies have shown that IL4I1 elevated levels of individuals tend to be more performance for basal subtype and exhibit enhanced response rates to diverse treatment modalities, specifically immunotherapy. Clinical data from the IMvigor 210 cohort confirmed a higher rate of response to immunotherapy and better survival benefits in patients with high IL4I1 expression. Discussion: To summarize, our research showed that elevated IL4I1 levels are indicative of an inflamed TME, the basal subtype, and a more favorable response to various treatment methods, especially immune checkpoint blockade therapy in BLCA.

Discovery and biological characterization of a novel mesoionic insecticide fenmezoditiaz.

BACKGROUND: Many piercing-sucking insects have developed resistance or cross-resistance to many insecticides targeting insect neural nicotinic acetylcholine receptor (nAChR). Here we are aiming to present the discovery of a novel mesoionic insecticide, fenmezoditiaz, by BASF through structure-based drug design (SBDD) approaches. It has recently been added to the Insecticide Resistance Action Committee mode of classification (IRAC 4E). It is being developed for plant protection against piercing-sucking pests, especially rice hopper complex. RESULTS: The soluble acetylcholine binding protein (AChBP) from the sea slug Aplysia californica was modified using site-directed mutagenesis and based on putative aphid nAChR subunit sequences to create soluble insect-like AChBPs. Among them, insect-like ß1 AChBP and native aphid membrane preparation showed the highest correlated biochemical affinity toward structurally diverse ligands. This mutant AChBP was used to understand how insect nAChRs structurally interact with mesoionics, which was then utilized to design novel mesoionics including fenmezoditiaz. It is an excellent systemic insecticide with diverse application methods and has a broad insecticidal spectrum, especially against piercing/sucking insects. It lacks cross-resistance for neonicotinoid resistant plant hoppers. Field-collected brown plant hopper populations from Asian countries showed high susceptibility. CONCLUSIONS: Fenmezoditiaz is a systemic insecticide with a broad spectrum, lack of cross-resistance and it could be an additional tool for integrated pest management and insecticide resistance management, especially for the rice hopper complex. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Novel Design of Eco-Friendly Super Elastomer Materials With Optimized Hard Segments Micro-Structure: Toward Next-Generation High-Performance Tires.

Recently, sustainable development has become a significant concern globally, and the energy crisis is one of the top priorities. From the perspective of the industrial application of polymeric materials, rubber tires are critically important in our daily lives. However, the energy consumption of tires can reach 6% of the world's total energy consumption per annum. Meanwhile, it is calculated that around 5% of carbon dioxide comes from the emission of tire rolling due to energy consumption. To overcome these severe energy and environmental challenges, designing and developing a high-performance fuel-saving tire is of paramount significance. Herein, a next-generation, eco-friendly super elastomer material based on macromolecular assembly technology has been fabricated. Hydroxyl-terminated solution-polymerized styrene-butadiene rubber (HTSSBR) with high vinyl contents prepared by anionic polymerization is used as flexible soft segments to obtain excellent wet skid resistance. Furthermore, highly symmetrical 1,5-naphthalene diisocyanate (NDI), different proportions of chain extender, and the cross-linking agent with moderate molecular length are selected as rigid hard segments to achieve simultaneous high heat resistance. Through this approach, a homogeneous network supported by uniformly distributed hard segment nanoparticles is formed because soft segments with equal length are chemically end-linked by the hard segments. This super elastomer material exhibits excellent wear resistance and low rolling resistance. More importantly, the wear resistance, rolling resistance, and wet-skid resistance are reduced by 85.4, 42.3, and 20.8%, respectively, compared to the elastomeric material conventionally used for tire. By taking advantage of this excellent comprehensive service performance, the long-standing challenge of the "magic triangle" plaguing the rubber tire industry for almost 100 years is resolved. It is anticipated that this newly designed and fabricated elastomeric material tailored for tires will become the next generation product, which could exhibit high potential for significantly cutting the fuel consumption and reducing the emission of carbon dioxide.

Toxicity of seven termiticides on the formosan and eastern subterranean termites.

Using both topical application and substrate (sand) treatments the toxicities of seven new generation soil termiticides were evaluated to determine the LD50 and LC50 against two economically important subterranean termite species, eastern subterranean termite, Reticulitermes flavipes (Kollar), and Formosan subterranean termite, Coptotermes formosanus Shiraki. The lethal dose toxicity (LD50) rankings for R. flavipes from highest to lowest were: fipronil > bifenthrin > chlorantraniliprole > cyantraniliprole > imidacloprid > chlorfenapyr > indoxacarb; the rankings for C. formosanus were fipronil > imidacloprid > chlorantraniliprole > cyanthraniliprole> bifenthrin > chlorfenapyr > indoxacarb. The respective lethal concentration toxicity (LC50) rankings were fipronil > bifenthrin > chlorfenapyr > indoxacarb > cyantraniliprole > chlorantraniliprole > imidacloprid for R. flavipes; and fipronil > chlorfenapyr > bifenthrin >imidacloprid > cyantraniliprole > chlorantraniliprole > indoxacarb for C. formosanus. The study provides an opportunity to directly compare toxicity, action speed, and bioavailability among this group of newer generation soil termiticides.

Group size effect on worker juvenile hormone titers and soldier differentiation in Formosan subterranean termite.

In a finite environment, population growth can lead to crowding, increased densities and stress. Termites live in highly organized societies and densities can increase astronomically as colonies grow. However, little is known about juvenile hormone (JH) changes in these insects as numbers increase, despite the fact that JH is a critical caste regulator in this insect. Using Formosan subterranean termites as a model, we evaluated minimum group size requirements for soldier differentiation and the effect of density (50, 100, 500, and 1000 individuals/experimental unit) on worker JH titers either with or without initial soldiers being present. The minimum group size investigation indicated that groups initiated with 5 workers were insufficient for soldier differentiation. Soldiers were produced in groups initiated with 10 or more workers. As density increased from 50 to 1000 individuals per experimental unit, worker JH levels were elevated. Presence of soldiers lessened the effect of density on rising worker JH titers, indicating that soldiers have the ability to down-regulate worker JH. The study provides direct evidence of a population density effect on JH in eusocial insects and sheds light on understanding of the regulatory mechanisms associated with termite soldier caste differentiation.

Liquid chromatography-electrospray ionization-mass spectrometric quantitation of juvenile hormone III in whole body extracts of the Formosan subterranean termite.

Juvenile hormone (JH) III is responsible for control of a variety of insect physiological and developmental states, including caste differentiation of the Formosan subterranean termite (Coptotermes formosanus Shiraki). We report here a simplified, efficient sample preparation and an optimized LC-ESI-MS method for quantifying JH III in whole body extracts. Sample preparation comprises hexane extraction (from termite whole bodies) and C18 cartridge purification. Previous LC-ESI-MS protocols exhibited the following two problems: (1) ion fragmentation differed when comparing spectra from insect samples and authentic JH III and (2) a JH III monitoring ion was not resolved from other unknown compounds in whole body samples from termites. To overcome these problems, we used a pentafluorophenyl LC column and water/acetonitrile containing ammonium acetate as solvent. In a mass chromatogram (m/z 235) of termite samples, a peak was detected at the retention time of authentic JH III, and MS(2) of this peak confirmed that the ion is a fragment of JH III, [M-CH(3)OH+H](+), being the base peak in both termites and authentic JH III samples. The protocol enables quantification of JH III in a single termite with signal/noise >10:1 and the limit of quantification is 21pg.

Application of ground penetrating radar in detecting the hazards and risks of termites and ants in soil levees.

A ground penetrating radar (GPR) technique was used to detect Formosan subterranean termite (Coptotermes formosanus) and red imported fire ant (Solenopsis invicta) hazards and risks (targets) in a soil levee at the London Avenue Canal in New Orleans, LA. To make this assessment, GPR signal scans were examined for features produced by termite or ant activities and potential sources of food and shelter such as nests, tree roots, and voids (tunnels). The total scanned length of the soil levee was 4,125 m. The average velocity and effective depth of the radar penetration was 0.080 m/ns and 0.61 m, respectively. Four hundred twenty-seven targets were identified. Tree roots (38), voids (31), fire ant nests (209), and metal objects (149) were detected, but no Formosan termite carton nests were identified. The lack of identified termite nests may be related to drowning events at the time to the flood. Based on the target density (TD), the two new floodwall and levee sections that were rebuilt or reinforced after they were destroyed by Hurricane Katrina in 2005 were determined to be at low potential risk from termites and ants. A merging target density (MTD) method indicated a high potential risk near one of the breached sections still remains. Foraging and nesting activity of Formosan subterranean termites and red imported fire ants may be a contributory factor to the levee failure at the London Avenue Canal.

Antifeedant activity and acute and residual toxicity of alkaloids from Sophora flavescens (leguminosae) against formosan subterranean termites (Isoptera: Rhinotermitidae).

Ku Shen, Sophora flavescens Aiton (Leguminosae), contains alkaloids that possess broad biological activities. This study showed that total matrines (a mixture of the alkaloids), and matrine and oxymatrine (two major alkaloids) had a strong antifeedant effect against Formosan subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae), at all tested concentrations (ranging from 0.01 to 5%). Total matrines and matrine also had significantly toxic effects at 5%. The estimated LD50 of total matrines and matrine was 12.3 and 8.6 microg per insect, respectively, after 24 h; 13.3 and 7.1 microg per insect after 48 h; and 10.1 and 4.8 microg per insect after 1 wk. The antifeedant and toxic properties of total matrines- and matrine-treated wood remained effective at least 12 mo after treatment under both light and dark storage conditions. These chemicals have great potential for commercial development as wood treatment agents.