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Thymic epithelial tumors (TETs) are rare tumors arising from the mediastinum. Among TETs, thymoma type B2, B3 and thymic carcinoma are highly malignant and often present invasion and dissemination. However, the biological characteristics of TETs have not been thoroughly studied, and their mechanisms of invasion and dissemination are largely unknown. α‐Actinin 4 (ACTN4) is a member of actin‐binding proteins and reportedly plays important roles in the progression of several cancers. In this study, we investigated the relationship between ACTN4 and characteristics of the malignant potential of TETs, such as invasion and dissemination. In vitro experiments using Ty‐82 thymic carcinoma cells revealed that overexpression of ACTN4 enhanced the proliferative and invasive ability of Ty‐82 cells; conversely, knockdown of ACTN4 attenuated the proliferative and invasive potential of Ty‐82 cells. In western blotting (WB) experiments, ACTN4 induced the phosphorylation of extracellular signal–regulated kinase and glycogen synthase kinase 3β to regulate the β‐catenin/Slug pathway. Furthermore, WB analysis of cancer tissue–origin spheroids from patients with TETs showed results similar to those for Ty‐82 cells. In vivo experiments showed that the knockdown of ACTN4 significantly suppressed the dissemination of Ty‐82 cells. A WB and immunohistochemistry staining comparison of primary and disseminated lesions of TETs using surgical specimens showed upregulated expression of ACTN4, β‐catenin, and Slug proteins in disseminated lesions. In summary, our study suggests ACTN4 is associated with malignant potential characteristics such as invasion and dissemination in TETs via the β‐catenin/Slug pathway. [ABSTRACT FROM AUTHOR]

The leucine-rich repeat-containing (LRRC) superfamily members are known for their significant roles in tumorigenesis and cellular proliferation. However, the specific regulatory role of LRRC45 in lung cancer remains unexplored. This study investigated the impact and underlying mechanisms of LRRC45 on the proliferative, migratory, and invasive capacities of lung adenocarcinoma (LUAD) cells, potentially identifying new targets for therapeutic intervention. The importance of LRRC45 in lung cancer was analyzed using the online databases of UCSC Xena, TCGA, TISIDB, and UALCAN, whereas to detect target gene expression, we used the qRT-PCR, Western blot, and immunofluorescence confocal. The cell growth was monitored by colony formation assay and migration was examined by cell migration assay. Finally, a xenograft mouse tumor model using A549 ​cells was used to explore the in vivo effect of LRRC45 in lung cancer. Inhibition of LRRC45 expression led to a notable decrease in proliferation, migration, and invasion of A549 and H1299 ​cells. LRRC45 silencing significantly reduced the tumor volume and improved the mice's survival. Additionally, inhibition of LRRC45 expression dramatically suppressed c-MYC, Slug, MMP2, and MMP9 expression. Overexpression of c-MYC and/or Slug in the LRRC45-deficient cells can partially or totally restore the LRRC45 deficiency-suppressed growth. Moreover, the overexpression of MMP2 and/or MMP9 could partially or totally restore LRRC45 deficiency-reduced cell metastasis. LRRC45 could promote the proliferative, migrative, and invasive capacities of lung cancer cells by increasing c-MYC, Slug, MMP2, and MMP9 expression, indicating the therapeutic implications and potential significance of these pathways in lung cancer. [ABSTRACT FROM AUTHOR]

This study aimed to examine the immunohistochemical expression of epithelial–mesenchymal transition biomarkers: P4HA2 and SLUG in colorectal carcinoma (CRC) specimens, then to assess their relation to clinicopathological features including KRAS mutations and patients' survival, and finally to study the correlation between them in CRC. The result of this study showed that SLUG and P4HA2 were significantly higher in association with adverse prognostic factors: presence of lympho-vascular invasion, perineural invasion, higher tumor budding, tumor stage, presence of lymph node metastasis, and presence of distant metastasis. CRC specimens with KRAS mutation were associated with significant higher SLUG and P4HA2 expression. High expression of both SLUG and P4HA2 was significantly unfavorable prognostic indicator as regards overall survival (OS) and disease-free survival (DFS). In KRAS mutated cases, high P4HA2 expression was the only significant poor prognostic indicator as regarding DFS. In conclusions, our data highlight that both SLUG and P4HA2 expression may serve as potentially important poor prognostic biomarkers in CRC and targeting these molecules may be providing a novel therapeutic strategy. In KRAS mutation group, high P4HA2 expression is the only independent prognostic factor for tumor recurrence, so it can be suggested to be a novel target for therapy. [ABSTRACT FROM AUTHOR]

The invasion of the terrestrial ecosystem by gastropods has immense negative impacts on ecosystem functions, health, and agricultural plants. The non‐native slug, Deroceras laeve (O. F. Müller, 1774), a recognised agricultural pest in native and invaded regions, was recently reported from the Darjeeling Himalayas, India. We assessed the plant palatability and preference of D. laeve using selected plants being farmed in Darjeeling Himalayas (basil, cabbage, coriander, lettuce, mint, pumpkin leaf, and spinach) by laboratory‐based choice and non‐choice experiments. Moreover, we evaluated the correlation between different chemical features of the plants with the consumption rate of D. laeve and observed the fecundity of D. laeve reared on different plant diets. The highest consumption rate of D. laeve was observed for pumpkin (12.99 ± 1.33 mg dry mass) and the lowest for mint (1.63 ± 0.13 mg dry mass), with a significant positive correlation between consumption rate and D. laeve body mass (for lettuce: R =.47, p =.0009 and other plant species: R =.52, p =.00004) was observed through the non‐choice experiment. Moreover, the consumption rate of the non‐native slug, D. laeve, was considerably higher than a controphic slug, Meghimatium bilineatum. In the choice experiment, D. laeve preferred lettuce, followed by pumpkin, cabbage, and coriander, even in the presence of detritus and significantly avoided spinach, mint, and basil. The consumption rate of D. laeve had a significant negative correlation with calcium (R = −.49, p =.003) and potassium (R = −.37, p =.03), and a positive correlation was observed for magnesium (R =.37, p =.03). However, no correlation was observed for zinc, silica, total carbohydrate, protein, and phenol content of the leaves. The highest fecundity of D. laeve was observed in the lettuce and cabbage diet, while no eggs were laid on the mint diet. Hence, the consumption of different leaves, irrespective of physical and chemical features (hairiness, amount of silicon, protein, carbohydrate, and phenol), suitable life history traits, and suitable habitats, may facilitate D. laeve as a potential agricultural pest in the Darjeeling Himalayas, India. [ABSTRACT FROM AUTHOR]

Breast cancer is trending its way as the most common cancer globally. Surgery remains the mainstream treatment modality. The gene expression signatures predict the prognosis in cancer patients. However, they are a limitation in resource-poor settings. India is predicted to see a rise in breast cancer patients in the years to come. New therapeutic target and prognostic indicators feasible to use are the need of the hour. Our study aims to evaluate the immunohistochemical expression of epithelial mesenchymal transition (EMT) markers, Snail + Slug and Twist, in breast cancer and their association with known prognostic indicators. The study was conducted on 60 patients of breast cancer who were primarily treated by surgery. IHC expression of Snail + Slug and Twist was evaluated and scored. They were categorized into high and low expression based on the median obtained on statistical analysis. Increased expression of EMT markers showed statistically significant association with the higher grade of the tumor and triple-negative and luminal B molecular subtype. Immunohistochemical expression of EMT markers Snail + Slug and Twist proves to be a reliable, efficient, and feasible in predicting the prognosis of breast cancer, and they should be targeted for novel therapeutic intervention. [ABSTRACT FROM AUTHOR]

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The relationship between the expression of zinc finger transcription factor (Slug), terminal deoxyribonucleotidyl transferase (TdT), Y chromosome sex determination region related high-speed swimming frame factor 9 (SOX9) protein and clinicopathological features and prognosis of thymoma patients was analyzed. 113 cases of thymoma tissues and adjacent tissues surgically resected in our hospital were selected from May 2016 to November 2018. The positive expression of Slug, TdT and SOX9 protein was determined by immunohistochemistry. The relationship between the expression of Slug, TdT and SOX9 protein and the clinicopathological features and prognosis of thymoma patients was analyzed. The positive expression rates of Slug, TdT and SOX9 protein in thymoma tissues were higher than those in adjacent tissues (P<0.05). There was no significant difference in the positive expression of Slug, TdT and SOX9 protein in thymoma tissues in terms of age, gender, tumor diameter, whether combined with myasthenia gravis and whether accompanied by macrovascular invasion (P>0.05). The positive expression of Slug, TdT and SOX9 protein in thymoma tissues was significantly different in Masaoka-Koga stage and WHO classification (P<0.05). The positive expression of Slug, TdT and SOX9 protein in thymoma tissues was positively correlated with Masaoka-Koga stage and WHO classification (P<0.05). The 5-year overall survival rate in 113 thymoma patients was 81.42% (92/113), the 5-year survival rate in Slug positive group was lower than that in Slug negative group (70.18% VS 92.86%). the 5-year survival rate in TdT positive group was lower than that in TdT negative group (79.790% VS 89.57%), the 5-year survival rate in SOX9 positive group was lower than that in SOX9 negative group (79.35% VS 90.48% ) (χ² =9.669, 9.515, 17.008, P<0.05). Cox proportional hazard regression model analysis showed that, Masaoka-Koga stage (stageIII/stageIV), WHO classification (B2/B3), positive expression of Slug protein, positive expression of TdT protein and positive expression of SOX9 protein were independent risk factors affecting the prognosis of thymoma patients (HR: 3.518, 2.921, 4.536, 1.402, 2.921, P<0.05). The expression of Slug, TdT and SOX9 in thymoma tissues are high, the expression of the three proteins are relate to the Masaoka-Koga stage and WHO classification, and they are independent risk factor affecting the 5-year survival rate of thymoma patients. [ABSTRACT FROM AUTHOR]

Objective: E26 transformation‐specific (ETS) factors have emerged as key mediators underlying human tumorigenesis. Here, we sought to characterize the expression pattern, biological roles, and clinical significance of ETS Variant Transcription Factor 5 (ETV5) in head neck squamous cell carcinoma (HNSCC). Subjects and Methods: ETV5 expression pattern in HNSCC was determined by bioinformatics interrogations and immunohistochemical staining in primary samples. The associations between its abundance with clinicopathological parameters, and patient survival were evaluated. Colony formation, CCK‐8, flow cytometry, wound healing, and Transwell invasion assays, as well as xenograft models, were utilized to determine the phenotypic changes after ETV5 silencing in vitro and vivo. The potential binding of ETV5 in the Slug promoter was determined by ChIP‐qPCR. Results: ETV5 was significantly overexpressed in HNSCC samples. Its overexpression is significantly associated with aggressiveness features and reduced survival. ETV5 knockdown significantly inhibited cell proliferation, migration, invasion, and induced apoptosis in vitro, and impaired tumor growth in vivo. Moreover, ETV5‐activated Slug transcription by binding its promoter region in HNSCC cells. Patients with ETV5highSlughigh had the worst survival across multiple HNSCC cohorts. Conclusions: Our findings reveal that ETV5 serves as a novel prognostic biomarker and putative oncogene for HNSCC progression likely by activating Slug transcription. [ABSTRACT FROM AUTHOR]

Ovarian cancer poses a significant threat to patients in its advanced stages, often with limited treatment options available. In such cases, palliative management becomes the primary approach to maintaining a reasonable quality of life. Therefore, the administration of any medication that can benefit patients without a curative option holds potential. Resveratrol, a natural compound known for its in vitro anticancer activities, has generated contrasting results in vivo and human studies. In this study, we aimed to assess the anticancer effects of resveratrol on ovarian cancer cells grown on the chorioallantoic membrane (CAM) of chicken embryos. Two ovarian cancer cell lines, OVCAR-8 and SKOV-3, were cultured in collagen scaffolds for four days before being implanted on the CAM of chicken embryos on day 7. Different doses of resveratrol were applied to the CAM every two days for six days. Subsequently, CAM tissues were excised, fixed, and subjected to histological analysis. Some CAM tumours were extracted to analyse proteins through Western blotting. Our findings indicate that specific doses of resveratrol significantly reduce angiogenic activities, pNF-κB levels, and SLUG protein levels by using immunohistochemistry. These results suggest that resveratrol may have the potential to impact the behaviour of ovarian cancer CAM tumours, thereby warranting further consideration as a complementary treatment option for women with incurable ovarian cancer. [ABSTRACT FROM AUTHOR]

Actin is a protein of central importance to many cellular functions. Its localization and activity are regulated by interactions with a high number of actin-binding proteins. In a yeast two-hybrid (Y2H) screening system, snail family transcriptional repressor 2 (SNAI2 or slug) was identified as a yet unknown potential actin-binding protein. We validated this interaction using immunoprecipitation and analyzed the functional relation between slug and actin. Since both proteins have been reported to be involved in DNA double-strand break (DSB) repair, we focused on their interaction during this process after treatment with doxorubicin or UV irradiation. Confocal microscopy elicits that the overexpression of actin fused to an NLS stabilizes complexes of slug and γH2AX, an early marker of DNA damage repair. [ABSTRACT FROM AUTHOR]

BACKGROUND: Slugs mechanically damage plant leaves, resulting in significant economic losses. However, there are limited cost‐efficient strategies available in slug management. By studying how slugs utilize plant volatiles to locate host plants, we can gain insights into the design of attractants and repellents. RESULTS: Bioassay results suggest slugs (Agriolimax agrestis) prefer to orientate to lettuce (Lactuca sativa), cabbage (Brassica oleracea L.), and young tobacco seedlings, compared with old tobacco seedlings. We analyzed the volatomics of lettuce, cabbage, young and old tobacco seedlings. 2‐(2‐butoxyethoxy)‐ethanol acetate (2EA) had high abundance while nonanal, decanal, and β‐cylocitral had relatively low content in volatiles. Old tobacco seedlings released significantly more hexanal but fewer 1,4‐dihydro‐4‐oxopyridazine (DO). In olfactory tests, hexanal, nonanal, decanal, and β‐cylocitral showed strong repellency to slugs, while DO at a dose of 500 ng/μL and 2EA at a dose of 1% were attractive to slugs. The two alkanes, hexadecane and heptadecane, had no effect on slug orientating to host plants. DO and 2EA can thus alleviate the repellency of hexanal, nonanal, decanal and β‐cylocitral. CONCLUSION: The high emission of hexanal in old tobacco seedlings helps repel slugs, while 2EA and DO attract slugs to lettuce and cabbage. These findings suggest that these chemicals can be utilized in the design of repellents and attractants, and contribute to constructing a push–pull system for slug control. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Simple Summary: Understanding diel variations in ground-dwelling invertebrates is an important issue for agricultural ecology, which has been extensively studied at the population level. However, contemporary studies on hourly variations in the field are scarce at the community level owing to the lack of an effective method for collecting hourly data. Therefore, this study used a novel, automatic method using infrared camera traps to photograph a ground-dwelling invertebrate community at 5 min intervals from 31 July to 29 September in farmland in Ningbo City, China. In total, 9 taxa and 1147 individuals were identified across 42 d in 217,728 photographs. The taxonomic richness and abundance of the ground-dwelling invertebrate community did not show significant hourly variations within each day nor significantly preferred active hours. Only millipedes had significant hourly variations within each day, with a significant preference for activity between 1:00 and 4:00. Additionally, slugs, beetles, and grasshoppers showed preferred active hours around sunset and midnight. This study provides a useful method for monitoring hourly changes in ground-dwelling invertebrate communities in farmlands as well as fine temporal resolution data to understand the responses of ground-dwelling invertebrate communities to climate change and human management. We evaluated the hourly dynamics of ground-dwelling invertebrate communities in farmland using infrared camera traps between August and September 2022. No significant variations within 24 h nor between any two time points of each day were observed in the taxonomic richness and abundance of the entire community. However, the periods from 4:00 to 7:00 and 13:00 to 20:00 showed relatively high taxonomic richness, while those from 2:00 to 6:00 and 16:00 to 21:00 showed relatively high abundance. Millipede abundance varied significantly in a 24 h period, with higher abundance from 3:00 to 4:00 and 1:00 to 2:00. Additionally, slug, beetle, and grasshopper abundances were significantly higher from 22:00 to 23:00, 17:00 to 18:00, and 23:00 to 24:00, respectively. The abundance of other taxa did not show significant variations between any two time points of a day. Predominant generalist predators showed positive correlation in their activity times. These results suggest that significant variations within each 24 h period are uncommon at either community or taxa (except for millipedes) levels in farmland ground-dwelling invertebrates. Further, while most taxa had significantly preferred active hours, the total community did not. Therefore, hourly dynamics should be considered to understand biodiversity maintenance. [ABSTRACT FROM AUTHOR]

Abstract Background Metastasis is still a major cause of poor pathological outcome and prognosis in esophageal squamous cell carcinoma (ESCC) patients. NUAK1 has been reported highly expressed in many human cancers and is associated with the poor prognosis of cancer patients. However, the role of NUAK1 and its underlying signaling mechanism in ESCC metastasis remain unclear. Methods Expression of NUAK1 in ESCC was detected by real-time quantitative RT-PCR (qRT-PCR), Western blotting and immunohistochemical staining. MTT, colony formation, wound-healing and transwell assays were used to determine the role NUAK1 in vitro. Metastasis was evaluated by use of an experimental pulmonary metastasis model in BALB/c-nu/nu mice. The mechanisms were assessed by using coimmunoprecipitation, immunofluorescence and dual-luciferase reporter gene experiments. Results NUAK1 was highly expressed in ESCC tissues compared with the adjacent normal esophageal epithelial tissues. Moreover, the elevated expression of NUAK1 positively correlated with tumor invasion depth, lymph node metastasis, pathological TNM stage, and poor survival in ESCC patients. Further experiments showed that NUAK1 overexpression did not change the cell viability and colony formation of ESCC cells, while remarkably promoted the migration and invasion in vitro and experimental pulmonary metastasis in vivo. Mechanistically, NUAK1 enhanced the transcription level of Slug, which enhanced the migratory and invasive capability of ESCC cells. Consistently, silencing Slug almost completely diminished the migration and invasion of NUAK1-overexpressing ESCC cells. Further studies demonstrated that NUAK1 upregulated the transcription activity of Slug through activating the JNK/c-Jun pathway. Conclusion These results demonstrated that NUAK1 promoted the metastasis of ESCC cells through activating JNK/c-Jun/Slug signaling, indicating NUAK1 is a promising therapeutic target for metastatic ESCC.

Molluscs are important pests of natural and agricultural ecosystems, by feeding on different parts of leaves, stems, flowers, buds, fruits and roots of different plant hosts, reducing the marketability of annual agricultural products and damage plant species in different habitats in the country. Moreover, they are intermediate hosts of human and cattle parasites, and therefore are of medicinal and veterinary importance. In this study, snails and slugs were sampled from nine designated stations located in the south and west regions of Tehran province, considering their natural condition, vegetation, location of gardens and fields, soil or subsoil types, from the beneath of rocks and trunks, water bodies and other areas related to the habitat of snails and slugs. Samples were made using sampling nets or gathered directly by hand from plants, shrubs and river banks. Overally, 17 species belonging to 12 genera from nine families were collected and identified. Identification was done according to morphometric characters including shape, size of shell, dextral and sinistral position of the shell, operculum, aperture, radula, mucus colour, respiratory pore, keel, renal ridge and reproduction system. The highest and lowest mollusc species diversity among the stations studied were turned to be 16 and 6 species belong to station 9 (west of Tehran province) and station 2 (south of Tehran province), respectively. The most commonly diversed family was Hellicidae with 5 species, i.e., Monacha cantiana, Euomphalia pisiformis, Helicella krynickii, Helicella derbentina, Caucasotachea atrolabiata. Also, Lymnaea truncatula is identified as the most frequent species, which has medical importance. Monacha cantiana was identified in the present study and reported for the first time from Iran. All the samples and their respective spatial and temporal information were made available in the museum of the Agricultural Zoology Research Department in Iranian Research Institute of Plant Protection.

Radiotherapy is widely used for cancer treatment, but paradoxically, it has been reported that surviving cancer cells can acquire resistance, leading to recurrence or metastasis. Efforts to reduce radioresistance are required to increase the effectiveness of radiotherapy. miRNAs are advantageous as therapeutic agents because it can simultaneously inhibit the expression of several target mRNAs. Therefore, this study discovered miRNA that regulated radioresistance and elucidated its signaling mechanism. Our previous study confirmed that miR-5088-5p was associated with malignancy and metastasis in breast cancer. As a study to clarify the relationship between radiation and miR-5088-5p identified as onco-miRNA, it was confirmed that radiation induced hypomethylation of the promoter of miR-5088-5p and its expression increased. On the other hand, miR-5088-5p inhibitors were confirmed to reduce radiation-induced epithelial-mesenchymal transition, stemness, and metastasis by reducing Slug. Therefore, this study showed the potential of miR-5088-5p inhibitors as therapeutic agents to suppress radioresistance.

Background: Metastasis is still a major cause of poor pathological outcome and prognosis in esophageal squamous cell carcinoma (ESCC) patients. NUAK1 has been reported highly expressed in many human cancers and is associated with the poor prognosis of cancer patients. However, the role of NUAK1 and its underlying signaling mechanism in ESCC metastasis remain unclear. Methods: Expression of NUAK1 in ESCC was detected by real-time quantitative RT-PCR (qRT-PCR), Western blotting and immunohistochemical staining. MTT, colony formation, wound-healing and transwell assays were used to determine the role NUAK1 in vitro. Metastasis was evaluated by use of an experimental pulmonary metastasis model in BALB/c-nu/nu mice. The mechanisms were assessed by using coimmunoprecipitation, immunofluorescence and dual-luciferase reporter gene experiments. Results: NUAK1 was highly expressed in ESCC tissues compared with the adjacent normal esophageal epithelial tissues. Moreover, the elevated expression of NUAK1 positively correlated with tumor invasion depth, lymph node metastasis, pathological TNM stage, and poor survival in ESCC patients. Further experiments showed that NUAK1 overexpression did not change the cell viability and colony formation of ESCC cells, while remarkably promoted the migration and invasion in vitro and experimental pulmonary metastasis in vivo. Mechanistically, NUAK1 enhanced the transcription level of Slug, which enhanced the migratory and invasive capability of ESCC cells. Consistently, silencing Slug almost completely diminished the migration and invasion of NUAK1-overexpressing ESCC cells. Further studies demonstrated that NUAK1 upregulated the transcription activity of Slug through activating the JNK/c-Jun pathway. Conclusion: These results demonstrated that NUAK1 promoted the metastasis of ESCC cells through activating JNK/c-Jun/Slug signaling, indicating NUAK1 is a promising therapeutic target for metastatic ESCC. [ABSTRACT FROM AUTHOR]

Snail family transcriptional repressor 2 (SNAI2, Slug) is a transcription factor that belong to the Slug/Snail superfamily. Site specific phosphorylation of slug (pSlugS158) is detected during the M phase, and thus, this phosphorylated protein is considered a novel marker for detecting mitotic figures. Herein, we investigated whether the detection of mitosis using pSlugS158 expression can be used in the histological grading of meningioma. We performed immunohistochemistry for pSlugS158 and PHH3 in tissue samples of 61 patients with meningioma and examined the association between mitotic counts using pSlugS158 and recurrence-free survival (RFS). The nuclear expression of pSlugS158 was observed in the cell with mitotic figures. Tumor grading based on pSlugS158 was significantly associated with the RFS (p <.001). It can be concluded that pSlugS158 is a useful and practical marker to detect mitosis and seems to be reliable for the counting of mitoses in histological grading of meningioma. [ABSTRACT FROM AUTHOR]

Breast carcinoma is now the most common cancer in the world. In view of its high mortality, there is a need to identify new prognostic biomarkers. Both IMP3 and SLUG have been implicated in cancer metastasis. This was a retrospective study conducted on 60 breast carcinoma cases using tissue microarrays. Demographic and clinicopathological details were recorded. Immunohistochemistry for IMP3 and SLUG was performed and evaluated in terms of percentage-cell-positivity and intensity of staining. A proforma was used to store data and was analyzed using SPSS v20. IMP3 positivity was found in 87% breast carcinoma cases and was significantly associated with tumor size (p = 0.03) and TNM stage (p = 0.024). IMP3 staining intensity showed significant association with histological grade (p = 0.009), TNM stage (p = 0.036), and molecular subtype (p = 0.03). SLUG immunoexpression was seen in 90% breast carcinoma cases and was significantly associated with TNM stage (p = 0.006). SLUG staining intensity was significantly associated with age (p = 0.025) and TNM stage (p = 0.004). IMP3 and SLUG immunopositivity and their staining intensities were significantly associated (p <0.001, p <0.001). IMP3 and SLUG percentage cell positivities were also significantly correlated (p <0.001). IMP3 and SLUG are, thus, poor prognostic markers with a role in tumor invasiveness and aggressiveness via epithelial-mesenchymal transition. Hence, IMP3 and SLUG-based targeted therapies may be useful in the treatment of breast carcinoma. [ABSTRACT FROM AUTHOR]

Phasmarhabditis californica, a commercially available biological control agent in England, Scotland, and Wales (Nemaslug 2.0 ®), was discovered for the first time in Washington State during 2022. Nematodes were recovered from the invasive gastropods Arion hortensis, Deroceras reticulatum, and Oxychilus sp. in garden centers in both Vancouver and Spokane. The 18S ribosomal RNA gene was used to identify the nematodes. This discovery builds upon previous reports of P. californica in California and Oregon and suggests that the species is widespread throughout the west coast of the U.S. Future research directions with P. californica are proposed.

Abstract Background Due to the lack of effective treatment, metastasis is the main cause of cancer related deaths. TGF-β pathway has been reported related to cervical cancer metastasis. However, mechanism is still unclear. Methods After agonist of TGF-β treatment, RNA sequencing revealed the expression profiles of circRNA in cervical cancer. In situ hybridization was used to analysis relationship between CDR1as and prognosis. Real-time PCR, Western blot, RNA interference, Transwell assay, Wound healing assay, RNA pulldown assay and RIP assays were performed in vitro. And in vivo cervical cancer model (including foot pad model and subcutaneous tumor formation) was also performed. Results CDR1as was found upregulated obviously following TGF-β activation. In situ hybridization showed CDR1as was positively correlated with lymph node metastasis and shortened survival length. Simultaneously, overexpression of CDR1as promoted cervical cancer metastasis in vitro and in vivo. It was also found that CDR1as could facilitate the orchestration of IGF2BP1 on the mRNA of SLUG and stabilize it from degradation. Silencing IGF2BP1 hampers CDR1as related metastasis in cervical cancer. Additionally, effective CDR1as has been proven to activate TGF-β signaling factors known to promote EMT, including P-Smad2 and P-Smad3. Conclusions Our study proved TGF-β signaling may promote cervical cancer metastasis via CDR1as.

Oilseed rape (OSR; Brassica napus) is a globally important crop which is increasingly under pressure from pests, pathogens and weeds. We investigated the potential of achieving multifunctional crop protection benefits by intercropping oilseed rape with legumes. A field experiment was conducted in which winter oilseed rape was intercropped with the annual frost sensitive legumes berseem clover (Trifolium alexandrinum) or spring faba bean (Vicia faba), or with the winter grain legumes winter faba bean or winter peas (Pisum sativum). We tracked damage to winter oilseed rape by autumn and spring pests (slugs and insects), pathogens, weed biomass, as well as oilseed rape and intercrop yield in each treatment. Intercropping treatments resulted in pest damage that was equivalent or lower than in oilseed rape alone. Follow up field and lab assessments for the frost sensitive legume intercrops provided evidence for a reduction in autumn pest damage to OSR. Each legume intercrop had its own benefits and drawbacks in relation to pest, pathogen and weed suppression, suggesting that the plant species selected for intercropping with oilseed rape should be based on the pests, pathogens and weeds of greatest concern locally to achieve relevant multifunctional benefits. Our study provides a framework for further experiments in which the multifunctional effects of intercropping on pests, pathogens and weeds can be quantified.

Actin is a protein of central importance to many cellular functions. Its localization and activity are regulated by interactions with a high number of actin-binding proteins. In a yeast two-hybrid (Y2H) screening system, snail family transcriptional repressor 2 (SNAI2 or slug) was identified as a yet unknown potential actin-binding protein. We validated this interaction using immunoprecipitation and analyzed the functional relation between slug and actin. Since both proteins have been reported to be involved in DNA double-strand break (DSB) repair, we focused on their interaction during this process after treatment with doxorubicin or UV irradiation. Confocal microscopy elicits that the overexpression of actin fused to an NLS stabilizes complexes of slug and γH2AX, an early marker of DNA damage repair.

Metastasis is the primary cause of death of hepatocellular carcinoma (HCC), while the mechanism underlying this severe disease remains largely unclear. The Kruppel‐like factor (KLF) family is one of the largest transcription factor families that control multiple physiologic and pathologic processes by governing the cellular transcriptome. To identify metastatic regulators of HCC, we conducted gene expression profiling on the MHCC97 cell series, a set of subclones of the original MHCC97 that was established by in vivo metastasis selection therefore harbouring differential metastatic capacities. We found that the expression of KLF9, a member of the KLF family, was dramatically repressed in the metastatic progeny clone of the MHCC97 cells. Functional studies revealed overexpression of KLF9 suppressed HCC migration in vitro and metastasis in vivo, while knockdown of KLF9 was sufficient to promote cell migration and metastasis accordingly. Mechanistically, we found the expression of KLF9 can reverse the pro‐metastatic epithelial‐mesenchymal transition (EMT) program via direct binding to the promoter regions of essential mesenchymal genes, thus repressing their expression. Interestingly, we further revealed that KLF9 was, in turn, directly suppressed by a mesenchymal transcription factor Slug, suggesting an intriguing negative feedback loop between KLF9 and the EMT program. Using clinical samples, we found that KLF9 was not only downregulated in HCC tissue compared to its normal counterparts but also further reduced in the HCC samples of whom had developed metastatic lesions. Together, we established a critical transcription factor that represses HCC metastasis, which is clinically and mechanically significant in HCC therapies. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the deadliest urological neoplasm. Up to date, no validated biomarkers are included in clinical guidelines for the screening and follow up of patients suffering from RCC. Slug (Snail2) and Snail (Snail1) belong to the Snail superfamily of zinc finger transcriptional factors that take part in the epithelial–mesenchymal transition, a process important during embryogenesis but also involved in tumor progression. We examined Slug and Snail immunohistochemical expression in patients with different stages of renal cell carcinomas with the aim to investigate their potential role as staging and prognostic factors. A total of 166 samples of malignant renal cell neoplasms were analyzed using tissue microarray and immunohistochemistry. Slug and Snail expressions were evaluated qualitatively (presence or absence), in nuclear and cytoplasmic cell compartments and compared in relation to clinical parameters. The Kaplan–Meier survival analysis showed the impact of the sarcomatoid component and Slug expression on the survival longevity. Cox regression analysis separated Slug as the only independent prognostic factor (p = 0.046). The expression of Snail was associated with higher stages of the disease (p = 0.004), especially observing nuclear Snail expression (p < 0.001). All of the tumors that had metastasized showed nuclear immunoreactivity (p < 0.001). In clear cell RCC, we showed a significant relationship between a high nuclear grade and nuclear Snail expression (p = 0.039). Our results suggest that Slug and Snail could be useful immunohistochemical markers for staging and prognosis in patients suffering from various RCCs, representing potential targets for further therapy strategies of renal cancer. [ABSTRACT FROM AUTHOR]

Most studies investigating the effect of habitat disturbance on biological invasions aim to evaluate whether disturbance promotes invasion success without identifying underlying mechanisms. However, these mechanisms are key to understand the role of habitat disturbance in biological invasions. Habitat attributes are known to be major determinants of alien plant invasions, but their role in alien animal invasions has been poorly studied, especially in disturbed habitats. To address this gap, we determined if logging can promote the invasion success of an alien slug species complex (Arion subfuscus s.l., hereafter Arion) (1) directly by making the habitat attributes more suitable for it, or (2) indirectly by causing the decline of native sympatric philomycid slugs (hereafter Philomycus), thus allowing Arion to "fill the void" left by native species decline. We surveyed Arion and Philomycus body mass and abundance (two common measures of invasion success), together with 10 habitat attributes, in logged and control stands, in two sites located in the temperate forest of southeastern Canada. Our findings suggest that logging promoted Arion invasion success either directly through logging-induced habitat changes, or indirectly with logging-induced habitat changes leading to Philomycus decline and Arion filling the void left by Philomycus decline. Taken together, our findings provide evidence that the mechanisms promoting Arion invasion success are site-specific. This study also highlights the importance of assessing more than one proxy of invasion success (e.g., abundance, body mass) to better understand the mechanisms associated with successful biological invasions. [ABSTRACT FROM AUTHOR]

B-cell leukemia/lymphoma 11A (BCL11A) may be one of the potential biomarkers of non-small cell lung cancer (NSCLC). However, its role in the development of this cancer has not yet been precisely established. The aim of this study was to investigate the expression of BCL11A at the mRNA and protein levels in NSCLC cases and non-malignant lung tissue (NMLT) and to determine the relationship between BCL11A expression and the clinicopathological factors and Ki-67, Slug, Snail and Twist. The localization and the level of BCL11A protein were examined using immunohistochemistry (IHC) on 259 cases of NSCLC, and 116 NMLT samples were prepared as tissue microarrays and using immunofluorescence (IF) in the following cell lines: NCI-H1703, A549 and IMR-90. The mRNA expression of BCL11A was determined using real-time PCR in 33 NSCLC cases, 10 NMLT samples and the cell lines. BCL11A protein expression was significantly higher in NSCLC cases compared to NMLT. Nuclear expression was found in lung squamous cell carcinoma (SCC) cells, while cytoplasmic expression was demonstrated in adenocarcinoma (AC) cells. Nuclear expression of BCL11A decreased with increasing malignancy grade and correlated positively with Ki-67 and Slug and Twist expression. The opposite relationships were found for the cytoplasmic expression of BCL11A. Nuclear expression of BCL11A in NSCLC cells may affect tumor cell proliferation and change their phenotype, thus promoting tumor progression. [ABSTRACT FROM AUTHOR]

Chronic inflammation facilitates tumor progression. We discovered that a subset of non-small cell lung cancer cells underwent a gradually progressing epithelial-to-mesenchymal (EMT) phenotype following a 21-day exposure to IL-1β, an abundant proinflammatory cytokine in the at-risk for lung cancer pulmonary and the lung tumor microenvironments. Pathway analysis of the gene expression profile and in vitro functional studies revealed that the EMT and EMT-associated phenotypes, including enhanced cell invasion, PD-L1 upregulation, and chemoresistance, were sustained in the absence of continuous IL-1β exposure. We referred to this phenomenon as EMT memory. Utilizing a doxycycline-controlled SLUG expression system, we found that high expression of the transcription factor SLUG was indispensable for the establishment of EMT memory. High SLUG expression in tumors of lung cancer patients was associated with poor survival. Chemical or genetic inhibition of SLUG upregulation prevented EMT following the acute IL-1β exposure but did not reverse EMT memory. Chromatin immunoprecipitation and methylation-specific PCR further revealed a SLUG-mediated temporal regulation of epigenetic modifications, including accumulation of H3K27, H3K9, and DNA methylation, in the CDH1 (E-cadherin) promoter following the chronic IL-1β exposure. Chemical inhibition of DNA methylation not only restored E-cadherin expression in EMT memory, but also primed cells for chemotherapy-induced apoptosis.

AbsractBACKGROUND: Tumor metastasis is the major reason for poor prognosis of hepatocellular carcinoma (HCC) patients after hepatic resection. SMYD3 has been demonstrated to promote liver tumor metastasis in mice. However, the detailed molecular mechanism is still largely unknown.MethodsThe effect of SMYD3 on invasiveness and metastasis of HCC was analyzed by immunohistochemistry, migration assay, invasion assay, wound healing assay and in vivo lung metastasis assay. Mass spectrometry analysis was conducted using proteins pulled down by H3K4me3 antibody in SMYD3-overexpressing cells. Luciferase reporter, chromatin immunoprecipitation, Electrophoretic mobility shift assay were used to measure the regulation of SLUG transcription by SMYD3-ANKHD1. In addition, the role of SMYD3-ANKHD1 in determining clinical outcomes for HCC patients was investigated by immunohistochemistry in 243 HCC tissues.ResultsSMYD3 was an independent prognostic factor of HCC and promoted migration and invasion of human HCC cells. ANKHD1 was identified by mass spectrometry as a co-regulator with SMYD3. ANKHD1 interacted with H3K4me3 when cells were overexpressing SMYD3. The pro-migratory and pro-invasive effects of SMYD3 were attenuated when ANKHD1 was knocked down by siRNA. Furthermore, we found that SMYD3 bound and activated the SLUG gene promoter in a manner associated with elevating H3K4me3, H3K9Ac and H3K14Ac. Knockdown of ANKHD1 could attenuate the SMYD3-dependent activation of Slug expression. We further detected the expression of SMYD3 and ANKHD1 in 243 HCC patients and found that patients with positive coexpression of SMYD3 and ANKHD1 (SMYD3+ANKHD1+) had the shortest overall and recurrence-free survival.ConclusionOur findings provide a novel molecular mechanism for the SMYD3-regulated HCC migration and metastasis, and indicates that SMYD3-ANKHD1 may be a potential target for treating HCC.

Abstract Background Many studies have reported the relationship between prognosis and Slug protein expression in breast cancer patients, but the results are discrepant. Therefore, there is a need for meta-analyses with high statistical power to investigate and further explore their relationship. Methods We used PubMed, Embase, the Cochrane Library, Scopus, MEDLINE, and the Web of Science to find studies on breast cancer and Slug. Overall survival (OS) and disease-free survival (DFS) were the study’s primary endpoints. We pooled hazard ratios (HRs) and odds ratios (ORs) to assess the association between Slug protein expression and prognostic and clinicopathological parameters. This study was performed using STATA version 14.0 for data analysis. (Stata Corporation, TX, USA). Results We conducted a literature search by searching six online databases. Ultimately, we obtained eight studies including 1458 patients through strict exclusion criteria. The results showed that increased Slug protein expression resulted in poorer OS (HR = 2.21; 95% CI = 1.47–3.33; P

Terrestrial slugs and snails are increasingly becoming serious pests of agricultural, horticultural and ornamental plants in Egypt, resulting in major economic losses.This paper provides a detailed morphological and anatomical description of the veronicellid slug Laevicaulis stuhlmanni (Simroth, 1895) that has been recently recorded from Egypt. This population from Egypt is compared with Laevicaulis populations recently reported and described from Libya as L. striatus (Simroth, 1896) and with available data in literature. Some notes and a distribution map of the veronicellids introduced in north-eastern Africa are provided.

Irisin (Ir) is an adipomyokine formed from fibronectin type III domain-containing protein 5 (FNDC5), which can be found in various cancer tissues. Additionally, FNDC5/Ir is suspected of inhibiting the epithelial-mesenchymal transition (EMT) process. This relationship has been poorly studied for breast cancer (BC). The ultrastructural cellular localizations of FNDC5/Ir were examined in BC tissues and BC cell lines. Furthermore, we compared serum levels of Ir with FNDC5/Ir expression in BC tissues. The aim of this study was to examine the levels of EMT markers, such as E-cadherin, N-cadherin, SNAIL, SLUG, and TWIST, and to compare their expression levels with FNDC5/Ir in BC tissues. Tissue microarrays with 541 BC samples were used to perform immunohistochemical reactions. Serum levels of Ir were assessed in 77 BC patients. We investigated FNDC5/Ir expression and ultrastructural localization in MCF-7, MDA-MB-231, and MDA-MB-468 BC cell lines and in the normal breast cell line (Me16c), which was used as the control. FNDC5/Ir was present in BC cell cytoplasm and tumor fibroblasts. FNDC5/Ir expression levels in BC cell lines were higher compared to those in the normal breast cell line. Serum Ir levels did not correlate with FNDC5/Ir expression in BC tissues but were associated with lymph node metastasis (N) and histological grade (G). We found that FNDC5/Ir correlated moderately with E-cadherin and SNAIL. Higher Ir serum level is associated with lymph node metastasis and increased grade of malignancy. FNDC5/Ir expression is associated with E-cadherin expression level. [ABSTRACT FROM AUTHOR]

In the epithelial–mesenchymal transition (EMT) process, cells lose their epithelial phenotype and gain mesenchymal features. This phenomenon was observed in the metastatic phase of neoplastic diseases, e.g., cervical cancer. There are specific markers that are expressed in the EMT. The aim of this study was to determine the localization of and associations between the immunohistochemical (IHC) expression of TWIST, SNAIL, and SLUG proteins in precancerous lesions and cervical cancer. The IHC analysis disclosed higher expressions of EMT markers in precancerous lesions and cervical cancer than in the control group. Moreover, stronger expression of TWIST, SNAIL, and SLUG was observed in cervical intraepithelial neoplasia grade 3 (CIN3) vs. CIN1, CIN3 vs. CIN2, and CIN2 vs. CIN1 cases (p < 0.05). In cervical cancer, IHC reactions demonstrated differences in TWIST, SNAIL, and SLUG expression in grade 1 (G1) vs. grade 2 (G2) (p < 0.0011; p < 0.0017; p < 0.0001, respectively) and in G1 vs. grade 3 (G3) (p < 0.0029; p < 0.0005; p < 0.0001, respectively). The results of our study clearly showed that existing differences in the expression of the tested markers in precancerous vs. cancerous lesions may be utilized in the diagnosis of cervical cancer. Further studies on bigger populations, as well as in comparison with well-known markers, may improve our outcomes. [ABSTRACT FROM AUTHOR]

Stress-mediated activation of the glucocorticoid receptor (GR) and specific stress-induced transcription factors stimulate herpes simplex virus 1 (HSV-1) productive infection, explant-induced reactivation, and immediate early (IE) promoters that drive expression of infected cell protein 0 (ICP0), ICP4, and ICP27. Several published studies concluded the virion tegument protein VP16, ICP0, and/or ICP4 drives early steps of reactivation from latency. Notably, VP16 protein expression was induced in trigeminal ganglionic neurons of Swiss Webster or C57BL/6J mice during early stages of stressinduced reactivation. If VP16 mediates reactivation, we hypothesized stress-induced cellular transcription factors would stimulate its expression. To address this hypothesis, we tested whether stress-induced transcription factors transactivate a VP16 cis-regulatory module (CRM) located upstream of the VP16 TATA box (2249 to 230). Initial studies revealed the VP16 CRM cis-activated a minimal promoter more efficiently in mouse neuroblastoma cells (Neuro-2A) than mouse fibroblasts (NIH-3T3). GR and Slug, a stress-induced transcription factor that binds enhancer boxes (E-boxes), were the only stress-induced transcription factors examined that transactivated the VP16 CRM construct. GR- and Slug-mediated transactivation was reduced to basal levels when the E-box, two 1/2 GR response elements (GREs), or NF-k B binding site was mutated. Previous studies revealed GR and Slug cooperatively transactivated the ICP4 CRM, but not ICP0 or ICP27. Silencing of Slug expression in Neuro-2A cells significantly reduced viral replication, indicating Slug-mediated transactivation of ICP4 and VP16 CRM activity correlates with enhanced viral replication and reactivation from latency. IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes lifelong latency in several types of neurons. Periodically cellular stressors trigger reactivation from latency. Viral regulatory proteins are not abundantly expressed during latency, indicating cellular transcription factors mediate early stages of reactivation. Notably, the glucocorticoid receptor (GR) and certain stress-induced transcription factors transactivate cis-regulatory modules (CRMs) essential for expression of infected cell protein 0 (ICP0) and ICP4, key viral transcriptional regulatory proteins linked to triggering reactivation from latency. Virion protein 16 (VP16) specifically transactivates IE promoter and was also reported to mediate early stages of reactivation from latency. GR and Slug, a stress-induced enhancer box (E-box) binding protein, transactivate a minimal promoter downstream of VP16 CRM, and these transcription factors occupy VP16 CRM sequences in transfected cells. Notably, Slug stimulates viral replication in mouse neuroblastoma cells suggesting Slug, by virtue of transactivating VP16 and ICP4 CRM sequences, can trigger reactivation in certain neurons. [ABSTRACT FROM AUTHOR]

Background: Esophageal Squamous Cell Carcinoma (ESCC) is a highly aggressive tumor with increased metastatic potential. Recent evidence suggests that esophageal CSCs have a crucial role in tumor initiation, progression, and resistance to conventional anti-cancer therapies. The study aimed to develop mouse model to mimic the late steps of the metastasis process using a tail-vein injection of esophageal CSCs. Methods and results: The sphere formation assay was used to enrich CSCs. For analysis of tumorigenicity, YM-1 adherent cells and enriched CSCs were injected subcutaneously into dorsal flank of nude mice. The expression of SLUG, E-cad, and CTHRC1 genes was examined by Real-Time qRT-PCR and immunohistochemistry (IHC) methods. To assess the metastatic potential of adherent YM-1 cells and their enriched CSCs, we injected the cells into the tail vein of nude mice. Our findings showed the up-regulation of SLUG and down-regulation of E-cad in the esophageal CSC-derived tumors (ECSCTs) compared to adherent cells-derived tumors. There was no statistically significant difference between CTHRC1 gene expressions in both groups of tumors. IHC staining confirmed the higher expression of SLUG protein in ECSCTs compared to adherent cell-derived tumors. Enriched CSCs were able to metastasize to the lungs and livers after three months, but, metastasis of adherent cells wasn't observed. Conclusion: Our study showed esophageal CSCs injected through the tail-vein injection can migrate and metastasize to the lung and liver after three months. The developed metastatic mouse model can be a valuable and relevant model to investigate the molecular and cellular mechanisms of metastasis and develop successful targeted therapies against ESCC. The present study is one of the few studies that investigate the metastasis of esophageal cancer stem cells (ESCC type) through injection into the tail vein of nude mice. [ABSTRACT FROM AUTHOR]

Transmission between hosts is crucial to the growth, development and reproduction of many parasites. As a consequence, parasites are under selection to maximise transmission success and exhibit many behavioural and morphological adaptations that allow detection of, and movement between, hosts. However, transmission success is not determined by parasites alone, but is also shaped by host behaviours. Often, host behaviours function to minimise the risk of exposure to parasites; in some cases, however, host behaviours may be manipulated by parasites to increase transmission success. In this study, we investigated transmission of the parasitic mite Riccardoella oudemansi between slug (Limacus maculatus) hosts, considering the role of both host and parasite behaviour in determining transmission success. Host-host transmission occurred when slugs were in physical contact, but mites were also capable of moving across the substrate to locate new hosts, a process facilitated by mucus trails. We found no strong evidence that slugs avoid parasitised conspecifics, or that mites manipulate slug behaviour to increase transmission. Finally, mites showed a preference for the mucus of parasitised slugs, but did not discriminate between mucus from their own host and another parasitised slug. A general preference for mucus from parasitised slugs is likely to be important in encouraging mites to remain in close contact with their host and may also facilitate host-switching and outbreeding. We encourage further study of parasitism by Riccardoella in limacid slugs, where cross-species variation in host social behaviour may drive differences in the rate and success of parasite transmission across slug species. [ABSTRACT FROM AUTHOR]

Background: Due to the lack of effective treatment, metastasis is the main cause of cancer related deaths. TGF-β pathway has been reported related to cervical cancer metastasis. However, mechanism is still unclear. Methods: After agonist of TGF-β treatment, RNA sequencing revealed the expression profiles of circRNA in cervical cancer. In situ hybridization was used to analysis relationship between CDR1as and prognosis. Real-time PCR, Western blot, RNA interference, Transwell assay, Wound healing assay, RNA pulldown assay and RIP assays were performed in vitro. And in vivo cervical cancer model (including foot pad model and subcutaneous tumor formation) was also performed. Results: CDR1as was found upregulated obviously following TGF-β activation. In situ hybridization showed CDR1as was positively correlated with lymph node metastasis and shortened survival length. Simultaneously, overexpression of CDR1as promoted cervical cancer metastasis in vitro and in vivo. It was also found that CDR1as could facilitate the orchestration of IGF2BP1 on the mRNA of SLUG and stabilize it from degradation. Silencing IGF2BP1 hampers CDR1as related metastasis in cervical cancer. Additionally, effective CDR1as has been proven to activate TGF-β signaling factors known to promote EMT, including P-Smad2 and P-Smad3. Conclusions: Our study proved TGF-β signaling may promote cervical cancer metastasis via CDR1as. [ABSTRACT FROM AUTHOR]

ObjectiveSquamous cell carcinoma (SCC) occurring in the tonsils (TSCC) has a poorer prognosis than SCC occurring in other regions of the oral cavity (non-tonsillar SCC [NTSCC]) because it easily metastasizes to distant organs. This study aimed to elucidate the molecular mechanisms underlying the migration and invasion of TSCC cells in vitro.Materials and methodsThis study focused on differential microRNA (miRNA) expression using microRNA microarrays and quantitative polymerase chain reaction in canine TSCC and NTSCC tissues and cell lines. A target gene of the miRNA involved in cell migration and invasion was validated by wound healing, transwell, and luciferase assays.ResultsmiR-203 expression was lower in TSCC tissues than in the normal oral mucosa and NTSCC tissues. Transfection of the miR-203 mimic resulted in the downregulation of mesenchymal marker protein expression and attenuation of cell migration and invasion in TSCC cells, but not in NTSCC cells. A dual-luciferase assay revealed that miR-203 directly targeted the mesenchymal transcription factor SLUG. SLUG overexpression enhances the migration of TSCC cells.ConclusionOur study indicates that the miR-203/SLUG axis may be involved in the metastatic mechanisms of TSCC.

We evaluated the hourly dynamics of ground-dwelling invertebrate communities in farmland using infrared camera traps between August and September 2022. No significant variations within 24 h nor between any two time points of each day were observed in the taxonomic richness and abundance of the entire community. However, the periods from 4:00 to 7:00 and 13:00 to 20:00 showed relatively high taxonomic richness, while those from 2:00 to 6:00 and 16:00 to 21:00 showed relatively high abundance. Millipede abundance varied significantly in a 24 h period, with higher abundance from 3:00 to 4:00 and 1:00 to 2:00. Additionally, slug, beetle, and grasshopper abundances were significantly higher from 22:00 to 23:00, 17:00 to 18:00, and 23:00 to 24:00, respectively. The abundance of other taxa did not show significant variations between any two time points of a day. Predominant generalist predators showed positive correlation in their activity times. These results suggest that significant variations within each 24 h period are uncommon at either community or taxa (except for millipedes) levels in farmland ground-dwelling invertebrates. Further, while most taxa had significantly preferred active hours, the total community did not. Therefore, hourly dynamics should be considered to understand biodiversity maintenance.

Pulmonary hypertension secondary to pulmonary fibrosis (PF-PH) is one of the most common causes of PH, and there is no approved therapy. The molecular signature of PF-PH and underlying mechanism of why pulmonary hypertension (PH) develops in PF patients remains understudied and poorly understood. We observed significantly increased vascular wall thickness in both fibrotic and non-fibrotic areas of PF-PH patient lungs compared to PF patients. The increased vascular wall thickness in PF-PH patients is concomitant with a significantly increased expression of the transcription factor Slug within the macrophages and its target prolactin-induced protein (PIP), an extracellular matrix protein that induces pulmonary arterial smooth muscle cell proliferation. We developed a novel translational rat model of combined PF-PH that is reproducible and shares similar histological features (fibrosis, pulmonary vascular remodeling) and molecular features (Slug and PIP upregulation) with human PF-PH. We found Slug inhibition decreases PH severity in our animal model of PF-PH. Our study highlights the role of Slug/PIP axis in PF-PH.

Abstract Background Downregulation of epithelial markers and upregulation of mesenchymal markers are the characteristics of the epithelial to mesenchymal transition (EMT) program, which provides the metastatic advantage of breast cancer. However, the mechanism underlying the switch of EMT markers remains poorly understood. Methods In this study, we used the affinity purification and mass spectrometry coupled approach to identify the interactome of Slug. CoIP, GST-pulldown, ChIP, Re-ChIP, qPCR and Immunoblot were used to investigate the underlying mechanism of Slug-PRMT5-LSD1 complex. The role of PRMT5 and LSD1 in breast cancer progression was evaluated both in vivo and in vitro. Results Here we found that the transcription factor Slug associates with PRMT5 and LSD1 in a complex and facilitates the breast cancer invasion in vitro. Mechanistically, PRMT5 and LSD1 work with Slug to exert dual transcriptional activities to inhibit E-cadherin expression by PRMT5-catalyzed H4R3me2s and LSD1-mediated demethylation of H3K4me2 on the E-cadherin (CDH1) promoter, and activate vimentin (VIM) expression via PRMT5-driven H3R2me2s and LSD1-mediated removal of H3K9me2. Importantly, PRMT5 and LSD1 are coordinately expressed in breast cancer patients and pharmacologic perturbation of both PRMT5 and LSD1 shows a synergetic effect on the inhibition of breast tumor growth and metastasis in vivo. Conclusions Our study suggests that PRMT5 and LSD1 function as a dual epigenetic modifier to promote Slug induced EMT program, suggesting that the inhibition of PRMT5 and LSD1 presents a potential therapeutic strategy against cancer metastasis.

Invasive species are one of the main causes of biodiversity loss worldwide. Pet trade is a well-known pathway for the introduction of non-native species. Prevention is the most effective, least time-consuming, and least financially demanding way to protect biodiversity against the spreading of invasive species. The main part of prevention is the early detection of a potentially high-risk species, as well as the successful implementation of prevention strategies in legislation and practice. This study summarizes the pre-introduction screening of pet-traded terrestrial gastropod species and their potential occurrence in the EU territory. Based on the list of species traded in the Czech Republic, one of the most important global hubs of the pet trade, 51 species (49 snails and 2 slugs) were analysed. Due to a lack of certain native occurrence data, only 29 species (28 snails and 1 slug) from 10 families were modelled using MaxEnt software. Twenty species from seven families have potential occurrence in the EU territory. Based on MaxEnt modelling, we considered the following species to be high-risk candidates for the EU: Anguispira alternata, A. strongylodes, Laevicaulis alte, Megalobulismus oblongus, Rumina decollata, and R. saharica. Based on this estimation, we present considerations with which to further improve the risk assessment and recommend continuous monitoring of the pet trade market. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal plasticity comprises reversible transitions among epithelial, hybrid epithelial/mesenchymal (E/M) and mesenchymal phenotypes, and underlies various aspects of aggressive tumor progression such as metastasis, therapy resistance, and immune evasion. The process of cells attaining one or more hybrid E/M phenotypes is termed as partial epithelial mesenchymal transition (EMT). Cells in hybrid E/M phenotype(s) can be more aggressive than those in either fully epithelial or mesenchymal state. Thus, identifying regulators of hybrid E/M phenotypes is essential to decipher the rheostats of phenotypic plasticity and consequent accelerators of metastasis. Here, using a computational systems biology approach, we demonstrate that SLUG (SNAIL2) – an EMT-inducing transcription factor – can inhibit cells from undergoing a complete EMT and thus stabilize them in hybrid E/M phenotype(s). It expands the parametric range enabling the existence of a hybrid E/M phenotype, thereby behaving as a phenotypic stability factor. Our simulations suggest that this specific property of SLUG emerges from the topology of the regulatory network it forms with other key regulators of epithelial-mesenchymal plasticity. Clinical data suggest that SLUG associates with worse patient prognosis across multiple carcinomas. Together, our results indicate that SLUG can stabilize hybrid E/M phenotype(s). [ABSTRACT FROM AUTHOR]

This study has reviewed the naturally occurring bioadhesives produced in marine and freshwater aqueous environments and in the mucinous exudates of some terrestrial animals which have remarkable properties providing adhesion under difficult environmental conditions. These bioadhesives have inspired the development of medical bioadhesives with impressive properties that provide an effective alternative to suturing surgical wounds improving closure and healing of wounds in technically demanding tissues such as the heart, lung and soft tissues like the brain and intestinal mucosa. The Gecko has developed a dry-adhesive system of exceptional performance and has inspired the development of new generation re-usable tapes applicable to many medical procedures. The silk of spider webs has been equally inspiring to structural engineers and materials scientists and has revealed innovative properties which have led to new generation technologies in photonics, phononics and micro-electronics in the development of wearable biosensors. Man made products designed to emulate the performance of these natural bioadhesive molecules are improving wound closure and healing of problematic lesions such as diabetic foot ulcers which are notoriously painful and have also found application in many other areas in biomedicine. Armed with information on the mechanistic properties of these impressive biomolecules major advances are expected in biomedicine, micro-electronics, photonics, materials science, artificial intelligence and robotics technology. [ABSTRACT FROM AUTHOR]

Abstract Objective Portal mesenchymal cells induce the epithelial differentiation of the bile ducts in the developing liver via one of the Delta-Notch signaling components, JAGGED1. Although this differential induction is crucial for normal liver physiology as its genetic disorder (Alagille syndrome) causes jaundice, the molecular mechanism behind JAGGED1 expression remains unknown. Here, we searched for upstream regulatory transcription factors of JAGGED1 using an integrated bioinformatics method. Results According to the DoRothEA database, which integrates multiple lines of evidence on the relationship between transcription factors and their downstream target genes, three transcription factors were predicted to be upstream of JAGGED1: SLUG, SOX2, and EGR1. Among these, SLUG and EGR1 were enriched in ACTA2-expressing portal mesenchymal cells in two previously reported human fetal liver single-cell RNA-seq datasets. JAGGED1-expressing portal mesenchymal cells tended to express SLUG rather than EGR1, supporting that SLUG induced JAGGED1 expression. Together with the higher confidentiality of SLUG (DoRothEA level A) over EGR1 (DoRothEA level D), we concluded that SLUG was one of the most important candidate transcription factors upstream of JAGGED1. These results add mechanistic insights into the developmental biology of how portal mesenchymal cells support biliary development in the liver.

Abstract Background Lymph node metastasis is the main cause of poor prognosis of head and neck squamous carcinoma (HNSCC) patients. N6-methyladenosine (m6A) RNA modification is an emerging epigenetic regulatory mechanism for gene expression, and as a novel m6A reader protein, IGF2BP2 has been implicated in tumor progression and metastasis. However, not much is currently known about the functional roles of IGF2BP2 in HNSCC, and whether IGF2BP2 regulates lymphatic metastasis through m6A modification in HNSCC remains to be determined. Methods The expression and overall survival (OS) probability of m6A-related regulators in HNSCC were analyzed with The Cancer Genome Atlas (TCGA) dataset and GEPIA website tool, respectively. The expression levels of IGF2BP2 were measured in HNSCC tissues and normal adjacent tissues. To study the effects of IGF2BP2 on HNSCC cell metastasis in vitro and in vivo, gain- and loss- of function methods were employed. RIP, MeRIP, luciferase reporter and mRNA stability assays were performed to explore the epigenetic mechanism of IGF2BP2 in HNSCC. Results We investigated 20 m6A-related regulators in HNSCC and discovered that only the overexpression of IGF2BP2 was associated with a poor OS probability and an independent prognostic factor for HNSCC patients. Additionally, we demonstrated that IGF2BP2 was overexpressed in HNSCC tissues, and significantly correlated to lymphatic metastasis and poor prognosis. Functional studies have shown that IGF2BP2 promotes both HNSCC cell migration as well as invasion via the epithelial-mesenchymal transition (EMT) process in vitro, and IGF2BP2 knockdown significantly inhibited lymphatic metastasis and lymphangiogenesis in vivo. Mechanistic investigations revealed that Slug, a key EMT-related transcriptional factor, is the direct target of IGF2BP2, and essential for IGF2BP2-regulated EMT and metastasis in HNSCC. Furthermore, we demonstrated that IGF2BP2 recognizes and binds the m6A site in the coding sequence (CDS) region of Slug and promotes its mRNA stability. Conclusions Collectively, our study uncovers the oncogenic role and potential mechanism of IGF2BP2, which serves as a m6A reader, in controlling lymphatic metastasis and EMT in HNSCC, suggesting that IGF2BP2 may act as a therapeutic target and prognostic biomarker for HNSCC patients with metastasis.

Partial epithelial‐to‐mesenchymal transition (pEMT) contributes to cellular heterogeneity that is associated with nodal metastases and unfavorable clinical parameters in head and neck squamous cell carcinomas (HNSCCs). We developed a single‐cell RNA sequencing signature‐based pEMT quantification through cell type‐dependent deconvolution of bulk RNA sequencing and microarray data combined with single‐sample scoring of molecular phenotypes (Singscoring). Clinical pEMT‐Singscores served as molecular classifiers in multivariable Cox proportional hazard models and high scores prognosticated poor overall survival and reduced response to irradiation as independent parameters in large HNSCC cohorts [The Cancer Genome Atlas (TCGA), MD Anderson Cancer Centre (MDACC), Fred Hutchinson Cancer Research Center (FHCRC)]. Differentially expressed genes confirmed enhanced cell motility and reduced oxidative phosphorylation and epithelial differentiation in pEMThigh patients. In patients and cell lines, the EMT transcription factor SLUG correlated most strongly with pEMT‐Singscores and promoted pEMT, enhanced invasion, and resistance to irradiation in vitro. SLUG protein levels in HNSCC predicted disease‐free survival, and its peripheral expression at the interphase to the tumor microenvironment was significantly increased in relapsing patients. Hence, pEMT‐Singscores represent a novel risk predictor for HNSCC stratification regarding clinical outcome and therapy response that is partly controlled by SLUG.

Highlights Skip N2 metastasis is related with better on-year survival rates in Lung Adenocarcinoma EMT regulator gene SLUG expression is suppressed in Skip N2 compared to Non-Skip N2 metastasis. Tumor metastatic site exhibit less Vimentin staining at Skip N2 lymph node Bioinformatic analyzes show that one of the genes with the highest expression correlation with SLUG was TP63, suggesting that they may be acting together in this process.