Micro- and nanoplastics (MNPs) have become ubiquitous contaminants of water and foods, resulting in high levels of human ingestion exposure. MNPs have been found in human blood and multiple tissues, suggesting that they are readily absorbed by the gastrointestinal tract (GIT) and widely distributed. Growing toxicological evidence suggests that ingested MNPs may pose a serious health threat. The potential genotoxicity of MNPs, however, remains largely unknown. In this study, genotoxicity of primary and environmentally relevant secondary MNPs was assessed in a triculture small intestinal epithelium (SIE) model using the CometChip assay. Aqueous suspensions of 25 and 1000 nm carboxylated polystyrene spheres (PS25C and PS1KC), and incinerated polyethylene (PEI PM_0.1) were subjected to simulated GIT digestion to create physiologically relevant exposures (digestas), which were applied to the SIE model at final MNP concentrations of 1, 5, and 20 μg/mL for 24 or 48 h. PS25C and PS1KC induced DNA damage in a time- and concentration-dependent manner. To our knowledge, this is one of the first assessment of MNP genotoxicity in an integrated in vitro ingestion platform including simulated GIT digestion and a triculture SIE model. These findings suggest that ingestion of high concentrations of carboxylated PS MNPs could have serious genotoxic consequences in the SIE. Full article

Heavy metal poisoning has a life-threatening impact on the human body to aquatic ecosystems. This necessitates designing a convenient green methodology for the fabrication of an electrochemical sensor that can detect heavy metal ions efficiently. In this study, boron (B) and nitrogen (N) co-doped laser-induced porous graphene (LIG_BN) nanostructured electrodes were fabricated using a direct laser writing technique. The fabricated electrodes were utilised for the individual and simultaneous electrochemical detection of lead (Pb²⁺) and cadmium (Cd²⁺) ions using a square wave voltammetry technique (SWV). The synergistic effect of B and N co-doping results in an improved sensing performance of the electrode with better sensitivity of 0.725 µA/µM for Pb²⁺ and 0.661 µA/µM for Cd²⁺ ions, respectively. Moreover, the sensing electrode shows a low limit of detection of 0.21 µM and 0.25 µM for Pb²⁺ and Cd²⁺ ions, with wide linear ranges from 8.0 to 80 µM for Pb²⁺ and Cd²⁺ ions and high linearity of R² = 0.99 in case of simultaneous detection. This rapid and facile method of fabricating heteroatom-doped porous graphene opens a new avenue in electrochemical sensing studies to detect various hazardous metal ions. Full article

Graphene has achieved mass production via various preparative routes and demonstrated its uniqueness in many application fields for its intrinsically high electron mobility and thermal conductivity. However, graphene faces limitations in assembling macroscopic structures because of its hydrophobic property. Therefore, balancing high crystal quality and good aqueous dispersibility is of great importance in practical applications. Herein, we propose a tape-wrapping strategy to electrochemically fabricate water-dispersible graphene (w-Gr) with both excellent dispersibility (~4.5 mg/mL, stable over 2 months), and well-preserved crystalline structure. A large production rate (4.5 mg/min, six times faster than previous electrochemical methods), high yield (65.4% ≤5 atomic layers) and good processability are demonstrated. A mechanism investigation indicates that the rational design of anode configuration to ensure proper oxidation, deep exfoliation and unobstructed mass transfer is responsible for the high efficiency of this strategy. This simple yet efficient electrochemical method is expected to promote the scalable preparation and applications of graphene. Full article

This study investigates the effects of the gulf stream (GS) on sea-level oscillations across various time scales and assesses the performance of a coastal and estuarine model nested within a global model in simulating these variations. It aims to improve boundary conditions to simulate sea-level oscillations more accurately by considering the influence of GS flow. An inverse correlation is observed between observed sea-level oscillation and GS flow, which becomes more pronounced over longer time scales. Using Delft3D, a high-resolution coastal and estuarine model is developed to simulate circulation dynamics in the central Indian River Lagoon (IRL), FL, and adjacent coastal areas on the Florida east coast. The model is nested into the HYCOM (Hybrid Coordinate Ocean Model), and meteorological forcings are derived from the NARR (North American Regional Reanalysis) model. The model demonstrates satisfactory performance across key parameters, including tide, salinity, water temperature, and currents. However, there remains a noticeable difference between the modeled and observed data. To address this, the model is executed with modified flow boundary conditions at eastern boundary nodes, integrating HYCOM tide, and observing low-frequency sea-level variations. The implementation of the new boundary conditions results in an improved simulation of sea-level oscillations. This study presents the conceptual framework and detailed methodologies employed in the creation of a high-resolution model tailored for estuarine and coastal areas nested into global models capable of satisfactorily simulating sea-level oscillations even when the global model does not represent GS effects. Full article

Theoretically rooted in public service logic (PSL), this article explores managers’ experiences constructing value propositions and facilitating the value creation process in a public sector environment. It reports on a qualitative study from a Norwegian municipal setting based on individual and focus group interviews supported by participant observations and relevant documents. The data were analyzed according to the guidelines of stepwise-deductive inductive analysis (SDI). The findings substantiate changes in the utilized supported housing forms and highlight urgency’s pervasive effect on transition processes to supported housing for individuals with intellectual disabilities and the need for around-the-clock support. This study contributes to public management research by examining the process of constructing value propositions and the managers’ efforts to contribute to the formation of more realistic expectations towards the municipality’s scope and level of service among prospective service users and their families. The article contributes to the PSL discourse by providing the complementary concept of expectation–reality mitigation as a particular form of expectation management suited for the complexities and constraints of value creation in public service settings. Full article

Microplastics as micropollutants are widely spread in aquatic areas that can have a toxic effect on aquatic life. To reduce the potential risk they pose, it is essential to detect the microplastics and the source of the contamination of the environment. Here, we designed and developed a droplet-based microfluidic impedance flow cytometer for in situ detection of microplastics in water. Impedance spectroscopy enables the direct measurement of the electrical features of microplastics as they move in water, allowing for sizing and identification of concentration. To show the feasibility of the developed method, pure and functionalized polystyrene beads ranging from 500 nm to 6 μm in four size groups and different concentrations were used. Focusing on three different frequencies (4.4 MHz, 11 MHz, and 22.5 MHz), the changes in the signal phase at frequencies of 4.4 MHz and 11 MHz are a strong indicator of microplastic presence. In addition, the functionalized microplastics showed different magnitudes of the measured signal phase than the pure ones. A k-nearest neighbors classification model demonstrated our developed system’s impressive 97.4% sensitivity in accurately identifying microplastics based on concentration. The equivalent circuit model revealed that the double-layer capacity of water droplets is significantly impacted by the presence of the microplastics. Our findings show the potential of droplet-based microfluidic impedance flow cytometry as a practical method for detecting microplastics in water. Full article

In cyanobacteria and chloroplasts (in algae and plants), ATP synthase plays a pivotal role as a photosynthetic membrane complex responsible for producing ATP from adenosine diphosphate and inorganic phosphate, utilizing a proton motive force gradient induced by photosynthesis. These two ATP synthases exhibit similarities in gene organization, amino acid sequences of subunits, structure, and functional mechanisms, suggesting that cyanobacterial ATP synthase is probably the evolutionary precursor to chloroplast ATP synthase. In this review, we explore the precise synthesis and assembly of ATP synthase subunits to address the uneven stoichiometry within the complex during transcription, translation, and assembly processes. We also compare the regulatory strategies governing ATP synthase activity to meet varying energy demands in cyanobacteria and chloroplasts amid fluctuating natural environments. Furthermore, we delve into the role of ATP synthase in stress tolerance and photosynthetic carbon fixation efficiency in oxygenic photosynthetic organisms (OPsOs), along with the current researches on modifying ATP synthase to enhance carbon fixation efficiency under stress conditions. This review aims to offer theoretical insights and serve as a reference for understanding the functional mechanisms of ATP synthase, sparking innovative ideas for enhancing photosynthetic carbon fixation efficiency by utilizing ATP synthase as an effective module in OPsOs. Full article

MYB transcription factors (TFs) have been shown to be important regulators of plant growth and development, and the R2R3−MYB family plays an important role in the regulation of plant primary and secondary metabolism, growth, and development. In this study, the PmMYB45 gene sequence was successfully cloned from Pinus massoniana, with an open reading frame of 1476 bp, encoding 491 amino acids. The results of subcellular localization and transcriptional self-activation showed that the gene was localized in the nucleus and was self-activating. qPCR showed that the highest expression of PmMYB45 was found in stems. PmMYB45 can promote lignin synthesis when overexpressed in tobacco. These results suggest that PmMYB45 promotes lignin synthesis by regulating the lignin biosynthesis pathway. These findings improve our understanding of the mechanism of lignin biosynthesis in P. massoniana and provide a basis for molecular breeding functions. It also provides insights into the role of the MYB transcription factor family in lignin accumulation. Full article

This study explores the influence of host–guest interaction on tourists’ pro-environment behavior. On the one hand, the experience attribute of host–guest interaction’s influence on tourists’ experiential value is sorted out. On the other hand, the relationship attribute of host–guest interaction’s activation effect on tourists’ personal norms is identified. Based on social exchange theory and normative activation theory, a structural equation model was established to depict the transmission mechanism from host–guest interaction to tourists’ pro-environment behavior. The data were collected from tourists in Taishan National Forest Park (n = 499). The results indicated that host–guest interaction quality activated tourists’ personal norms through consequence awareness, thus promoting tourists’ pro-environment behavior. Meanwhile, the quality of host–guest interaction positively influenced tourists’ pro-environment behavior through emotional experience value. Host–guest interaction quantity promoted tourists’ pro-environment behavior by activating personal norms through responsibility ascription. In addition, although frequent host–guest interactions can enhance the social experience and functional experience value of tourists, the latter two cannot stimulate tourists’ pro-environmental behavior. This study provides practical implications for promoting the sustainable development of national forest parks. Full article

Background: The current manuscript’s aim was to determine the human papillomavirus (HPV) genotype-specific prevalence and distribution among individuals, males, and females, of different ages in the region of Apulia, Italy, highlighting the possible variables involved in the carcinogenicity mechanism. In addition, we proposed two hypothetical models of HPV’s molecular dynamics, intending to clarify the impact of prevention and therapeutic strategies, explicitly modeled by recent survey data. Methods: We presented clinical data from 9647 participants tested for either high-risk (HR) or low-risk (LR) HPV at the affiliated Bari Policlinic University Hospital of Bari from 2011 to 2022. HPV DNA detection was performed using nested-polymerase chain reaction (PCR) and multiplex real-time PCR assay. Statistical analysis showed significant associations for all genders and ages and both HR- and LR-HPV types. A major number of significant pairwise associations were detected for the higher-risk types and females and lower-risk types and males. Results: The overall prevalence of HPV was 50.5% (n-4.869) vs. 49.5% (n-4.778) of the study population, of which 74.4% (n-3621) were found to be HPV high-risk (HR-HPV) genotypes and 57.7% (n-2.807) low-risk HPV (LR-HPV) genotypes, of which males were 58% and females 49%; the three most prevalent HR-HPV genotypes were HPV 53 (n707-15%), 16 (n704-14%), and 31 (n589-12%), and for LR-HPV, they were 42 (19%), 6 (16%), and 54 (13%); 56% of patients screened for HPV were ≤ 30 years old, 53% were between 31 and 40 years old, 46% were 41–50 and 51–60 years old, and finally, 44% of subjects were >60 years old. Conclusions: Our study provided comprehensive epidemiological data on HPV prevalence and genotype distribution among 9647 participants, which could serve as a significant reference for clinical practice, and it implied the necessity for more effective screening methods for HPV carcinogenesis covering the use of more specific molecular investigations. Although this is a predominantly descriptive and epidemiological study, the data obtained offer not only a fairly unique trend compared to other studies of different realities and latitudes but also lead us to focus on the HPV infection within two groups of young people and adults and hypothesize the possible involvement of dysbiosis, stem cells, and the retrotransposition mechanism. Full article

Influenza viruses cause highly contagious respiratory diseases that cause millions of deaths worldwide. Rapid detection of influenza viruses is essential for accurate diagnosis and the initiation of appropriate treatment. We developed a loop-mediated isothermal amplification and lateral flow assay (LAMP-LFA) capable of simultaneously detecting influenza A and influenza B. Primer sets for influenza A and influenza B were designed to target conserved regions of segment 7 and the nucleoprotein gene, respectively. Optimized through various primer set ratios, the assay operated at 62 °C for 30 min. For a total of 243 (85 influenza A positive, 58 influenza B positive and 100 negative) nasopharyngeal swab samples, the performance of the influenza A/B multiplex LAMP-LFA was compared with that of the commercial Allplex^TM Respiratory Panel 1 assay (Seegene, Seoul, Korea). The influenza A/B multiplex LAMP-LFA demonstrated a specificity of 98% for the non-infected clinical samples, along with sensitivities of 94.1% for the influenza A clinical samples and 96.6% for the influenza B clinical samples, respectively. The influenza A/B multiplex LAMP-LFA showed high sensitivity and specificity, indicating that it is reliable for use in a low-resource environment. Full article

We report the case of a 61-year-old woman who was referred to the Oral Surgery and Implantology Unit of the University Hospitals of Geneva to take care of edentulous sites after the dental avulsions of teeth 11 and 21 following traumatic shock due to endotracheal intubation under general anesthesia. The dental history revealed that the patient had a history of generalized chronic periodontitis that had been treated several years earlier. The treatment consisted, for the first time to our knowledge, of the immediate insertion of implants at sites 11 and 21 with simultaneous bone augmentation in a single surgical procedure and immediate restorations. Full article

Benign and malignant mediastinal lesions are not infrequently encountered in clinical practice. Mediastinoscopy has long been considered the gold standard in evaluating mediastinal pathology. Since its introduction into clinical practice, endobronchial-ultrasonography-guided transbronchial fine needle aspiration (EBUS-TBNA) has replaced mediastinoscopy as the initial procedure of choice to evaluate mediastinal lesions and to stage lung cancer. Its diagnostic yield in benign mediastinal lesions and less common malignancies, however, has remained limited. This has led different proceduralists to investigate additional procedures to improve the diagnostic yield of EBUS-TBNA. In recent years, different published reports concluded that the addition of EBUS-guided intranodal forceps biopsy (IFB) and transbronchial cryobiopsy (TBCB) to EBUS-TBNA increases the diagnostic yield especially in benign mediastinal lesions and uncommon mediastinal malignancies. The purpose of this review is to describe how EBUS-IFB and EBUS-TBCB are performed, to compare their diagnostic yields, and to discuss their limitations and their potential complications. In addition, the review will conclude with a proposed algorithm on how to incorporate EBUS-IFB and EBUS-TBCB into clinical practice. Full article

Ribwort plantain (Plantago lanceolata L.) is a common weed in the winter rainfall region of South Africa. This weed is widespread across vineyards, orchards, and roadsides in the region. The weed has already evolved resistance to glyphosate and paraquat; however, the mechanism of paraquat resistance has not been documented. This study aimed to investigate the resistance mechanisms in this resistant (R) biotype. Dose–response trials conducted with R biotypes from the Robertson area reconfirmed paraquat resistance. Dose–response trials established that the paraquat rate causing 50% mortality (LD₅₀) for the R biotype is three times greater than for the susceptible (S) biotype. To find out how paraquat affected the photosynthetic performance of P. lanceolata, the quantum yield of photosystem II was measured. The photosystem reaction centres of the R biotype recovered 24 h after paraquat treatment. To evaluate paraquat transport in the plant cell, selective transport inhibitors were applied. Plantago lanceolata (S) biotypes had the highest electrolyte leakage after paraquat treatment. A combined radio/UV-HPLC was used for the separation and identification of paraquat and its metabolites. Paraquat degradation was not observed, indicating that metabolism was not a resistance mechanism within the R biotype. To assess leaf absorption and translocation, [¹⁴C]-labelled paraquat was applied to fully expanded leaves. There were no significant differences in paraquat absorption. However, paraquat translocation differed significantly across the R and S biotypes, indicating that non-target site resistance through reduced paraquat translocation was the main mechanism of resistance in the R biotype. As the resistance of weed species to post-emergence herbicides continues to increase, achieving sustainable weed management necessitates the implementation of diversified weed control strategies. Full article

Mycotoxins often contaminate rice, which are the secondary metabolites of fungi. Ustiloxins, a type of mycotoxin that has often been overlooked, pose a significant risk to human health. Therefore, identifying and controlling the pollution of ustiloxins in rice is required. In this study, we examined the natural contamination of rice with ustiloxins and their link to climate conditions. A total of 300 paddy samples were collected from six regions in southern China, and concentrations of ustiloxins A, B, C, D, and F were analyzed by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results showed that the occurrence of ustiloxins A, B, C, D, and F in paddies was found to be 55.7%, 41.3%, 29.0%, 93.7%, and 96.7%, respectively. Ustiloxin A had the highest mean (177.8 µg/kg) and maximum (3620.9 µg/kg) concentration, followed, in order, by ustiloxins C, B, D, and F. Furthermore, ustiloxin levels were significantly different depending on their origin, with the highest concentration in rice from Changde and Yueyang. And the regional difference in ustiloxins was related to the diversity of climate. A positive correlation between ustiloxin occurrence and mean humidity and precipitation was found in July and August of different regions, while mean temperature indicated a negative dependence. This is an essential survey of the contamination of rice with ustiloxins throughout southern China. The influence of climatic conditions on ustiloxins contamination was evaluated for the first time in our study. Overall, the rice samples examined in this study exhibited a high distribution of ustiloxins, suggesting that regulatory limits and the establishment of maximum allowable levels of ustiloxins in rice are necessary. This study provides a basis and guidance for the pollution situation and control strategy of ustiloxins in China. Full article

Adaptive characteristics of plants, such as those associated with photosynthesis and resource use efficiency, are usually affected by synthesis costs and resource availability. The impact of extreme climate events such as long-term drought on plant physiological functions needs to be examined, particularly as it concerns the internal management of water and nitrogen (N) resources. In this study, we evaluated the resource management strategies for water and N by xerophytic shrubs, Artemisia ordosica and Salix psammophila, under extreme summer drought. This was carried out by comparing the plants’ physiological status during periods of wet and dry summer conditions in 2019 and 2021. Compared with the wet period, A. ordosica and S. psammophila both decreased their light-saturated net carbon (C) assimilation rate (A_sat), stomatal conductance (g_s), transpiration rate (E), leaf N content per leaf area (N_area), and photosynthetic N use efficiency (PNUE) during the summer drought. Whether in wet or dry summers, the gas-exchange parameters and PNUE of A. ordosica were generally greater than those associated with S. psammophila. The instantaneous water use efficiency (IWUE) response to drought varied with species. As a drought-tolerant species, the A. ordosica shrubs increased their IWUE during drought, whereas the S. psammophila shrubs (less drought-tolerant) decreased theirs. The divergent responses to drought by the two species were largely related to differences in the sensitivity of g_s, and as a result, E. Compared with A. ordosica, S. psammophila’s inferior plasticity regarding g_s response affected its ability to conserve water during drought. Our research illustrates the need for assessing plasticity in g_s when addressing plant adaptation to long-term drought. A high dry-season IWUE in xerophytic shrubs can benefit the plants by augmenting their C gain. Full article

Cultivated grasslands are an important part of grassland ecosystems and have been proven to be major carbon sinks, then playing an important role in the global carbon balance. The effect of cultivated grassland type (Medicago sativa, Triticum aestivum, Secale cereale, and Vicia villosa grasslands) on carbon flux (including net ecosystem CO₂ exchange (NEE), ecosystem respiration (ER), and gross ecosystem productivity (GEP)) downstream of the Yellow River was studied via the static chamber technique and a portable photosynthetic system. Bare land was used as a control. The results showed that the four cultivated grassland types were mainly carbon sinks, and bare land was a carbon source. The cultivated grassland types significantly affected carbon flux. The average NEE and GEP of the grassland types were in the following order from high to low: Medicago sativa, Secale cereale, Triticum aestivum, and Vicia villosa grassland. Stepwise regression analysis showed that among all measured environmental factors, soil pH, soil bulk density (BD), soil organic carbon (SOC), and soil microbial carbon (MBC) were the main factors affecting CO₂ flux. The combined influence of soil BD, SOC, and pH accounted for 77.6% of the variations in NEE, while soil BD, SOC, and MBC collectively explained 79.8% of changes in ER and 72.9% of the changes in GEP. This finding indicates that Medicago sativa grassland is a cultivated grassland with a high carbon sink level. The changes in carbon flux were dominated by the effects of soil physicochemical properties. Full article

There is a wind interference effect between greenhouses in a group arrangement of solar greenhouse groups. To ensure the structural integrity of greenhouse groups situated in valleys, it becomes imperative to analyze both the wind pressure distribution patterns and the wind interference effects. This arises from the recognition that the wind load coefficients applicable to solar greenhouse groups nestled within valleys deviate from those observed in flat plains. The application of the contour modeling method facilitated a realistic reconstruction of the authentic topography within the study area. Subsequently, a wind field simulation was executed specifically for the constructed valley. The resultant wind field data for the studied valley area were then obtained. In the valley, nine solar greenhouses were systematically arranged in a three by three configuration. Special attention was directed towards assessing the surface wind pressures derived meticulously from the simulated wind field and wind direction angle of 0°. The findings elucidate the following: (a) The wind speed ratio exhibits a diminution on the leeward side of the mountain as compared to the windward side, with a notably reduced wind speed ratio observed in proximity to the mountain. (b) An amplification effect is discernible in the peripheral zone adjacent to the leading row of greenhouses, proximate to the incoming airflow. Particular emphasis is warranted regarding the reversal of wind direction observed in the secondary row of greenhouses positioned along the north wall and front roof, specifically at a wind angle of 0°, owing to the pronounced influence of interference effects. Hence, when undertaking the design and construction of a cluster of solar greenhouses within the valley terrain of Tibet, meticulous consideration must be directed towards both the meticulous calculation of wind loads within the periphery of the greenhouses and the judicious selection of the grouping’s location. Full article

The economic return for peanut (Arachis hypogaea L.) in Ghana is often low due to limitations in the availability of inputs or their adoption, which are needed to optimize yield. Six experiments were conducted in Ghana in 2020 and 2021 to determine the impact of planting date, cultivar, fertilization, pest management practices, and harvest date on peanut yield, financial return, and pest reaction. A wide range of interactions among these treatment factors were often observed for infestations of aphids (Aphis gossypii Glover); groundnut rosette disease (Umbravirus: Tombusviridaee); millipedes (Peridontopyge spp.); white grubs (Schyzonicha spp.); wireworms (Conoderus spp.); termites (Microtermes and Odontotermes spp.); canopy defoliation as a result of early leaf spot disease caused by Passalora arachidicola (Hori) and late leaf spot caused by Nothopassalora personata (Berk. and M. A. Curtis); and the scarification and boring of pods caused by arthropod feeding. Pod yield and economic return increased for the cultivar Chitaochi and Sarinut 2 when fertilizer was applied and when fertilizer was applied at early, mid-, and late planting dates. Pod yield and economic return increased when a combination of locally derived potassium soaps was used for aphid suppression and one additional hand weeding was used in the improved pest management practice compared with the traditional practice without these inputs. Pearson correlations for yield and economic return were negatively correlated for all pests and damage caused by pests. The results from these experiments can be used by farmers and their advisors to develop production packages for peanut production in Ghana. Full article

Norbormide (NRB) is a Rattus-selective toxicant, which was serendipitously discovered in 1964 and formerly marketed as an eco-friendly rodenticide that was deemed harmless to non-Rattus species. However, due to inconsistent efficacy and the emergence of second-generation anticoagulants, its usage declined, with registration lapsing in 2003. NRBs’ lethal action in rats entails irreversible vasoconstriction of peripheral arteries, likely inducing cardiac damage: however, the precise chain of events leading to fatality and the target organs involved remain elusive. This unique contractile effect is exclusive to rat arteries and is induced solely by the endo isomers of NRB, hinting at a specific receptor involvement. Understanding NRB’s mechanism of action is crucial for developing species-selective toxicants as alternatives to the broad-spectrum ones currently in use. Recent research efforts have focused on elucidating its cellular mechanisms and sites of action using novel NRB derivatives. The key findings are as follows: NRB selectively opens the rat mitochondrial permeability transition pore, which may be a factor that contributes to its lethal effect; it inhibits rat vascular K_ATP channels, which potentially controls its Rattus-selective vasoconstricting activity; and it possesses intracellular binding sites in both sensitive and insensitive cells, as revealed by fluorescent derivatives. These studies have led to the development of a prodrug with enhanced pharmacokinetic and toxicological profiles, which is currently undergoing registration as a novel efficacious eco-sustainable Rattus-selective toxicant. The NRB-fluorescent derivatives also show promise as non-toxic probes for intracellular organelle labelling. This review documents in more detail these developments and their implications. Full article

IL-36 cytokines are emerging as beneficial in immunity against pathogens and cancers but can also be detrimental when dysregulated in autoimmune and autoinflammatory conditions. Interest in targeting IL-36 activity for therapeutic purposes is rapidly growing, yet many unknowns about the functions of these cytokines remain. Thus, the availability of robust research tools is essential for both fundamental basic science and pre-clinical studies to fully access outcomes of any manipulation of the system. For this purpose, a floxed Il1rl2, the gene encoding the IL-36 receptor, mouse strain was developed to facilitate the generation of conditional knockout mice. The targeted locus was engineered to contain an inverted mCherry reporter sequence that upon Cre-mediated recombination will be flipped and expressed under the control of the endogenous Il1rl2 promoter. This feature can be used to confirm knockout in individual cells but also as a reporter to determine which cells express the IL-36 receptor IL-1RL2. The locus was confirmed to function as intended and further used to demonstrate the expression of IL-1RL2 in barrier tissues. Il1rl2 expression was detected in leukocytes in all barrier tissues. Interestingly, strong expression was observed in epithelial cells at locations in direct contact with the environment such as the skin, oral mucosa, the esophagus, and the upper airways, but almost absent from epithelial cells at more inward facing sites, including lung alveoli, the small intestine, and the colon. These findings suggest specialized functions of IL-1RL2 in outward facing epithelial tissues and cells. The generated mouse model should prove valuable in defining such functions and may also facilitate basic and translational research. Full article