bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite Element Modeling and Simulation of a Submerged Wave Energy Converter System for Application to Oceanic Islands in Tropical Atlantic
Authors: Bouchonneau Nadège , Coutrey Arnaud , Bruère Vivianne Marie , Araújo Moacyr , da Silva Alex Costa
Published: February 2023

The development of efficient and sustainable marine energy converter systems is a great challenge, especially in remote areas such as oceanic islands. This work proposes a numerical modeling methodology to assess the mechanical behavior of a wave energy converter (WEC) to be applied outside Fernando de Noronha Island (Pernambuco, Brazil). First, oceanographic data collected in situ were analyzed to determine different sea state scenarios in the region. The Airy theory and second-order Stokes’ theory were used to obtain the velocity profiles for the maximum and operational swells. These profiles were then implemented in a flow model developed in COMSOL Multiphysics software (Burlington, MA, USA) to calculate the wave distributions of pressure on the WEC structure. Finally, wave pressure distributions obtained from simulations were implemented in a static analysis of the system by the finite element method using SolidWorks (France). The results highlighted the most critical system inclination and the parts of the WEC structure more likely to be damaged under extreme swell conditions. The 0° inclination was the most critical situation, leading to the exceeding of the elastic limits of some parts of the WEC structure. The methodology developed in this work showed to be efficient to study and propose project improvement for the strength of the WEC system.
Evaluation of Combustion Stability and Exhaust Emissions of a Stationary Compression Ignition Engine Powered by Diesel/n-Butanol and RME Biodiesel/n-Butanol Blends
Authors: Tutak Wojciech , Jamrozik Arkadiusz , Grab-Rogaliński Karol
Published: February 2023

In recent years, the interest in renewable fuels has increased mainly due to regulations regulating the permissible limits of toxic components of exhaust gases emitted by reciprocating engines. This paper presents the results of a comparison of the effects of fueling a compression-ignition piston engine with a mixture of diesel fuel and n-butanol, as well as RME (Rapeseed Oil Methyl Esters) biodiesel and n-butanol. The tests were carried out for a constant load and a wide energetic share of fuels in the mixture. The main focus was on the assessment of combustion stability, the uniqueness of the combustion stages, and the assessment of the fuel type influence on the CA50 angle. The tests show that RME offers the possibility of efficient combustion with n-butanol with up to 80% energy share. The share of n-butanol has a positive effect on the engine’s efficiency and very effectively reduces soot emissions. Without the influence on COVIMEP, the share of n-butanol up to 40% in the mixture with diesel fuel and up to 80% in the mixture with RME was recorded. Combustion of RME with n-butanol was more stable. The share of n-butanol in the mixture with diesel fuel caused an increase in NOx emissions, and co-combustion with RME caused a decrease in emissions.
RingFFL: A Ring-Architecture-Based Fair Federated Learning Framework
Authors: Han Lu , Huang Xiaohong , Li Dandan , Zhang Yong
Published: February 2023

In the ring-architecture-based federated learning framework, security and fairness are severely compromised when dishonest clients abort the training process after obtaining useful information. To solve the problem, we propose a Ring- architecture-based Fair Federated Learning framework called RingFFL, in which we design a penalty mechanism for FL. Before the training starts in each round, all clients that will participate in the training pay deposits in a set order and record the transactions on the blockchain to ensure that they are not tampered with. Subsequently, the clients perform the FL training process, and the correctness of the models transmitted by the clients is guaranteed by the HASH algorithm during the training process. When all clients perform honestly, each client can obtain the final model, and the number of digital currencies in each client’s wallet is kept constant; otherwise, the deposits of clients who leave halfway will be compensated to the clients who perform honestly during the training process. In this way, through the penalty mechanism, all clients either obtain the final model or are compensated, thus ensuring the fairness of federated learning. The security analysis and experimental results show that RingFFL not only guarantees the accuracy and security of the federated learning model but also guarantees the fairness.
An Advanced Fractional Order Method for Temperature Control
Authors: Cajo Ricardo , Zhao Shiquan , Birs Isabela , Espinoza Víctor , Fernández Edson , Plaza Douglas , Salcan-Reyes Gabriela
Published: February 2023

Temperature control in buildings has been a highly studied area of research and interest since it affects the comfort of occupants. Commonly, temperature systems like centralized air conditioning or heating systems work with a fixed set point locally set at the thermostat, but users turn on or turn off the system when they feel it is too hot or too cold. This configuration is clearly not optimal in terms of energy consumption or even thermal comfort for users. Model predictive control (MPC) has been widely used for temperature control systems. In MPC design, the objective function involves the selection of constant weighting factors. In this study, a fractional-order objective function is implemented, so the weighting factors are time-varying. Furthermore, we compared the performance and disturbance rejection of MPC and Fractional-order MPC (FOMPC) controllers. To this end, we have chosen a building model from an EnergyPlus repository. The weather data needed for the EnergyPlus calculations has been obtained as a licensed file from the ASHRAE Handbook. Furthermore, we acquired a mathematical model by employing the Matlab system identification toolbox with the data obtained from the building model simulation in EnergyPlus. Next, we designed several FOMPC controllers, including the classical MPC controllers. Subsequently, we ran co-simulations in Matlab for the FOMPC controllers and EnergyPlus for the building model. Finally, through numerical analysis of several performance indexes, the FOMPC controller showed its superiority against the classical MPC in both reference tracking and disturbance rejection scenarios.
Metal-Coordinated Dynamics and Viscoelastic Properties of Double-Network Hydrogels
Authors: Zhu Shilei , Wang Yan , Wang Zhe , Chen Lin , Zhu Fengbo , Ye Yanan , Zheng Yong , Yu Wenwen , Zheng Qiang
Published: February 2023

Biological soft tissues are intrinsically viscoelastic materials which play a significant role in affecting the activity of cells. As potential artificial alternatives, double-network (DN) gels, however, are pure elastic and mechanically time independent. The viscoelasticization of DN gels is an urgent challenge in enabling DN gels to be used for advanced development of biomaterial applications. Herein, we demonstrate a simple approach to regulate the viscoelasticity of tough double-network (DN) hydrogels by forming sulfonate–metal coordination. Owing to the dynamic nature of the coordination bonds, the resultant hydrogels possess highly viscoelastic, mechanical time-dependent, and self-recovery properties. Rheological measurements are performed to investigate the linear dynamic mechanical behavior at small strains. The tensile tests and cyclic tensile tests are also systematically performed to evaluate the rate-dependent large deformation mechanical behaviors and energy dissipation behaviors of various ion-loaded DN hydrogels. It has been revealed based on the systematic analysis that robust strong sulfonate–Zr4+ coordination interactions not only serve as dynamic crosslinks imparting viscoelastic rate-dependent mechanical performances, but also strongly affect the relative strength of the first PAMPS network, thereby increasing the yielding stress σy and the fracture stress at break σb and reducing the stretch ratio at break λb. It is envisioned that the viscoelasticization of DN gels enables versatile applications in the biomedical and engineering fields.
Detecting Vertical Root Fractures Using Modified Methylene Blue Dye: A Preliminary In Vitro Study
Authors: Alamri Hadi Mohammed , Altamimi Abdullah , Mirza Mubashir Baig , Aldosimani Mazen A. , Ghabbani Hani , Aljarbou Fahd
Published: February 2023

Diagnostically, vertical root fractures (VRFs) can be a frustrating experience for the dentist. Misdiagnosis could result in significant time and effort losses involved in erroneously intervening endodontically and/or periodontally. Certainly, diagnosing VRFs is often very difficult, and diagnoses based on speculations have led to the extraction of many salvageable teeth. This study was conducted in the radiology unit of College of Dentistry, Prince Sattam bin Abdulaziz University, between December 2021 and June 2022 to evaluate the ability to detect VRFs following the use of a novel radio-opaque dye using periapical radiographs (PARs) and cone-beam computed tomography (CBCT). After carefully inducing VRFs on extracted, single-rooted, virgin premolars (n = 26), they were assigned to control (n = 2) and experimental groups (n = 24). The fracture site of the tooth in the control group received methylene blue dye, whereas the experimental group received a novel dye. Two differently angled PARs were obtained for all the teeth, followed by a CBCT image. Three blinded investigators participated in scoring a Likert scale form with a set of questions. Inter-/intra-examiner reliability showed excellent consistency using Cronbach’s alpha test. The Z-test revealed CBCT and PAR to be equally adept at detecting VRFs, with the mean values showing no statistically significant differences. The extent of the VRFs and dye penetration were significantly better when angled radiographs and axial view CBCT were evaluated. Within the limitations of this study, the dye tested showed promising initial results as an aid in radiographically detecting VRFs. The use of such minimally invasive methods is critically needed for diagnosing and managing VRFs. However, further testing should be performed prior to its clinical use.
Exogenous Melatonin Application Induced Morpho-Physiological and Biochemical Regulations Conferring Salt Tolerance in Ranunculus asiaticus L.
Authors: Eisa Eman Abdelhakim , Honfi Péter , Tilly-Mándy Andrea , Mirmazloum Iman
Published: February 2023

This study presents the effects of exogenous melatonin application at different concentrations (50, 100, and 200 μM) on the morphological, physiological, and antioxidant defense systems of the buttercup plant under salinity stress (4.5 and 5.5 dS·m−1 EC). Expectedly, the salinity stress negatively affected the plant growth parameters, cell membrane stability, and POX enzyme activity of R. asiaticus compared to non-stressed plants. However, in a dose-dependent manner, exogenous melatonin foliar application decreased the salt stress-induced symptoms of retarded vegetative growth, physiological characteristics, and oxidative stress level. The results obtained, revealed the significant effectiveness of exogenous melatonin treatment at 200 μM concentration under salt stress conditions by enhancing the plant growth traits such as chlorophyll and carotenoids content, relative water content, proline content, peroxidase enzyme activity (POD), and by the decreased electrolyte leakage rate, and Na+ content, as well as delaying the emergence of flower buds under salinity stress. The salt tolerance index percentages (STI%) for all estimated characters are also calculated for all studied parameters. This study uncovered the beneficial effect of melatonin in reducing salt stress symptoms that can be used to reduce the salinity effect in ranunculus plant production.
Comparative Transcriptome Analysis of High and Low Thujone-Producing Artemisia argyi Reveals Candidate Genes for Thujone Synthetic and Regulatory Pathway
Authors: Zhao Tingting , Chen Changjie , Li Jinxin , Luo Dandan , Miao Yuhuan , Gui Chun , Liu Qi , Liu Dahui
Published: February 2023

Artemisia argyi Levl. et Van (A. argyi) is a traditional medicinal plant, which is widely used in health, food and medicine. Thujone is an important cyclic monoterpene derivative in the volatile oil of A. argyi leaves with multiple efficacy. Although the thujone synthetic pathway has been preliminarily analyzed in very few species, genes related to the thujone content in A. argyi leaves remain largely unknown. In this study, we identify candidate genes involved in the synthesis and regulation of thujone content in A. argyi leaves by the comparative transcriptome analysis of two group materials with high and low thujone content. A total of 89 candidate genes related to thujone content are identified including one gene involved in the mevalonate pathway, three genes involved in the methylerythritol phosphate pathway, 19 genes involved in the metabolic process from geranyl pyrophosphate to thujone (four b-terpene synthase, five cytochrome P450, five dehydrogenase, and five reductase-encoding genes) and 66 transcription factor-encoding genes. Taken together, our results provide valuable gene resources for further analyzing the synthetic and regulatory pathway of thujone in A. argyi.
Association between Feelings of Trust and Security with Subjective Health among Mexican Migrants in the New York City Area
Authors: Gaitán-Rossi Pablo , Vilar-Compte Mireya , Ferré-Eguiluz Isabel , Ortiz Luis , Garcia Erika
Published: February 2023

The size of the foreign-born population living in the United States makes migrants’ health a substantive policy issue. The health status of Mexican immigrants might be affected by the level of social capital and the social context, including the rhetoric around immigration. We hypothesize that a diminished perception of trust and safety in the community has a negative impact on self-reported health. In a cross-sectional study, we conducted a survey among 266 Mexican Immigrants in the New York City Area who used the Mexican Consulate between May and June 2019 for regular services provided to documented and undocumented immigrants. A univariate and bivariate descriptive analysis by trust and security items first shows the diversity of the Mexican population living in the US and the conditions of vulnerability. Then, logistic regression models estimate the association between trust and security items with self-reported health status. Results show that safety is consistently associated with good self-rated health, especially when rating the neighborhood, and trust showed mixed results, more reliant to the way it is operationalized. The study illustrates a pathway by which perceptions of the social context are associated with migrants’ health.
Impact of Coding Educational Programs (CEP) on Digital Media Problematic Use (DMPU) and on Its Relationship with Psychological Dependence and Emotional Dysregulation
Authors: Marconi Pier , Scognamiglio Rosamaria , Marchiori Elisabetta , Angeloni Daniele , Mascia Maria , Penna Maria
Published: February 2023

Alongside the positive effects linked to the introduction of digital technologies into our lives, particular dysfunctional behaviors in the use of digital tools have appeared, through which the expression of conditions such as addiction, difficulties in affective and behavioral self-regulation and mental health problems have been channeled. The present study aims to investigate, in a sample of young students aged m = 12.91 (ds = 0.56) years, whether Coding Educational Programs (CEP), deployed to 44.9% of the sample, is effective in psychological dependence, emotional self-regulation and Digital Media Problematic Use (DMPU), as self-assessed through questionnaires (DERS, DSRS, IAT, MPIQ and MPPUS). CEP had no effect on emotional dysregulation or on DMPU. They were effective in the time management of mobile phone use, with students rescheduling from daytime use on working days to daytime use on the weekend. Moreover, people who attended CEP more frequently used smartphones for orienting themselves and for obtaining information. In conclusion, CEP are effective in achieving a more functional and important use of smartphones and better time management. It is possible that CEP effect on metacognition could reduce DMPU if alternative ways to regulate emotions are available.
Young Adults’ Perception of Forests Using Landscape-Image-Sketching Technique: A Case Study of Changsha, Central China
Authors: Luo Fen , Wang Chen , Lei Haiqian , Xiao Zhijun
Published: February 2023

The forest-landscape image is the bridge for communication between human beings and the forest. The aim of this paper is to construct the landscape-image conceptual model from the personal perception of the forest, with what people are looking at and how they are viewing themselves as a part of the forest. This research constructed a forest-landscape image by young adults by utilizing the landscape-image-sketching technique and selecting 140 young adults who had lived in Changsha, Central China for ten years, using convenience sampling, during April and May 2018. The results demonstrated that the forest was considered as the people’s life world, as rural scenery around the respondents’ homes, instead of the perception of the objective forest, an important habitat for animals and a limited resource supplier for human living. In fact, the natural values of the forest, such as the ecological and aesthetic values, received more attention than the social ones of the forest, including the life, production, and cultural values. Finally, it is important to raise the public’s awareness of the objective entity of the forest and to guide the variety of experiences for the respondents in the forest.
Using Nuclear Energy for Maritime Decarbonization and Related Environmental Challenges: Existing Regulatory Shortcomings and Improvements
Authors: Wang Qiuwen , Zhang Hu , Zhu Puxin
Published: February 2023

In recent years, the use of nuclear energy as propulsion for merchant ships has been proposed as a means of promoting the transition toward maritime decarbonization and environmentally sustainable shipping. However, there are concerns that nuclear-powered merchant ships could pose risks to the marine environment in the event of accidents, such as collisions, machinery failure or damage, fire, or explosions. The current international regulatory framework for nuclear-powered merchant ships is insufficient to address these risks. This research aims to address this gap by conducting a policy analysis of the existing regulations and a critical examination of their effectiveness in addressing the environmental risks of nuclear-powered merchant ships. Through this analysis, the study identifies the shortcomings and insufficiencies in the current framework and explores potential solutions to improve it, with the goal of enhancing the international community’s ability to mitigate the potential impacts of radioactive marine pollution from nuclear-propelled ships in an era of maritime decarbonization.
Tooth Loss and Caries Experience of Elderly Chileans in the Context of the COVID-19 Pandemic in Five Regions of Chile
Authors: Beltrán Víctor , Flores Marco , Sanzana Cristina , Muñoz-Sepúlveda Fernanda , Alvarado Eloy , Venegas Bernardo , Molina Juan Carlos , Rueda-Velásquez Sandra , von Marttens Alfredo
Published: February 2023

Risk factors associated with tooth loss have been studied; however, the current status of the epidemiological profiles and the impact of the pandemic on the oral health of the elderly is still unknown. This study aims to determine the experience of caries and tooth loss among elderly Chilean citizens in five regions and to identify the risk factors associated with tooth loss. The sample includes 135 participants over 60 years old assessed during COVID-19 lockdown. Sociodemographic variables such as education and RSH (Social Registry of Households) were obtained through a teledentistry platform called TEGO. The history of chronic diseases such as diabetes, obesity, depression and dental caries reported by DMFT index scores were incorporated. The statistical analysis included Adjusted Odds Ratios (ORs) to assess risk factors associated with the lack of functional dentition. Multivariate hypothesis testing was used to compare the mean equality of DMFT and its components between regions (p-value < 0.05). Individuals with RSH ≤ 40% were at higher risk of having no functional dentition with OR 4.56 (95% CI: 1.71, 12.17). The only mean difference between regions was the filled tooth component. Tooth loss was associated with multidimensional lower income, where the elderly belonging to the 40% most vulnerable population had a higher prevalence of non-functional dentition. This study highlights the importance of implementing a National Oral Health Policy that focuses on oral health promotion and minimally invasive dentistry for the most vulnerable population.
Comparison and Evaluation of GHG Emissions during Simulated Thermophilic Composting of Different Municipal and Agricultural Feedstocks
Authors: Zeng Jianfei , Michel Frederick C. , Huang Guangqun
Published: February 2023

Composting is widely used to recycle a variety of different organic wastes. In this study, dairy manure, chicken litter, biosolids, yard trimmings and food waste were selected as representative municipal and agricultural feedstocks and composted in simulated thermophilic composting reactors to compare and evaluate the GHG emissions. The results showed that the highest cumulative emissions of CO2, CH4 and N2O were observed during yard trimmings composting (659.14 g CO2 kg−1 DM), food waste composting (3308.85 mg CH4 kg−1 DM) and chicken litter composting (1203.92 mg N2O kg−1 DM), respectively. The majority of the carbon was lost in the form of CO2. The highest carbon loss by CO2 and CH4 emissions and the highest nitrogen loss by N2O emission occurred in dairy manure (41.41%), food waste (0.55%) and chicken litter composting (3.13%), respectively. The total GHG emission equivalent was highest during food waste composting (365.28 kg CO2-eq ton−1 DM) which generated the highest CH4 emission and second highest N2O emissions, followed by chicken litter composting (341.27 kg CO2-eq ton−1 DM), which had the highest N2O emissions. The results indicated that accounting for GHG emissions from composting processes when it is being considered as a sustainable waste management practice was of great importance.
COVID-19 Related Early Google Search Behavior and Health Communication in the United States: Panel Data Analysis on Health Measures
Authors: Wang Binhui , Liang Beiting , Chen Qiuyi , Wang Shu , Wang Siyi , Huang Zhongguo , Long Yi , Wu Qili , Xu Shulin , Jinna Pranay , Yang Fan , Ming Wai-Kit , Liu Qian
Published: February 2023

The COVID-19 outbreak at the end of December 2019 spread rapidly all around the world. The objective of this study is to investigate and understand the relationship between public health measures and the development of the pandemic through Google search behaviors in the United States. Our collected data includes Google search queries related to COVID-19 from 1 January to 4 April 2020. After using unit root tests (ADF test and PP test) to examine the stationary and a Hausman test to choose a random effect model, a panel data analysis is conducted to investigate the key query terms with the newly added cases. In addition, a full sample regression and two sub-sample regressions are proposed to explain: (1) The changes in COVID-19 cases number are partly related to search variables related to treatments and medical resources, such as ventilators, hospitals, and masks, which correlate positively with the number of new cases. In contrast, regarding public health measures, social distancing, lockdown, stay-at-home, and self-isolation measures were negatively associated with the number of new cases in the US. (2) In mild states, which ranked one to twenty by the average daily new cases from least to most in 50 states, the query terms about public health measures (quarantine, lockdown, and self-isolation) have a significant negative correlation with the number of new cases. However, only the query terms about lockdown and self-isolation are also negatively associated with the number of new cases in serious states (states ranking 31 to 50). Furthermore, public health measures taken by the government during the COVID-19 outbreak are closely related to the situation of controlling the pandemic.
Understanding the Impact of the COVID-19 Pandemic on the Perception and Use of Urban Green Spaces in Korea
Authors: Kim Jiwon , Ko Youngjin , Kim Whijin , Kim Gaeun , Lee Jeongmin , Eyman Olebogeng Thelma G. , Chowdhury Sarwat , Adiwal Julie , Son Yowhan , Lee Woo-Kyun
Published: February 2023

Faced with the prospect that the impact of the COVID-19 pandemic and climate change will be far-reaching and long-term, the international community is showing interest in urban green space (UGS) and urban green infrastructure utilization as a solution. In this study, we investigated how citizens’ perceptions and use of UGS have changed during COVID-19. We also collected their ideas on how UGS can raise its usability. As a result, more people became to realize the importance of UGS. In particular, the urban environmental purification function from UGS was recognized as giving great benefits to respondents. On the other hand, the patterns of UGS use were mixed with decreasing UGS use to maintain social distancing or increasing UGS use to maintain health or substitute other restricted facilities. More than half of respondents had their UGS visit patterns impacted by COVID-19. In particular, the increase rate of UGS use was rather high in the group that seldom used UGS before COVID-19. In addition, they increased the use of UGS to replace other limited facilities, and thus tended to demand an increase in rest facilities. Based on these results, this paper suggested securing social support and sustainability for the policy by reflecting users’ demand in landscape planning related to the increase of UGS in the city. This study can contribute to improving the resilience of UGS and the sustainability of urban space planning.
Pilot Study of the Long-Term Effects of Radiofrequency Electromagnetic Radiation Exposure on the Mouse Brain
Authors: Spandole-Dinu Sonia , Catrina Ana-Maria , Voinea Oana Cristina , Andone Alina , Radu Speranța , Haidoiu Cerasela , Călborean Octavian , Popescu Diana Mihaela , Suhăianu Vladimir , Baltag Octavian , Tuță Leontin , Roșu Georgiana
Published: February 2023

The increasing radiofrequency (RF) electromagnetic radiation pollution resulting from the development and use of technologies utilizing RF has sparked debate about the possible biological effects of said radiation. Of particular concern is the potential impact on the brain, due to the close proximity of communication devices to the head. The main aim of this study was to examine the effects of long-term exposure to RF on the brains of mice in a real-life scenario simulation compared to a laboratory setting. The animals were exposed continuously for 16 weeks to RF using a household Wi-Fi router and a laboratory device with a frequency of 2.45 GHz, and were compared to a sham-exposed group. Before and after exposure, the mice underwent behavioral tests (open-field test and Y-maze); at the end of the exposure period, the brain was harvested for histopathological analysis and assessment of DNA methylation levels. Long-term exposure of mice to 2.45 GHz RF radiation increased their locomotor activity, yet did not cause significant structural or morphological changes in their brains. Global DNA methylation was lower in exposed mice compared to sham mice. Further research is needed to understand the mechanisms behind these effects and to understand the potential effects of RF radiation on brain function.
CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells
Authors: Aye Cho-Cho , Hammond Dean E. , Rodriguez-Cuenca Sergio , Doherty Mary K. , Whitfield Phillip D. , Phelan Marie M. , Yang Chenjing , Perez-Perez Rafael , Li Xiaoxin , Diaz-Ramos Angels , Peddinti Gopal , Oresic Matej , Vidal-Puig Antonio , Zorzano Antonio , Ugalde Cristina , Mora Silvia
Published: February 2023

CBL is rapidly phosphorylated upon insulin receptor activation. Mice whole body CBL depletion improved insulin sensitivity and glucose clearance; however, the precise mechanisms remain unknown. We depleted either CBL or its associated protein SORBS1/CAP independently in myocytes and assessed mitochondrial function and metabolism compared to control cells. CBL- and CAP-depleted cells showed increased mitochondrial mass with greater proton leak. Mitochondrial respiratory complex I activity and assembly into respirasomes were reduced. Proteome profiling revealed alterations in proteins involved in glycolysis and fatty acid degradation. Our findings demonstrate CBL/CAP pathway couples insulin signaling to efficient mitochondrial respiratory function and metabolism in muscle.
Targeting the Gastrin-Releasing Peptide Receptor (GRP-R) in Cancer Therapy: Development of Bombesin-Based Peptide–Drug Conjugates
Authors: Gomena Jacopo , Vári Balázs , Oláh-Szabó Rita , Biri-Kovács Beáta , Bősze Szilvia , Borbély Adina , Soós Ádám , Ranđelović Ivan , Tóvári József , Mező Gábor
Published: February 2023

Targeted tumour therapy has proved to be an efficient alternative to overcome the limitations of conventional chemotherapy. Among several receptors upregulated in cancer cells, the gastrin-releasing peptide receptor (GRP-R) has recently emerged as a promising target for cancer imaging, diagnosing and treatment due to its overexpression on cancerous tissues such as breast, prostate, pancreatic and small-cell lung cancer. Herein, we report on the in vitro and in vivo selective delivery of the cytotoxic drug daunorubicin to prostate and breast cancer, by targeting GRP-R. Exploiting many bombesin analogues as homing peptides, including a newly developed peptide, we produced eleven daunorubicin-containing peptide–drug conjugates (PDCs), acting as drug delivery systems to safely reach the tumour environment. Two of our bioconjugates revealed remarkable anti-proliferative activity, an efficient uptake by all three tested human breast and prostate cancer cell lines, high stability in plasma and a prompt release of the drug-containing metabolite by lysosomal enzymes. Moreover, they revealed a safe profile and a consistent reduction of the tumour volume in vivo. In conclusion, we highlight the importance of GRP-R binding PDCs in targeted cancer therapy, with the possibility of further tailoring and optimisation.
Melatonin Promotes the Development of Secondary Hair Follicles in Adult Cashmere Goats by Activating the Keap1-Nrf2 Signaling Pathway and Inhibiting the Inflammatory Transcription Factors NFκB and AP-1
Authors: Diao Xiaogao , Duan Chunhui , Yao Lingyun , Qin Jiaxin , He Liwen , Zhang Wei
Published: February 2023

Exogenous melatonin (MT) has been used to promote the growth of secondary hair follicles and improve cashmere fiber quality, but the specific cellular-level mechanisms involved are unclear. This study was carried out to investigate the effect of MT on the development of secondary hair follicles and on cashmere fiber quality in cashmere goats. The results showed that MT improved secondary follicle numbers and function as well as enhanced cashmere fiber quality and yield. The MT-treated goat groups had high secondary-to-primary ratios (S:P) for hair follicles, greater in the elderly group (p < 0.05). Antioxidant capacities of secondary hair follicles improved fiber quality and yield in comparison with control groups (p < 0.05/0.01). Levels of reactive oxygen and nitrogen species (ROS, RNS) and malondialdehyde (MDA) were lowered (p < 0.05/0.01) by MT. There was significant upregulation of antioxidant genes (for SOD-3; GPX-1; NFE2L2) and the protein of nuclear factor (Nrf2), and downregulation of the Keap1 protein. There were significant differences in the expression of genes for secretory senescence-associated phenotype (SASP) cytokines (IL-1β, IL-6, MMP-9, MMP-27, CCL-21, CXCL-12, CXCL-14, TIMP-1,2,3) plus their protein of key transcription factors, nuclear factor kappa B (NFκB) and activator protein-1 (AP-1), in comparison with the controls. We concluded that MT could enhance antioxidant capacity and reduce ROS and RNS levels of secondary hair follicles through the Keap1-Nrf2 pathway in adult cashmere goats. Furthermore, MT reduced the expression of the SASP cytokines genes by inhibiting the protein of NFκB and AP-1 in the secondary hair follicles in older cashmere goats, thus delaying skin aging, improving follicle survival, and increasing the number of secondary hair follicles. Collectively, these effects of exogenous MT enhanced the quality and yield of cashmere fibers, especially at 5–7 years old.
Neurovascular Unit Compensation from Adjacent Level May Contribute to Spontaneous Functional Recovery in Experimental Cervical Spondylotic Myelopathy
Authors: Li Guang-Sheng , Chen Guang-Hua , Wang Kang-Heng , Wang Xu-Xiang , Hu Xiao-Song , Wei Bo , Hu Yong
Published: February 2023

The progression and remission of cervical spondylotic myelopathy (CSM) are quite unpredictable due to the ambiguous pathomechanisms. Spontaneous functional recovery (SFR) has been commonly implicated in the natural course of incomplete acute spinal cord injury (SCI), while the evidence and underlying pathomechanisms of neurovascular unit (NVU) compensation involved in SFR remains poorly understood in CSM. In this study, we investigate whether compensatory change of NVU, in particular in the adjacent level of the compressive epicenter, is involved in the natural course of SFR, using an established experimental CSM model. Chronic compression was created by an expandable water-absorbing polyurethane polymer at C5 level. Neurological function was dynamically assessed by BBB scoring and somatosensory evoked potential (SEP) up to 2 months. (Ultra)pathological features of NVUs were presented by histopathological and TEM examination. Quantitative analysis of regional vascular profile area/number (RVPA/RVPN) and neuroglial cells numbers were based on the specific EBA immunoreactivity and neuroglial biomarkers, respectively. Functional integrity of blood spinal cord barrier (BSCB) was detected by Evan blue extravasation test. Although destruction of the NVU, including disruption of the BSCB, neuronal degeneration and axon demyelination, as well as dramatic neuroglia reaction, were found in the compressive epicenter and spontaneous locomotor and sensory function recovery were verified in the modeling rats. In particular, restoration of BSCB permeability and an evident increase in RVPA with wrapping proliferated astrocytic endfeet in gray matter and neuron survival and synaptic plasticity were confirmed in the adjacent level. TEM findings also proved ultrastructural restoration of the NVU. Thus, NVU compensation changes in the adjacent level may be one of the essential pathomechanisms of SFR in CSM, which could be a promising endogenous target for neurorestoration.
Adverse Human Health Effects of Chromium by Exposure Route: A Comprehensive Review Based on Toxicogenomic Approach
Authors: Shin Dong Yeop , Lee Sang Min , Jang Yujin , Lee Jun , Lee Cheol Min , Cho Eun-Min , Seo Young Rok
Published: February 2023

Heavy metals are defined as metals with relatively high density and atomic weight, and their various applications have raised serious concerns about the environmental impacts and potential human health effects. Chromium is an important heavy metal that is involved in biological metabolism, but Cr exposure can induce a severe impact on occupational workers or public health. In this study, we explore the toxic effects of Cr exposure through three exposure routes: dermal contact, inhalation, and ingestion. We propose the underlying toxicity mechanisms of Cr exposure based on transcriptomic data and various bioinformatic tools. Our study provides a comprehensive understanding of the toxicity mechanisms of different Cr exposure routes by diverse bioinformatics analyses.
Mineralocorticoid Receptor Antagonism Attenuates Multiple Organ Failure after Renal Ischemia and Reperfusion in Mice
Authors: Park Eun Jung , Je Jihyun , Dusabimana Theodomir , Yun Seung Pil , Kim Hye Jung , Kim Hwajin , Park Sang Won
Published: February 2023

Renal ischemia reperfusion (IR) injury is a major cause of acute kidney injury (AKI) that is often complicated by multiple organ failure of the liver and intestine. The mineralocorticoid receptor (MR) is activated in patients with renal failure associated with glomerular and tubular damage. We thus investigated whether canrenoic acid (CA), a mineralocorticoid receptor (MR) antagonist, protects against AKI-induced hepatic and intestinal injury, suggesting the underlying mechanisms. Mice were divided into five groups: sham mice, mice subjected to renal IR, and mice pretreated with canrenoic acid (CA; 1 or 10 mg/kg) 30 min prior to renal IR. At 24 h after renal IR, the levels of plasma creatinine, alanine aminotransferase and aldosterone were measured, and structural changes and inflammatory responses of the kidney, liver, and intestine were analyzed. We found that CA treatment reduced plasma creatinine levels, tubular cell death and oxidative stress induced by renal IR. CA treatment also decreased renal neutrophil infiltration and inflammatory cytokine expression and inhibited the release of high-mobility group box 1 induced by renal IR. Consistently, CA treatment reduced renal IR-induced plasma alanine transaminase, hepatocellular injury and neutrophil infiltration, and inflammatory cytokine expression. CA treatment also decreased small intestinal cell death, neutrophil infiltration and inflammatory cytokine expression induced by renal IR. Taken together, we conclude that MR antagonism by CA treatment protects against multiple organ failure in the liver and intestine after renal IR.
Comprehensive Analysis of Mitochondrial Dynamics Alterations in Heart Diseases
Authors: Morciano Giampaolo , Boncompagni Caterina , Ramaccini Daniela , Pedriali Gaia , Bouhamida Esmaa , Tremoli Elena , Giorgi Carlotta , Pinton Paolo
Published: February 2023

The most common alterations affecting mitochondria, and associated with cardiac pathological conditions, implicate a long list of defects. They include impairments of the mitochondrial electron transport chain activity, which is a crucial element for energy formation, and that determines the depletion of ATP generation and supply to metabolic switches, enhanced ROS generation, inflammation, as well as the dysregulation of the intracellular calcium homeostasis. All these signatures significantly concur in the impairment of cardiac electrical characteristics, loss of myocyte contractility and cardiomyocyte damage found in cardiac diseases. Mitochondrial dynamics, one of the quality control mechanisms at the basis of mitochondrial fitness, also result in being dysregulated, but the use of this knowledge for translational and therapeutic purposes is still in its infancy. In this review we tried to understand why this is, by summarizing methods, current opinions and molecular details underlying mitochondrial dynamics in cardiac diseases.
Disulfiram/Cu Kills and Sensitizes BRAF-Mutant Thyroid Cancer Cells to BRAF Kinase Inhibitor by ROS-Dependently Relieving Feedback Activation of MAPK/ERK and PI3K/AKT Pathways
Authors: Xie Jingyi , Liu Juan , Zhao Man , Li Xinru , Wang Yubo , Zhao Yuelei , Cao Hongxin , Ji Meiju , Chen Mingwei , Hou Peng
Published: February 2023

BRAFV600E, the most common genetic alteration, has become a major therapeutic target in thyroid cancer. Vemurafenib (PLX4032), a specific inhibitor of BRAFV600E kinase, exhibits antitumor activity in patients with BRAFV600E-mutated thyroid cancer. However, the clinical benefit of PLX4032 is often limited by short-term response and acquired resistance via heterogeneous feedback mechanisms. Disulfiram (DSF), an alcohol-aversion drug, shows potent antitumor efficacy in a copper (Cu)-dependent way. However, its antitumor activity in thyroid cancer and its effect on cellular response to BRAF kinase inhibitors remain unclear. Antitumor effects of DSF/Cu on BRAFV600E-mutated thyroid cancer cells and its effect on the response of these cells to BRAF kinase inhibitor PLX4032 were systematically assessed by a series of in vitro and in vivo functional experiments. The molecular mechanism underlying the sensitizing effect of DSF/Cu on PLX4032 was explored by Western blot and flow cytometry assays. DSF/Cu exhibited stronger inhibitory effects on the proliferation and colony formation of BRAFV600E-mutated thyroid cancer cells than DSF treatment alone. Further studies revealed that DSF/Cu killed thyroid cancer cells by ROS-dependent suppression of MAPK/ERK and PI3K/AKT signaling pathways. Our data also showed that DSF/Cu strikingly increased the response of BRAFV600E-mutated thyroid cancer cells to PLX4032. Mechanistically, DSF/Cu sensitizes BRAF-mutant thyroid cancer cells to PLX4032 by inhibiting HER3 and AKT in an ROS-dependent way and subsequently relieving feedback activation of MAPK/ERK and PI3K/AKT pathways. This study not only implies potential clinical use of DSF/Cu in cancer therapy but also provides a new therapeutic strategy for BRAFV600E-mutated thyroid cancers.
Development of a Propidium Monoazide-Based Viability Quantitative PCR Assay for Red Sea Bream Iridovirus Detection
Authors: Kim Kyung-Ho , Kang Gyoungsik , Woo Won-Sik , Sohn Min-Young , Son Ha-Jeong , Park Chan-Il
Published: February 2023

Red sea bream iridovirus (RSIV) is an important aquatic virus that causes high mortality in marine fish. RSIV infection mainly spreads through horizontal transmission via seawater, and its early detection could help prevent disease outbreaks. Although quantitative PCR (qPCR) is a sensitive and rapid method for detecting RSIV, it cannot differentiate between infectious and inactive viruses. Here, we aimed to develop a viability qPCR assay based on propidium monoazide (PMAxx), which is a photoactive dye that penetrates damaged viral particles and binds to viral DNA to prevent qPCR amplification, to distinguish between infectious and inactive viruses effectively. Our results demonstrated that PMAxx at 75 μM effectively inhibited the amplification of heat-inactivated RSIV in viability qPCR, allowing the discrimination of inactive and infectious RSIV. Furthermore, the PMAxx-based viability qPCR assay selectively detected the infectious RSIV in seawater more efficiently than the conventional qPCR and cell culture methods. The reported viability qPCR method will help prevent the overestimation of red sea bream iridoviral disease caused by RSIV. Furthermore, this non-invasive method will aid in establishing a disease prediction system and in epidemiological analysis using seawater.
Gene Structural Specificity and Expression of MADS-Box Gene Family in Camellia chekiangoleosa
Authors: Zhou Pengyan , Qu Yanshu , Wang Zhongwei , Huang Bin , Wen Qiang , Xin Yue , Ni Zhouxian , Xu Li’an
Published: February 2023

MADS-box genes encode transcription factors that affect plant growth and development. Camellia chekiangoleosa is an oil tree species with ornamental value, but there have been few molecular biological studies on the developmental regulation of this species. To explore their possible role in C. chekiangoleosa and lay a foundation for subsequent research, 89 MADS-box genes were identified across the whole genome of C. chekiangoleosa for the first time. These genes were present on all the chromosomes and were found to have expanded by tandem duplication and fragment duplication. Based on the results of a phylogenetic analysis, the 89 MADS-box genes could be divided into either type I (38) or type II (51). Both the number and proportion of the type II genes were significantly greater than those of Camellia sinensis and Arabidopsis thaliana, indicating that C. chekiangoleosa type II genes experienced a higher duplication rate or a lower loss rate. The results of both a sequence alignment and a conserved motif analysis suggest that the type II genes are more conserved, meaning that they may have originated and differentiated earlier than the type I genes did. At the same time, the presence of extra-long amino acid sequences may be an important feature of C. chekiangoleosa. Gene structure analysis revealed the number of introns of MADS-box genes: twenty-one type I genes had no introns, and 13 type I genes contained only 1~2 introns. The type II genes have far more introns and longer introns than the type I genes do. Some MIKCC genes have super large introns (≥15 kb), which are rare in other species. The super large introns of these MIKCC genes may indicate richer gene expression. Moreover, the results of a qPCR expression analysis of the roots, flowers, leaves and seeds of C. chekiangoleosa showed that the MADS-box genes were expressed in all those tissues. Overall, compared with that of the type I genes, the expression of the type II genes was significantly higher. The CchMADS31 and CchMADS58 genes (type II) were highly expressed specifically in the flowers, which may in turn regulate the size of the flower meristem and petals. CchMADS55 was expressed specifically in the seeds, which might affect seed development. This study provides additional information for the functional characterization of the MADS-box gene family and lays an important foundation for in-depth study of related genes, such as those involved in the development of the reproductive organs of C. chekiangoleosa.
Effect of Some Plant-Based Substances on Microbial Content and Sperm Quality Parameters of Bull Semen
Authors: Cojkic Aleksandar , Hansson Ingrid , Johannisson Anders , Morrell Jane M.
Published: February 2023

The rapid emergence of antibacterial resistance requires alternatives to antibiotics to be found, including for semen preservation. One of the possible alternatives would be to use plant-based substances with known antimicrobial effects. The objective of this study was to test the antimicrobial effect of pomegranate powder, ginger, and curcumin extract in two concentrations on bull semen microbiota after exposure for <2 h and 24 h. An additional aim was to evaluate the effect of these substances on sperm quality parameters. The bacterial count in semen was low from the beginning; however, a reduction was present for all tested substances compared with control. A reduction in bacterial count in control samples was also observed with time. Curcumin at a concentration of 5%, reduced bacterial count by 32% and was the only substance that had a slight positive effect on sperm kinematics. The other substances were associated with a decline in sperm kinematics and viability. Neither concentration of curcumin had a deleterious effect on sperm viability parameters measured by flow cytometry. The results of this study indicate that curcumin extract at a concentration of 5% can reduce the bacterial count and does not have a negative influence on bull sperm quality.
Tumor Mutational Burden for Predicting Prognosis and Therapy Outcome of Hepatocellular Carcinoma
Authors: Gabbia Daniela , De Martin Sara
Published: February 2023

Hepatocellular carcinoma (HCC), the primary hepatic malignancy, represents the second-highest cause of cancer-related death worldwide. Many efforts have been devoted to finding novel biomarkers for predicting both patients’ survival and the outcome of pharmacological treatments, with a particular focus on immunotherapy. In this regard, recent studies have focused on unravelling the role of tumor mutational burden (TMB), i.e., the total number of mutations per coding area of a tumor genome, to ascertain whether it can be considered a reliable biomarker to be used either for the stratification of HCC patients in subgroups with different responsiveness to immunotherapy, or for the prediction of disease progression, particularly in relation to the different HCC etiologies. In this review, we summarize the recent advances on the study of TMB and TMB-related biomarkers in the HCC landscape, focusing on their feasibility as guides for therapy decisions and/or predictors of clinical outcome.