Breast cancer treatment mostly revolved around radiation therapy and surgical interventions, these treatments doesn’t provide satisfactory relief to the patients and carry unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in the treatment of human breast cancer cells. In the present study, we have tested the effect FMSP-nanoparticles on human breast cancer cells (MCF-7). We have tested different concentrations (1.25µg/1mL, 12.5µg/mL and 50µg/1mL) of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced a concentration dependent effect on the cancer cells, dose of 1.25µg/mL produced no significant effect on the cancer cell morphology and cell death, whereas dosages of 12.5µg/mL and 50µg/mL respectively showed significant nuclear augmentation, disintegration, chromatic condensation followed by dose dependent cell death. Our results demonstrate FMSP-nanoparticles have ability to induce cell death in MCF-7 cells and may be considered as a potential anti-cancer agent for breast cancer treatments.

In the field of recommender systems, difficult negative samples that are easily misclassified by classifiers have higher learning value. In order to solve the problem that the existing graph convolutional network lacks the exploration of negative sampling strategy, a multivariate sampling based on graph convolution collaborative filtering recommendation model was proposed. Firstly, part of the information in the positive sample was injected into the negative sample, and the high quality difficult negative sample was selected by the inner product method. Then, contrastive learning is used to maximize the similarity between the difficult negative samples and the positive samples, so that the difficult negative samples are as close to the positive samples as possible in the feature space. Ultimately, a multi-task approach was employed to concurrently enhance both the recommendation supervision task and the contrastive learning task. To validate the effectiveness of our approach, we conducted comparative evaluations utilizing three publicly accessible datasets. The experimental outcomes indicate that our proposed model surpasses the baseline model in terms of performance.

Objective: To explore the acceptability and feasibility of conducting comprehensive, community-based, hy-brid (in-person and virtual) mental health screening and feedback with diverse youth in the community. Methods: The Screening and Support for Youth intervention provides comprehensive assessment and thera-peutic feedback in community settings including symptoms, diagnoses, functional impairment, suicide, and clinical risk. Symptom severity, seven diagnoses and suicidality were assessed with the Kiddie Computer-ized Adaptive Test. Functional impairment was evaluated by youth self-report on the Weiss Functional Im-pairment Rating Scale. Measures were scored according to nationally developed norms and an algorithm was developed to aggregate symptoms and functioning to determine clinical risk. The results were discussed with participants in a motivational interview to promote insight and engagement in an online intervention. Results: Methodological innovations included using a QR code for recruitment, integrated in-person and virtual participation, and expansion from in-person recruitment within the schools to virtual engagement with youth throughout the community. The final sample included disproportionately more Black or African American and Hispanic youth as compared to school and community statistics, suggesting that hybrid re-search may facilitate recruitment of diverse populations. Qualitative interviews indicated that the screening and feedback raised youth awareness of their wellbeing and/or distress, its impact on their functioning, and engagement with options for improving wellbeing. Conclusion: Hybrid research, developed as a necessity during the pandemic, proved advantageous to the feasibility and acceptability of community-based recruit-ment of at risk, minoritized youth.

The learning system is primarily based on teaching, and teaching through digital resources is referred to as e-learning. As the world progresses towards success day by day, the use of technology, digital devices, and modern techniques is becoming increasingly prevalent. The global shift from traditional paperwork to digital learning is one of the most significant changes in the education sector. However, many factors have created numerous hurdles during the online setup. The Covid-19 pandemic has led to serious problems all over the world, with the education sector being one of the most affected. One of the greatest challenges students face during online education is the lack of digital infrastructure, especially in remote areas of Pakistan. The biggest challenge is connecting students with teachers due to limited internet access. Without proper internet connectivity, both students and teachers cannot access educational materials. In this context, the government plays a crucial role in providing adequate facilities to students, particularly in primary schools. If proper infrastructure is not made available during this pandemic, students will be deprived of a good quality education. Therefore, good infrastructure is essential for effective online education. With the proper resources in place, students will be able to receive a quality education.

Objective: To explore the effect of time exposure to flat screen electronic devices with LED 14 lighting and the Mediterranean diet on macular pigment optical density (MPOD). Methods: MPOD 15 was measured by heterochromatic flicker photometry in 164 eyes (47 of young women 20-31 years 16 and 35 adult women 42-70 years). Exclusion criteria: evidence of macular degeneration and eyes 17 with cataracts. Data on the use of electronic devices and Mediterranean diet adherence were col- 18 lected through a survey. Nonparametric analysis of variance and independent sample t-tests were 19 used to compare subjects. Results: Significant differences (p<0.01) were found in total time of expo- 20 sure to LEDs (hours per day) between both groups (9.31 ± 3.74 young women vs 6.33 ± 3.64 old 21 women). The MPOD values for the young and adult populations were significantly different: 0.38 ± 22 0.16 and 0.47 ± 0.15 (p<0.01), respectively. When comparing both groups for the same time of expo- 23 sure to LEDs, differences were obtained between MPOD values of both populations: For total expo- 24 sures greater than 6 hours per day, the MPOD values were lower in young women than in adult 25 ones (0.37 ± 0.14 vs 0.50 ± 0.14, p<0.01). On the other hand, a significantly higher adherence was 26 found in the old women in comparison with the young women (OW 9.23± 2.50 vs YW 7.70 ± 2.08, 27 p<0.01), with higher MPOD values, (OW (0.52 ± 0.14) vs (YW (0.34 ± 0.18). Conclusions: Higher 28 MPOD values are observed with decreasing exposure time to electronic devices with LED lighting 29 screens and high adherence to the Mediterranean diet.

Background: Mitral regurgitation (MR) is a common valvular disorder linked to high morbidity and mortality. For patients unsuitable for surgery, transcatheter mitral edge-to-edge repair (TEER) with the MitraClip® G4 system offers an alternative. This study aims to evaluate procedural, echocardiographic, functional, and quality of life (QoL) outcomes in patients who underwent TEER with the MitraClip® G4 system, along with possible predictors of New York Heart Associa-tion (NYHA) class I at 30 days and 1 year. Methods: Patients with moderate-to-severe (3+) or se-vere (4+) degenerative MR (DMR) or functional MR (FMR), classified as NYHA class III or IV, who underwent TEER with the MitraClip® G4 system at our center between January 2021 and De-cember 2023 were included. Results: A total of 83 patients [71% FMR, 66% male, median (IQR) age 70 (11) years] underwent TEER, with 100% procedural success. MR ≤2+ was achieved in 100% and 98% of patients at 30 days and 1 year, respectively. NYHA class I or II was achieved in 100% and 96.8% of patients at 30 days and 1 year, respectively. The Kansas City Cardiomyopathy Ques-tionnaire (KCCQ) score improved from 51±20 at baseline to 69±15 at 30 days (p< 0.001) and 70.5±15 at 1 year (p< 0.001). Lower baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) pre-dicted achieving NYHA class I at 30 days (HR: 0.63, 95% CI: 0.41–0.95, p = 0.030), while lower Eu-ropean System for Cardiac Operative Risk Evaluation II (EuroSCORE II) and NT-proBNP pre-dicted it at 1 year [(HR: 0.50, 95% CI: 0.28–0.89, p = 0.019), (HR: 0.67, 95% CI: 0.44–0.99, p = 0.049), respectively]. Conclusions: The MitraClip® G4 system provides significant improvements in MR severity, functional class, and QoL. Lower NT-proBNP and EuroSCORE II were strong predictors of achieving optimal functional status (NYHA class I).

This study examines the feasibility and efficacy of utilizing generative AI technology to create inclusive online dating educational materials, focusing on integrating easy-to-read principles to enhance accessibility while improving efficiency and reducing the cost of material production. As online dating becomes increasingly prevalent, providing easily comprehensible safety education for special populations, such as individuals with disabilities and adolescents, is of paramount importance. This research developed an innovative AI-generated educational framework that combines easy-to-read principles with generative AI technology, aiming to enhance both the accessibility and production efficiency of educational materials. The study compared three AI generation strategies: independent generation by ChatGPT, independent generation by Claude, and Claude utilizing materials generated by ChatGPT. We evaluated 36 educational units through a mixed-methods approach for readability and accessibility. Results indicate that ChatGPT performed optimally in generating easily readable content (average compliance rate of 93.00%), followed by the strategy Claude using ChatGPT-generated materials (91.67%). Statistical analysis revealed significant differences among these strategies (p < 0.05). The research also found that employing AI generation technology significantly reduced material production time and costs, providing educators with a more efficient tool. The findings of this study underscore the significant potential of generative AI technology in creating inclusive educational resources. This not only opens up new avenues for enhancing online safety awareness and educational accessibility for special populations but also provides material developers with more efficient, cost-effective production methods. The empirical evidence presented here for the application of AI in inclusive education is a significant step forward. The study also proposes recommendations for future research and practice, aiming to further improve the accessibility, effectiveness, and production efficiency of online dating education.

Background: Inflammatory Bowel disease (IBD) is one of the worldwide health issues with increasing incidence. Recent data point out that those patients can have a defective immune system, rendering response to vaccinations suboptimal. Since 1990, Hepatitis B Virus (HBV) vaccination has been introduced among the compulsory childhood vaccinations in Oman. Given the questionable immunogenicity of vaccinations in IBD patients, we designed this study to quantify the immune response to scheduled HBV vaccine in IBD patients and compare it with that in a matching control cohort of healthy blood donors at Sultan Qaboos University Hospital (SQUH). Methods: This is a retrospective case-control study that was conducted between the 1st of July 2023 and the 31st of May 2024 at SQUH. Using the hospital information System (HIS), a total of 252 participants were enrolled in our study and divided into two groups. Group (1) included 126 IBD patients and group (2) included 126 healthy controls. Baseline demographics, medical comorbidities and viral serologies before and after vaccination were collected. The primary outcome of the study was to compare the long term immune response to HBV vaccine between the two groups. The secondary outcomes included identifying possible risk factors for suboptimal vaccine response. Results: One hundred and twenty-six participants were included in each group. Durable protective immune response to HBV vaccine was attained in 29 patients (23%) of the IBD group compared to 109 participants (86.5%) of the control group. There was a statistically significant association (p = 0.0156) between prednisolone treatment and low immune response to HBV vaccine. Moreover, esomeprazole usage exhibited a statistically significant association (p < 0.0001) with suboptimal response to HBV vaccine. Meanwhile, there was no statistically significant correlation between low immunogenicity to HBV vaccine and age, sex, type of IBD, comorbidities, and BMI. Conclusions: IBD patients are less immunogenic to HBV vaccination compared to healthy controls. Factors like esomeprazole and/or corticosteroid therapy might be associated with poor immune response. These findings highlight the importance of reassessing the immunogenicity of HBV vaccination and probably other protective vaccinations in all IBD patients as part of their standard of care.

Emotional agility and social intelligence at small to medium-sized enterprises (SMEs) can be an invigorating experience, filled with opportunities for growth, innovation, and collaboration. This research aims to investigate the Omani entrepreneurs’ emotions and intelligence at workplace through self-experiences in SMEs. A sample of 222 Omani entrepreneurs participated in online survey that was designed to attain the objectives of this research. Data was collected using google drive and analyzed using multiple regression path analysis. The results revealed that emotional agility and social intelligence have positive and significant impact on employee thriving at work in Omani SMEs. Further, openness to experience mediates the relationships between entrepreneurs’ emotions and intelligence and sustainable workplace. These results confirm the effective role of openness to experience among Omani entrepreneurs where they should adopt new strategies and techniques to improve their skills and support their SMEs. This research highlighted the role of interpersonal skills including agility and intelligence of entrepreneurs in Arab context.

According to current forecasts, global heating is likely to exceed 2,8°C by the end of the century. This makes substantial adaptation measures necessary to secure a broad basis for livelihoods provision and the conservation of biodiversity. While the implementation of top-down and technocratic adaptation efforts is the majority, related adaptation shortcomings of socio-economic and ecological nature are becoming more and more apparent. Community-based adaptation (CBA) with its participatory, inclusive and needs-based bottom-up approach offers a promising and powerful alternative. This article uses a semi-systematic literature review approach to screen the current literature and identify core issues of CBA. Linking communality, locality, multidimensionality, power imbalances, transformative potential, localisation, the triad of adaptation metrics and adaptation with nature to corresponding potential actions for practical implementations provides a more holistic conceptualisation and broadens the horizons for further learnings, research and improved application.

Here, we report an ultrasoft extra long-lasting reusable hydrogel-based sensor that enables high quality electrophysiological recording with low motion artifacts. The developed sensor can be used and stored in the ambient environment for months before being reused again. The developed sensor is made of a self-adhesive electrical-conductivity-enhanced ultrasoft hydrogel, mounted in an Ecoflex-based frame. Hydrogel’s conductivity was enhanced by incorporating polypyrrole (PPy), resulting in the conductivity of 0.25 S m-1. Young’s modulus of the sensor is only 12.9 kPa and it is stretchable up to 190%. The sensor was successfully used for the electrocardiography (ECG) and electromyography (EMG). Our results indicate that using developed hydrogel-based sensor, the signal-to-noise ratio of recorded electrophysiological signals was improved in comparison to that when medical grade silver/silver chloride (Ag/AgCl) wet gel electrodes were used (33.55 dB in comparison to 22.16 dB). Due to the ultra-softness, high stretchability, and self-adhesion of the developed sensor, it can conform to the skin and therefore, it shows low susceptibility to motion artifacts. Also, the sensor shows no sign of irritation or allergic reaction that usually occurs after long-term wearing medical grade Ag/AgCl wet gel electrodes on the skin. Further, the sensor is fabricated using a low cost and scalable fabrication process.

This paper presents the five-parameter Exponentiated Weibull Weibull (EWW) distribution with Weibull base failure rate parameterization, developed to model the dropout times of students in an online class module. Parameters of the model were estimated using both Maximum Likelihood and Bayesian estimation procedures to determine the most effective estimation method. Simulation results indicate that, across various hazard types and censoring levels, Bayesian estimates are more accurate and precise than Maximum Likelihood estimates. Real-life data analysis of online students module presentation supports these findings, showing significantly lower standard deviations for Bayesian estimates compared to Maximum Likelihood estimates, highlighting the efficiency of Bayesian estimation for the EWW distribution. Additionally, a comparative goodness-of-fit analysis demonstrated that the EWW distribution better fits the student dropout times dataset than Weibull Weibull (WW), Weibull Exponential (WE), and Exponential Weibull (EW) distributions. The median dropout time estimated using the EWW distribution is 24 days, suggesting that instructors should closely monitor student attendance around this period.

Klebsiella pneumoniae, a member of the ESKAPE pathogen group, is a prominent cause of hospital-acquired infections. The WHO recognized carbapenem-resistant K. pneumoniae as a critical-one priority pathogen. These resilient superbugs have the ability to form biofilms and present a significant global threat. In the present study, we isolated and characterized a bacteriophage SAKp02, from hospital sewage, infectious to carbapenem-resistant K. pneumoniae patient isolates. SAKp02 could infect 43 of 72 clinical isolates, indicating a broad host spectrum. Whole genome analysis classified SAKp02 within the family Casjensviridae, with a 59,343 bp genome encoding 82 ORFs. Comparative genomic analysis revealed significant differences between SAKp02 and its closest viruses, indicating a distinct genetic makeup positioning it as a novel phage strain within the lineage. The SAKp02 genome comprises bacteriolytic enzymes, including holin, endolysin, and phage depolymerase, crucial for bacterial lysis and biofilm disruption. It reduced biofilm biomass by over threefold compared to the control and eradicated 99% of viable cells within a 4-hour treatment period. Scanning electron microscopy corroborated the ability of the phage to dismantle biofilm matrices and lyse bacterial cells. Safe and effective treatments are warranted, and hence, the fully characterized lytic phages with therapeutic potential against drug-resistant clinical isolates of bacteria are needed. Our study is the first to report the antibacterial and antibiofilm activity of Casjensviridae phages, and our discovery of a novel K. pneumoniae phage broadens the arsenal against the bacteria.

: Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth and progression of ovarian tumor cells. However, no attention has been shown to their origin so far. It has been mainly assumed that CAFs in primary OC arise from the activation of resident fibroblasts. Here, we compare CAFs with ovarian location to CAFs found in peritoneal implants from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial-related markers. Therefore, as in peritoneal carcinomatosis, CAFs in primary ovarian carcinomas could be originated via a mesothelia-to-mesenchymal transition (MMT) process. The detection of mesothelial-derived CAFs in tumors confined to the ovary and associated biomarkers could be the key to early detection of peritoneal spread in affected patients.

This article addresses the emergence of a niche for sustainable agricultural production in the province of García Rovira, Colombia. It examines the intervention of the Colombian planning regime, which implements agendas for sustainable territorial development. However, these agendas are not adequately aligned with provincial realities, resulting in a productive decline. From a multi-level perspective, a niche of production linked to the landscape is identified, highlighting sustainable practices and innovation. The study seeks to understand how planning influences the emergence of such niches and what factors boost their transition to sustainability. Through a mixed methodology, growing sectors are highlighted, and the profiles of the producers involved are outlined. The main conclusion is that the planned intervention is inefficient, as the niche of sustainable production emerges without its clear influence. Therefore, it is proposed to re-evaluate planning using alternative analysis frameworks to detect emerging productive dynamics, serving as a basis for future plans.

This paper presents a novel framework for Collaborative Learning Networks (CLNs) in classrooms, aiming to optimize resource utilization and enhance educational services. The study addresses the inefficiencies of traditional education models, particularly the underutilization of computational resources and limited access to specialized software. The proposed framework employs a mix of task-based and random allocation strategies to distribute computational tasks within the CLN, considering each device’s capabilities and task requirements. The findings show significant improvement in resource utilization, facilitated by device-to-device collaboration and task sharing, thus enriching students’ learning experiences. This work contributes to optimizing resource utilization in education, advancing the field of CLNs.

Recent years have witnessed significant advances in reinforcement learning (RL), which has registered remarkable success in solving various sequential decision-making problems in machine learning. Most of the successful RL applications, e.g., the games of Go and Poker, robotics, and autonomous driving, involve the participation of more than one single agent, which naturally fall into the realm of multi-agent RL (MARL), a domain with a relatively long history, and has recently re-emerged due to advances in single-agent RL techniques. Although, typically, the communication protocol between agents is manually specified and not altered during training, recently, some papers have shown signs of trying to emerge a communication between agents on the one hand and, on the other hand, to understand what is exchanged between agents. So, there is a growing body of literature on this topic which includes qualitative and quantitative studies and the ones that apply mixed methods. This study presents the scoping review of the methodological strategies undertaken in a total of 16 research articles. The results present the critical appraisal of quantitative methods in terms of validity and reliability and for qualitative methods considering four trustworthiness factors. In the end, relevant insights are further explored with implications and reflections on how they can benefit one's research in the field.

The extent of access to energy of displaced populations in settlements and camps in Africa is largely unknown, given 94% of displaced persons without access to electricity and 81% with a reliance on biomass for cooking. A multitude of contextual factors, such as the location and the characteristics of housing, the legal status, the socio-cultural background and the availability of humanitarian and public services impact the living conditions and the needed energy services. Limitations in accessing energy services have direct, multilayered, and far-reaching implications, including impacts on health, nutrition, education, protection, and livelihood. The objective of this article is to contribute to a more comprehensive understanding of the current state of energy ac-cess in displacement contexts on the African continent by identifying and utilizing existing data. After a screening of the vast and various available information, setting up of a database, consoli-dating the gathered data as well as assessing the quality through a quality assessment method, the currently available information is visualized and discussed. Remarkable differences in the access to electricity for displaced persons across the countries are found. For both electricity and clean cooking, the availability for displaced persons ranges from nearly no access at all up to an access rate of 100%. More strikingly, the results also show that besides South Africa, and the se-lected countries in the Maghreb region, the access to both clean cooking and electricity for dis-placed persons is remarkably low. At the same time, the poor data quality does not allow to draw solid conclusions nor impactful implementation activities. Novel conceptual frameworks and indicators are needed. Future research needs to focus on a more comprehensive understand-ing of how energy is interwoven in the lives of displaced persons, before a set of energy indicators can be derived. It is essential that the concerned persons, the displaced persons themselves are in-cluded in the research in a meaningful way.

Agriculture contributes towards South African economy, but this sector is highly vulnerable to risks imposed by climate change. Smallholder maize farmers are specifically susceptible to climate change impacts. Maize crop plays a crucial role in the country's food security as it is considered a stable food for households and source of feed for livestock. The study aimed to analyze the socio-economic factors influencing smallholder maize farmers’ willingness to adopt climate-smart agriculture. It was conducted in three different areas due to their specific agro-ecological zones. Multipurpose research design was used to gather data, and multistage random sampling to choose the study areas. Subsequently, 209 purposively selected farmers were interviewed face-to-face using structured questionnaires and focus discussion groups. Descriptive statistics and Double-hurdle regression model were used to analyze the data. Descriptive results indicated that 81%, 67%, and 63% farmers were willing to adopt CSA in Ga-Makanye, Gabaza, and Giyani, respectively. Empirical results from the first and second hurdles of the regression analysis showed that farmers’ education, crop diversification, information about CSA positively influenced the decision to adopt CSA while household size and agricultural experience negatively influenced the decision to adopt CSA. It is recommended that the Department of Agriculture, Land Reform, and Rural Development should provide CSA workshops and educational programs to farmers to enhance their knowledge and decision-making processes regarding adaptation strategies.

The global craft beer market is witnessing substantial growth, with a particular spotlight on sour beers. These unique brews are created through lactic fermentation initiated by lactic acid bacteria (LAB). However, the presence of hops, renowned for their antimicrobial properties, can pose a limitation within the realm of sour beer production. This research aims to explore and assess the potential of sour beer as a probiotic beverage. It involves a comparative analysis of the viability of Lacticaseibacillus paracasei subsp. paracasei F19 (F19) and 431 (L431) in a sour beer with an International Bitterness Unit (IBU) value of 26.65, alongside examining the ex-pression of genes such as horA, horB, horC, hitA, bsrA, and recA, which are associated with hop resistance. The study encompasses the development of two formulations of sour beers characterized by both high hop content and a robust probiotic count (8.44 – 8.77 log CFU/mL). The findings suggest that both probiotic strains of F19 and L431, are well-suited to produce sour beers with elevated hop levels, demonstrating excellent stability. Notably, the expression of genes responsible for hops resistance exhibited distinct modulation patterns among the two strains. It appears that a higher concentration of bsrA, as observed in strain L431, may be more effective in mitigating the effects of hop-related stress, potentially surpassing the combined expression of horA and bsrA. Nonetheless, further research is essential to validate this observation in gene expression. F19 and L431 emerge as promising candidates for the development of sour beers with increased hop intensity.

This study investigates the impact of brand lovemark on three customer behavioral outcomes (i.e., green brand loyalty, willingness to pay a deposit, and machine use intention) in coffee shops’ CSR practices. We used a scenario-based experimental design on CSR practices in two coffee shop brands (i.e., Starbucks and Dunkin'). The study demonstrates that consumers with a high level of brand lovemark respond more positively to CSR practices of coffee shops than do customers with a low level of brand lovemark. In addition, the interactions between brand lovemark and gender appear to be important in all three behavioral outcomes. Specifically, it confirms that men and women show different levels of behavior outcomes depending on their level of brand lovemark. Theoretical and managerial implications are also suggested with the direction for future study.

Gas turbine engines are widely used in various industries such as aviation, power generation, and marine propulsion due to their high efficiency and reliability. The combustion chamber of a gas turbine engine design contains a number of elements, including as the chamber's size and form, the fuel injection system, the ignition system, and the cooling system and it plays a critical role in the performance and efficiency of the engine. This research discusses the fabrication of a combustion chamber model for a gas turbine engine. The aim of this research is to develop a combustion chamber that is cost-effective, easily available, and can be fabricated in less time. The research covers the different types of combustion chambers used in gas turbine engines and compares their advantages and disadvantages. It then selects the best type of combustion chamber for the gas turbine engine based on its cost, availability, and fabrication time, Efficiency and high power to fuel ratio. The report also describes the fabrication process involved, including the techniques and materials used, along with safety precautions and environmental protection measures. Lastly, the research suggests future improvements and potential applications for the fabricated combustion chamber model.

As both governments and customers push for sustainable and recyclable textile products, textile companies will have to change their linear business model to a circular one. The aim of the present work is to help these companies take action by providing an update of the state-of-the-art of textile recycling technologies. Extensive desktop research was performed in order to prepare an overview of existing textile recycling technologies, their current state and prognosis, including also facilitating technologies for sorting and disintegration of textile products as well as virtual platforms that connect stakeholders and inform consumers.

Wellness tourism is a growing segment that destinations can rely on to increase tourism flows and revive underdeveloped rural areas. This study elicits tourists' preferences for wellness tourism products and the redevelopment of a wellness destination in a depopulated rural area. The re-search included 595 participants in Central Greece using on-site, face-to-face surveys. The survey data was analyzed using a two-step process. First, conjoint analysis was applied to determine the combination of wellness tourism product attributes that maximize visitors’ utility. In the second step, we elicited visitors' willingness to pay (WTP) for improvements in tourism product attributes using the contingent valuation method. Findings indicate that the combination of attributes that maximizes the preference structure of respondents includes time of visit from September to Oc-tober, duration of visit from 1 to 7 days, wellness tourism as the primary purpose of the visit, and wellness activities that contain both physical activities and training as well as spiritual and emo-tional enhancement. Using binary logistic regression, the analysis indicates that respondents are willing to pay 47.33€ per visit on average further to develop wellness tourism products in the study area. Empirical results confirmed that sustainability issues, quality, and entrepreneurship factors positively impact visitors' WTP for revitalizing wellness products. In contrast, a longer duration of stay in the area and respondents' age negatively impact their WTP. These findings suggest that structuring a customer-driven tourism product will enhance the rural destination's efforts to attract high-yield visitors and advance the rural economy. Furthermore, practical im-plications reveal that Destination Management Organizations will benefit from research results to foster targeted management plans.

This study proposes self-calibration of capacitor mismatch errors for high-resolution pipeline analog-to-digital converters (ADCs). The proposed calibration circuit recursively amplifies the capacitor mismatch error by re-utilizing a multiplying digital-to-analog converter in a pipeline stage without increasing the circuit complexity, and the amplified error voltage is converted into digital code by utilizing the remaining pipeline stages. Error correction is performed by subtracting the digital code from the ADC output during normal operation. A prototype of a 12-bit pipeline ADC is fabricated in a 0.18 µm standard CMOS process. The ADC comprises eight 1.5-bit stages, followed by a 4-bit flash ADC as the final stage; the capacitor mismatch errors in the first two pipeline stages are corrected by utilizing the proposed self-calibration technique. At a sampling rate of 30 MS/s, the measured differential and integral nonlinearities improve from +0.82/-0.75 and +1.12/-1.79 to +0.45/-0.41 and +0.47/-0.91 after calibration, respectively. Further, the measured dynamic performances improve significantly with calibration. For an input frequency of 2.09 MHz, the ADC achieves a spurious-free dynamic range (SFDR) and signal-to-noise and distortion ratios (SNDR) of 69.3dB and 63.9dB before calibration, respectively. After calibration, the SFDR and SNDR increase to 84.1dB and 68.9dB, respectively, and the effective number of bits is approximately 11.1bit. The power consumption of the ADC is 35mW under 1.8V supply, and the resulting figure of merit is 514fJ/conversion step.

Current methods for the hardening step of functional coatings over different materials imply the use of high temperatures, high energy consumption or long periods of time, which have repercussions on the speed and cost of the product. We report here a simple and low cost methodology for the functionalization of low cost stainless steel, which is modular, depending of the functionality pursued: a levelling layer for smooth the surface of the material, an “easy to clean” property, or both of them. The research is based on sol-gel coatings cured under UV light without requiring high thermal hardening processes making it applicable to plastics and other sensible materials and possessing high chemical and thermal stability. The film ensures lower processing costs, and higher rates of hardening if the adequate medium-pressure lamps are employed. This formulation is also well defined for scaling up the process, so it is possible to perform a continuous coating in large areas by employing mild processing conditions (low temperature, atmospheric pressure). In addition, the sol gel solution was fully characterized and studied in order to guarantee a long service life before deposition, with a focus on industrial applications in the domestic sector.

High temperature titanium alloys are widely used in aerospace hot parts, however, the thermal barrier temperature of 600 oC limits its service temperature. In this paper, a two-step hot-dip plating method is proposed to prepare the composite coating containing Ce on the surface of titanium alloy, which can make the oxidation resistance temperature of titanium alloy reach 800 oC The microstructure, phase composition and element distribution of Ce-containing Ti-Al-Si hot-dip coating, Ce-containing Ti-Al-Si pre-oxidation coating and Ce-containing Ti-Al-Si high-temperature oxidation coating were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), respectively. The results show that the Ti-Al-Si hot-dip coating containing Ce is mainly composed of (Ti,Ce)(Al,Si)3 alloy phase layer, and the Ti-Al-Si pre-oxidation coating containing Ce is mainly composed of Ti-Al binary system phase layer and dense Al2O3 layer rich in CeO2. Ce in the high temperature oxidation coating of Ti-Al-Si containing Ce is mainly distributed in Ti3Al, TiAl, TiAl3+Ti5Si3 mixed phase layer and Al2O3. The addition of Ce can promote the formation of continuous Al2O3 layer, improve the uniformity of composite coating, prevent the spread of cracks, and improve the high temperature oxidation resistance of Ti-Al-Si coating.

- Power grids of the future will likely incorporate more renewable energy distributed generation (REDG), also known as alternative energy systems. REDG units are increasingly being used in electrical transmission networks because to the overall positive effects they have on power networks. REDG systems are the backbone of smart electric networks and are essential to the operation of the smart grid. These REDG systems can additionally improve system reliability by providing some customers with a backup generator in the event of power interruptions. The report offers a thorough evaluation of the existing body of information on the topic of electric vehicles' (EVs') future interactions with the smart grid. The combination of the EVs' potential deployment and the smart grid's conceptual goal presents challenges in electric grid infra-structure, communication, and control. The proposal for connecting EVs to the grid is based on research into cutting-edge smart metering and communication systems. In the context of the vehicle-to-grid (V2G) phenomenon, the possibilities, benefits, and limitations of various EV smart charging systems are also fully examined. There is a fast growing percentage of distributed energy that is wind and solar photovoltaic. Their variable power output, however, introduces fresh challenges for those responsible for organizing, operating, and controlling the power grid. While fluctuations in the electric grid are problematic, they may be mitigated by the entry of EVs into the energy market. As such, we do a comprehensive literature search to learn more about the exciting research gap that needs to be filled and the most recent possible answer that involves EVs. Additionally, we take a close look at the practicality of the sophisticated V2G technology. The smart grid is a developing concept for the world's energy infrastructure, and this study analyzes in depth how EVs interact with it.

Type 2 diabetes mellitus may be complicated with chronic complications including diabetic neuropathy (DN). Timely diagnosis is crucial in treatment and maybe reversal of this complication. C reactive protein to albumin ratio (CAR) is considered as a marker of inflammation in various diseases that characterized with acute or chronic inflammation. Since diabetic neuropathy and type 2 diabetes mellitus are also associated with chronic, low grade inflammation, we aimed to study CAR levels of type 2 diabetic subjects with diabetic neuropathy and to compare to those in patients without diabetic neuropathy. Type 2 diabetic patients presented to our institutional outpatient clinics were divided into two according to the presence of DN. Subjects with DN were listed as DN group and others were as non-DN group. Characteristics and laboratory data, including CAR, in DN and non-DN groups were compared. Median CAR of the DN and non-DN groups were 2,19 (0,2-49)% and 0,56 (0,02-5,8)%, respectively (p&lt;0.001). CAR was significantly and positively correlated with age (r=0.15, p&lt;0.001), weight (r=0.19, p=0.01), BMI (r=0.11, p=0.03), waist circumference (r=0.10, p=0.046), fasting plasma glucose (r=0.14, p=0.004), serum creatinine (r=0.25, p&lt;0.001), triglyceride (r=0.17, p&lt;0.001), and LDL-cholesterol (r=0.13, p=0.001) levels. Moreover, CAR was inversely correlated with eGFR levels (r=-0.16, p&lt;0.001). The sensitivity and specificity of CAR (when higher than 1,02%) in predicting diabetic neuropathy were 78% and 73%, respectively (AUC: 0.84, p&lt;0.001, 95% CI: 0,82-0,87). Moreover, high CAR level was an independent risk factor of diabetic neuropathy (p&lt;0.001, OR: 1.34, 95% CI: 0.48-1.62). In conclusion, elevated CAR levels could be considered as a marker of diabetic neuropathy.

Brewers’ spent grain (BSG) is an important waste produced in beer companies with a high po-tential to be transformed into commercial by-products. The present paper reports a forecasting technology study with the aid of bibliographic review and patent analysis tools aiming to in-vestigate the maturity of certain technologies, considering the use of BSG on a closed-loop bio-refinery and circular bioeconomy concept integrated into a brewery. To evaluate the possibili-ties of production of high-added value products in Brazil, it was presented an overview of BSG’s scientific, technological, and marketing products and applications. The comparison between numbers of articles versus patents shows that the solutions proposed by research articles are not being transformed into maturated viable technologies. The results suggest that there is a gap between the scientific research in the institutions and their applications in industry, which lead to the destination of the BSG for more economically attractive investments when compared to research in Brazil. Ultimately, from the carried-out analysis, it was possible to propose a brew-ing process connected to the biorefinery system, showing the possibility to the newly arising brewery industries.

Antibiotics are the most magnificent discovery of 20th century that have saved millions of lives from infectious diseases. Microbes have developed acquired antimicrobial resistance (AMR) to many drugs due to high selection pressure from increasing use and misuse of antibiotics over the years. The transmission and acquisition of AMR occur primarily via human–human interface both within and outside of the healthcare facilities. A huge number of interdependent factors related to healthcare and agriculture govern the development of AMR through various drug resistance mechanisms. The emergence and spread of AMR from the unrestricted use of antimicrobials in livestock feed has been a major contributing factor. The prevalence of AMR bacteria has attained its incongruous level worldwide and threatening global public health as silent pandemic, necessitating urgent intervention. Therapeutic options of AMR bacterial infections are limited resulting in significant morbidity and mortality with high financial impact. The paucity in discovery and supply of new novel antimicrobials to treat life-threatening AMR infections stands in sharp contrast to demand. Immediate interventions to contain AMR include surveillance and monitoring, minimizing over the counter antibiotics and antibiotics in food animals, access to quality and affordable medicines, vaccines and diagnostics, and enforcement of legislation. An orchestral collaborative action within and between multiple national and international organizations are required urgently, otherwise, a post-antibiotic era can be a real possibility than an apocalyptic fantasy for the 21st century. This narrative review highlights on the basis, mechanisms and factors in microbial resistance and key strategies to combat antimicrobial resistance.

Food demand and food supply have been heavily affected by Covid-19 pandemic. To understand changes in households’ behavior related to the pandemic, we investigate the willingness to pay for local organic apples pre- and during Covid-19. Besides, we assess whether the changes occurred within the family, estimating also separate models for the two members of the couple. Our findings show that respondents show a positive price premium for local organic apples whose consumption helps reducing the environmental costs associated with food production. The median estimated values during the pandemic range from 34% to 250%. Overall, respondents show a positive mean willingness to pay which increase with the pandemic. The socio-economic variables are the most important in explaining the willingness to pay, while the behavioral variables have more heterogeneous results even if the lifestyle and the request for information through the label are important variables. The pandemic tends to narrow the gaps in preferences between members of the couple. In conclusion, the local and organic dimension is embodied in the short chain in which knowledge and trust in the producer are crucial elements in the consumer's choices.

Drought stress is a major production constraint in crops globally. Crop wild relatives are important source of resistance and tolerance for both biotic and abiotic stresses, respectively. A breeding program was initiated to introgress drought tolerance in sunflower through hybridization between the wild species Helianthus argophyllus and the cultigen pool of H. annuus. Selection was carried out in the F2 to F5 segregating populations for high cuticular waxes, smaller leaf area, single heading and high oil content. The selected F5 breeding lines were compared with non-adapted elite sunflower germplasm in a replicated randomized complete block research project using different water treatments comparing fully irrigated (T0), with 75 (T1), 50 (T2) and 25% (T3) irrigation treatments. The comparison between the two types of germplasm showed that drought tolerant breeding lines had comparatively lesser decreases in leaf area, shoot weight and root shoot ratio 10 under the various drought treatments. Leaf area of the drought selected F5 lines were smaller than that of the elite germplasm under controlled irrigated treatments, but they maintained their leaf area under the drought treatments. Several drought resistant promising lines D-2, D-5, and D-27 were identified and showed high leaf area, great root length and increase root to shoot ratio under the highest stressed treatments (T3). Some of the lines could be directly used for the development of drought tolerant hybrids. Combining ability test indicated D-27 (F7) as good general combiner for seed yield plant−1 and oil contents when mated with male line RSIN.82. These hybrids could help to minimize seed yield losses due to water stress and to achieve profitable cultivation of sunflower in 18 arid regions of Pakistan.

In the context of Covid-19 virus containment, there is a lack of acceptance of preventive measures in the population. The present work investigated which factors influence the belief in of scientific propositions compared belief in conspiracy theories. The focus here was on the determinants of conspiracy beliefs in the context of Covid-19 related media content. Using an online questionnaire (N = 175), results indicate that scientific compared to conspiracy theoretical media content led to higher acceptance. Furthermore, Need for Cognition (NFC-K), a conspiracy theoretical worldview (CMQ), and openness to experience (NEO-FFI) were positively associated with conspiracy beliefs derived from Facebook postings. In addition, a conspiracy theoretical worldview was negatively associated with belief in scientific media content. Furthermore, agreeableness was unrelated to conspiracy beliefs, although it was positively associated with conspiracy theoretical worldview. The results imply promising persuasion strategies for reducing conspiracy theoretical beliefs and to increase the acceptance of preventive measures.

Enteropathogens, namely Salmonella and Campylobacter, are a concern in global public health and have been attributed in numerous risk assessments to a poultry source. During the last decade a large body of research addressing this problem has been published. The literature reviewed contains review articles on certain aspects of poultry production chain, however in the past decade there hasn’t been a review on the through production chain, farm to fork, production of poultry. This review, a pool of 514 articles were selected for relevance via a systematic screening process (from >7500 original search articles). These studies identified a diversity of management and intervention strategies for the elimination or reduction of enteropathogens in poultry production. Many studies were laboratory or limited field trials with implementation in true commercial operations being problematic. Entities considering using commercial anti-enteropathogen products and interventions are advised to perform an internal validation and fit for purpose trial as Salmonella and Campylobacter serovars and biovars may have regional diversity. Future research should focus on non-chemical application within the processing plant and how synergistic through chain intervention may contribute to reducing the overall carcass burden of enteropathogen, coupled with increased consumer education on safe handling and cooking of poultry.

Extensive in-situ resource utilisation (ISRU) will be essential to enable long-duration stays on Luna and Mars and reduce reliance on resupply from Earth. Early development of ISRU technologies has focused on standalone capabilities for specific targets related to life support and ascent propellant. An unexplored opportunity remains for greatly expanding the scope of materials that can be supplied by ISRU, and for integrating various technology platforms into a larger system. Recent advances in power-to-X technology aimed at decarbonising the global economy have made it possible to drive key chemical processes using electricity with small-scale, modular reactor. This paper proposes a vision for an integrated system of ISRU processes based on power-to-X technology to produce oxygen, hydrogen, water, methane, polymers, metal alloys, and synthetic fertilisers, using Martian regolith, atmosphere, and ice. A ‘building block’ strategy is adopted to convert raw materials into versatile intermediaries, which can then be combined to form essential products. A wider range of raw materials are available on Mars compared to Luna, suggesting greater opportunity for ISRU deployment to compensate for the greater time and cost requirements for a Mars resupply mission.

Air corridors are an integral part of the advanced air mobility infrastructure. They are the virtual highways in the sky for transportation of people and cargo in the controlled airspace at an altitude of around 1000 ft. to 2000 ft. above the ground level. This paper presents fundamental insights into the design of air corridors with high operational efficiency as well as zero collisions. It begins with the definitions of air cube, skylane or track, intersection, vertiport, gate, and air corridor. Then, a multi-layered air corridor model is proposed. Traffic at intersections is analyzed in detail with examples of vehicles turning in different directions. The concept of capacity of an air corridor is introduced along with the nature of distribution of locations of vehicles in the air corridor and collision probability inside the corridor are discussed. Finally, the results of simulations of traffic flows are presented.

Current commitments by European governments seek to improve energy consumption as a means to reduce carbon emissions from building stock by 2050. Within such context, retrieving reliable three-dimensional contours from point clouds becomes an important step in developing facade retrofitting solutions since facade retrofitting projects often make use of as-built 3D models to help reduce inaccuracies by narrowing interpretation and measurement errors. This work aims to provide a method that uses topology-based parametric modelling for reconstructing building envelopes from point clouds. Through a semi-automated process that gives permanent visual feedback, the user adjusts parameters to custom standards of acceptability. A solution under the form of a Grasshopper definition delivers building envelope 3D contours in various file formats as a means for increasing interoperability. The main contributions of this work consist of a parametric reconstruction workflow capable of solving building topology for retrieving 3D contours, a strategy to bypass point cloud occlusion, and a strategy for converting those contours into an IFC model directly from the parametric modelling environment.

Autonomous systems require identifying the environment and it has a long way to go before putting it safely into practice. In autonomous driving systems, the detection of obstacles and traffic lights are of importance as well as lane tracking. In this study, an autonomous driving system is developed and tested in the experimental environment designed for this purpose. In this system, a model vehicle having a camera is used to trace the lanes and avoid obstacles to experimentally study autonomous driving behavior. Convolutional Neural Network models were trained for Lane tracking. For the vehicle to avoid obstacles, corner detection, optical flow, focus of expansion, time to collision, balance calculation, and decision mechanism were created, respectively.

The study is an attempt to enquire into the preference of undergraduate students, after a considerable and over a year-long experience with Online Teaching and Learning (OTL), under the emergency preventive measure of switching from the traditional face-to-face classes to online. The study followed an exploratory approach, with a quantitative survey followed by a qualitative one, and a convenient sampling method to collect responses from a substantial sample size. The study is positioned after more than a year of remote classes by the undergraduate student, and hence represents highly experienced reflections and preferences from these students, as compared to other studies conducted last year. The study has profound implications in considering, and questioning, the importance of on-campus classes, and significance of the physical presence of a tutor in the class, and its effect on the learning experience of undergraduate students.

The wide adoption of the recently coined fog and edge computing paradigms alongside conventional cloud computing creates a novel scenario, known as the cloud continuum, where services may benefit from the overall set of resources to optimize their execution. To operate successfully, such a cloud continuum scenario demands for novel management strategies, enabling a coordinated and efficient management of the entire set of resources, from the edge up to the cloud, designed in particular to address key edge characteristics, such as mobility, heterogeneity and volatility. The design of such a management framework poses many research challenges and has already promoted many initiatives worldwide at different levels. In this paper we present the results of one of these experiences driven by an EU H2020 project, focusing on the lessons learnt from a real deployment of the proposed management solution in three different industrial scenarios. We think that such a description may help understand the benefits brought in by a holistic cloud continuum management and also may help other initiatives in their design and development processes.

RNA editing involves the insertion, deletion or substitution of single nucleotides within a RNA molecule, without altering the DNA sequence. Adenosine to inosine (A-to-I) editing consists of an RNA modification where single adenosines along the RNA sequence are converted into inosines. Such a biochemical transformation is catalyzed by enzymes belonging to the family of adenosine deaminases acting on RNA (ADARs) and occurs either co- or post-transcriptionally. Initially, the A-to-I RNA editing phenomenon was discovered and studied in messenger RNAs (mRNAs), where it can influence RNA splicing and cause the recoding of codon sequences. The employment of more powerful, high-throughput detection methods has recently revealed that A-to-I editing widely occurs in non-coding RNAs, including microRNAs (miRNAs). MiRNAs are a class of small regulatory non-coding RNAs (ncRNAs) acting as translation inhibitors, known to exert relevant roles in controlling cell cycle, proliferation, and cancer development. Indeed, a growing number of recent researches have evidenced the importance of miRNA editing in cancer biology by exploiting various detection and validation methods. Herein, we briefly overview early and currently available A-to-I miRNA editing detection and validation methods and discuss the significance of A-to-I miRNA editing in human cancer.

Stakeholder input into the decision-making process when developing public health programs and policies is crucial. This article presents an innovative approach, involving online participation with a wide group of stakeholders located in different geographic locations, for policy consensus by research methodology. The results of the project have been used to propose assumptions regarding a strategy for preventing blood-borne diseases in Poland. The research was conducted iteratively using a multi-stage qualitative methodology to explore risk assessment involving blood-borne infections. The final output of the entire project is a list of key problems/challenges and solutions associated with medical and nonmedical services that are connected to the breakage of tissue continuity. Qualitative research is rare in risk assessment as priority is usually given to statistical data and end-points (quantitative studies ). Statistical data on health risk allows to assess the health implications, while the methodology applied also allowed diagnosis of the processes leading to these effects. In addition to policy preparation for blood-borne illnesses, the methodology employed in the study can also be used to successfully explore other areas of public health policy decisions.

This short note proposes a national Geographic Information System (GIS) - based health infrastructure to deal with epidemics and pandemics. Currently, there is no pan-India health infrastructure available that can compile, update, and report the spread of epidemic diseases. It not only curtails the opportunity of finding the real-time data on the spatial distribution of a disease but prevents one to inquire into the causes of the disease through epidemiological analysis. The proposed infrastructure in this study is a pan-India one and can broadly be divided into two parts, hotspot mapping and accessibility to services. In the first part, hospitals are proposed to act as nodes of data collection, sending data to a national GIS portal. This portal shall have the capabilities of plotting the data using map rendering services such as Google and Bing Maps. This way, hotspots can be visualized in no time, benefitting the government and common citizenry alike. The second part deals with the accessibility of citizenry to a wide range of services, i.e., healthcare services, grocery outlets, emergency services, baby food, and many other essential services of the day to day life. In order to implement this, we propose that the government need to enforce a mandatory submission of locational coordinates of all Goods and Services Tax (GST) enrolled service providers. Once the coordinates are submitted, the government can effectively control the opening and closing of services and inform the citizenry at the same time. The proposed infrastructure is going to help deal with the extraordinary situations during epidemic and pandemics similar to what the world is currently facing in the form of Corona Virus Disease 2019 (COVID-19). Furthermore, the infrastructure can be scaled up or down as per the spread of a disease. The health-GIS platform proposed in this concept paper, shall help India in controlling and managing the epidemic more efficiently.

Despite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance, culminating in relapse and metastatic disease continue to be associated with fatal disease. Cancer stem cells (CSCs) are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis. Whilst the debate on whether CSCs are the origins of the primary tumor rages on, CSCs have been further characterised in many cancers with data illustrating that CSCs display great abilities to self-renew, withstand therapies due to enhanced epithelial to mesenchymal (EMT) properties, enhanced expression of ABC membrane transporters, activation of several survival signaling pathways and increased immune evasion DNA repair mechanisms. CSCs also display great heterogeneity with the consequential lack of specific CSC markers presenting a great challenge to their targeting. In this updated review we re-visit CSCs within the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs. These promising strategies include targeting CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-associated drug resistance and metastasis.

Sharing the same raw material, recycling and composting are in direct conflict with incineration of municipal solid waste in combined heath and power plants. Indeed, waste-to-energy plants in regions with high recycling rates import urban waste from other countries to use otherwise unused capacity, and raise revenues. Using the case of Italy’s second largest and economically most developed region, I discuss the economic viability of municipal solid waste incineration to produce electricity and heath in the context of the increasing role of electricity production from renewable energy sources as well as of the emerging mass-scale uptake of bioplastics. Four lessons and three guidelines aimed to local authorities and policy makers emerge from the present study.

This paper aims to investigate the criteria of behaviour of certain type of third order neutral generalized difference equations with distributed delay. With the technique of generalized Riccati transformation and Philos-type method, some oscillation criteria are obtained to ensure convergence and oscillatory solution of suitable example is listed to illustrate the main result.

Sensory evaluation has been widely applied in assessing the quality of many consumer products that directly serve human needs such as food, beverages, clothing, etc. This paper first examined the inherent deficiencies in this approach, due mainly to the essentially subjective nature of human sensory preference. It then argued that instinctively designating certain materials attributes as sensory perceptions is unnecessary; considering every scientific concept is in essence the processed results of our sensory organs/brains, i.e., all quantities were initially human perceptions. Scientific advances have inevitably generated gradual transformation of such human perceptions as warmth and heaviness into objective parameters measurable in physical quantities like temperature and kilograms. Then using existing successful examples, it demonstrated firmly how the sensory attributes can be assessed by more reliable instrumental methods, and envisioned the key steps to turning a perception into scientifically measurable parameter(s).

Pain is a major problem in sick newborn infants, especially for those needing intensive care. Pharmacological pain relief is the most commonly used but may be ineffective, have side effects, including long-term neurodevelopmental sequelae. The effectiveness and safety of alternative analgesic methods are ambiguous. The objective is to review the effectiveness and safety of non-pharmacological methods of pain relief in newborn infants and to identify those that are the most effective. PubMed and Google Scholar were searched using the terms: ‘infant’, ‘premature’, ‘pain’, ‘acupuncture’, ‘skin to skin contact’, ‘sucrose’ ‘massage’, ‘musical therapy’ and ‘breastfeeding’. We included 24 studies assessing different methods of non-pharmacological analgesic techniques. Most resulted in some degree of analgesia but many were ineffective and some were even detrimental. Sucrose, for example, was often ineffective but more effective than music therapy, massage, breast milk (for extremely premature infants) or non-invasive electrical stimulation acupuncture. There were also conflicting results for acupuncture, skin to skin care and musical therapy. Most non-pharmacological methods of analgesia provide some modicum of relief for preterm infants but none are completely effective and there is no clearly superior method. Study is also required to assess potential long-term consequences of any of these methods.

Aiming at the problem of model error and tracking dependence in the process of intelligent vehicle motion planning, an intelligent vehicle model transfer trajectory planning method based on deep reinforcement learning is proposed, which obtain an effective control action sequence directly. Firstly, an abstract model of the real environment is extracted. On this basis, Deep Deterministic Policy Gradient (DDPG) and vehicle dynamic model are adopted to jointly train a reinforcement learning model, and to decide the optimal intelligent driving maneuver. Secondly, the actual scene is transferred to equivalent virtual abstract scene by transfer model, furthermore, the control action and trajectory sequences are calculated according to trained deep reinforcement learning model. Thirdly, the optimal trajectory sequence is selected according to evaluation function in the real environment. Finally, the results demonstrate that the proposed method can deal with the problem of intelligent vehicle trajectory planning for continuous input and continuous output. The model transfer method improves the model generalization performance. Compared with the traditional trajectory planning, the proposed method output continuous rotation angle control sequence, meanwhile, the lateral control error is also reduced.

Glaucoma is a disease associated with retina of eye. Presently, millions of human being is suffering from this disease. Early detection of these diseases can save the people from blindness. Therefore, various methods have been developed for its detection. In this paper, we have studied the reported methods and summarized their performance in terms of accuracy of detection.

While the mobile phone is the world’s most popular media device, it is actually not one single medium, but is effectively used as a different medium by different user groups. The article characterizes polymodal differences in mobile apps usage among different user groups, including gender, education, occupation, screen size, and price. We monitored the complete app usage of 10,725 smartphone users for one month each (56 million sessions, recording almost 1 million hours). Our key contribution consists in developing and analyzing a theoretical framework to classify the over 16,000 apps used into five categories. Exploring nine research questions we provide a broad characterization by asking who, with which characteristics, uses which kinds of apps in what extensity and intensity? For example, it is not the young and high occupational grades that use the mobile phone as a human-to-machine computer (including gaming and artificial intelligence tools). Large screen size is related to extensive long sessions, while a small screen size is related to intensive frequent usage. The results go beyond providing ample empirical evidence for the inherently polymodal nature of the mobile phone, but also proposes a framework on how to possibility deal with it analytically.

Revitalization of open water bodies into recreational areas are becoming widely popular in many parts of Sri Lanka. Understanding community perception and expectation on recreational development have important policy and cost-effectiveness implications. This paper explores the public perspectives on development, conservation and value of the open water recreational development at Diyatha Uyana and surrounding area. Contingent Valuation Method has been applied to estimate peoples’ Willingness To Pay for recreational spaces in the selected area. A total of 300 residents from different socioeconomic backgrounds were selected randomly for the study. Enjoying peace and relaxation, taking children to play and breath clean air were mentioned as most important aspects of open water body areas. More frequent visits occur to enjoy peace and relaxation, breath clean air and enjoy the natural landscape. Almost all the participants were agreed upon conserving open water body areas in urban settings. Willingness to pay was significantly associated with income and occupation status. It yielded a monthly average payment of Rs.446.93 per household for another five years’ time. The limited budget was the main reason for not willing to pay. This paper is significant as there is no contingent valuation method study has been carried on water body development in Sri Lanka.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

The planar cell polarity (PCP) of epithelial ciliated cells is essential for effective mucociliary clearance (MCC) in the sinonasal mucosa. We hypothesize that MCC coordination is impaired in nasal polyp (NP) mucosae due to suppressed expression of a series of CPLANE (ciliogenesis and planar cell polarity effector) complex proteins in chronic rhinosinusitis (CRS) patients. To inves-tigate this hypothesis, we subjected sinonasal mucosal samples to live video recording to measure mucociliary transport velocity (MCTV) and scanning electron microscopy to evaluate surface morphology. The expression and distribution of a panel of PCP proteins, e.g. WDPCP and FUZ, were investigated in relation to inflammatory cytokine levels and clinical features. The mean MCTV of NP mucosae was significantly lower than that of the inferior turbinate mucosae. The CRS group with NPs (CRSwNP group) (n=28) showed increased expression of IL-13 and CCL26 mRNA compared to CRS patients without NPs (n=25) and controls (n=30). WDPCP and FUZ mRNA levels were significantly decreased in NP mucosae compared to ethmoid sinus mucosae in CRSwNP patients. WDPCP protein distribution was reduced in the cytoplasmic region of ciliated cells in CRSwNP patients. We conclude that suppression of WDPCP in ciliated cells is responsible for the impaired MCC of nasal polyps with type-2 inflammation. This mechanism might explain the decreased clearance and the potential for worsening symptoms of CRSwNP.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with the clear cell RCC (ccRCC) the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of polymorphisms in genes HVEM and CD160 on susceptibility to ccRCC and patient overall survival (OS) with over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, and two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within additional HVEM SNPs, rs8725 and rs1886730, is associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of the disease. Moreover, the rs1886730 SNP was found to be associated with patients' OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as patient’s OS.

Human adipose stem cell-derived extracellular vesicles (hASC-EVs) are key mediators of paracrine signaling with promising therapeutic applications. Although hASC-EVs are derived from human cells and are less immunogenic, their immunogenicity cannot be completely excluded. Here, we evaluate the immune responses of ICR and C57BL/6 mice to high doses of hASC-EVs for 10 days after injection. Lymphocyte subpopulations are analyzed using flow cytometry at 0.5, 1, 3 and 24 h post injection. In the spleen and blood of C57BL/6 mice, neutrophils sharply increased at 0.5 h and decreased at 3 h following hASC-EV treatment. We observe increased proportions of monocytes, macrophages, and natural killer cells at 3 h but returned to similar level of vehicle control at 24 h post injection in the spleen and blood of ICR mice. Although the in vivo experiments reveal different immune responses to hASC-EV treatment in C57BL/6 and ICR strains, no major changes occur in human peripheral blood mononuclear cell composition after applying hASC-EVs in vitro. In conclusion, unlike those in mice, immune responses to hASC-EVs in humans are not detectable, indicating a minimal risk of fatal side-effects from hASC-EV-based therapies.

Pericytes are increasingly recognized as being important in the control of blood-brain barrier permeability and vascular flow. Research on this important cell type has been hindered by widespread confusion regarding the phenotypic identity and nomenclature of pericytes and other perivascular cell types. In addition, pericyte heterogeneity and mouse-human species differences have contributed to confusion. Herein we summarize our present knowledge on the identification of pericytes and pericyte subsets in humans, primarily focusing on recent findings in humans and nonhuman primates. Precise identification and definition of pericytes and pericyte subsets in humans may help us to better understand pericyte biology and develop new therapeutic approaches specifically targeting disease-associated pericyte subsets.

Publically available (own) transcriptomic data were re-analyzed to quantify the alteration of functional pathways in the thyroid cancer, establish the gene hierarchy, identify potential gene targets and predict the effects of their manipulation. The expression data were generated from one case of papillary thyroid carcinoma (PTC) and from genetically manipulated BCPAP (papillary) and 8505C (anaplastic) human thyroid cancer cell lines. The study used the genomic fabric perspective that considers the transcriptome as a multi-dimensional mathematical object based on the three independent characteristics that can be derived for each gene from the expression data. We found remarkable remodeling of the thyroid hormone synthesis, cell cycle, oxidative phosphorylation and apoptosis pathways. Serine peptidase inhibitor, Kunitz type, 2 (SPINT2) was identified as the Gene Master Regulator of the investigated PTC. The substantial increase of the expression synergism of SPINT2 with apoptosis genes in the cancer nodule with respect to the surrounding normal tissue (NOR) suggests that its experimental overexpression may force the PTC cells into apoptosis with negligible effect on the NOR cells. The predictive value of the expression coordination for the expression regulation was validated with data from 8505C and BCPAP cells before and after lentiviral transfection with DDX19B.

At present more than 9 million people die of cancer every year. Simple and broad-spectrum drugs are still an urgent need for cancer patients. Recently, we proposed a new hypothesis that intracellular osmotic pressure (IOP) is the driving force of cell division, and abnormal tumor proliferation is the result of uncontrolled IOP in cells. On the one hand, aneuploidy and abnormal function of Na⁺/K⁺ pump lead to a faster rise of IOP in tumor cell than normal cells, on the other hand, abnormality of cytoskeleton assembly leads to the decrease of tolerance limit of cell membrane (TLCM) of tumor cells for resisting IOP. This hypothesis predicts: 1)Tumor cells were more intolerant to hypotonic stress than normal cells. 2) Maligancies may be sellectively killed by a suddenn increase of IOP and combined with decrease of the TLCM of tumors. Na⁺/K⁺ pump inhibitors can promotely increase the IOP of tumor cells and cytoskeleton inhibitors can dramatically lower the TLCM of tumor cells. Therefore, Na⁺/K⁺ pump and cytoskeleton inhibitors may have a synergetic effect to kill tumor cells. 3) Molecules regulating cell osmolality may be new targets for cancer treatment.

BACKGROUND: Treatment failure in primary as well as metastatic cancer patients, caused by chemo and radio resistance, has truncated the research for the applicability of personalized medicine. The use of stem cells and cancer stem cells in such a treatment approach will be reviewed in this study. RESULTS: CRC stem cells prove to be a promising asset for CRC treatment optimization both by serving as biomarkers for the current therapy modalities by means of treatment personalization and patient/tumor stratification, as well as in the development of targeted therapies, selective for the stem cell population. Similar conclusions are drawn, regarding mesenchymal stromal cells and their effect in CRC therapy; while resident stromal cells of tumor microenvironment seem to promote the tumorigenic and metastatic processes in addition to conferring to the chemo- and radio resistance, under certain conditions they are able to improve the treatment outcome of CRC chemotherapy, e.g. by targeted enzyme/prodrug treatment of CRC cells. CONCLUSION: This review, truncates the dynamic potential of cancer stem cells and other stem cell types in CRC treatment personalization as well as, in the improvement of current treatment approaches opting to a higher therapeutic rate, improved prognosis, survival and quality of life for CRC patients.

Rapid development and deployment of vaccines greatly reduced mortality and morbidity during the COVID-19 pandemic. The most widely used COVID-19 vaccines approved by national regulatory authorities require intramuscular administration. SARS-CoV-2 initially infects the upper respiratory tract where the infection can be eliminated with little or no symptoms by an effective immune response. Failure to eliminate SARS-CoV-2 in the upper respiratory tract results in lower respiratory tract infections that can lead to severe disease and death. Presently used intramuscularly administered COVID-19 vaccines are effective in reducing severe disease and mortality but are not entirely able to prevent asymptomatic and mild infections as well as person to person transmission of the virus. Individual and population differences also influence susceptibility to infection and the propensity to develop severe disease. This article provides a perspective on the nature and the mode of delivery COVID-19 vaccines that can optimize protective immunity in the upper respiratory tract to reduce infections and virus transmission as well as severe disease.

Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice. MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by improved glucose tolerance and higher blood insulin levels. 7S,14R-diHDHA-treated MSCs increased insulin+ β-cell ratio and decreased glucogan+ α-cell ratio in islets, as well as reduced macrophages in pancreas. 7S,14R-diHDHA induced MSC functions in promoting MIN6 β-cell viability and insulin secretion. 7S,14R-diHDHA induced MSC paracrine functions by increasing the generation of hepatocyte growth factor and vascular endothelial growth factor. Furthermore, 7S,14R-diHDHA enhanced MSC functions to ameliorate diabetes-caused pericyte loss in diabetic retinopathy by increasing their density in retina in db/db mice. Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7S,14R-diHDHA-primed MSCs.

Deep Learning (DL) has made significant advances in computer vision with the advent of Vision Transformers (ViT). Unlike Convolutional Neural Networks (CNNs), ViTs use self-attention to extract both local and global features from image data, and then use residual connections to feed these features directly into a fully networked multilayer perceptron head. In hospitals, hematologists prepare peripheral blood smears (PBSs) and read them under a medical microscope to detect abnormalities in blood counts such as leukemia. However, this task is time-consuming and prone to human error. This study investigates the transfer learning process of Google ViT and ImageNet CNNs to automate the reading of PBSs. The study used two online PBS datasets, PBC and BCCD, and transferred them into balanced datasets to investigate the influence of data amount and noise immunity on both neural networks. The PBC results show that Google ViT is an excellent DL neural solution for data scarcity. The BCCD results show that Google ViT is superior to ImageNet CNNs in dealing with unclean, noisy image data because it is able to extract both global and local features and use residual connections, despite the additional time and computational overhead.

Exposure to environment polluting chemicals (EPCs), which are ligands of the aryl hydrocarbon receptor (AhR), is associated with the development of type 2 diabetes (T2D). This study explores the mechanisms by which AhR ligands contribute to β-cell failure in T2D. Incubation of rat RINm5F pancreatic β-cells with low-dose 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most potent AhR ligand, inhibited glucose-stimulated insulin secretion (GSIS). A single injection of TCDD in wild type mice reduced the size of Langerhans islets, but not in AhR liver knock-out mice (AhR-LKO). RNA-seq database analysis identified Serpine1, encoding for plasminogen activator inhibitor type-1 (PAI-1) as a TCDD-mediated secretory protein that are synthesized in an AhR-dependent manner in the liver. Elevated PAI-1 levels were shown to induce caspase 3/7-dependent apoptosis in RINm5F cells, suggesting a novel pathway through which EPCs exacerbate T2D. These findings support the hypothesis that chronic exposure to AhR ligands may directly inhibit GSIS in pan-creatic β-cells and indirectly induced β-cell apoptosis through increased PAI-1. This study provides new insights into the EPC-PAI-1 axis as a missing link between pancreatic β-cell failure and the progression of T2D and offers a potential target for therapeutic intervention.

Red blood cell (RBC) alloimmunization and antibodies formation against non-self-antigen on red cells may occur after blood transfusion, pregnancies or other exposures. The RBC alloimmunization rates varies from 2% to 6% according to recent studies. The antibody screen is performed to identify or confirm the presence of antibodies in patient’s serum or plasma, as a preoperative or pretransfusion tests. The antibody identification process and major crossmatch are provided to improve the safety of red blood transfusion administration. I report three examples associated with clinically significant single and multiple alloantibodies. Ultimately, I summarize key points for a clinical transfusion practice.

Objective: We evaluated the possibility of diagnosing pleural mesothelioma (PM) through pleural effusion cytology in a multicentric prospective clinical trial (MesoCyto study). Methods: We included patients with pleural effusion and suspected PM scheduled for thoracentesis and pleural biopsy. Both pleural effusion cytology including cell block and pleural biopsy were independently performed and compared to assess the diagnostic reliability of pleural effusion cytology. The primary endpoint aimed to demonstrate that the specificity of PM diagnosis by pleural effusion cytology reached 100%. Secondary endpoints included the frequency of adverse events during thoracentesis and pleural biopsy and assessment of diagnostic accuracy of pleural effusion cytology for each histological type. Results: Of the 50 enrolled patients, histological examination confirmed PM in 42 patients; 29 patients met the diagnostic criteria of PM in pleural effusion cytology and received a cytological diagnosis. Of the remaining 21 patients, 13 displayed atypical cells suggestive of PM based on pleural effusion cytology but did not meet the diagnostic criteria, and in 8, atypical cells were not identified and PM diagnostic criteria were not met. Thus, pleural effusion cytology specificity was 100%. The diagnostic concordance rate by pleural effusion cytology for each histological type was 72.2% for epithelioid, 75% for biphasic, and 0% for sarcomatoid. No adverse events were associated with thoracentesis, but the incidence of adverse events during pleural biopsy was 14%. Conclusions: PM can potentially be diagnosed through only pleural effusion cytology including the cell block method using immunohistochemical staining.

Cellular therapies exhibit immense potential in treating complex diseases with sustained response. Manufacture of cell therapies involves purification and engineering of specific cells from a donor or patient to achieve a therapeutic response upon injection. Magnetic cell sorting targeting the presence or absence of surface markers is commonly used for upfront purification. However, emerging research is showing that optimal therapeutic phenotypes are characterized not only by the presence or absence of specific antigens but also on antigen density. Unfortunately, current cell purification tools like magnetic or fluorescence activated cell sorting lack the resolution to differentiate populations based on antigen density while maintaining scalability. Utilizing a technique known as Digital Magnetic Sorting (DMS) we demonstrate proof of concept for a scalable, magnetic based approach to fractionate cell populations based on antigen density level. Targeting CD4 on human leukocytes, DMS demonstrated fractionation into CD4High T cells and CD4Low monocytes/neutrophils as quantified by flow cytometry and single cell RNA sequencing. DMS also demonstrated high throughput processing at throughputs 5-10X faster than flow cytometry. We believe DMS can be leveraged and scaled to enable antigen density-based sorting in cell therapy manufacturing, leading to the production of more potent and sustainable cellular therapies.

Background: Lung cancer remains the leading cause of cancer-related mortality globally, predo-minantly affecting older individuals. Despite the increasing use of immune checkpoint inhibitors (ICIs) like nivolumab in non-small cell lung cancer (NSCLC), the efficacy and safety in elderly pa-tients, particularly those aged 65 and above, remain underexplored due to their underrepresenta-tion in clinical trials. Methods: This retrospective study analyzed data from 60 elderly patients (≥65 years) with metastatic NSCLC who received nivolumab as second-line or later therapy between January 2020 and May 2023. Results: The median age was 67 years, with a predominance of males (78%). Nivolumab was administered for a median of 8 cycles, with 33.3% of patients recei-ving 15 or more cycles. The median OS was 23 months, and the 1-, 3-, and 5-year survival rates were 93.3%, 54.1%, and 18.6%, respectively. Multivariate analysis identified adenocarcinoma histology, fewer than 15 cycles of nivolumab, and non-response to prior therapies as independent predictors of poor OS. Nivolumab treatment was generally well-tolerated, with 45% of patients experiencing at least grade 1 toxicity. Conclusion: Nivolumab is effective and well-tolerated in elderly patients with metastatic NSCLC, providing survival benefits comparable to those observed in younger populations. The number of treatment cycles and initial response to therapy are key determinants of survival, underscoring the importance of continued treatment in this age group.

Human Papillomavirus (HPV) related cancers account for a large percentage of cancers. The tumor microenvironment (TME) is a complex structure and contributes significantly to tumor development, progression, and invasion. The TME is particularly pronounced in HPV-related cancers and HPV is known to influence the TME. In cancer research, there is an urgent need for new models to deepen our understanding of the pathophysiology of the disease and to facilitate the development of innovative therapies. In this context, 3D cell culture has emerged as a promising method in cancer research, that offers significant potential compared to conventional approaches. 3D modelling can produce results that are more consistent with clinical outcomes without the ethical concerns and problems of animal models. In this review, our aim is to discuss the tumor microenvironment in HPV-related cancers and demonstrate the importance of advancing 3D cell culture models for this purpose.

Background: Ubiquitination is an important post-transcriptional modification crucial for maintaining cell homeostasis. As a deubiquitination enzyme, ubiquitin-specific protease 1 (USP1) is associated with tumor progression; however, its role in bladder cancer is unknown. This study was aimed to analyze USP1 expression and study its roles in bladder cancer. Methods: The web server GEPIA was used to analyze the USP1 expression. To explore USP1 function in bladder cancer, we constructed USP1-knockout cell lines in UMUC3 cells. A FLAG-USP1 (WT USP1) plasmid and a plasmid FLAG-USP1 C90S (catalytic-inactive mutant) used to overexpress USP1 in T24 cells. CCK8, colony formation, and transwell assays were used to assess cell viability, proliferation and migration. RNA sequencing (RNA-seq) and dual-luciferase reporter assays were performed to screen the pathway. Coimmunoprecipitation and immunofluorescence were used to explore the interaction between USP1 and c-MYC. Xenograft mouse model was used to study the role of USP1 in bladder cancer. Results: USP1 expression is upregulated in human bladder cancer cells and correlated with poor patient prognosis. USP1 overexpression promoted cell proliferation, clone formation, and migration; this was attenuated by genetic ablation of USP1. Furthermore, we observed that USP1- deficiency inhibited tumor formation in vivo. Mechanistically, the c-MYC pathway was remarkably activated compared with the other pathways. Furthermore, USP1 could directly interact with c-MYC. and increase c-MYC stability depending on the catalytic activity of USP1. Conclusions: Our results suggest that high expression of USP1 promotes bladder cancer progression by stabilizing c-MYC; hence, USP1 it may serve as a novel therapeutic target for treating bladder cancer.

Silver nanoparticles (AgNPs) have arisen as promising specialists in malignant growth treatment, especially in further developing radiotherapy results. In vitro examinations feature AgNPs' capacity to increment radiosensitivity in disease cell lines, prompting uplifted cell demise and decreased clonogenic endurance. Outstandingly, AgNPs display insignificant poisonousness to ordinary cells, recommending potential for specific focusing of disease cells during radiotherapy. The blend of AgNPs with cisplatin shows huge cytotoxicity and oxidative pressure, particularly in tumoral cells, underscoring the requirement for additional investigation of this therapeutic methodology. AgNPs likewise show guarantee in prompting oxidative pressure in pancreatic disease cells, recommending an expected application in pancreatic malignant growth treatment. In co-openness situations, AgNPs, when joined with cadmium, prompt metabolic variation, showing compromised cell safeguard systems. Moreover, AgNPs display potential in tweaking ABC carrier action, offering a procedure to defeat multidrug obstruction in disease cells. While featuring the significant capability of AgNPs in disease treatment, the rundown highlights the need for continuous exploration to clarify their components, well-being profiles, and clinical applications. Combining AgNPs with radiotherapy presents a promising road, tending to limits in ordinary disease therapies and underlining their multifunctionality in forming the eventual fate of malignant growth therapeutics.

Dendritic cells (DCs) are known as major antigen-presenting cells, and lymph nodes (LNs) play an important role in the DC-mediated immune response. This study focused on infiltration of CD1a-positive DCs (CD1a-DCs) in regional LNs in 70 cases of gallbladder cancer (GBC). The results showed that LNs infiltration by CD1a-DCs was associated with unfavorable clinical outcomes in patients with GBC in univariate analyses, but all cases categorized as CD1a-DCs high group at regional LNs had nodal metastasis. Therefore, LNs infiltration by CD1a-DCs was not an independent prognostic factor identified by multivariate analyses. The subgroup analyses in cases with LN metastasis group (n = 32), significant impact of CD1a-DCs infiltration into metastatic LNs was not observed. In contrast, CD1a-DCs infiltration into primary tumor had a significant impact on surgical outcomes. As the results of previous reports that focused on CD1a-DCs infiltration in regional LNs of other organs were varied, the role and significance of CD1a-DCs infiltration in regional LNs may be different according to the tumor histology or primary site. Accumulation of further studies is needed to clarify the role and significance of CD1a-DCs infiltration into regional LNs of solid cancers.

This paper deals with the formulation of a Cobot kinematic model by developing both the direct and inverse kinematics and choosing the noa transformation matrix for defining the end-effector position and orientation with respect to the base frame. These algorithms have been validated via software in Matlab environment and by means of suitable experimental tests, which have been carried out by using a UR5e Cobot. Moreover, a specific industrial application regarding the robotized assembling of a multi-cylinder IC engine, has been designed in terms of layout and corresponding automatic cycle that is intended as a sequence of the robot elementary actions. In particular, the proposed robotized cell is composed by the UR5e Cobot along with its controller and a suitable electropneumatic circuit that includes a PLC with its user interface, which are both governed by means of a specific electronic board and a switch control box. The IC engine in scale of 1:5 and specific parts of the end-effector, which takes the role of vacuum gripper and torque limiting screwdriver, have been designed and manufactured by using a 3D printer.

Recent advancements in nanotechnology have led to the development of multifunctional iron oxide nanoparticles, presenting new opportunities in cancer therapy. This study aimed to synthesize and evaluate citric acid-coated/ folic acid conjugated nanoparticles loaded with doxorubi-cin and investigate their efficacy in experimental tumor models. For synthesis, controlled co-precipitation method was employed to produce highly dispersive, multifunctional nanofluids with a narrow size distribution of iron oxide nanoparticles. Nanoparticles were characterized using Dynamic Light Scattering (DLS) and Electrophoretic Light Scattering (ELS) for size distribution and zeta potential, X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) for structure and morphology, Vibrating Sample Magnetometry (VSM) for magnetic properties, and UV-Visible (UV-Vis) and Fourier-Transform Infra-red (FTIR) spectroscopy for modification confirmation. In vitro experiments employed RM1 (prostate cancer) and MEC1 (Chronic lymphocytic leukemia) cell lines to assess cytotoxicity and drug delivery efficiency. Fluorescence microscopy confirmed the intracellular delivery of doxorubicin by these nanoparticles, highlighting their potential for targeted therapy. As a result, nanoparticles conjugated with folic acid showed reduced efficacy over time. This study underscores the critical role of nanoparticle modifications in optimizing therapeutic outcomes. Future research should focus on further refining nanoparticle formulations and long-term effects in vivo, for development of effective and safe agents for targeted cancer treatment.

The mechanistic Target of Rapamycin Complex 1 (mTORC1) regulates ribosome biogenesis and the transcription of ribosomal genes. Its inactivation impacts protein synthesis necessary for transport of cell adhesion molecule. In Dictyostelium discoideum, the activity of mechanistic Target of Rapamycin Complex 2 (mTORC2) is crucial for cAMP synthesis and relay, processes that depend on heterotrimeric G-proteins and Ras GTPases. Mutants lacking rip3 or lst-8 genes exhibit impaired adenyl cyclase activation and cAMP signaling, resulting in deficient expression of the cell adhesion protein CsaA. Despite this, rip3^- cells, which have impaired mTORC2, upregulate Cad-1 expression, a cell adhesion protein regulated by Ras-GTPases, to compensate for the loss of CsaA. lst-8^- cells, which have both mTORC1 and mTORC2 inactivated, show reduced nutrient sensing, premature CsaA expression and solitary cell behavior. These cells also show defective transport of adhesion proteins to the cell surface, impeding aggregation. Similar defects are observed with caffeine treatment, suggesting both mTORC1 and mTORC2 inhibition. This study highlights the interplay between mTORC1 and mTORC2 in regulating cell adhesion and aggregation through cAMP signaling and protein synthesis pathways in Dictyostelium.

Equine laminitis is a debilitating condition characterized by the breakdown of the dermal–epidermal junction, resulting in severe lameness and pain, often requiring euthanasia. This study aimed to establish an in vitro model of laminitis using a continuous keratinocyte cell line exposed to anoxia-reoxygenation and activated neutrophil supernatant. A significant decrease in keratinocytes metabolism was noted during the reoxygenation period, indicative of cellular stress. Adding muscle-derived mesenchymal stem/stroma cells during reoxygenation demonstrated a protective effect, restoring keratinocytes metabolic activity. Moreover, incubation of keratinocytes with activated neutrophil supernatant or myeloperoxidase alone induced increased keratinocyte myeloperoxidase activity, which was modulated by stem cells. These findings underscore the potential of muscle-derived mesenchymal stem/stroma cells in mitigating inflammation and restoring keratinocyte metabolism, offering insights for future cell therapy research in laminitis treatment.

Vegetative desiccation tolerance has evolved within the genus Craterostigma and Lindernia. A centre of endemism and diversification for these plants appears to occur in ancient tropical montane rainforests of east Africa in Kenya and Tanzania. Lindernia subracemosa, a desiccation-sensitive relative of C. plantagineum, occurs in these rainforests and experiences adequate rainfall and thus does not require desiccation tolerance. However, sharing this inselberg habitat, another species Lindernia brevidens does retain vegetative desiccation tolerance and is also related to the resurrection plant C. plantagineum found in South Africa. Leaf material was collected from all three species at different stages of hydration: fully hydrated, half-dry (ca. 45% relative water content), and fully desiccated. Cell wall monosaccharide datasets were collected from all three species. Comprehensive microarray polymer profiling (CoMPP) was performed using ca. 27 plant cell wall specific antibody and carbohydrate binding module probes. Global datasets do not show significant differences between the selected species suggesting that cell wall modifications in response to vegetative desiccation involve subtle cell wall remodelling not reflected by compositional analysis and that the plants and their walls are constitutively protected against desiccation.

The objective of this paper was to study the expression pattern of the GLOD4 gene in the testis and its regulatory effect on testicular cells. Currently, the regulated mechanism through are unclear. Here, we explored how GLOD4 functions in goat leydig cells to enhance our understanding of spermatogenesis and improve reproduction in breeding rams. In this study, we demonstrated that the localization of GLOD4 in testicular cells using immunohistochemistry and subcellular localization analyses. Subsequently, we analyzed the GLOD4 expression pattern in 4 age-based groups (0, 6, 12, and 18 months old) using real-time quantitative polymerase chain reaction (qRT‒PCR) and protein blotting. Finally, we performed GLOD4 gene silencing and overexpression studies in testicular cells from goats and explored the effects of GLOD4 on cell proliferation, the cell cycle, steroid hormone secretion and the expression of candidate testosterone hormone-regulated genes. GLOD4 was mainly expressed in testicular leydig cells, and the subcellular localization results showed that the GLOD4 protein was mainly localized in the cytoplasm and nucleus. Silencing of GLOD4 significantly suppressed the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3β-HSD and CYP17A1 and the mRNA expression levels of cell-cycle related genes CDK6, PCNA, and Cyclin E. Moreover, the cell cycle was blocked at the G2/M phase after GLOD4 silencing, which significantly suppressed testosterone secretion. In contrast, GLOD4 overexpression significantly increased the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3β-HSD, and CYP17A1 and increased the expression of the cell-cycle related genes CDK6, PCNA, and Cyclin E. Moreover, GLOD4 overexpression promoted the cell cycle from G0/G1 phases to enter the S phase and G2/M phases,promoted the secretion of testosterone. Taken together, our experimental results indicate that GLOD4 may affect the development of cells in Qianbei Ma goats of different ages by influencing the cell cycle, Proliferation and testosterone hormone synthesis. These findings enhance our understanding of the functions of GLOD4 in the cells of goats.

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of T-cell lymphomas characterised by high relapse rates and no curative treatments unless the allogeneic stem cell transplantation. The main complication in the management of this kind of malignancy is the variability that characterises the genetic and clinical features among the CTCL subtypes. JAK/STAT, MAPK/ERK, PI3K/Akt, and NF-kB are those signalling pathways that are found altered in CTCL and that are responsible for promoting both T-cell malignancy and the pro-tumorigenic microenvironment. Thus, targeting key players of these pathways can be an advantageous therapeutic option for CTCL. In this review, we aim to summarise the different approaches that precisely inhibit the kinases of each cited signalling. JAK inhibitors seem to be the most promising kinase inhibitors for CTCL. However, adverse events have been reported especially in patients with immunosuppression or an underlying autoimmune disease. More studies are needed, especially clinical trials, to investigate the benefits of these drugs for the treatment of cutaneous T-cell lymphomas.

Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine and oncology applications, Ad based platforms offer advantages including ease of genetic manipulation, scale of production and well established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that may need to be overcome for adenovirus based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects upon the downstream impact of an adenovirus-based therapeutic. This review focusses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, both in context of the innate and adaptive immune responses. We summarize different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications.

Amitriptyline is a tricyclic antidepressant commonly used for depressive disorders and pre-scribed off-label for several neurological conditions like neuropathic pain, migraine and anxiety. Amitriptyline potentiates the monoaminergic transmission by blocking the reuptake of norepi-nephrine and serotonin. However, antidepressants also act on additional targets that contribute to either therapeutic or adverse effects and may suggest new indications for their repurposing. Furthermore, since depression is often a co-morbidity in patients with chronic conditions (i.e. cancer, neurodegenerative diseases) the use of antidepressants interfering with pathways in-volved in cell homeostasis may affect the progression and outcome of these pathologies. Here we investigate the effects of amitriptyline on proliferation and autophagy in human SH-SY5Y neuroblastoma cells. Dose and time-dependent upregulation of the autophagy markers LC3II and autophagy receptor p62, with accumulation of LAMP1 positive compartments, were observed in SH-SY5Y cells exposed to amitriptyline. Alteration of autophagy was accompanied by reduced cell viability and decreased clonogenic capacity, without a significant induction of apoptosis. Decrease viability and clonogenic activity were still observed in autophagy deficient Atg5 -/- MEF and following pre-treatment of SH-SY5Y culture with the autophagy inhibitor chloroquine suggesting that the amitriptyline’s effects on cell proliferation were not caused by the modulation of autophagy. Our findings demonstrate that amitriptyline acts on pathways that are crucial for cell and tissue homeostasis and pose the basis for further studies on the potential application of these effects and the consequences during long-term antidepressant treatment.

Fine dust causes various disorders, including cardiovascular, neurological, renal, reproductive, motor, systemic, respiratory, and cancerous diseases. Therefore, it is necessary to study functional materials to prevent these problems. In this study we used various methods, including quantitative PCR, flow cytometry, ELISA, and Alizarin O staining, to study the beneficial effects of erucic acid against fine dust. Erucic acid and erucic acid-induced exosomes (EIE) strongly suppress the attenuation of osteocytic differentiation and inflammation induced by fine dust. Erucic acid effectively suppresses inflammation in fibroblasts exposed to fine dust. Notably, despite exposure to fine dust, EIE promoted osteocytic differentiation in adipose-derived stem cells (ASC) and osteogenesis in macrophages, in addition to phagocytosis. Dramatic upregulation of RunX2 and BMP7 by EIE indicates that it is a strong activator of osteocytic differentiation in ASC and protects them from the effects of fine dust. Moreover, EIE induces immune activity and acts as an osteogenic trigger for macrophages. Therefore, this study suggests the potential use of erucic acid and erucic acid-induced exosomes (EIE) as biomaterials to prevent environment-borne diseases.

This study explores the use of remote ultrasound vibration to enhance welding strength. It examines the effects of 20 kHz, and 40 kHz High Power Ultrasound Transducers (HPUT) in contact and contactless modes during ultrasonic assistance laser welding. Employing shear tests and microscopy for assessment, the research evaluates ultrasound's impact on welding strength and identifies the optimal transducer. Theoretical and numerical analyses investigate vibration transmission into the welding area, particularly examining the vibration distribution and cavitation initiation within the molten pool area. Results indicate that ultrasound-assisted welding increases pull test performance, including the resistance force and strain, and improves microscopic structural integrity. Numerical simulations suggest that narrow-band vibration intensifies pressure in specific welding zones. Contactless ultrasound application also shows enhanced welding quality, offering a promising alternative to current methods. This work contributes to electric car technology by suggesting improvements in welding techniques for power battery systems.

Neurodegenerative diseases that include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS), arise due to numerous causes like protein accumulation and autoimmunity, characterized by neurologic depletion which lead to incapacity in normal physiological function such as thinking and movement in these patients. Glial cells perform a critical role in protective neuronal function; in the case of neuroinflammation, glial cell dysfunction can promote the development of neurodegenerative diseases. MiRNA participates in gene regulation and plays a vital role in many biological processes in the body; in the central nervous system (CNS), it can play an essential part in neural maturation and differentiation. In neurodegenerative diseases, miRNA dysregulation occurs, enhancing the development of these diseases. In this review, we discuss neurodegenerative diseases (Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)) and how miRNA is preserved as a diagnostic biomarker or therapeutic agent in these disorders. Finally, we highlighted miRNA as therapy.

The mechanisms underlying the establishment of asymmetric structures during development remain elusive. The wing of Drosophila is asymmetric along the Anterior-Posterior (AP) axis, despite that its growth signals that drive its growth are presumably symmetric. Here, we investigated the contribution of cell recruitment, a process that drives wing fate differentiation in Drosophila, to the asymmetric shape and pattern of the adult wing. Genetic impairment of cell recruitment results in a significant reduction in adult wing asymmetry, primarily affecting the region between longitudinal vein 5 and the wing margin (L5-M). Morphometric analysis reveals that the lack of cell recruitment results in a more symmetric wing with respect to the AP, suggesting a contribution of cell recruitment to the establishment of asymmetry in the adult wing. A close examination of the expression of the wing selector gene vestigial (vg) in wing disc does not support this hypothesis. However, the circularity of the Vg pattern significantly increase in recruitment-impaired wing disc, suggesting that while the decrease of the L5-M region in the adult wing may not be attributed to cell recruitment, it could contribute to the overall asymmetry of the adult wing. We conclude that cell recruitment, a widespread mechanism that participates in growth and patterning of several developing systems, could drive, at least partially, the asymmetric shape of the Drosophila wing.

Background and objectives: sickle cell disease is the most common hemoglobinopathy in the world. It is considered to be a real public health problem. Sickle cell patients are subjected to several factors causing inflammation such as iron metabolism. The study aimed to look for inflammation in children with sickle cell disease in Cameroon, identify the factors associated with inflammation, and raise the consequences for the patient including the iron profile and the profile of the hemogram. Materials and methods: We conducted an analytical cross-sectional study for 03 months. The sickle cell disease patients coming and/or followed at the Hematology Department of the Regional Hospital of Bafoussam and the Central Hospital of Yaoundé have been recruited. The exploration of inflammation was made by determining CRP, IL6, and ferritin concentrations. The hematological parameters and iron profile were evaluated using standard methods. Statistical analysis of the data was performed; Univariate and multivariate logistic regression analyses allowed to identification of factors associated with inflammation in patients, using the statistical tool R version 4.1.1.. The proportions were compared with the chi-square test when the expected numbers were greater than 5 and the Fisher test when not. Results: The frequency of inflammation in the population was 42.3%. Hyperferritinemia was significantly greater (p<0.001) in patients with inflammation compared to the non-inflammatory patients (96.8% and 76.7% respectively). Patients with inflammation showed a significant elevation of iron parameters (p<0.05). In addition, ferritin and IL6 elevation were associated with inflammation during sickle cell disease respectively (Or = 4.96; 95% CI [1.15-36.42]; p=0.056) and (Or =6.23; 95% CI [1.43-45.96]; p=0.030). Conclusions: The elevated iron in plasma is an effect of inflammation in sickle cell patients. Hence the need of controlling inflammation and iron in the latter is necessary.

To elucidate the cellular immune response to coronavirus disease (COVID-19) among children, we assessed cellular immunity in 8 children post-vaccination for COVID-19 and 11 children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, using the T-SPOT®.COVID assay for both the spike (S) and nucleocapsid (N) proteins. In the vaccinated group, the T-SPOT®.COVID assay for the S protein yielded positive results in all eight children. In contrast, in the post-infection group, the assay for the N protein was positive in 5 of 11 children, with 3 of these 5 children requiring hospital admission, including 2 who needed mechanical ventilation. Therefore, the T-SPOT®.COVID assay is valuable for assessing cellular immunity against COVID-19, and most children infected with COVID-19 may not develop such immunity unless the disease severity is significant.

Vibrio parahaemolyticus is an important human pathogen that is currently the leading cause of shellfish-borne gastroenteritis in the world. Particularly, the pandemic strain has the capacity to induce cytotoxicity and enterotoxicity through its Type 3 Secretion System (T3SS2) that leads to massive cell death. However, the specific mechanism by which T3SS2 induces cell death remain unclear and the contribution in mitochondrial stress is not fully understood. In this work, we evaluated the contribution of T3SS2 of V. parahaemolyticus to generate mitochondrial stress and cell death during infection in human intestinal HT-29 cells. To evaluate this, infection assays were carried out to evaluate mitochondrial transition pore opening, mitochondrial fragmentation, ATP quantification, and cell viability during infection. Our results showed that the Δvscn1 (T3SS2+) mutant strain contributes to generating the sustained opening of the mitochondrial transition pore. Furthermore, it generates perturbations in the ATP production in infected cells, leading to a significant decrease in cell viability and loss of membrane integrity. Our results suggest that T3SS2 from V. parahaemolyticus plays a role in generating mitochondrial stress and cell death in human intestinal HT-29 cells. It is important to highlight that this study represents the first report indicating the involvement of T3SS2 from V. parahaemolyticus in generating mitochondrial stress, its impact on the mitochondrial pore, and its effect on ATP production in human cells.

Background: Large-cell neuroendocrine carcinoma presents significant treatment challenges owing to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. Methods: In this non-randomized study, patients with metastatic LCNEC were treated with ei-ther standard chemotherapy plus atezolizumab or standard chemotherapy alone. The primary outcomes measured were progression-free survival (PFS) and overall survival (OS), with an ex-ploratory analysis of miR375 in plasma as a potential biomarker. Results: Of the 22 screened patients, 17 met the inclusion criteria and were stratified into the atezolizumab and chemotherapy (n=10) or chemotherapy alone(n=7) groups. After a median follow-up of 23.3 months, the 12-month survival rate for the atezolizumab group was 57.1% (95% CI: 32.6%-100%) and 45.7% at 24 months (95% CI: 22.4%-93.2%). In contrast, the chemotherapy group had a 14.3% survival rate at both 12 and 24 months (95% CI: 2.33%-87.7%). The log-rank test for survival showed a statistically significant difference in the atezolizumab-treated group (chi-squared = 4, df = 1, p = 0.04). A non-significant correlation was found between disease pro-gression and elevated levels of miR375. Conclusions: This pilot study suggests that atezolizumab combined with chemotherapy may be effective in treating metastatic LCNEC. The non-significant correlation between plasma miR375 levels and disease progression suggests its biomarker potential, warranting further validation research.

MicroRNAs, short non-protein coding RNAs, are overexpressed in GCTs. Circulating levels of germ cell tumor (GCT)- associated miRNAs, such as miR-371a-3p, can be utilized as efficient and cost-effective alternatives in diagnosing and managing patients presenting with GCTs. This quality of miRNAs has demonstrated favorable performance characteristics as a reliable blood-based biomarker with high diagnostic accuracy compared to current serum tumor markers (STMs) including α-fetoprotein (AFP), beta human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH). The conventional STMs exhibit limited specificity and sensitivity. Potential clinical implications of miRNAs include impact on de-escalating or intensifying treatment, detecting recurrence at earlier stages, and lessening the necessity of cross-sectional imaging or invasive tissue biopsy for non-teratomatous GCTs. Here we also highlight the outstanding issues that must be addressed prior to clinical implementation. Standards for measuring circulating miRNAs and determining ideal cutoff values are essential for integration into current clinical guidelines.

Apoptotic cells possess immunomodulatory effects that can be utilized to treat imbalanced immune conditions. Information on the preclinical safety of such treatment is sparse. In this study, the safety of apoptotic cells (Allocetra-OTS) was assessed in a GLP toxicological study on Sprague Dawley rats. Three doses of Allocetra-OTS or vehicle were administered intravenously (IV) for 3 consecutive days. Animals in the Main study were sacrificed on day 4, while animals from the Recovery groups were kept for 14 or 28 days. Allocetra-OTS was well tolerated, and no adverse effects were observed in body weight, clinical signs, food consumption or ophthalmologic observation. Thus, the No Observed Adverse Effect Level (NOAEL) dose was determined as the highest dose administered. An observed elevation in immune cells was suspected to be due to Allocetra-OTS; similarly to other clinical chemistry parameters, however, it was resolved in the Recovery phases. Splenomegaly and a dose-related Extramedullary Hematopoiesis (EMH) in the red pulp were observed, with no adverse events, and were considered to be a normal and expected reaction following IV administration of cell-based therapies. In conclusion, under the conditions of this study Allocetra-OTS was concluded to be safe, further supporting its potential candidacy for clinical studies

Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation, plays a pivotal role in various pathological conditions, including neurodegenerative diseases. While reasonable evidence for ferroptosis exist e.g. in Parkinson’s disease or Alzheimer’s disease, there are only few reports on amyotrophic lateral sclerosis (ALS), a fast progressive and incurable neurodegenerative disorder characterized by progressive motor neuron degeneration. Initial studies, however, highlight that ferroptosis might be significantly involved in ALS. Key features of ferroptosis include oxidative stress, glutathione depletion, mitochondrial and dysfunction alterations in mitochondrial morphology, mediated by proteins such as GPX4, xCT, ACSL4 FSP1, Nrf2 and TfR1. Induction of ferroptosis involves small molecule compounds like erastin and RSL3, which disrupt system Xc- and GPX4 activity, respectively, yielding in lipid peroxidation and cellular demise. Mutations in Fused in Sarcoma (FUS) are associated with familial ALS. Pathophysiological hallmarks of FUS-ALS involve mitochondrial dysfunction and oxidative damage, implicating ferroptosis as putative cell death pathway in motor neuron demise. However, mechanistic understanding of ferroptosis in ALS, particularly FUS-ALS, remains limited. Here, we investigated ferroptosis vulnerability in a FUS-ALS cell model, revealing mitochondrial disturbance and increased susceptibility for ferroptosis in cells harboring the mutant FUS variant. This was accompanied by altered expression of ferroptosis-associated proteins, particularly by dramatic reduction of xCT expression, leading to cellular imbalance of the redox system and increased lipid peroxidation. Iron chelation with deferoxamine as well as inhibition of the mitochondrial calcium uniporter (MCU) significantly alleviated ferroptotic cell death and lipid peroxidation. These findings suggest a link between ferroptosis and FUS-ALS, offering potential therapeutic targets.

Phosphatase and tensin homolog (PTEN) is a negative regulator of the phosphoinositide 3-kinases/protein kinase B (PI3K/AKT) signaling pathway. Notably, its active site harbors a cysteine residue that is susceptible to oxidation by hydrogen peroxide (H2O2). This oxidation inhibits the phosphatase function of PTEN, critically contributing to the activation of the PI3K/AKT pathway. Upon stimulation of cell surface receptors, the activity of NADPH oxidase 2 (NOX2) generates a transient amount of H2O2, serving as a mediator in this pathway by oxidizing PTEN. The mechanism underlying this oxidation, occurring despite the presence of highly efficient and abundant cellular oxidant-protecting and reducing systems, continues to pose a perplexing conundrum. Here, we demonstrate that the presence of bicarbonate (HCO3-) promoted the rate of H2O2-mediated PTEN oxidation, probably through the formation of peroxymonocarbonate (HCO4-), consequently potentiated the phosphorylation of AKT. In essence, our findings consolidate the crucial role of HCO3- in the redox regulation of PTEN by H2O2, lead to the presumption regarding HCO4- as a signaling molecule during cellular physiological processes.

The receptor Tyrosine Kinase (RTK) pathway and the downstream related Mitogen Activated Protein Kinase (MAPK) cascades are crucial signal transduction pathways that preside over various cellular processes, including proliferation, differentiation, apoptosis, and responses to stressors. They are well described in solid malignancies, where many of the involved factors are used as prognostic molecular markers or targets for precision therapy. Germ cell tumors (GCTs) are relatively rare. However, they are the most diagnosed malignancies occurring in the testis (TGCT) among men aged between 15 and 40 years. Despite high aneuploidy and a paucity of somatic mutations, several genomic and transcriptomic assays have identified few significantly mutated somatic genes, primarily KIT and K-RAS, so affecting, at various levels, the KIT–RAS–RAF–MEK–ERK cascade. This review focuses on the most recent investigations about this signaling pathway in TGCTs concerning their development, natural history, response to standard chemotherapy protocols (i.e., cisplatin-based), and on the efforts being made to identify targetable markers for possible precision medicine approaches.

Phosphatase and tensin homolog (PTEN) is a tumor suppressor due to its ability to regulate cell survival, growth and proliferation by down-regulating PI3K/AKT signaling pathway. In addition, PTEN plays an essential role in other physiological events associated with cell growth demands, such as ischemia-reperfusion, nerve injury and immune response. Therefore, recently PTEN inhibition has emerged as a potential therapeutic intervention in these situations. Increasing evidence demonstrates that reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), are produced and required for the signaling in many important cellular processes under such physiological conditions. ROS have been shown to oxidize PTEN at the cysteine residue of its active site, consequently inhibiting its function. Here we provide an overview of studies that highlight the role of oxidative inhibition of PTEN in physiological processes.

Cytokinesis, as the last stage of the cell division cycle, is a tightly controlled process amongst all eukaryotes, and defective division can lead to severe cellular consequences, and is implicated in serious human diseases and conditions such as cancer. Both mammalian cells and the fission yeast Schizosaccharomyces pombe use binary fission to divide into two equal sized daughter cells. Similar to mammalian cells, in S. pombe such cytokinetic division is driven by the assembly of an actin-myosin contractile ring (ACR) at the cell equator between the two cell tips. The ACR is composed of a complex network of membrane scaffold proteins, actin filaments, myosin motors, and other cytokinesis regulators. Contraction of the ACR leads to the formation of a cleavage furrow which is severed by the endosomal sorting complex required for transport (ESCRT) proteins leading to the final cell separation during the last stage of cytokinesis, abscission. This review describes recent findings defining the three phases to establish cytokinesis in S. pombe: ACR assembly, ACR constriction, and its coordination with septation. Collectively, we provide an overview of current understanding of the mechanisms regulating the ACR-mediated cytokinesis in S. pombe with a potential role of ESCRT proteins in this process.

Hepatocellular carcinoma (HCC) is characterized by uncontrolled cellular proliferation driven by aberrant signal transduction. Cells respond to potential carcinogenic signals by inducing cellular senescence (CS) as a defense mechanism. However, assessing CS levels in various tumors is challenging due to heterogeneity and the lack of universal CS markers. This study integrates single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from HCC samples to analyze gene expression profiles. HCC-specific senescence-related pathways are identified, and genes from these pathways distinguish molecular subtypes associated with senescence in HCC. These subtypes exhibit significant variations in biological and clinical attributes. A specific CS risk model is developed, revealing associations between CS scores and prognosis, clinical staging, immune infiltration, immunotherapy response, and drug sensitivity. The key gene G6PD is identified as a potential senescence-related target in liver cancer. Molecular experiments confirm the effective suppression of HepG2 cell proliferation, invasion, and migration upon G6PD knockdown. In summary, this analysis enhances our understanding of HCC-specific senescence molecular features and introduces a novel senescence-related biomarker, offering promising implications for future research.

Localized jawbone invasion is a milestone in the progression of oral squamous cell carcinoma (OSCC). The factors that promote this process are not well understood. Sclerostin is known to be involved in bone metabolism and there are preliminary reports of its involvement in bone tumors and metastasis. To identify a possible involvement of sclerostin in the bone invasion process of OSCC, sclerostin expression was analyzed in vitro in two different human OSCC tumor cell lines by qRT-PCR, and the effect of recombinant human (rh)-sclerostin treatment on tumor cell capabil-ities was evaluated using proliferation, migration, and invasion assays. Undifferentiated human mesenchymal stem cells (hMSCs) were osteogenically differentiated and co-cultured with OSCC tumor cells to demonstrate potential interactions on migration characteristics. Sclerostin expres-sion was evaluated in clinical cases by immunohistochemistry at the OSCC jawbone interface in a cohort of 15 patients. Sclerostin expression was detected in both OSCC tumor cell lines in vitro and was also detected at the OSCC jawbone interface in clinical cases. Tumor cell proliferation rate, migration and invasion ability were increased by rh-sclerostin treatment. The migration rate of tumor cells co-cultured with osteogenically differentiated hMSCs was increased. The re-sults presented are the first data suggesting a possible involvement of sclerostin in the bone inva-sion process of OSCC, which needs to be further investigated

(1) Background: China holds the highest esophageal squamous cell carcinoma (ESCC) incidence areas in the world, with some areas of incidence over 100 per 100,000. Despite extensive public health efforts, its etiology is still poorly understood. This study aims to review and summarize past research into potential etiologic factors for ESCC in China. (2) Methods: Relevant observational and intervention studies were systematically extracted from four databases using key terms, reviewed using Rayyan software, and summarized into Excel tables. (3) Results: Among the 207 studies included in this review, 130 studies were focused on genetic etiologic factors, followed by 22 studies focused on dietary-related factors, 18 studies focused on HPV-related factors, and 37 studies focused on other factors. (4) Conclusions: ESCC in China involves a variety of factors including genetic variations, gene-environment interactions, dietary factors like alcohol, tobacco use, pickled vegetables, and salted meat, dietary behavior such as hot food/drink consumption, infections like HPV, poor oral health, gastric atrophy, and socioeconomic factors. Public health measures should prioritize genetic screening for relevant polymorphisms, conduct comprehensive investigations into environmental, dietary, and HPV influences, enhance oral health education, and consider socioeconomic factors overall as integral strategies to reduce ESCC in high-risk areas of China.