bluuebunny/crossref_metadata_2025 huggingface dataset:
Zinc portioning and allocation patterns among various tissues confers variations in Zn use efficiency and bioavailability in lentil genotypes
Authors: Rasheed Naser , Maqsood Muhammad Aamer , Aziz Tariq , Ashraf Muhammad Imran , Saleem Ifra , Ehsan Shabana , Nawaz Allah , Bilal Hafiz Muhammad , Xu Minggang
Published: January 2024

Zinc (Zn) is essential for plants and animals as it plays significant roles in several physiological and biological processes. Its deficiency in soil results in low Zn content food and is one of the major reasons for Zn malnutrition in humans. Biofortification of crops with zinc (Zn) is a viable approach to combat malnutrition, especially in developing countries. A hydroponic study was executed to study response and Zn partitioning in various lentil genotypes. Eight preselected lentil genotypes (Line-11504, Mansehra-89, Masoor-2006, Masoor-85, Line-10502, Markaz-09, Masoor-2004, and Shiraz-96) were grown in solution culture with two Zn levels (control and adequate Zn). Plants were sown in polythene lined iron trays with a two inch layer of prewashed riverbed sand. After 10 days of germination, seedlings were transplanted to a 25L capacity container with nutrient solution for 15 days, and afterward, these plants were divided into two groups, receiving either 2.0 mM Zn or no Zn levels. Three plants of each genotype were harvested at the vegetative growth stage (60 DAT) and the remaining three at physiological maturity (117 DAT). Plants were partitioned into roots, shoots, and grains at harvest. Significant variations in root and shoot dry matter production, grain output, partitioning of Zn in plant parts (root, shoot, and grain), grain phytate reduction, and Zn bioavailability were observed among genotypes. Lentil root accumulated more Zn (54 mg kg-1) with respect to shoot Zn (51 mg kg-1) under Zn supply. The Zn efficient genotypes (Line-11504 and Mansehra-89) produced more root and shoot dry weights at both harvests. There was a positive correlation between the relative growth rate of root and grain phytate concentration (r = 0.55) and [phytate]:[Zn] ratio (r = 0.67). Zn-efficient genotype Mansehra-89 had a maximum root shoot ratio (0.57) and higher grain Zn (60 mg kg-1) with a respectively reduced grain phytate (17 µg g-1) and thus, had more Zn bioavailability (3.01 mg d-1). The genotypic ability for Zn uptake and accumulation within different plant tissues may be incorporated into future crop breeding to improve the nutrition of undernourished consumers.
Why does a leader’s other-oriented perfectionism lead employees to do bad things? Examining the role of moral disengagement and moral identity
Authors: Jiang Feng , Zhang Weipeng , Zhang Hongyan , Zhang Zhe
Published: January 2024

Introduction

Moral disengagement is an essential concept in organizational behavioral ethics, as it is strongly related to employee behaviors and attitudes. What is not clear, however, is which leader traits are directly associated with employees’ moral disengagement and which are indirectly associated with unethical behavior. This study draws on a social cognitive perspective that links leaders’ other-oriented perfectionism (LOOP) with unethical employee behavior. Specifically, we propose that LOOP provides employees with excuses and encouragement to engage in unethical pro-organizational behavior (UPB).

Methods

We analyzed data collected from 266 full-time employees at two-time points, and used mediated and moderated structural equation models to test the hypotheses, and the findings largely support our claims.

Results

The results suggest that LOOP effectively promotes employees’ involvement in UPB. Moderated mediation tests suggest that the positive indirect impact of LOOP on employees’ unethical behavior via moral disengagement was attenuated by higher employees’ moral identity.

Discussion

In summary, the results indicate that when leaders emphasize only perfection and make unrealistic demands on their employees, the latter perceive that engaging in unethical behavior is demanded by the leader, that the responsibility is not theirs, and thus they are more willing to engage in unethical behavior. This study discusses the implications of these findings from both practical and theoretical perspectives.
The effect of music tempo on movement flow
Authors: Zhang Jian , Huang Yanqun , Dong Yifan , Li Jutao , Zhu Liming , Zhao Mingxuan
Published: January 2024

There has been much controversy over the effects of music tempo on movement flow. In this study, a single-factor repeated-measurement design was used to explore the effect of music tempo (fast, slow, and no music control) on movement flow by measuring both subjective experiences and objective electroencephalographic (EEG) characteristics during brisk walking. In the experiment, 20 college students walked briskly on a treadmill using EEG equipment. Each participant walked for 10 min on three different days. Their brain waves were recorded during brisk walking on a treadmill. After each walk, the participants completed a form of short flow state scale-2 (S FSS-2), which covered nine major aspects of flow. The results showed that music tempo had a significant effect on subjective experiences and objective physiological characteristics; that is, a higher subjective flow level for fast-tempo music in brisk walking and a significant enhancement of mean power values in the subconscious brain waves of the delta, theta, alpha, and beta bands for fast tempo music were observed. A fast tempo facilitated the movement flow. The findings of this study can be instructive for the use of music in exercises to improve sports training outcomes.
Sponge city construction and population health
Authors: Li Yue
Published: January 2024

Introduction

This paper focuses on the construction of sponge cities and their effects on population health. Sponge cities in China both solve stormwater problems and are a systemic transformation in the urban construction paradigm, addressing related issues arising from high-speed urbanization. Whether sponge city construction in China can promote population health has received scant attention. Most previous studies have focused on urban environments and population health, with few exploring the potential effects on population health caused by urban environment changes due to urban policies. This study hypothesizes that sponge city construction improves the urban environment, and thus, population health.

Methods

Using panel data from 119 prefecture-level cities between 2011 and 2019 and the China Labor-force Dynamics Survey (CLDS), based on China’s sponge city pilot policy, a quasi-natural experiment is conducted using Difference-in-Differences (DID) model to identify the health effects of the sponge city policy.

Results

The findings show that sponge city pilot policy not only reduced ecological environment pollution and promoted the quality of built environment, but also significantly improved population health by 10.4%. This mechanism is mainly due to the restorative effects of the built environment.

Discussion

The health effects vary across city administrative levels, and especially among non-older adults and local populations. Compared with the cities at higher administrative level, the health effect in lower administrative level is significantly positive, indicating that there is a diminishing marginal effect of sponge city construction. This study extends the causal identification chain of the impact of urban environment on population health to urban policies and provide insights into policy objectives for sponge city construction.
Adolescents’ life between violence and discipline. Medical care in the “Jugendhäuser” juvenile detention centers in East Germany in the 1960s–1980s
Authors: Kosenko Oxana , Steger Florian
Published: January 2024

Background

In 1952–1989, special juvenile detention centers, called Jugendhäuser, were established in the German Democratic Republic. There, juvenile delinquents had to not only complete their sentences, but they were also supposed to be re-educated into conscious socialist personalities through a system of collective education proposed by Soviet pedagogue Anton Makarenko. Among twelve Jugendhäuser in East Germany, the ones in Halle and Dessau were considered to have the most severe conditions due to the praxis of mental and physical violence. For the first time, based on the personal files of former juvenile prisoners and archival documents of medical services, we reconstruct a picture of the health status of prisoners and medical care in both these Jugendhäuser.

Methods

We analyzed personal files of juvenile prisoners from the Archive of the Correctional Facility in Halle and unpublished documents from the Saxony-Anhalt State Archive, Magdeburg Department, the State Archive in Leipzig and the Stasi Records Archive in Halle. For the examination of these sources, we implemented the historical-critical method.

Results

The Jugendhäuser had a system of outpatient and inpatient treatment. Although the medical services rated the level of health care as good at those detention centers, numerous complaints from juveniles, as well as cases of failure to provide assistance, indicated certain deficiencies. Cases of violence in juvenile prisons were common, especially in the Jugendhaus Halle. Brawls between inmates led to injuries and sometimes even to deaths. Fear of beatings resulted in desperate acts such as self-harm, suicide and escapes from prison.

Conclusion

The health status of young prisoners in the Jugendhäuser in Halle and Dessau was negatively affected by violence and often by lack of medical care. The prevalence of violence can be attributed to challenges of the penal system as well as deficiencies of the medical services. Since repressive means were used to overcome the violence, such efforts were not successful. The medical services did not offer specialized care for juveniles with mental and learning disorders or those who required psychological or even psychotherapeutic support. Physical health issues were also often ignored due to the stigmatization of sick juveniles as malingerers.
Vaccination against emerging and reemerging infectious diseases in places of detention: a global multistage scoping review
Authors: Moazen Babak , Ismail Nasrul , Agbaria Nisreen , Mazzilli Sara , Petri Davide , Amaya Arianna , D’Arcy Jemima , Plugge Emma , Tavoschi Lara , Stöver Heino
Published: January 2024

Background

Despite the elevated risks of infection transmission, people in prisons frequently encounter significant barriers in accessing essential healthcare services in many countries. The present scoping review aimed to evaluate the state of availability and model of delivery of vaccination services within correctional facilities across the globe.

Methods

Following the methodological framework for scoping reviews and adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews criteria, we conducted a systematic search across four peer-reviewed literature databases (Medline via PubMed, Web of Science, the Cochrane Library, Science Direct, and EBSCO), as well as 14 sources of grey literature. Two researchers meticulously examined the identified papers independently to extract pertinent data published between 2012 and 2022. The quality of the selected publications was assessed using established quality assessment tools.

Results

Of the 11,281 identified papers 52 met the inclusion criteria. With the exception of one, all the included publications presented data from high-income countries, predominantly originating from the United States. Across the world, the most prevalent vaccines available in prison settings were COVID-19 and HBV vaccines, typically distributed in response to health crises such as pandemics, epidemics, and local outbreaks. Vaccine coverage and uptake rates within correctional facilities displayed noteworthy disparities among various countries and regions. Besides, individual and organizational barriers and facilitating factors of vaccination in prison settings emerged and discussed in the text.

Discussion

The lack of vaccination services combined with low rates of vaccination coverage and uptake among people living and working in correctional facilities represents a cause for concern. Prisons are not isolated from the broader community, therefore, efforts to increase vaccine uptake among people who live and work in prisons will yield broader public health benefits.
Short-term effects of air pollutants on hospital admissions for asthma among older adults: a multi-city time series study in Southwest, China
Authors: Zhang Yuqin , Yang Xi , Jiang Wanyanhan , Gao Xi , Yang Biao , Feng Xing Lin , Yang Lian
Published: January 2024

Background

This study aimed to explore the relationship between air pollution and hospital admissions for asthma in older adults, and to further assess the health and economic burden of asthma admissions attributable to air pollution.

Methods

We collected information on asthma cases in people over 65 years of age from nine cities in Sichuan province, as well as air pollution and meteorological data. The relationship between short-term air pollutant exposure and daily asthma hospitalizations was analyzed using the generalized additive model (GAM), and stratified by gender, age, and season. In addition, we assessed the economic burden of hospitalization for air pollution-related asthma in older adults using the cost of disease approach.

Results

The single pollutant model showed that every 1 mg/m3 increase in CO was linked with an increase in daily hospitalizations for older adults with asthma, with relative risk values of 1.327 (95% CI: 1.116–1.577) at lag7. Each 10 μg/m3 increase in NO2, O3, PM10, PM2.5 and SO2, on asthma hospitalization, with relative risk values of 1.044 (95% CI: 1.011–1.078), 1.018 (95% CI: 1.002–1.034), 1.013 (95% CI: 1.004–1.022), 1.015 (95% CI: 1.003–1.028) and 1.13 (95% CI: 1.041–1.227), respectively. Stratified analysis shows that stronger associations between air pollution and asthma HAs among older adult in females, those aged 65–69 years, and in the warm season, although all of the differences between subgroups did not reach statistical significance. During the study period, the number of asthma hospitalizations attributable to PM2.5, PM10, and NO2 pollution was 764, 581 and 95, respectively, which resulted in a total economic cost of 6.222 million CNY, 4.73 million CNY and 0.776 million CNY, respectively.

Conclusion

This study suggests that short-term exposure to air pollutants is positively associated with an increase in numbers of asthma of people over 65 years of age in Sichuan province, and short-term exposure to excessive PM and NO2 brings health and economic burden to individuals and society.
COVID-19 lateral flow test image classification using deep CNN and StyleGAN2
Authors: Pannipulath Venugopal Vishnu , Babu Saheer Lakshmi , Maktabdar Oghaz Mahdi
Published: January 2024

Introduction

Artificial intelligence (AI) in healthcare can enhance clinical workflows and diagnoses, particularly in large-scale operations like COVID-19 mass testing. This study presents a deep Convolutional Neural Network (CNN) model for automated COVID-19 RATD image classification.

Methods

To address the absence of a RATD image dataset, we crowdsourced 900 real-world images focusing on positive and negative cases. Rigorous data augmentation and StyleGAN2-ADA generated simulated images to overcome dataset limitations and class imbalances.

Results

The best CNN model achieved a 93% validation accuracy. Test accuracies were 88% for simulated datasets and 82% for real datasets. Augmenting simulated images during training did not significantly improve real-world test image performance but enhanced simulated test image performance.

Discussion

The findings of this study highlight the potential of the developed model in expediting COVID-19 testing processes and facilitating large-scale testing and tracking systems. The study also underscores the challenges in designing and developing such models, emphasizing the importance of addressing dataset limitations and class imbalances.

Conclusion

This research contributes to the deployment of large-scale testing and tracking systems, offering insights into the potential applications of AI in mitigating outbreaks similar to COVID-19. Future work could focus on refining the model and exploring its adaptability to other healthcare scenarios.
Intelligent weight prediction of cows based on semantic segmentation and back propagation neural network
Authors: Xu Beibei , Mao Yifan , Wang Wensheng , Chen Guipeng
Published: January 2024

Accurate prediction of cattle weight is essential for enhancing the efficiency and sustainability of livestock management practices. However, conventional methods often involve labor-intensive procedures and lack instant and non-invasive solutions. This study proposed an intelligent weight prediction approach for cows based on semantic segmentation and Back Propagation (BP) neural network. The proposed semantic segmentation method leveraged a hybrid model which combined ResNet-101-D with the Squeeze-and-Excitation (SE) attention mechanism to obtain precise morphological features from cow images. The body size parameters and physical measurements were then used for training the regression-based machine learning models to estimate the weight of individual cattle. The comparative analysis methods revealed that the BP neural network achieved the best results with an MAE of 13.11 pounds and an RMSE of 22.73 pounds. By eliminating the need for physical contact, this approach not only improves animal welfare but also mitigates potential risks. The work addresses the specific needs of welfare farming and aims to promote animal welfare and advance the field of precision agriculture.
The anti-obesogenic and anti-diabetic properties of marine collagen peptides
Authors: Wong Rina P. M. , Zhou Zhong Kai , Strappe Padraig M.
Published: January 2024

Marine collagen hydrolysates and purified peptides can be sourced from a variety of species. Application of collagen peptides to animal models of diabetes and obesity is contributing to the goal of elucidating a mode of action and their broad spectrum application includes wound healing and bone fracture, both of which are significant co-morbidities of diabetes and obesity related illnesses.
Game Theory—More Than Just Games
Authors: Aumann Robert
Published: January 2024

With Yonatan Aumann, Department of Computer Science, Bar Ilan University, Ramat Gan, Israel.

Game theory is not about games. It is a scientific field that uses logic to understand how decisions should be made, taking into account the choices of others. Despite its name, it deals with serious real-life situations like business, politics or even war. This article explains what game theory is about, and how it can be used in many real-world settings. I will explain how game theory uncovers the roots of cooperation, and why its study is important for reducing hostility. We will conclude with an elegant game theory method which you can apply in your everyday life.
Helping Future Schoolteachers Discover and Teach Soil: An Example of Project-Based Learning
Authors: Aran Delphine
Published: January 2024

In addition to fundamental knowledge, the teaching provided at primary school develop children’s perceptions of the world, particularly that of the effects of human activities on the environment. However, despite its importance in these issues, soil is virtually absent from school curricula, and even more so from the training of future schoolteachers. In order to provide knowledge about soil and its crucial role in the challenges facing humanity, an educational project has been developed at the University of Lorraine for students on the multidisciplinary bachelor’s degree in teaching course during the past 5 years. Over fifty students follow traditional soil science courses and then use their knowledge in an active-learning setting. Within the framework of a project-based learning, they organize and carry out an activity session focusing on soil in a class of elementary school pupils, which is a kind of practice for their future teaching careers. The students follow the different stage in building their project. They design their workshop around a soil-linked theme of their choice, respecting the curriculum expectations. They establish a scientific approach to the chosen question and draw up the timetable for their activity, specifying the learning objectives and the resources to be used. They then carry out their activity session with a class at a partner school. The project is assessed on the basis of the students’ concrete achievements, as well as their effective analysis of their work. This type of project-based teaching engages students because it gives them the opportunity to take ownership of the discipline through the production of a tangible output. Building and then carrying out the activity session helps to develop students’ independence, creativity, and teamwork while at the same time imposing a framework that they must respect. It also enabled them to create a good quality animation, even though for most of them this was their first introduction to the subject of soils.
A Novel Robust Control System Design and Its Application to Servo Motor Drive
Authors: Lai Chiu-Keng , Chen Jun-Ze , Chan Shang-Ting
Published: January 2024

This paper proposes a new control system by integrating integral state feedback control and sliding mode control to eliminate the influences from the reference input change, external load, and parameter variations. For most control systems, integral action is used to overcome the reference input change and external load. However, its control performance cannot be guaranteed. State feedback control is used to dominate the pole location of the closed-loop control system. However, the system parameters determine their pole locations and may change due to uncertainties. Thus, the characteristics of the closed-loop control system are changed. Sliding mode control is used to compensate for the effect of the parameter variations and make the system invariant. The resulting system combines linear state feedback and sliding mode control to guarantee the desired performance. This shows that the proposed system can be easily applied and designed. A servo control system is used to demonstrate the performance, and simulations and experiments are carried out to evaluate the newly defined structure. They show that the strategies and control design can reach robust performance even with uncertainties or external load, and the chattering of the sliding mode control can be minimized.
Development and Application of Open Rotor Discrete Noise Prediction Program Using Time-Domain Methods
Authors: Wang Hanyi , Shan Peng , Zhou Yicheng
Published: January 2024

The aerodynamic noise of an open rotor is one of the critical challenges that must be considered in its design and application. FODNOPP, a program specifically programmed to predict the aerodynamic discrete noise of single- and counter-rotating open rotors (such as propellers, propfans, and rotorcraft rotors) at subsonic, transonic, and supersonic helical blade tip speeds, has recently been developed by the first author. This program is composed of four prediction codes, namely code a1, code a2, code b, and code c, each based on Farassat-derived formulations Formu 1-RTE, Formu 1A, Formu 1-Sph, and Formu 3, providing time-domain solutions to the Ffowcs Williams–Hawkings equation. Four verification examples for both propeller low-speed flight noise and counter-rotating propfan take-off noise are presented, along with an application case for transonic helical tip speed counter-rotating propfan cruise noise. The results demonstrate the accuracy of FODNOPP in calculating the noise for these verification cases. And in the counter-rotating propfan cruise noise case, the maximum harmonic sound pressure level of the rear propfan is 5.5 dB higher than that of the front propfan. FODNOPP can be referred to as a comprehensive design tool, and it offers valuable guidance for engineering design focused on rotor-related noise reduction.
Mixture of Attention Variants for Modal Fusion in Multi-Modal Sentiment Analysis
Authors: He Chao , Zhang Xinghua , Song Dongqing , Shen Yingshan , Mao Chengjie , Wen Huosheng , Zhu  Dingju , Cai Lihua
Published: January 2024

With the popularization of better network access and the penetration of personal smartphones in today’s world, the explosion of multi-modal data, particularly opinionated video messages, has created urgent demands and immense opportunities for Multi-Modal Sentiment Analysis (MSA). Deep learning with the attention mechanism has served as the foundation technique for most state-of-the-art MSA models due to its ability to learn complex inter- and intra-relationships among different modalities embedded in video messages, both temporally and spatially. However, modal fusion is still a major challenge due to the vast feature space created by the interactions among different data modalities. To address the modal fusion challenge, we propose an MSA algorithm based on deep learning and the attention mechanism, namely the Mixture of Attention Variants for Modal Fusion (MAVMF). The MAVMF algorithm includes a two-stage process: in stage one, self-attention is applied to effectively extract image and text features, and the dependency relationships in the context of video discourse are captured by a bidirectional gated recurrent neural module; in stage two, four multi-modal attention variants are leveraged to learn the emotional contributions of important features from different modalities. Our proposed approach is end-to-end and has been shown to achieve a superior performance to the state-of-the-art algorithms when tested with two largest public datasets, CMU-MOSI and CMU-MOSEI.
Mitophagy-Mediated Tumor Dormancy Protects Cancer Cells from Chemotherapy
Authors: Sun Yunqing , Chen Yang , Liu Zhenan , Wang Jingjing , Bai Junqiang , Du Ruixue , Long Mingshu , Shang Zhengjun
Published: January 2024

Despite obvious tumor shrinkage, relapse after chemotherapy remains a main cause of cancer-related mortality, indicating that a subpopulation of cancer cells acquires chemoresistance and lingers after treatment. However, the mechanism involved in the emergence of chemoresistant cells remains largely unknown. Here, we demonstrate that the degradation of mitochondria via autophagy leads to a dormant state in a subpopulation of cancer cells and confers on them resistance to lethal cisplatin (DDP) exposure. The surviving DDP-resistant cells (hereafter, DRCs) have a lower metabolic rate but a stronger potential malignant potential. In the absence of DDP, these DRCs exhibit an ever-increasing self-renewal ability and heightened tumorigenicity. The combination of chloroquine and DDP exerts potent tumor-suppressive effects. In summary, our findings illuminate the mechanism between mitophagy and tumor dormancy and prove that targeting mitophagy might be a promising approach for overcoming chemoresistance in head and neck squamous cell carcinoma (HNSCC).
Imaging Molecular Targets and Metabolic Pathways in Breast Cancer for Improved Clinical Management: Current Practice and Future Perspectives
Authors: Ndlovu Honest , Lawal Ismaheel O. , Mokoala Kgomotso M. G. , Sathekge Mike M.
Published: January 2024

Breast cancer is the most frequently diagnosed cancer and leading cause of cancer-related deaths worldwide. Timely decision-making that enables implementation of the most appropriate therapy or therapies is essential for achieving the best clinical outcomes in breast cancer. While clinicopathologic characteristics and immunohistochemistry have traditionally been used in decision-making, these clinical and laboratory parameters may be difficult to ascertain or be equivocal due to tumor heterogeneity. Tumor heterogeneity is described as a phenomenon characterized by spatial or temporal phenotypic variations in tumor characteristics. Spatial variations occur within tumor lesions or between lesions at a single time point while temporal variations are seen as tumor lesions evolve with time. Due to limitations associated with immunohistochemistry (which requires invasive biopsies), whole-body molecular imaging tools such as standard-of-care [18F]FDG and [18F]FES PET/CT are indispensable in addressing this conundrum. Despite their proven utility, these standard-of-care imaging methods are often unable to image a myriad of other molecular pathways associated with breast cancer. This has stimulated interest in the development of novel radiopharmaceuticals targeting other molecular pathways and processes. In this review, we discuss validated and potential roles of these standard-of-care and novel molecular approaches. These approaches’ relationships with patient clinicopathologic and immunohistochemical characteristics as well as their influence on patient management will be discussed in greater detail. This paper will also introduce and discuss the potential utility of novel PARP inhibitor-based radiopharmaceuticals as non-invasive biomarkers of PARP expression/upregulation.
Biodegradation of Polystyrene by Galleria mellonella: Identification of Potential Enzymes Involved in the Degradative Pathway
Authors: Venegas Sebastián , Alarcón Carolina , Araya Juan , Gatica Marcell , Morin Violeta , Tarifeño-Saldivia Estefanía , Uribe Elena
Published: January 2024

Galleria mellonella is a lepidopteran whose larval stage has shown the ability to degrade polystyrene (PS), one of the most recalcitrant plastics to biodegradation. In the present study, we fed G. mellonella larvae with PS for 54 days and determined candidate enzymes for its degradation. We first confirmed the biodegradation of PS by Fourier transform infrared spectroscopy- Attenuated total reflectance (FTIR-ATR) and then identified candidate enzymes in the larval gut by proteomic analysis using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Two of these proteins have structural similarities to the styrene-degrading enzymes described so far. In addition, potential hydrolases, isomerases, dehydrogenases, and oxidases were identified that show little similarity to the bacterial enzymes that degrade styrene. However, their response to a diet based solely on polystyrene makes them interesting candidates as a potential new group of polystyrene-metabolizing enzymes in eukaryotes.
Mesenchymal Stem Cells from Familial Alzheimer’s Patients Express MicroRNA Differently
Authors: Rochín-Hernández Lory J. , Rochín-Hernández Lory S. , Padilla-Cristerna Mayte L. , Duarte-García Andrea , Jiménez-Acosta Miguel A. , Figueroa-Corona María P. , Meraz-Ríos Marco A.
Published: January 2024

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the predominant form of dementia globally. No reliable diagnostic, predictive techniques, or curative interventions are available. MicroRNAs (miRNAs) are vital to controlling gene expression, making them valuable biomarkers for diagnosis and prognosis. This study examines the transcriptome of olfactory ecto-mesenchymal stem cells (MSCs) derived from individuals with the PSEN1(A431E) mutation (Jalisco mutation). The aim is to determine whether this mutation affects the transcriptome and expression profile of miRNAs and their target genes at different stages of asymptomatic, presymptomatic, and symptomatic conditions. Expression microarrays compare the MSCs from mutation carriers with those from healthy donors. The results indicate a distinct variation in the expression of miRNAs and mRNAs among different symptomatologic groups and between individuals with the mutation. Using bioinformatics tools allows us to identify target genes for miRNAs, which in turn affect various biological processes and pathways. These include the cell cycle, senescence, transcription, and pathways involved in regulating the pluripotency of stem cells. These processes are closely linked to inter- and intracellular communication, vital for cellular functioning. These findings can enhance our comprehension and monitoring of the disease’s physiological processes, identify new disorder indicators, and develop innovative treatments and diagnostic tools for preventing or treating AD.
Radiation-Detoxified Form of Endotoxin Effectively Activates Th1 Responses and Attenuates Ragweed-Induced Th2-Type Airway Inflammation in Mice
Authors: Bácsi Attila , Ágics Beatrix , Pázmándi Kitti , Kocsis Béla , Sándor Viktor , Bertók Lóránd , Bruckner Geza , Sipka Sándor
Published: January 2024

Urbanization with reduced microbial exposure is associated with an increased burden of asthma and atopic symptoms. Conversely, environmental exposure to endotoxins in childhood can protect against the development of allergies. Our study aimed to investigate whether the renaturation of the indoor environment with aerosolized radiation-detoxified lipopolysaccharide (RD-LPS) has a preventative effect against the development of ragweed-induced Th2-type airway inflammation. To explore this, cages of six-week-old BALB/c mice were treated daily with aerosolized native LPS (N-LPS) or RD-LPS. After a 10-week treatment period, mice were sensitized and challenged with ragweed pollen extract, and inflammatory cell infiltration into the airways was observed. As dendritic cells (DCs) play a crucial role in the polarization of T-cell responses, in our in vitro experiments, the effects of N-LPS and RD-LPS were compared on human monocyte-derived DCs (moDCs). Mice in RD-LPS-rich milieu developed significantly less allergic airway inflammation than mice in N-LPS-rich or common environments. The results of our in vitro experiments demonstrate that RD-LPS-exposed moDCs have a higher Th1-polarizing capacity than moDCs exposed to N-LPS. Consequently, we suppose that the aerosolized, non-toxic RD-LPS applied in early life for the renaturation of urban indoors may be suitable for the prevention of Th2-mediated allergies in childhood.
Mutual Effects of Orexin and Bone Morphogenetic Proteins on Catecholamine Regulation Using Adrenomedullary Cells
Authors: Soejima Yoshiaki , Iwata Nahoko , Yamamoto Koichiro , Suyama Atsuhito , Nakano Yasuhiro , Otsuka Fumio
Published: January 2024

Orexins are neuronal peptides that play a prominent role in sleep behavior and feeding behavior in the central nervous system, though their receptors also exist in peripheral organs, including the adrenal gland. In this study, the effects of orexins on catecholamine synthesis in the rat adrenomedullary cell line PC12 were investigated by focusing on their interaction with the adrenomedullary bone morphogenetic protein (BMP)-4. Orexin A treatment reduced the mRNA levels of key enzymes for catecholamine synthesis, including tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanie decarboxylase (Ddc) and dopamine β-hydroxylase (Dbh), in a concentration-dependent manner. On the other hand, treatment with BMP-4 suppressed the expression of Th and Ddc but enhanced that of Dbh with or without co-treatment with orexin A. Of note, orexin A augmented BMP-receptor signaling detected by the phosphorylation of Smad1/5/9 through the suppression of inhibitory Smad6/7 and the upregulation of BMP type-II receptor (BMPRII). Furthermore, treatment with BMP-4 upregulated the mRNA levels of OX1R in PC12 cells. Collectively, the results indicate that orexin and BMP-4 suppress adrenomedullary catecholamine synthesis by mutually upregulating the pathway of each other in adrenomedullary cells.
Modified Crosstalk between Phytohormones in Arabidopsis Mutants for PEP-Associated Proteins
Authors: Bychkov Ivan A. , Andreeva Aleksandra A. , Vankova Radomira , Lacek Jozef , Kudryakova Natalia V. , Kusnetsov Victor V.
Published: January 2024

Plastid-encoded RNA polymerase (PEP) forms a multisubunit complex in operating chloroplasts, where PEP subunits and a sigma factor are tightly associated with 12 additional nuclear-encoded proteins. Mutants with disrupted genes encoding PEP-associated proteins (PAPs) provide unique tools for deciphering mutual relationships among phytohormones. A block of chloroplast biogenesis in Arabidopsis pap mutants specifying highly altered metabolism in white tissues induced dramatic fluctuations in the content of major phytohormones and their metabolic genes, whereas hormone signaling circuits mostly remained functional. Reprogramming of the expression of biosynthetic and metabolic genes contributed to a greatly increased content of salicylic acid (SA) and a concomitant decrease in 1-aminocyclopropane-1-carboxylic acid (ACC) and oxophytodienoic acid (OPDA), precursors of ethylene and jasmonic acid, respectively, in parallel to reduced levels of abscisic acid (ABA). The lack of differences in the free levels of indole-3-acetic acid (IAA) between the pap mutants and wild-type plants was accompanied by fluctuations in the contents of IAA precursors and conjugated forms as well as multilayered changes in the expression of IAA metabolic genes. Along with cytokinin (CK) overproduction, all of these compensatory changes aim to balance plant growth and defense systems to ensure viability under highly modulated conditions.
CD99 Modulates the Proteomic Landscape of Ewing Sarcoma Cells and Related Extracellular Vesicles
Authors: De Feo Alessandra , Manfredi Marcello , Mancarella Caterina , Maqueda Joaquín J. , De Giorgis Veronica , Pignochino Ymera , Sciandra Marika , Cristalli Camilla , Donadelli Massimo , Scotlandi Katia
Published: January 2024

Ewing sarcoma (EWS) is an aggressive pediatric bone tumor characterized by unmet clinical needs and an incompletely understood epigenetic heterogeneity. Here, we considered CD99, a major surface molecule hallmark of EWS malignancy. Fluctuations in CD99 expression strongly impair cell dissemination, differentiation, and death. CD99 is also loaded within extracellular vesicles (EVs), and the delivery of CD99-positive or CD99-negative EVs dynamically exerts oncogenic or oncosuppressive functions to recipient cells, respectively. We undertook mass spectrometry and functional annotation analysis to investigate the consequences of CD99 silencing on the proteomic landscape of EWS cells and related EVs. Our data demonstrate that (i) the decrease in CD99 leads to major changes in the proteomic profile of EWS cells and EVs; (ii) intracellular and extracellular compartments display two distinct signatures of differentially expressed proteins; (iii) proteomic changes converge to the modulation of cell migration and immune-modulation biological processes; and (iv) CD99-silenced cells and related EVs are characterized by a migration-suppressive, pro-immunostimulatory proteomic profile. Overall, our data provide a novel source of CD99-associated protein biomarkers to be considered for further validation as mediators of EWS malignancy and as EWS disease liquid biopsy markers.
A Multi-Omics Approach Reveals Enrichment in Metabolites Involved in the Regulation of the Glutathione Pathway in LIN28B-Dependent Cancer Cells
Authors: Stocchero Matteo , Corallo Diana , Bresolin Silvia , Pantile Marcella , Pirillo Paola , Bortolozzi Roberta , Menegazzo Sara , Boso Daniele , Viola Giampietro , Baraldi Eugenio , Biffi Alessandra , Giordano Giuseppe , Aveic Sanja
Published: January 2024

The RNA-binding protein LIN28B, identified as an independent risk factor in high-risk neuroblastoma patients, is implicated in adverse treatment outcomes linked to metastasis and chemoresistance. Despite its clinical significance, the impact of LIN28B on neuroblastoma cell metabolism remains unexplored. This study employs a multi-omics approach, integrating transcriptome and metabolome data, to elucidate the global metabolic program associated with varying LIN28B expression levels over time. Our findings reveal that escalating LIN28B expression induces a significant metabolic rewiring in neuroblastoma cells. Specifically, LIN28B prompts a time-dependent increase in the release rate of metabolites related to the glutathione and aminoacyl-tRNA biosynthetic pathways, concomitant with a reduction in glucose uptake. These results underscore the pivotal role of LIN28B in governing neuroblastoma cell metabolism and suggest a potential disruption in the redox balance of LIN28B-bearing cells. This study offers valuable insights into the molecular mechanisms underlying LIN28B-associated adverse outcomes in neuroblastoma, paving the way for targeted therapeutic interventions.
Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review
Authors: Pușcaș Amalia , Ștefănescu Ruxandra , Vari Camil-Eugen , Ősz Bianca-Eugenia , Filip Cristina , Bitzan Jana Karlina , Buț Mădălina-Georgiana , Tero-Vescan Amelia
Published: January 2024

Trimetazidine (TMZ), used for treating stable angina pectoris, has garnered attention in the realm of sports due to its potential performance-enhancing properties, and the World Anti-Doping Agency (WADA) has classified TMZ on the S4 list of prohibited substances since 2014. The purpose of this narrative mini-review is to emphasize the biochemical aspects underlying the abusive use of TMZ among athletes as a metabolic modulator of cardiac energy metabolism. The myocardium’s ability to adapt its energy substrate utilization between glucose and fatty acids is crucial for maintaining cardiac function under various conditions, such as rest, moderate exercise, and intense effort. TMZ acts as a partial inhibitor of fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase (KAT), shifting energy production from long-chain fatty acids to glucose, reducing oxygen consumption, improving cardiac function, and enhancing exercise capacity. Furthermore, TMZ modulates pyruvate dehydrogenase (PDH) activity, promoting glucose oxidation while lowering lactate production, and ultimately stabilizing myocardial function. TMZs role in reducing oxidative stress is notable, as it activates antioxidant enzymes like glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). In conclusion, TMZs biochemical mechanisms make it an attractive but controversial option for athletes seeking a competitive edge.
Linking Gene Fusions to Bone Marrow Failure and Malignant Transformation in Dyskeratosis Congenita
Authors: Güllülü Ömer , Mayer Benjamin E. , Toplek Fran Bačić
Published: January 2024

Dyskeratosis Congenita (DC) is a multisystem disorder intrinsically associated with telomere dysfunction, leading to bone marrow failure (BMF). Although the pathology of DC is largely driven by mutations in telomere-associated genes, the implications of gene fusions, which emerge due to telomere-induced genomic instability, remain unexplored. We meticulously analyzed gene fusions in RNA-Seq data from DC patients to provide deeper insights into DC’s progression. The most significant DC-specific gene fusions were subsequently put through in silico assessments to ascertain biophysical and structural attributes, including charge patterning, inherent disorder, and propensity for self-association. Selected candidates were then analyzed using deep learning-powered structural predictions and molecular dynamics simulations to gauge their potential for forming higher-order oligomers. Our exploration revealed that genes participating in fusion events play crucial roles in upholding genomic stability, facilitating hematopoiesis, and suppressing tumors. Notably, our analysis spotlighted a particularly disordered polyampholyte fusion protein that exhibits robust higher-order oligomerization dynamics. To conclude, this research underscores the potential significance of several high-confidence gene fusions in the progression of BMF in DC, particularly through the dysregulation of genomic stability, hematopoiesis, and tumor suppression. Additionally, we propose that these fusion proteins might hold a detrimental role, specifically in inducing proteotoxicity-driven hematopoietic disruptions.
URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia–Ischemia and Enhances Neurogenesis in Females
Authors: Beldarrain Gorane , Chillida Marc , Hilario Enrique , Herrero de la Parte Borja , Álvarez Antonia , Alonso-Alconada Daniel
Published: January 2024

The need for new and effective treatments for neonates suffering from hypoxia–ischemia is urgent, as the only implemented therapy in clinics is therapeutic hypothermia, only effective in 50% of cases. Cannabinoids may modulate neuronal development and brain plasticity, but further investigation is needed to better describe their implication as a neurorestorative therapy after neonatal HI. The cannabinoid URB447, a CB1 antagonist/CB2 agonist, has previously been shown to reduce brain injury after HI, but it is not clear whether sex may affect its neuroprotective and/or neurorestorative effect. Here, URB447 strongly reduced brain infarct, improved neuropathological score, and augmented proliferative capacity and neurogenic response in the damaged hemisphere. When analyzing these effects by sex, URB447 ameliorated brain damage in both males and females, and enhanced cell proliferation and the number of neuroblasts only in females, thus suggesting a neuroprotective effect in males and a double neuroprotective/neurorestorative effect in females.
Lamivudine, Doravirine, and Cabotegravir Downregulate the Expression of Human Endogenous Retroviruses (HERVs), Inhibit Cell Growth, and Reduce Invasive Capability in Melanoma Cell Lines
Authors: Zanrè Valentina , Bellinato Francesco , Cardile Alessia , Passarini Carlotta , Monticelli Jacopo , Di Bella Stefano , Menegazzi Marta
Published: January 2024

This study explores the impact of antiretroviral administration on the expression of human endogenous retroviruses (HERVs), cell growth, and invasive capability of human melanoma cell lines in culture. We investigated three antiretrovirals—lamivudine, doravirine, and cabotegravir—in A375, FO-1, and SK-Mel-28, BRAF-mutated, and in MeWo, P53-mutated, melanoma cell lines. The findings indicate a general capability of these drugs to downregulate the expression of HERV-K Pol and Env genes and hinder cell viability, mobility, and colony formation capacity of melanoma cells. The antiretroviral drugs also demonstrate selectivity against malignant cells, sparing normal human epithelial melanocytes. The study reveals that the integrase inhibitor cabotegravir is particularly effective in inhibiting cell growth and invasion across different cell lines in comparison with lamivudine and doravirine, which are inhibitors of the viral reverse transcriptase enzyme. The investigation further delves into the molecular mechanisms underlying the observed effects, highlighting the potential induction of ferroptosis, apoptosis, and alterations in cell cycle regulatory proteins. Our findings showed cytostatic effects principally revealed in A375, and SK-Mel-28 cell lines through a downregulation of retinoblastoma protein phosphorylation and/or cyclin D1 expression. Signs of ferroptosis were detected in both A375 cells and FO-1 cells by a decrease in glutathione peroxidase 4 and ferritin expression, as well as by an increase in transferrin protein levels. Apoptosis was also detected in FO-1 and SK-Mel-28, but only with cabotegravir treatment. Moreover, we explored the expression and activity of the stimulator of interferon genes (STING) protein and its correlation with programmed death-ligand 1 (PD-L1) expression. Both the STING activity and PD-L1 expression were decreased, suggesting that the antiretroviral treatments may counteract the detrimental effects of PD-L1 expression activation through the STING/interferon pathway triggered by HERV-K. Finally, this study underscores the potential therapeutic significance of cabotegravir in melanoma treatment. The findings also raise the prospect of using antiretroviral drugs to downregulate PD-L1 expression, potentially enhancing the therapeutic responses of immune checkpoint inhibitors.