Advocacy in pediatric gastroenterology: An academic clinician's impact and guide.

The current state of policy-making necessitates clinicians and their organizations to be more engaged. This article provides practical examples of how to engage in various levels of advocacy within pediatric gastroenterology.

Pneumothorax and pulmonary hemorrhage after C-arm cone-beam computed tomography-guided percutaneous transthoracic lung biopsy: incidence, clinical significance, and correlation.

OBJECTIVE: This study aimed to assess the incidence and clinical significance of pneumothorax (PTX) and pulmonary hemorrhage (PH) after percutaneous transthoracic lung biopsy (PTLB) guided by C-arm cone-beam computed tomography (CBCT). Furthermore, this study aimed to examine the relationships between PTX and PH with demographics, clinical characteristics, imaging, and PTLB parameters. METHODS: A retrospective analysis was conducted on 192 patients who underwent PTLB at our hospital between January 2019 and October 2022. Incidences of PTX and PH were recorded. PTX was considered clinically significant if treated with chest tube insertion (CTI), and PH if treated with bronchoscopes or endovascular treatments. The various factors on PTX and PH were analyzed using the Chi-squared test and Student t-test. Logistic regression analyses were then used to determine these factors on the correlation to develop PTX and PH. RESULTS: PTX occurred in 67/192 cases (34.9%); CTI was required in 5/67 (7.5%). PH occurred in 63/192 cases (32.8%) and none of these cases required bronchoscopes or endovascular treatments. Lesion diameter (ORPTX = 0.822; ORPH = 0.785), presence of pulmonary emphysema (ORPH = 2.148), the number of samples (ORPH = 1.834), the use of gelfoam (ORPTX = 0.474; ORPH = 0.341) and ablation (ORPTX = 2.351; ORPH = 3.443) showed statistically significant correlation to PTX and PH. CONCLUSIONS: CBCT-guided PTLB is a safe and effective method for performing lung biopsies. The use of gelfoam has been shown to reduce the occurrence of PTX and PH. However, caution should be exercised when combining radiofrequency ablation with PTLB, as it may increase the risk of PTX and PH.

Enhancing the health knowledge and health literacy of recently resettled refugees through classroom-based instructional methods.

Health education can elevate health literacy, which is associated with health knowledge, health-seeking behaviors and overall improved health outcomes. Refugees are particularly vulnerable to the effects of low health knowledge and literacy, which can exacerbate already poor health stemming from their displacement experience. Traditional learning methods including classroom-based instruction are typically how health-related information is presented to refugees. Through a series of interactive classes focused on specific health topics relevant to the resettled refugee population, this study evaluated the effectiveness of a classroom-based health education model in enhancing the health knowledge of recently resettled refugees. We used the Wilcoxon signed-rank test to evaluate differences in pre- and post-class knowledge through test performance. We found a significant improvement in health knowledge in two refugee groups: females and those who were employed. Culturally and socially sensitive considerations including language inclusiveness, class timing, transportation and childcare provisions are important when creating an educational program for individuals with refugee backgrounds. Developing focused approaches to instruction that enhance health knowledge could lead to better health literacy and ultimately improve health-related behaviors and outcomes in the refugee population.

Parental Depression and Self-Stigma Among Chinese Young People Living With Depression: A Qualitative Study.

Self-stigma is detrimental to psychosocial well-being and the recovery journey among people living with depression. However, there has been limited research exploring the experience of stigma internalization when depression runs in families. This study aims to address this gap by (1) characterizing the manifestations of self-stigma among individuals living with depression whose parent(s) also have depression and (2) exploring the potential mechanisms underlying the impact of parental depression on self-stigma. Essential principles of the constructivist grounded theory approach were adopted to collect data through in-depth interviews with 27 participants aged 15-30, living in Mainland China. Many participants perceived depression running in their family as an endless disaster and an incurable illness. These beliefs further led to stigmatizing emotions (such as suppression, anger, and guilt) and behaviors (such as concealment and social withdrawal). Participants also highlighted ambivalent intergenerational relationships, tense family atmospheres, lower parental emotional involvement and support, and a lack of family flexibility due to parental depression. Furthermore, parental depression impacted participants' self-stigma by interfering with family relationships, family functioning, and parenting styles. It also shaped their perceptions of family, illness attribution, and public stigma. Additionally, parental depression had an impact on participants' social functioning, self-esteem, and personality, making them more susceptible to self-stigma. This study emphasizes the crucial role that the family plays in the internalization of stigma among individuals living with depression. It suggests that family dynamics, rather than family structure or economic backgrounds alone, shape this process.

Nutrition Content of Young Child Formulas.

OBJECTIVE: European Society for Pediatric Gastroenterology, Hepatology and Nutrition and the American Academy of Pediatrics state that young child formula (YCF) is not considered necessary for healthy children. Despite these recommendations, YCF accounts for approximately 13% of overall formula sales. Five percent of infants less than 1 year of age in the United States are being fed YCF. The purpose of this study is to identify the most Internet recommended and encountered YCF in the United States and determine if they meet nutritional recommendations for use in children 0-3 years. STUDY DESIGN: We used the search terms "toddler formula," "toddler milk," "follow-up formula," or "young child formula" in Google and DuckDuckGo to identify the most like encountered or recommended YCF on the Internet. We compared their labeled nutrients to Food and Drug Administration (FDA) Infant Formula Act (IFA) and international nutrient recommendations, given the absence of US nutrient requirements for YCF recommendations, for children 12-36 months. RESULTS: Twenty-nine YCF were reviewed. On average, YCF did not meet nutrient recommendations for infants and toddlers with 2.17 and 4.6 ingredients not meeting formula recommendations for younger and older infants, respectively, and between 3 and 4 ingredients for 12-36 months. CONCLUSIONS: Nutrition content of YCF are variable and do not meet FDA IFA requirements or YCF international recommendations. Increased US regulation is needed for YCF. It is important for health care providers to ask patients what they are feeding their infants and toddlers so they can educate parents on potential nutritional safety concerns.

Sociodemographic Differences of Hospitalization and Associations of Resource Utilization for Failure to Thrive.

OBJECTIVES: This study examines the sociodemographic differences between elective and nonelective admissions for failure to thrive (FTT). We investigate associations between admission type and hospital resource utilization, including length of stay and feeding tube placement. METHODS: We included children <2 years old with FTT in the nationwide Kids' Inpatient Database. We described differences between elective and nonelective admissions using Fisher exact and t tests. To assess associations of admission type and hospital resource utilization, we used negative binomial and logistic regression for length of stay and feeding tube placement, respectively. RESULTS: In this study of 45,920 admissions (37,224 nonelective vs 8696 elective), we found differences by race and ethnicity, income, and insurance type, among other factors. Compared to elective admissions, nonelective admissions had higher proportions of infants who were Black, Hispanic, and of lower-income. Nonelective admissions were associated with longer lengths of stay (incidence rate ratio 1.46; 95% CI: 1.37-1.55), independent of child age, sex, neighborhood income, insurance, admission day, chronic conditions, and location. Nonelective admissions were associated with lower odds of feeding tube placement compared to elective admissions (adjusted odds ratio 0.62; 0.56-0.68). In the stratified analyses, children of racial and ethnic minority groups admitted nonelectively versus electively had relatively higher odds of feeding tube placement, while White children had relatively lower odds of feeding tube placement. CONCLUSION: There are various sociodemographic differences between elective and nonelective FTT admissions. Future research is warranted to elucidate drivers of these differences, particularly those related to racial and ethnic disparities and structural racism.

Model-based reinforcement learning with non-Gaussian environment dynamics and its application to portfolio optimization.

The rapid development of quantitative portfolio optimization in financial engineering has produced promising results in AI-based algorithmic trading strategies. However, the complexity of financial markets poses challenges for comprehensive simulation due to various factors, such as abrupt transitions, unpredictable hidden causal factors, and heavy tail properties. This paper aims to address these challenges by employing heavy-tailed preserving normalizing flows to simulate the high-dimensional joint probability of the complex trading environment under a model-based reinforcement learning framework. Through experiments with various stocks from three financial markets (Dow, NASDAQ, and S&P), we demonstrate that Dow outperforms the other two based on multiple evaluation metrics in our testing system. Notably, our proposed method mitigates the impact of unpredictable financial market crises during the COVID-19 pandemic, resulting in a lower maximum drawdown. Additionally, we explore the explanation of our reinforcement learning algorithm, employing the pattern causality method to study interactive relationships among stocks, analyzing dynamics of training for loss functions to ensure convergence, visualizing high-dimensional state transition data with t-SNE to uncover effective patterns for portfolio optimization, and utilizing eigenvalue analysis to study convergence properties of the environment's model.

Adult astrocytes from reptiles are resistant to proinflammatory activation via sustaining Vav1 expression.

Adult mammalian astrocytes are sensitive to inflammatory stimuli in the context of neuropathology or mechanical injury, thereby affecting functional outcomes of the central nervous system (CNS). In contrast, glial cells residing in the spinal cord of regenerative vertebrates exhibit a weak astroglial reaction similar to those of mammals in embryonic stages. Macrophage migration inhibitory factor (MIF) participates in multiple neurological disorders by activation of glial and immune cells. However, the mechanism of astrocytes from regenerative species, such as gecko astrocytes (gAS), in resistance to MIF-mediated inflammation in the severed cords remains unclear. Here, we compared neural stem cell markers among gAS, as well as adult (rAS) and embryonic (eAS) rat astrocytes. We observed that gAS retained an immature phenotype resembling rat eAS. Proinflammatory activation of gAS with gecko (gMIF) or rat (rMIF) recombinant protein was unable to induce the production of inflammatory cytokines, despite its interaction with membrane CD74 receptor. Using cross-species screening of inflammation-related mediators from models of gMIF- and rMIF-induced gAS and rAS, we identified Vav1 as a key regulator in suppressing the inflammatory activation of gAS. The gAS with Vav1 deficiency displayed significantly restored sensitivity to inflammatory stimuli. Meanwhile, gMIF acts to promote the migration of gAS through regulation of CXCL8 following cord lesion. Taken together, our results suggest that Vav1 contributes to the regulation of astrocyte-mediated inflammation, which might be beneficial for the therapeutic development of neurological diseases.

Survey-Based Study on Food Insecurity During COVID-19 for Households With Children on a Prescribed Gluten-Free Diet.

Gluten-free (GF) foods are generally costlier than their gluten-containing counterparts. We conducted an anonymous electronic survey to assess food insecurity in households with a child on a prescribed GF diet and how this relates to GF diet adherence during the COVID-19 pandemic. The proportion of households who screened positive using the Hunger Vital Sign was similar to national rates (19%-24%). Approximately 5% of families who screened food secure reported GF food insecurity. Parent-reported intentional gluten consumption due to limited GF food availability in the household increased during the pandemic (7.5%). Food insecurity should be considered in the management of celiac disease.

Macrophages promote growth, migration and epithelial-mesenchymal transition of renal cell carcinoma by regulating GSDMD/IL-1ß axis.

BACKGROUND: Macrophages are highly enriched in renal cell carcinoma, and the inflammatory cytokines secreted by macrophages are remarkably associated with the survival rate of renal cell carcinoma. However, the relationship between gasdermin D (GSDMD) expression driven by macrophage and the invasion of renal cell carcinoma is not clear. METHODS: The Caki-2 and 786-O cells were co-cultured with monocytes cells (THP-1) derived macrophages, then the bio function changes of Caki-2 and 786-O cells and epithelial-mesenchymal transition of cancer cells were detected. Also, the role of IL-1ß in Caki-2 and 786-O cells and macrophage interaction were investigated. Then, the animal model was used to confirm the role of communication of GSDMD with renal cell carcinoma in the tumor microenvironment. RESULTS: CD68 and GSDMD were overexpressed in human renal cell carcinoma. GSDMD contributed to the secretion of IL­1ß in macrophages and was associated with the proliferation rate of renal cell carcinoma cells. Furthermore, silencing GSDMD elicited renal cell carcinoma cells motility through epithelial-mesenchymal transition change. The in vivo study confirmed that GSDMD promoted tumor progression and GSDMD knockout impaired renal cell carcinoma growth and metastases. Finally, the interactions between macrophages and renal cell carcinoma cells promoted renal cell carcinoma proliferation and metastasis, possibly mediated by IL-1ß. CONCLUSION: To our knowledge, this study showed that the GSDMD expressed by macrophages contributed to renal cell carcinoma cell growth, metastases, and epithelial-mesenchymal transition through regulating GSDMD/IL-1ß axis and may be a novel therapeutic target and a potential biomarker for treating and diagnosing renal cell carcinoma.

Efficacy and safety of anti-PD-1/PD-L1 therapy in the treatment of advanced colorectal cancer: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors have shown promise in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) advanced colorectal cancer (CRC) immunotherapy, and many clinical trials have been conducted. OBJECTIVE: To evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in advanced CRC. METHOD: PubMed, Web of Science, Embase, and The Cochrane Library were searched for relevant studies up to September 2021. A retrospective cross-sectional data analysis was performed and Stata 16 software was used for analyses. RESULTS: Sixteen studies including 1503 patients were analyzed. The objective response rate (ORR) of anti-PD-1/PD-L1 was 23% (95% CI 0.14, 0.31); the overall 1-year survival rate (OSR) was 57% (95% CI 0.42, 0.73). The ORR of MSI-H/dMMR advanced CRC was 37% (95% CI 0.25, 0.48) and that of microsatellite stable/mismatch repair proficient (MSS/pMMR) disease was 11% (95% CI 0.06, 0.16). The ORR was 42% in the BRAF mutant subgroup and 19% in the RAS mutant group. The ORR was 14% in the PD-L1 ( +) subgroup and 32% in the PD-L1(-) subgroup. The rate of adverse effects was 85% (95% CI 0.80, 0.91). CONCLUSION: Anti-PD-1/PD-L1 therapy in MSI-H/dMMR advanced CRC was associated with improved survival. Anti PD-1/PD-L1 combined with antiangiogenic drugs, targeted agents, or chemotherapy might be effective in MSS mCRC. Immunotherapy was effective for the BRAF mutant and KRAS/NRAS(RAS) mutant CRC. Low expression of PD-L1 was a potential predictive marker for positive response and outcome. The high incidence of adverse events at 85% was worthy of further investigation. Further analysis with a higher number of high-quality studies is needed to verify the conclusions.

Nutritional and Safety Concerns of Infant Feeding Trends.

OBJECTIVE: The American Academy of Pediatrics (AAP) and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommend either exclusively breastfeeding for at least 6 months or an u.S. Food and Drug Administration-reviewed infant formula or donor breast milk from an established milk bank as alternatives. The purpose of this study was to establish the prevalence of contemporary infant feeding practices such as informal human milk sharing, imported European infant formula, toddler formula and homemade formula and gain insight into the parental reasoning for their choices. STUDY DESIGN: An anonymous, cross-sectional, voluntary electronic survey was sent to active prescribers to a Yumi (a baby food subscription company) list server in April and May 2021. Basic demographic, utilization of infant feeding practices and general feeding practices were collected. RESULTS: Of 2315 respondents, at least 18% of the families were following at least one contemporary feeding practice. Thirty six percent of parents using donor breast milk obtained it from unregulated sources, 14% of the respondents were using European infant formula, 5% were using toddler formula for their infants, and 2% were making homemade infant formula. CONCLUSION: The AAP has clear guidelines on infant nutrition and breastfeeding and when not possible, FDA reviewed infant formula or donor breast milk from an established milk bank as alternatives. Yet, our study found that at least 18% of the families across the united States were following at least one contemporary feeding practice with possible nutritional and safety concerns. it is important for pediatric gastroenterologists and dieticians to ask their patients how they are feeding their infants and be aware of these feeding practices that may pose significant health risks.

circYap inhibits oral squamous cell carcinoma by arresting cell cycle.

OBJECTIVE: Circular RNAs (circRNAs) involve in the development and progression of tumour. The mechanism of circRNAs in oral squamous cell carcinoma (OSCC) has remained unclear. This study aimed to investigate the role of circular Yes-associated protein (circYap) in OSCC. METHODS: Quantification reverse transcription-polymerase chain reaction (qRT-PCR) was applied to measure circYap expression in patients with OSCC tissues and cells. Flow cytometry was performed to evaluate cell cycle. circYap interaction with CDK4 was detected by RNA immunoprecipitation (RIP) and RNA pull-down. The interaction of Cyclin D1 and CDK4 was determined using co-immunoprecipitation (co-IP). RESULTS: We showed that circYap expression was downregulated in OSCC tissues. Using small interfering circular (Si-circYap) and overexpression plasmid, we found that circYap overexpression inhibited proliferation and arrested cell cycle in OSCC cells, while, circYap knockdown yielded the opposite result. Cyclin D1/CDK4 complexes and nuclear translocation is essential for cell cycle progression. We found that CDK4 interacted with circYap was increased when circYap overexpression, meanwhile, Cyclin D1/CDK4 complexes and of nuclear distribution were decreased. CONCLUSIONS: Our findings suggest that circYap impedes progression of OSCC. Overexpression of circYap suppresses proliferation and cell cycle through binding to CDK4 to block formation and nuclear translocation of Cyclin D1/CDK4 complexes. Thus, circYap may serves as a valuable therapeutic target for OSCC.

Improving protein domain classification for third-generation sequencing reads using deep learning.

BACKGROUND: With the development of third-generation sequencing (TGS) technologies, people are able to obtain DNA sequences with lengths from 10s to 100s of kb. These long reads allow protein domain annotation without assembly, thus can produce important insights into the biological functions of the underlying data. However, the high error rate in TGS data raises a new challenge to established domain analysis pipelines. The state-of-the-art methods are not optimized for noisy reads and have shown unsatisfactory accuracy of domain classification in TGS data. New computational methods are still needed to improve the performance of domain prediction in long noisy reads. RESULTS: In this work, we introduce ProDOMA, a deep learning model that conducts domain classification for TGS reads. It uses deep neural networks with 3-frame translation encoding to learn conserved features from partially correct translations. In addition, we formulate our problem as an open-set problem and thus our model can reject reads not containing the targeted domains. In the experiments on simulated long reads of protein coding sequences and real TGS reads from the human genome, our model outperforms HMMER and DeepFam on protein domain classification. CONCLUSIONS: In summary, ProDOMA is a useful end-to-end protein domain analysis tool for long noisy reads without relying on error correction.

Hypoxia downregulated miR-4521 suppresses gastric carcinoma progression through regulation of IGF2 and FOXM1.

BACKGROUND: MicroRNAs (miRNAs) show considerable promise as therapeutic agents to improve tumor treatment, as they have been revealed as crucial modulators in tumor progression. However, our understanding of their roles in gastric carcinoma (GC) metastasis is limited. Here, we aimed to identify novel miRNAs involved in GC metastasis and explored their regulatory mechanisms and therapeutic significance in GC. METHODS: The microRNA expression profiles of GC tumors at different stages and at different metastasis statuses were compared respectively using the stomach adenocarcinoma (STAD) miRNASeq dataset in TCGA. Using the above method, miR-4521 was picked out for further study. miR-4521 expression in GC tissues was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). Highly and lowly invasive cell sublines were established using a repetitive transwell assay. Gain-of-function and loss-of-function analyses were performed to investigate the functions of miR-4521 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Moreover, we investigated the therapeutic role of miR-4521 in a mouse xenograft model. RESULTS: In this study, we found that miR-4521 expression was downregulated in GC tissues compared with adjacent normal tissues and that its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. Functional experiments revealed that miR-4521 inhibited GC cell invasion and metastasis in vitro and in vivo. Further studies showed that hypoxia repressed miR-4521 expression via inducing ETS1 and miR-4521 mitigated hypoxia-mediated metastasis, while miR-4521 inactivated the AKT/GSK3ß/Snai1 pathway by targeting IGF2 and FOXM1, thereby inhibiting the epithelial-mesenchymal transition (EMT) process and metastasis. In addition, we demonstrated that therapeutic delivery of synthetic miR-4521 suppressed gastric carcinoma progression in vivo. CONCLUSIONS: Our results suggest an important role for miR-4521 in regulating GC metastasis and hypoxic response of tumor cells as well as the therapeutic significance of this miRNA in GC.

Disparities in Telehealth Utilization Within Pediatric Gastroenterology: One Academic Center's Experience.

OBJECTIVES: While the use of telemedicine has accelerated significantly with the recent pandemic, it has also magnified disparities in access to telemedicine. This study aims to look at telemedicine utilization patterns within a large pediatric gastroenterology practice. METHODS: A retrospective study of ambulatory care visits within Yale-New Haven Hospital's pediatric gastroenterology practice during the peak expansion of the telemedicine program was conducted. Zip code-level socioeconomic data were obtained using the Distressed Communities Index. A multivariate logistic regression to evaluate disparities between the use of video versus telephone visits was computed, and unadjusted and adjusted odds ratios with 95% confidence intervals (CIs) were obtained. RESULTS: A total of 1273 clinic visits were included in analysis. The majority of the patients listed English as their preferred language, had private insurance, and identified as non-Hispanic White. When adjusting for co-variates, having public insurance/Medicaid was associated with decreased odds of having video over telephone visits (adjusted odds ratio [aOR] 0.60; 95% CI 0.44-0.80). Those whose primary language was not English continued to have a statistically significant decreased odds of using video visits (Spanish aOR 0.24; 95% CI 0.13-0.44; other aOR 0.29; 95% CI 0.12-0.72). Within the adjusted multivariate logistic regression, race/ethnicity and SES were, however, no longer found to have a statistically significant decreased odds of video visits. CONCLUSIONS: The accelerated implementation of telemedicine within pediatric gastroenterology has given rise to disparities in its use. Further studies are needed to understand these disparities and develop interventions to lessen this gap in usage.

Detecting Bacterial Cell Viability in Few µL Solutions from Impedance Measurements on Silicon-Based Biochips.

Using two different types of impedance biochips (PS5 and BS5) with ring top electrodes, a distinct change of measured impedance has been detected after adding 1-5 µL (with dead or live Gram-positive Lysinibacillus sphaericus JG-A12 cells to 20 µL DI water inside the ring top electrode. We relate observed change of measured impedance to change of membrane potential of L. sphaericus JG-A12 cells. In contrast to impedance measurements, optical density (OD) measurements cannot be used to distinguish between dead and live cells. Dead L. sphaericus JG-A12 cells have been obtained by adding 0.02 mg/mL of the antibiotics tetracycline and 0.1 mg/mL chloramphenicol to a batch with OD0.5 and by incubation for 24 h, 30 °C, 120 rpm in the dark. For impedance measurements, we have used batches with a cell density of 25.5 × 108 cells/mL (OD8.5) and 270.0 × 108 cells/mL (OD90.0). The impedance biochip PS5 can be used to detect the more resistive and less capacitive live L. sphaericus JG-A12 cells. Also, the impedance biochip BS5 can be used to detect the less resistive and more capacitive dead L. sphaericus JG-A12 cells. An outlook on the application of the impedance biochips for high-throughput drug screening, e.g., against multi-drug-resistant Gram-positive bacteria, is given.

Macrophage migration inhibitory factor derived from spinal cord is involved in activation of macrophages following gecko tail amputation.

Macrophages and their initiation of acute inflammation have been defined to be functionally important in tissue repair and regeneration. In injury-induced production of macrophage migration inhibitory factor (MIF), which has been described as a pleiotropic protein that participates in multiple cellular and biologic processes, it is unknown whether it is involved in the regulation of macrophage events during the epimorphic regeneration. In the model of gecko tail amputation, the protein levels of gecko MIF (gMIF) have been determined to be significantly increased in the nerve cells of the spinal cord in association with the recruitment of macrophages to the lesion site. gMIF has been shown to interact with the CD74 receptor to promote the migration of macrophages through activation of Ras homolog gene family member A and to trigger inflammatory responses through MAPK signaling pathways. The determination of microsphere phagocytosis also indicated that gMIF could enhance macrophage phagocytosis. gMIF-mediated recruitment and activation of macrophages have been found to be necessary for gecko tail regeneration, as evidenced by the depletion of macrophages using clodronate liposomes. The results present a novel function of MIF during the epimorphic regeneration, which is beneficial for insights into its pleiotropic property.-Wang, Y., Wei, S., Song, H., Zhang, X., Wang, W., Du, N., Song, T., Liang, H., Chen, X., Wang, Y. Macrophage migration inhibitory factor derived from spinal cord is involved in activation of macrophages following gecko tail amputation.

Knockdown of PLOD3 suppresses the malignant progression of renal cell carcinoma via reducing TWIST1 expression.

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD3), also known as lysyl hydroxylase 3 (LH3) has been demonstrated to be overexpressed in several kinds of cancers and facilitate cell migration. Currently, we aimed to reveal the role of PLOD3 in renal cell carcinoma (RCC) progression, and explore whether TWIST1 (Twist family bHLH transcription factor 1) is involved in this process. Fifty-eight paired RCC tissues and normal tissues were collected and subjected to qPCR and immunohistochemistry (IHC) technology to detect the expression levels of PLOD3. The clinical value of PLOD3 in predicting RCC progression was then explored. Cell-Counting Kit-8 (CCK-8), wound healing, transwell chambers and tumor-bearing experiments were applied to monitor cell proliferation, migration, invasion and tumorigenesis. Protein levels were determined by using western blotting technology to assess cell apoptosis and epithelial to mesenchymal transition (EMT). PLOD3 expression was enhanced in RCC tissues and cells, which predicted higher T (tumor), N (lymph node) and M (metastasis) stages, histological grade and TNM (tumor, lymph node, metastasis) stage. PLOD3 downregulation in RCC A498 cells obviously inhibited cell proliferation, migration, invasion, EMT and tumorigenesis and increased cell apoptosis. PLOD3 overexpression led to opposite results in RCC A704 cells. PLOD3 downregulation reduced the expression levels of TWIST1, ß-catenin and p-AKT. In addition, TWIST1 overexpression rescued the repressions of cell proliferation, migration, invasion, EMT and the activation of ß-catenin and AKT signaling in addition to apoptosis promotion induced by PLOD3 downregulation. Collectively, this study illustrated that PLOD3 knockdown suppressed RCC malignance via inhibiting TWIST1-mediated activation of ß-catenin and AKT signaling.

Charged domains in ferroelectric, polycrystalline yttrium manganite thin films resolved with scanning electron microscopy.

We have investigated ferroelectric charged domains in polycrystalline hexagonal yttrium manganite thin films (Y1Mn1O3, Y0.95Mn1.05O3, Y1Mn0.99Ti0.01O3, and Y0.94Mn1.05Ti0.01O3) by scanning electron microscopy (SEM) in secondary electron emission mode with a small acceleration voltage. Using SEM at an acceleration voltage of 1.0 kV otherwise homogenous surface charging effects are reduced, polarization charges can be observed and polarization directions (±Pz) of the ferroelectric domains in the polycrystalline thin films can be identified. Thin films of different chemical composition have been deposited by pulsed laser deposition on Pt/SiO2/Si structures under otherwise same growth conditions. Using SEM it has been shown that different charged domain density networks are existing in polycrystalline yttrium manganite thin films.