Comprehensive behavioural assessment of TERT in bladder cancer.

BACKGROUND: Telomerase activity plays a crucial role in cancer development and progression. Thus, telomerase activation through the interplay of mutations and epigenetic alterations in the telomerase reverse transcriptase (TERT) promoter may provide further insight into bladder cancer induction and progression. METHODS: In this study 100 bladder tumour tissues were selected, and four molecular signatures were analysed: THOR methylation status, TERT promotor mutation, telomere length, and TERT expression. RESULTS: In our study, 88% of bladder cancer patients had an hypermethylation of the THOR region and 60% had mutations in the TERT promoter region. TERT promoter methylation was observed in all stages and grades of bladder cancer. While, TERT promoter mutations were detected in advanced stages and grades. In our cohort, high levels of TERT expression and long telomeres have been found in noninvasive cases of bladder cancer, with a significant association between TERT expression and Telomere length. Interestingly, patients with low TERT expression and cases with long telomeres had significantly longer Disease-free survival and overall survival. CONCLUSION: The methylation and mutations occurring in the TERT promoter are implicated in bladder carcinogenesis, offering added prognostic and supplying novel insight into telomere biology in cancer.

Investigation of THOR-AV 5F Biofidelity in Sled Test Conditions with A Semi-Rigid Seat.

THOR-AV 5F, a modified THOR-5F dummy, was designed to represent both upright and reclined occupants in vehicle crashworthiness studies. The dummy was evaluated in four test conditions: a) 25° seatback, 15 km/h, b) 25° seatback, 32 km/h, c) 45° seatback, 15 km/h, d) 45° seatback, 32 km/h. The dummy's biomechanical responses were compared against those of postmortem human subjects (PMHS) tested in the same test conditions. The latest National Highway Traffic Safety Administration (NHTSA) BioRank method was used to provide a biofidelity ranking score (BRS) for each data channel in the tests to assess the dummy's biofidelity objectively. The evaluation was categorized into two groups: restraint system and dummy. In the four test conditions, the restraint system showed good biofidelity with BRS scores of 1.49, 1.47, 1.15, and 1.79, respectively. The THOR-AV 5F demonstrated excellent biofidelity in three test conditions: 25° seatback, 15 km/h (BRS = 0.76); 25° seatback, 32 km/h (BRS = 0.89); and 45° seatback, 32 km/h (BRS = 0.93). In the fourth test condition, 45° seatback, 15 km/h, the dummy demonstrated good biofidelity with a BRS score of 1.06. The dummy demonstrated good durability. No damage was identified with a full inspection conducted after the tests.

THOR-05F biofidelity evaluation in reclined and upright seated postures subjected to frontal crash pulses.

The THOR 5th percentile female dummy (THOR-05F) was evaluated for two seating postures/positions in frontal impacts using a generic automotive seat environment. The conditions included 2 crash pulses: a 15 km/h test that utilized 4.5 g acceleration and a 3-point restraint with 2 kN load limiter, and a 32 km/h test that utilized 9.5 g acceleration and a 3-point restraint with a 4.5 kN load limiter and pretensioner, and two seatback angles: 25°, a nominal upright posture, and 45°, a moderate reclined posture. The BRS scores were calculated using the NHTSA BioRank method. Overall biofidelity rating was consider excellent for both seating postures. This evaluation provides an understanding of the THOR-05F response and biofidelity evaluation of the ATD in two seating postures (nominal and reclined). This is essential in the assessment and development of safety measures in emerging ADS-equipped vehicles.

Abdominal biofidelity assessment of 5th percentile female ATD responses relative to recently developed belt and bar loading corridors.

OBJECTIVE: The objective of this study was the quantitative evaluation and comparison of the responses of the Hybrid III 5th percentile female (HIII-05F) and the 5th percentile female Test Device for Human Occupant Restraint (THOR-05F) anthropomorphic test devices (ATDs) subjected to abdominal loading conditions. METHOD: The HIII-05F and THOR-05F were subjected to 3 different abdominal loading conditions: fixed-back belt pull (low compression), fixed-back belt pull (high compression), and free-back rigid bar impact at 6 m/s. The stroke of the impact was controlled to represent injurious and noninjurious loading conditions as observed in the experiments with postmortem human subjects (PMHS). Quantitative comparisons were made between the ATD abdominal force and compression responses and biofidelity corridors obtained from matched-pair PMHS tests under identical loading conditions, using the most recent version of the NHTSA Biofidelity Ranking System (BRS). RESULTS: The overall THOR-05F BRS scores across all tests (BRS score = 1.84) indicated good biofidelity. For the belt loading test conditions, the average BRS scores for both THOR-05F (BRS scores = 1.45 and 1.34) and HIII-05F (BRS scores = 1.42 and 1.01) showed good biofidelity. For the rigid bar loading condition, the THOR-05F (BRS score = 2.74) showed better biofidelity compared to HIII-05F (BRS score = 10.63), with the HIII-05F exhibiting poor performance in this condition. The average pressures recorded by the abdomen pressure twin sensors (APTS) in the current study ranged from 45 to 130 kPa, increasing proportionally with higher stroke and loading rate. CONCLUSIONS: Overall, the THOR-05F BRS scores were better than the HIII-05F BRS scores, which suggests improved biofidelity of the THOR-05F abdomen. The abdominal insert in the HIII-05F did not provide enough room for compression, leading to higher stiffness and occupant motion as observed in the rigid bar tests. Because of practical challenges in measuring abdomen deflection in a soft ATD abdomen component, use of APTS in THOR-05F provides the ability to measure the restraint loading to the abdomen and assess the risk of abdominal injury. With good BRS scores observed in this study for THOR-05F, pressure and other measurements included in the THOR-05F may be used to develop abdominal injury risk functions in the future.

NeuTHOR Station-A Novel Integrated Platform for Monitoring BNCT Clinical Treatment, Animal and Cell Irradiation Study at THOR.

(1) Background: A well-established Boron Neutron Capture Therapy (BNCT) facility includes many essential systems, which are the epithermal neutron beam system, on-line monitoring system (OMS), QA/QC (quality assurance or quality control) system, boron concentration (BC) measurement system, and treatment planning system (TPS). Accurate data transmission, monitoring, and deposition among these systems are of vital importance before, during, and after clinical, animal, and cell BNCT irradiation. This work developed a novel integrated platform NeuTHOR Station (NeuTHORS) for BNCT at Tsing Hua Open-pool Reactor (THOR). Apart from the data of the OMS and QA/QC system, the data of BC and TPS can be loaded on NeuTHORS before BNCT clinical, animal, and cell irradiation. (2) Methods: A multi-paradigm computer programming language c# (c sharp) was used to develop the integrated platform NeuTHORS. The design of NeuTHORS is based on the standard procedures of BNCT treatment or experiment at THOR. Moreover, parallel testing with OMS-BNCT (the former OMS) and QA/QC of THOR was also performed for more than 70 times to verify the validation of NeuTHORS. (3) Results: According to the comparisons of the output, NeuTHORS and OMS-BNCT and QA/QC of THOR show very good consistency. NeuTHORS is now installed on an industrial PC (IPC) and successfully performs the monitoring of BNCT Treatment at THOR. Patients' f BC and TPS data are also input into NeuTHORS and stored on IPC through an internal network from BC measurement room and TPS physicist. Therefore, the treatment data of each patient can be instantaneously established after each BNCT treatment for further study on BNCT. NeuTHORS can also be applied on data acquisition for a BNCT-related study, especially for animal or cell irradiation experiments. (4) Conclusions: A novel integrated platform NeuTHOR Station for monitoring BNCT clinical treatment and animal and cell irradiation study has been successfully established at THOR. With this platform, BNCT radiobiology investigations will be efficiently performed and a thorough data storage and analysis system of BNCT treatments or experiments can thus be systematically built up for the further investigation of BNCT at THOR.

A current assessment of the THOR 50M in rear impacts.

OBJECTIVE: This study presents a comparison of the Test Device for Human Occupant Restraint (THOR) 50M and Hybrid III (HIII) 50M anthropomorphic test device (ATD) geometries and rear impact head and neck biofidelity to each other and to postmortem human surrogate (PMHS) data to evaluate the usefulness of the THOR in rear impact testing. METHODS: Both ATDs were scanned in a seated position on a rigid bench seat. A series of rear impact sled tests with the rigid bench seat with no head restraint support were conducted with a HIII-50M at 16 and 24 kph. Tests at each speed were performed twice with the THOR-50M to allow an assessment of the repeatability of the THOR-50M. A comparison of the test results from THOR-50M testing were made to the results of a previous study that included PMHS. Rear impact sled tests with both ATDs in a modern seat were then conducted at 40 kph. RESULTS: The THOR-50M head was 48.4 mm rearward and 60.1 mm higher than the HIII-50M head when seated in the rigid bench seat. In the repeated rigid bench testing at 16 and 24 kph, the THOR-50M head longitudinal and vertical accelerations, upper neck moment, and overall kinematics showed good test-to-test repeatability. In the rigid bench tests, the THOR-50M neck experienced flexion prior to extension in the 16 kph tests, where the neck of the HIII only experienced extension. At 24 kph both ATDs only experienced extension. The THOR-50M head displaced more rearward at both test velocities. The rigid bench tests show that the THOR-50M neck allows for more extension motion or articulation than the HIII-50M neck. The rigid bench test also shows that the head longitudinal and vertical accelerations, angular head kinematics, and upper neck moments were reasonably comparable between the ATDs. The THOR-50M results were closer to the average of the PMHS results than the HIII-50-M results, with the exception of the upper neck. In the 40 kph tests, with a modern seat design, the THOR-50M resulted in more deformation of the seatback with greater head restraint loading than the HIII-50M. The THOR-50M head backset distance was less. CONCLUSION: This study provides insight into the differences and similarities between the THOR and the HIII-50M ATD geometries, instrumentation responses, and kinematics, as well as the repeatability of the THOR-50M in rear impacts testing. The overall geometries of the THOR-50M and the HIII-50M are similar. The seated head position of the THOR-50M is slightly further rearward and higher than the HIII-50M. The results indicate that the THOR-50M matches the PMHS results more closely than the HIII-50M and may have improved neck biofidelity in rear impact testing. The results indicate that the studied THOR-50M responses are repeatable within expected test-to-test variations in rear impacts. Early data suggest that the THOR-50M can be used in rear impact testing, though a more complete understanding of the THOR-50M differences to the HIII ATDs will allow for better correlation to the existing body of HIII rear impact testing.

Head injury criteria assessment using head kinematics from crash tests and accident reconstructions.

OBJECTIVE: The aim of this study was to assess head injury criteria based on their correlation to brain strain in a Finite Element (FE) head model (the KTH Royal Institute of Technology model), by simulation of head kinematics data from frontal and side crash tests with Anthropomorphic Test Devices (ATDs), and from Human Body Model (HBM) accident reconstructions. METHODS: Six Degrees of Freedom (DoF) head kinematic data was extracted from 221 crash tests, consisting of frontal impacts with the THOR-50M ATD, near-side and far-side impacts with the WorldSID-50M ATD, and from 19 FE HBM accident reconstructions. The head injury criteria HIC15, HIP, BrIC, UBrIC, DAMAGE and CIBIC were calculated, and FE head model simulations were conducted using the six DoF kinematics data. The 100th, 99th, and 95th percentile Maximum Principal Strains (MPS) of the brain were extracted and linear regression models with respect to the injury criteria were created. The injury criteria were then evaluated based on the coefficient of determination, R2, and the Normalized Root Mean Square Error (NRMSE) of each regression model. RESULTS: For all the data sets combined and for the WorldSID far-side data, CIBIC had the best goodness of fit, with R2 of 0.76 and 0.85. For frontal impacts with THOR and the combined ATD data set, DAMAGE had highest R2, 0.83 and 0.78, respectively. Injury criteria including translational accelerations were ranked lower, and BrIC were among the three lowest ranked for most data sets evaluated. UBrIC generally ranked after DAMAGE and CIBIC with respect to the goodness of fit but had the lowest NRMSE for all data sets. CONCLUSIONS: The two mass-spring-damper brain surrogate model criteria, DAMAGE and CIBIC, were best in capturing the head model MPS response for both the THOR and WorldSID data sets. BrIC had lower correlation to the head model MPS and performed marginally better than the linear acceleration only criteria for all the data sets combined. This study supports the suitability of DAMAGE and CIBIC as brain injury criteria to be used with THOR-50M and WorldSID-50M in vehicle crash test conditions, as they outperform BrIC.

Investigating the psychological and physiological responses to isolation and confinement using the THOR space analog simulation / Investigando las respuestas psicológicas y fisiológicas al aislamiento y confinamiento utilizando la simulación análoga espacial THOR

This research investigates astronaut performance under simulated space conditions, using THOR, an analog astronaut training protocol, during a week-long confinement in an Analog Astronaut Training Center in Poland. Materials and Five participants, including four military and one civilian, underwent a week of isolation. Tests were conducted to assess heart rate variability ­HRV­, psychological health, and sleep patterns. Data collection and analysis were standardized, with an alpha level of p < 0.05 and power of 80%. The study found reductions in fat percentage and weight, while muscle mass and water content remained stable. HRV showed significant changes. Increased sleep and state anxiety levels were noted, along with decreased cognitive abilities. Personality traits exhibited heightened hostility and social anxiety, culminating in psychological discomfort. HRV values were normal with variations likely due to stress. A significant correlation was found between mental performance and HRV, indicating potential influence of sleep on cognitive function during isolation. The study highlights the need for more research on the psycho-logical and physiological implications of long-duration space missions and similar high-demand environments.

Esta investigación examina el rendimiento de los astronautas análogos bajo condiciones espaciales simuladas durante una semana de confina-miento en un Centro de Entrenamiento de Astronautas Análogos en Polonia. Cinco participantes, incluyendo cuatro militares y un civil, fueron sometidos a una semana de aislamiento. Se realizaron pruebas para evaluar la variabilidad de la frecuencia cardíaca ­HRV­, la salud psicológica y los patrones de sueño. La recolección y análisis de datos fueron estandarizados, con un nivel alfa de p < 0.05 y una potencia del 80%. El estudio encontró reducciones en el porcentaje de grasa y peso, mientras que la masa muscular y el contenido de agua permanecieron estables. La HRV mostró cambios significativos. Se observaron niveles elevados de sueño y ansiedad estado, junto con disminuciones en las habilidades cognitivas. Los rasgos de personalidad mostraron una hostilidad y ansiedad social aumentada, culminando en incomodidad psicológica. Los valores de HRV fueron normales con variaciones probablemente debidas al estrés. Se encontró una correlación significativa entre el rendimiento mental y la HRV, indicando la posible influencia del sueño en la función cognitiva durante el aislamiento. El estudio resalta la necesidad de más investigaciones sobre las implicaciones psicológicas y fisiológicas de las misiones espaciales de larga duración y entornos similares de alta demanda.

THOR is a targetable epigenetic biomarker with clinical implications in breast cancer.

BACKGROUND: Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of death among women worldwide. Early BC is potentially curable, but the mortality rates still observed among BC patients demonstrate the urgent need of novel and more effective diagnostic and therapeutic options. Limitless self-renewal is a hallmark of cancer, governed by telomere maintenance. In around 95% of BC cases, this process is achieved by telomerase reactivation through upregulation of the human telomerase reverse transcriptase (hTERT). The hypermethylation of a specific region within the hTERT promoter, termed TERT hypermethylated oncological region (THOR) has been associated with increased hTERT expression in cancer. However, its biological role and clinical potential in BC have never been studied to the best of our knowledge. Therefore, we aimed to investigate the role of THOR as a biomarker and explore the functional impact of THOR methylation status in hTERT upregulation in BC. RESULTS: THOR methylation status in BC was assessed by pyrosequencing on discovery and validation cohorts. We found that THOR is significantly hypermethylated in malignant breast tissue when compared to benign tissue (40.23% vs. 12.81%, P < 0.0001), differentiating malignant tumor from normal tissue from the earliest stage of disease. Using a reporter assay, the addition of unmethylated THOR significantly reduced luciferase activity by an average 1.8-fold when compared to the hTERT core promoter alone (P < 0.01). To further investigate its biological impact on hTERT transcription, targeted THOR demethylation was performed using novel technology based on CRISPR-dCas9 system and significant THOR demethylation was achieved. Cells previously demethylated on THOR region did not develop a histologic cancer phenotype in in vivo assays. Additional studies are required to validate these observations and to unravel the causality between THOR hypermethylation and hTERT upregulation in BC. CONCLUSIONS: THOR hypermethylation is an important epigenetic mark in breast tumorigenesis, representing a promising biomarker and therapeutic target in BC. We revealed that THOR acts as a repressive regulatory element of hTERT and that its hypermethylation is a relevant mechanism for hTERT upregulation in BC.

Feasibility of a Hospital Information System for a Military Public Organization in the Light of the Multi-Criteria Analysis.

The healthcare environment presents a large volume of personal and sensitive patient data that needs to be available and secure. Information and communication technology brings a new reality to healthcare, promoting improvements, agility and integration. Regarding high-level and complex decision-making scenarios, the Brazilian Navy (BN), concerning its healthcare field, is seeking to provide better management of its respective processes in its hospital facilities, allowing accurate control of preventive and curative medicine to members who work or have served there in past years. The study addresses the understanding, structure and clarifying variables related to the feasibility of technological updating and installing of a Hospital Information System (HIS) for BN. In this scenario, through interviews and analysis of military organization business processes, criteria and alternatives were established based on multi-criteria methodology as a decision aid. As methodological support for research and data processing, THOR 2 and PROMETHEE-SAPEVO-M1 methods were approached, both based on the scenarios of outranking alternatives based on the preferences established by the stakeholders in the problem. As a result of the methodological implementation, we compare the two implemented methods in this context, exposing the Commercial Software Purchase and Adoption of Free Software, integrated into Customization by the Marine Studies Foundation, as favorable actions to be adopted concerning HIS feasibility. This finding generates a comprehensive discussion regarding the BN perspective and changes in internal development in the military environment, prospecting alignment to the culture of private organizations in Information Technology for healthcare management. In the end, we present some conclusions concerning the study, exploring the main points of the decision-making analysis and for future research.

LncRNA THOR promotes endometrial cancer progression through the AKT and ERK signaling pathways.

The long noncoding RNA (lncRNA) THOR is highly conserved and expressed in various human cancer tissues, although its potential role and underlying mechanism in endometrial cancer (EC) remain unknown. This study aims to explore THOR's biological function and molecular mechanism in EC progression. THOR expression in EC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR) and in situ hybridization (ISH). THOR expression based on The Cancer Genome Atlas (TCGA) and clinical sample analyses was significantly higher in EC tissues than normal tissues, and higher THOR levels were closely associated with poor overall survival in EC. Additionally, a positive correlation between ISH-detected THOR expression and pathological grade was observed. CCK-8, colony formation, and transwell migration and invasion assays revealed that THOR significantly enhances the proliferation, migration, and invasion abilities of EC cells. Moreover, IGF2BP1 protein expression and ERK and AKT protein phosphorylation levels in EC cells increased significantly with THOR overexpression in EC cells. In conclusion, our findings suggest that THOR promotes EC cell growth and invasion, and IGF2BP1-mediated AKT and ERK signaling pathways activation might be involved. Clinically, THOR is significantly expressed in EC, and high THOR expression correlates with poor prognosis, making it a potential prognostic marker for EC.

Differential DNA Methylation of THOR and hTAPAS in the Regulation of hTERT and the Diagnosis of Cancer.

BACKGROUND: Although DNA methylation in the gene promoters usually represses gene expression, the TERT hypermethylated oncological region (THOR) located 5' of the hTERT gene is hypermethylated when hTERT is expressed in diverse cancer types, including urothelial cancer (UC). METHODS: Comprehensive MeDIP and DNA methylation array analyses complemented by the technically independent method of bisulfite genomic sequencing were applied on pathologically reviewed and classified urothelial carcinoma specimens and healthy urothelial tissue samples to reveal the methylation status of THOR in detail. RESULTS: The detailed DNA methylation profiles reveal the exact positions of differentially methylated CpG dinucleotides within THOR in urothelial cancer and provide evidence ofa diverging role of methylation of these CpGs in the regulation of hTERT. In particular, our data suggest a regulating mechanism in which THOR methylation acts on hTERT expression through epigenetic silencing of the lncRNA hTERT antisense promoter-associated (hTAPAS), which represses hTERT. CONCLUSIONS: These findings precisely define the most differentially methylated CpGs of THOR in early urothelial cancer, enabling optimal design of Methylation-Specific PCR (MSPCR) primers to reliably probe these methylation differences for diagnostic and prognostic purposes. In addition, this strategy presents a prime example that is also applicable to many other malignancies. Finally, the first evidence for the underlying epigenetic mechanism regulating hTERT expression through the methylation status of THOR is provided.

Sex differences in authorship in cardiothoracic surgery during the early coronavirus disease 2019 pandemic.

Objectives: The coronavirus disease 2019 (COVID-19) pandemic negatively impacted cardiothoracic (CT) surgery, with changes in clinical, academic, and personal responsibilities. We hypothesized that the pandemic may disproportionately impact female academic CT surgeons, accentuating preexisting sex disparities. This study assessed sex differences in authorship of 2 major CT surgery journals during the early part of the COVID-19 pandemic. Methods: All accepted submissions to The Annals of Thoracic Surgery and The Journal of Thoracic and Cardiovascular Surgery between April and August of 2019 and the same period in 2020 were reviewed. Article type and author characteristics were obtained from the journals. Author sex was predicted using a validated multinational database (Genderize.io) and verified with authors' institutional and public professional profiles. Results: In total, 1106 submissions were accepted during the 2019 period, whereas 900 articles (18.6% decrease) were accepted during the same period in 2020. Original research articles comprised 33.3% of the 2019 articles but only 4.9% of the 2020 articles. Female authors contributed to 39.3% (23.1% original research and 16.2% nonoriginal articles) and 29.4% (3.3% original research and 26.1% nonoriginal articles) of articles during the 2019 and 2020 periods, respectively. This represents a marked change in the type of articles that female authors contributed to. Conclusions: Early on during the COVID-19 pandemic, the type of articles accepted, and authorship demographic changed. There was a decrease in contribution of female-authored CT surgery articles submitted to both journals, especially for original research. Future research will elucidate the long-term impact of the pandemic on sex disparities in academic productivity.

A Comparison of the Mid-Size Male THOR and Hybrid III ATDs in Vehicle Frontal Crash Tests.

In order to evaluate the THOR-50M as a front impact Anthropomorphic Test Device (ATD) for vehicle safety design, the ATD was compared to the H3-50M in matching vehicle crash tests for 20 unique vehicle models from 2 vehicle manufacturers. For the belted driver condition, a total of fifty-four crash tests were investigated in the 56.3 km/h (35 mph) front rigid barrier impact condition. Four more tests were compared for the unbelted driver and right front passenger at 40.2 km/h (25 mph) in the flat frontal and 30-degree right oblique rigid barrier impact conditions. The two ATDs were also evaluated for their ability to predict injury risk by comparing their fleet average injury risk to Crash Investigation Sampling System (CISS) accident data for similar conditions. The differences in seating position and their effect on ATD responses were also investigated. This study showed that the belted THOR-50M injury responses were higher than the H3-50M by 25%-180%, in all reported ATD responses, except chest acceleration. For one unbelted condition, the THOR-50M reported 200%-300% higher neck responses than the H3-50M, primarily due to head contact to the roof structure in a mid-sized sedan. The THOR-50M overpredicted the injury risk based on chest deflection compared to the CISS accident data by at least a factor of 4 times. The THOR-50M also overpredicted the injury risk based on BrIC by at least a factor of 10 times. Future work is needed to investigate these overpredictions with respect to ATD construction, injury risk curves, and seating procedures.

Long Non-Coding RNA THOR Depletion Inhibits Human Non-Small Cell Lung Cancer Cell Growth.

Long non-coding RNA (LncRNA) THOR (Lnc-THOR) is expressed in testis and multiple human malignancies. Lnc-THOR association with IGF2BP1 (IGF2 mRNA-binding protein 1) is essential for stabilization and transcription of IGF2BP1 targeted mRNAs. We tested its expression and potential functions in non-small cell lung cancer (NSCLC). In primary NSCLC cells and established cell lines, Lnc-THOR shRNA or CRISPR/Cas9-mediated knockout (KO) downregulated IGF2BP1 target mRNAs (IGF2, Gli1, Myc and SOX9), inhibiting cell viability, growth, proliferation, migration and invasion. Significant apoptosis activation was detected in Lnc-THOR-silenced/-KO NSCLC cells. Conversely, ectopic overexpression of Lnc-THOR upregulated IGF2BP1 mRNA targets and enhanced NSCLC cell proliferation, migration and invasion. RNA-immunoprecipitation and RNA pull-down assay results confirmed the direct binding between Lnc-THOR and IGF2BP1 protein in NSCLC cells. Lnc-THOR silencing and overexpression were ineffective in IGF2BP1-KO NSCLC cells. Forced IGF2BP1 overexpression failed to rescue Lnc-THOR-KO NSCLC cells. In vivo, intratumoral injection of Lnc-THOR shRNA adeno-associated virus potently inhibited A549 xenograft tumor growth in nude mice. At last we show that Lnc-THOR is overexpressed in multiple NSCLC tissues and established/primary NSCLC cells. Collectively, these results highlighted the ability of Lnc-THOR in promoting NSCLC cell growth by associating with IGF2BP1, suggesting that Lnc-THOR represents a promising therapeutic target of NSCLC.

Sagittal plane moment responses of the THOR-05F anthropomorphic test device.

OBJECTIVE: Anthropomorphic test devices (ATD) are used in crashworthiness studies to advance safety in automotive, military, aviation, and other environments. The Test Device for Human Occupant Restraint (THOR) is an advancement over the widely used Hybrid III ATD. The female version THOR-05F is different from the male as it is not a scaled-down version of the male, and it is based on the recognition that the cervical spines (necks) of females have a different response than males. The objective of this study is to evaluate its response at dynamic rates of loading and compare it with previous postmortem human surrogate (PMHS) responses under sagittal plane bending. METHODS: The head/neck assembly was separated from the thorax, and a lower neck plate was attached to the head/neck assembly to mount the preparation to the frame of an electro-hydraulic testing device. A custom upper neck interface plate was attached to a novel angular displacement test device that converted the linear motion of the vertical electrohydraulic piston to moment loading at the occipital condyle joint. The neck was preconditioned by applying a sinusoidal 10-degree flexion-extension cycle for 90 s and then three repeat dynamic tests at a target rate of 90 Nm/s. Flexion and extension tests were performed with and without the front and rear neck cables of the THOR-05F neck. Targets were fixed to the upper neck adapter plate, occipital condyle joint, mid-spine aluminum puck, and lower neck adapter plate. The targets' three-dimensional positions were measured using a seven-camera optical motion capture system. Upper neck load cell and occipital condyle potentiometer data were sampled at 20 kHz, and loading rates were determined by calculating the sagittal moment slope between 15% and 85% of the signal. RESULTS: The mean occipital condyle angle versus sagittal moment response from the 12 tests (three tests each with and without cables and under flexion and extension) are given in the body of the manuscript. With and without cables, the loading rates for flexion tests were 89.3 ± 0.5 Nm/s and 86.3 ± 0.4 Nm/s, and for extension tests they were 90.8 ± 1.2 Nm/s and 88.0 ± 1.5 Nm/s. The average peak sagittal moments were 34.2 ± 0.3 Nm and 30.3 ± 0.2 Nm for flexion and 50.6 ± 0.3 Nm and 47.0 ± 0.3 Nm for extension tests. The mean peak occipital condyle angles were 23.5 ± 0.2 deg and 25.3 ± 0.1 deg for flexion and 22.7 ± 0.2 deg and 25.8 ± 0.1 deg for extension. CONCLUSION: Using the angular motion as a basis and comparing it with the previously conducted PMHS tests, the THOR-05F neck has approximately twice the stiffness of the human under sagittal plane bending.

Investigation of the lncRNA THOR in Mice Highlights the Importance of Noncoding RNAs in Mammalian Male Reproduction.

THOR is a highly conserved testis-specific long noncoding RNA (lncRNA). The interaction between THOR and the development of the male reproductive system remains unclear. Herein, CRISPR/Cas9 technology was used to establish a stable THOR-deficient mouse model, and the relationship between THOR and the fertility of adult male mice was investigated. The male mice in which THOR was deleted were smaller than the WT male mice. Moreover, their survival rate was reduced by 60%, their fertility was reduced by 50%, their testicular size and sperm motility were reduced by 50%, their testicular cell apoptosis was increased by 7-fold, and their ratio of female-to-male offspring was imbalanced (approximately 1:3). Furthermore, to elucidate the mechanisms of male reproductive system development, the mRNA levels of THOR targets were measured by qRT-PCR. Compared with WT mice, the THOR-deficient mice exhibited significantly decreased mRNA levels of IGF2BP1, c-MYC, IGF1, and IGF2. MEK-ERK signaling pathway expression was downregulated as determined by Western blot. We found that THOR targeted the MER-ERK signaling pathway downstream of IGF2 by binding to IGF2BP1 and affected testicular and sperm development in male mice. These results may also provide perspectives for exploring the roles of lncRNAs in human reproductive development and the pathogenesis and potential therapeutic targets of infertility.

Microstructure and Mechanical Properties of Modern 11%Cr Heat-Resistant Steel Weld Joints.

In addition to good high-temperature creep resistance and adequate heat resistance, steels for the power industry must have, among other things, good weldability. Weldability of such steels is one of the criteria determining whether or not the material is suitable for applications in the power industry. Therefore, when materials such as martensitic steel Thor 115 (T115) are introduced into the modern power industry, the quality and properties of welded joints must be assessed. The paper presents the results of metallographic and mechanical investigations of T115 martensitic steel welded joints. The analysis was carried out on joints welded with two filler metals: WCrMo91 (No. 1) and EPRI P87 (No. 2). The scope of the investigations included: microstructural investigations carried out using optical, scanning and transmission electron microscopy and mechanical testing, i.e., Vickers microhardness and hardness measurement, static tensile test and impact test. The macro- and microstructural investigations revealed correct structure of the weld, without welding imperfections. The microstructural investigations of joint No. 1 revealed a typical structure of this type of joint, i.e., the martensitic structure with numerous precipitates, while in joint No. 2, the so-called Nernst's layers and δ-ferrite patches were observed in the weld fusion zone as well as the heat affected zone (HAZ). The mechanical properties of the test joints met the requirements for the base material. A slight influence of the δ-ferrite patch on the strength properties of joint No. 2 was observed, and its negative effect on the impact energy of HAZ was visible.

Microbial Community Interactions Are Sensitive to Small Changes in Temperature.

Microbial communities are essential for human and environmental health, often forming complex interaction networks responsible for driving ecosystem processes affecting their local environment and their hosts. Disturbances of these communities can lead to loss of interactions and thereby important ecosystem functionality. The research on what drives interactions in microbial communities is still in its infancy, and much information has been gained from the study of model communities. One purpose of using these model microbial communities is that they can be cultured under controlled conditions. Yet, it is not well known how fluctuations of abiotic factors such as temperature affect their interaction networks. In this work, we have studied the effect of temperature on interactions between the members of the model community THOR, which consists of three bacterial species: Pseudomonas koreensis, Flavobacterium johnsoniae, and Bacillus cereus. Our results show that the community-intrinsic properties resulting from their interspecies interactions are highly dependent on incubation temperature. We also found that THOR biofilms had remarkably different abundances of their members when grown at 11, 18, and 25°C. The results suggest that the sensitivity of community interactions to changes in temperature is influenced, but not completely dictated, by different growth rates of the individual members at different temperatures. Our findings likely extend to other microbial communities and environmental parameters. Thus, temperature could affect community stability and may influence diverse processes including soil productivity, bioprocessing, and disease suppression. Moreover, to establish reproducibility between laboratories working with microbial model communities, it is crucial to ensure experimental stability, including carefully managed temperature conditions.

Carboxymethylated chitosan alleviated oxidative stress injury in retinal ganglion cells via IncRNA-THOR/IGF2BP1 axis.

BACKGROUND: Glaucoma is an advanced nerve disorder described by the deterioration of axon and RGCs. CMCS has been previously used as an anti-apoptotic and anti-oxidant agent. OBJECTIVE: The current study aimed to explore the protective impact of CMCS against H2O2-induced injury in glaucoma in vitro. METHODS: The relative expression of lncRNA THOR and the protein expression of IGF2BP1 in H2O2-induced RGC-5 cells were detected by RT-PCR and western blot methods respectively. The cell viability was measured using MTT assay while apoptosis rate was measured by flow cytometry. Moreover, ROS level was measured using ROS assay kit. Furthermore, the relations between THOR and IGF2BP1 were determined by using RNA pull-down. RESULTS: The expression of THOR was reduced in H2O2-induced RGCs. Also, RGCs viability was inhibited while the level of ROS and cell apoptosis were enhanced. CMCS treatment considerably enhanced the expression of THOR and IGF2BP1 protein and cell viability but reduced ROS level and cell apoptosis. Moreover, IGF2BP1 protein was positively regulated by lncRNA THOR. CMCS protected the RGCs from oxidative stress via regulating lncRNA THOR/IGF2BP1. CONCLUSION: CMCS enhanced the cell viability and reduced the cell apoptosis and ROS level and protected RGCs from oxidative stress via lncRNATHOR/IGF2BP1 pathway, potentially suggesting a new therapeutic strategy for the treatment of glaucoma.