Activation of hedgehog/glioma‐associated oncogene homolog (HH/GLI) signaling induces basal cell carcinoma (BCC) and establishes an immunosuppressive tumor microenvironment. HH/GLI signaling inhibits ...the activity of antitumoral T cells via programmed death ligand 1/programmed death‐1 immune checkpoint signaling and the recruitment of immunosuppressive regulatory T cells. BCCs also show strong infiltration with antitumoral neutrophils. The data support the evaluation of combination treatments with HH inhibitors and immune checkpoint blockers.
Genetic activation of hedgehog/glioma‐associated oncogene homolog (HH/GLI) signaling causes basal cell carcinoma (BCC), a very frequent nonmelanoma skin cancer. Small molecule targeting of the essential HH effector Smoothened (SMO) has proven an effective therapy of BCC, though the frequent development of drug resistance poses major challenges to anti‐HH treatments. In light of recent breakthroughs in cancer immunotherapy, we analyzed the possible immunosuppressive mechanisms in HH/GLI‐induced BCC in detail. Using a genetic mouse model of BCC, we identified profound differences in the infiltration of BCC lesions with cells of the adaptive and innate immune system. Epidermal activation of Hh/Gli signaling led to an accumulation of immunosuppressive regulatory T cells, and to an increased expression of immune checkpoint molecules including programmed death (PD)‐1/PD‐ligand 1. Anti‐PD‐1 monotherapy, however, did not reduce tumor growth, presumably due to the lack of immunogenic mutations in common BCC mouse models, as shown by whole‐exome sequencing. BCC lesions also displayed a marked infiltration with neutrophils, the depletion of which unexpectedly promoted BCC growth. The study provides a comprehensive survey of and novel insights into the immune status of murine BCC and serves as a basis for the design of efficacious rational combination treatments. This study also underlines the need for predictive immunogenic mouse models of BCC to evaluate the efficacy of immunotherapeutic strategies in vivo.
Recording and reproducing mandibular movements have been of key importance in the practice of dentistry for over a century. Recently, it has become possible to use digital technologies for these ...tasks. This study presents a preliminary method to try to identify the mandibular instantaneous centres of rotation based solely on intraoral scanners.
The dentitions of four participants were scanned, multiple inter-occlusal registrations and buccal scans were performed in closed and opened positions. Blender software was used to align the meshes during the post-scan digital workflow. Bite alignment accuracy was assessed and then improved with a strict exclusion protocol. An automated algorithm was used to find rotations between closed stage and open stage meshes.
Our exclusion protocol reduced the bite alignment error significantly (p = 0.001) and the root-mean-square error value of the meshes decreased from 0.09 mm (SD = 0.15) to 0.03 mm (SD = 0.017). However, the remaining translational error caused an unexpectedly large shift in the axis of rotation (mean = 1.35 mm, SD = 0.77) with a 41.83: 1 ratio. As found in other studies, our results showed even a small amount of error during registration can shift the axis of rotation a large amount. This phenomenon will compromise the results of common pantographic methods which assume a rotation axis of the condyle. It also adds valuable information to the concept of instantaneous centers of rotation by revealing their true characteristics.
Distribution and abundance of the most harmful click beetles (Coleoptera: Elateridae) were sampled with sex pheromone traps at 11 sites in the Carpathian lowlands in 2022. Samples provided the first ...Hungarian data on Agriotes sordidus, occurring northwest of the country with low abundances. The most abundant species was A. rufipalpis, while A. ustulatus, A. lineatus and A. sputator were also common. The reordering of the species rank and the absence of A. obscurus from the Transdanubian sites, compared to data collected between 2010 and 2013, may refer to the climatic changes during the last decade.
Véleményem szerint a jogalkotó nem gondolt bele abba, hogy ha valóban előáll az a helyzet, hogy teljesen megszűnnek a büntetés végrehajtási (bv.) intézetek túlzsúfoltsági körülményei, akkor a ...következőkkel kell szembesülni: a kérelmezők az egyéb elhelyezési körülményeik miatti sérelmek okozta személyiségi jogaik megsértése miatt igényeik pénzbeli kompenzálására irányuló érvényesítésétől teljesen el lesznek zárva, a bírósághoz fordulás joga kizáródik. „Faramuci” helyzetbe kerülnek tehát a fogvatartottak, mert sem a Bv. tv. szerinti kártalanítási eljárásban, sem pedig a Pp.-n, illetve Ptk.-n alapuló személyiségi jogok megsértése iránt indított perben érdemi jogorvoslatra nem biztos, hogy számíthatnak. Ez pedig korántsem biztos, hogy „kiállna egy EJEB előtti próbát”, hiszen jogállami keretek között elképzelhetetlen a számonkérhetőség lehetőségének kvázi el nem ismerése.
The caddisfly fauna of the Transcarpathian part of the Pannonian Lowland was poorly studied formerly. Here, we present the results of a six-year survey (2015-2020) carried out in four sampling sites ...of the Ukrainian part of the Bereg Plain and provide the actualised checklist of this area. Actually, 7346 specimens of 53 caddisfly species were collected. The number of known caddisfly species increased from 13 to 61. Two species
and
, which formerly were considered extinct in the Pannonian Ecoregion, were detected and another especially rare species (e.g.
was also recorded. The fauna of the region cover a significant part of both Hungarian and Ukrainian caddisfly fauna. Assemblages of four characteristic habitat types of the region showed significant differences considering their quantitative and qualitative composition, substrate, current, hydrological- and feeding types. The high diversity and natural value of the small lowland watercourses were proven using a new Caddisfly Conservation Index (CCI) calculated, based on vulnerability and rarity of species. The fauna and assemblages showed a unique character mainly independent from large rivers of the region.
The dried bean beetle,
Acanthoscelides obtectus
, is an economically important, worldwide pest of legume crops including dry beans,
Phaseolus vulgaris
. Assessment of
A. obtectus
infestation levels ...in pre-harvest field crops and post-harvest granaries is difficult to achieve because there is no effective monitoring tool for early detection so that interventions can be deployed as needed. Because
A. obtectus
is a generic pollen and nectar feeder, we adopted an electrophysiological (EAG) screening approach, using the antennae of female
A. obtectus
to identify physiologically active, volatile phytochemicals, which could then be investigated for their attractiveness to
A. obtectus
in laboratory behavioral assays and preliminary field tests. Of the 27 compounds tested in EAG screening, 5 compounds, i.e., methyl anthranilate, methyl eugenol, benzyl alcohol, (
RS
)-lavandulol, and 2-phenylethanol, elicited stronger EAG responses than the standard (1-phenylethanol). In 4-arm olfactometer bioassays, female
A. obtectus
preferred the olfactometer arm containing the odor of either methyl anthranilate or benzyl alcohol compared to the solvent control. In preliminary field tests using these 2 compounds as a binary mixture, at least 5 times as many beetles were caught on baited traps compared to non-baited traps. The field data also suggested that benzyl alcohol was primarily responsible for the field activity of the blend. We hypothesize that the attraction of
A. obtectus
to the combined benzyl alcohol/methyl anthranilate and the single benzyl alcohol baits is connected to the species` nectar- and pollen-feeding behaviour and not to its intraspecific communication. To our knowledge, this is the first evidence that
A. obtectus
behavior in the field can be modified by the deployment of plant-derived semiochemicals.
The diurnal bees, lepidopterans, and other pollinators are among the most studied flower‐visiting insect taxa. They mostly play distinct functions in temperate grasslands and ecotones of ...grassland‐forest mosaics (such as in forest steppes). Although orthopterans are widely distributed in these habitats, however, their flower visitation is nearly unknown, especially in the temperate zone. During the development of traps with chemical lures to catch Lepidoptera pests, large numbers of Orthoptera were caught that provide a chance for studying the flower visitation and odor and indirectly the host plant preference of seven temperate zone Tettigoniidae species. Data on the attractivity of isoamyl alcohol‐based semisynthetic lures for Meconema thalassinum and efficiency of phenylacetaldehyde‐based lures on Leptophyes albovittata and Phaneroptera falcata were reported for the first time. Additionally, analysis of nature photos collected from internet sources, as part of a passive citizen science also supports the revealed preference of these species. Based on photos, the studied orthopterans mainly visit Asteraceae species including the most preferred Tanacetum vulgare, Pulicaria dysenterica, Achillea millefolium, Solidago canadensis, and Centaurea scabiosa. Based on catches of volatile traps, the first data were recorded on the attractivity of phenylacetaldehyde‐ and isoamyl alcohol‐based lures on three temperate zone Orthoptera species. Results of a passive citizen science study strengthen these results that may increase the knowledge on the host plant and habitat preference of Orthoptera species.
The flower visitation and host plant preference of seven temperate zone Tettigoniidae species were studied during the development of traps with chemical lures. Large numbers of Orthoptera were caught, providing an opportunity for analysis. Based on data from chemical lures and nature photos, the studied Orthoptera species mainly visit Asteraceae species, including the most preferred Tanacetum vulgare, Pulicaria dysenterica, Achillea millefolium, Solidago canadensis, and Centaureae scabiosa.
Oak lace bug (
Corythucha arcuata
) has continuously spread through Europe since its appearance in 2000, and it has become a dangerous pest of
Quercus
species in most countries. Despite of its high ...abundance in the surrounding countries it was found in West Ukraine only in 2020. During our investigation carried out in 2020 OLB was detected in all studied large forest patches of the Ukrainian part of the Carpathian Lowland. These were one of the newest distribution data from Ukraine after its appearance in the far coast of Black See near Yalta (South Ukraine). OLB most live on
Q. robur
and
Q. petraea
but in an orchard located near an infested forest patch we found infested sweet cherry (
P. avium
) trees, which is a new, formerly not mentioned cultivated host of the pest.
Immune homeostasis in peripheral tissues is, to a large degree, maintained by the differentiation and action of regulatory T cells (Treg) specific for tissue Ags. Using a novel mouse model, we have ...studied the differentiation of naive CD4
T cells into Foxp3
Treg in response to a cutaneous Ag (OVA). We found that expression of OVA resulted in fatal autoimmunity and in prevention of peripheral Treg generation. Inhibiting mTOR activity with rapamycin rescued the generation of Foxp3
T cells. When we varied the level of Ag expression to modulate TCR signaling, we found that low Ag concentrations promoted the generation of Foxp3
T cells, whereas high levels expanded effector T cells and caused severe autoimmunity. Our findings indicate that the expression level of tissue Ag is a key determinant of the balance between tissue-reactive effector and peripheral Foxp3
T cells, which determines the choice between tolerance and autoimmunity.
Levocetirizine dihydrochloride active ingredient was microencapsulated using nano spray-drying technology for preparing microparticles containing topical gel against edema. Hydroxyl propyl methyl ...cellulose (HPMC) was used as a carrier polymer during spray drying. The active ingredient content of the nano spray-dried products was 52.81% (
/
) and 51.33% (
/
) for ex vivo and in vivo experiments, respectively, and the average particle size was 2.6 µm. X-ray diffraction analysis indicated an amorphous state of the active ingredient embedded in the amorphous matrix of the polymer. Dermal oil gels composed of Miglyol 812 gelated by Dermofeel viscolid included 5% (
/
) (for ex vivo) and 10% (
/
) (for in vivo) active ingredient without or with 0.05% (
/
) menthol penetration enhancer. Qualitative ex vivo penetration studies using a confocal Raman microscopic correlation mapping were executed on human abdominal skin. The results showed that the active ingredient was enriched in the epidermis and upper dermis layer of the skin using oleogel loaded with the nano spray-dried drug-HPMC composite. Menthol addition to the oleogel resulted in the concentration of levocetirizine in the dermis. In vivo tests were performed on a mouse model of croton oil-induced ear edema. Negative control and Fenistil-treated groups were compared using the prepared oil gels with and without menthol. Without penetration enhancer, 20 µL of our oil gel loaded with nano spray-dried levocetirizine dihydrochloride composite showed similar effectiveness to the same volume of Fenistil gel, while 5 µL menthol containing sample was sufficient to eliminate the skin irritation similarly to 20 µL Fenistil.
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