bluuebunny/crossref_metadata_2025 huggingface dataset:
Point of Sale Advertising and Promotion of Cigarettes, Electronic Cigarettes, and Heated Tobacco Products in Warsaw, Poland—A Pilot Study
Authors: Koczkodaj Paweł , Cuchi Paloma , Ciuba Agata , Gliwska Elwira , Peruga Armando
Published: December 2021

Prevalence of smoking and e-cigarette use among teenagers in Poland is high. Polish law bans most advertising and promotion for cigarettes, e-cigarettes, and heated tobacco products (HTPs). This study investigates marketing for these products at points of sale (POS) near secondary schools in Warsaw, Poland, noting if the advertising and promotion were allowed under current Polish laws. All POS within 250 m radii of five selected secondary schools in each of three Warsaw districts were assessed for tobacco and e-cigarette direct advertising, inside and outside; offers of gifts or promotional discounts; tobacco merchandising, and tobacco displays. Of the 112 POS surveyed, 83% exposed customers to some form of advertising or promotion of cigarettes, e-cigarettes, or HTPs; in 76%, advertising or promotion that violated Polish law was present. More than 80% of POS surveyed displayed tobacco products; in 19%, these products were displayed near products of interest to minors. POS density observed here was 30.3 per km2, higher than in other European cities. In Poland, a high proportion of POS near schools violates the law banning the advertisement and promotion of tobacco and nicotine consumer products through a dense tobacco retailer network.
How Does Gender Moderate Customer Intention of Shopping via Live-Streaming Apps during the COVID-19 Pandemic Lockdown Period?
Authors: Zhao Yuyang , Bacao Fernando
Published: December 2021

Shopping through Live-Streaming Shopping Apps (LSSAs) as an emerging consumption phenomenon has increased dramatically in recent years, especially during the COVID-19 lockdown period. However, insufficient studies have focused on the psychological processes undergone in different customer demographics while shopping via LSSAs under pandemic conditions. This study integrated the Unified Theory of Acceptance and Use of Technology 2 with Flow Theory into a Stimulus-Organism-Response framework to investigate the psychological processes of different customer demographics during the COVID-19 lockdown period. A total of 374 validated data were analyzed by covariance-based structural equation modelling. The statistical results demonstrated by the proposed model showed a significant discrepancy between different gender groups, in which Flow, as a mediator, representing users’ engagement and immersion in shopping via LSSAs, was significantly moderated by gender where connection between stimulus components, hedonic motivation, trust and social influence and response component perceived value are concerned. This study contributed a theoretical development and a practical framework to the explanation of the mental processes of different customer demographics when using an innovative e-commerce technology. Furthermore, the results can support the relevant stakeholders in e-commerce in their comprehensive understanding of customers’ behavior, allowing better strategical and managerial development.
Does Schoolmate and Teacher Support Buffer against the Effect of Adverse Childhood Experiences on Emotional and Behavioural Problems?
Authors: Lackova Rebicova Miriama , Dankulincova Veselska Zuzana , Husarova Daniela , Madarasova Geckova Andrea , Jansen Danielle E. M. C. , van Dijk Jitse P. , Reijneveld Sijmen A.
Published: December 2021

This study aims to explore the associations of schoolmate and teacher support with emotional and behavioural problems (EBP) and whether schoolmate and teacher support affects the associations of adverse childhood experiences (ACE) and of EBP in adolescence. We obtained data from 5220 students aged from 11 to 15 (48.7% boys), who participated in the Health Behaviour in a School-aged Children study (2018, Slovakia). Using logistic regression adjusted for gender, age and family affluence we assessed the modification of the relations of ACE and EBP by schoolmate and teacher support. Schoolmate and teacher support decreased the probability of EBP (Odds Ratios, 95% confidence intervals: 0.76, 0.74|0.79; and 0.86, 0.83|0.89, respectively). However, we found no statistically significant interactions of schoolmate and teacher support regarding the association of ACE with EBP. Schoolmate and teacher support decreased the likelihood of EBP among adolescents but do not buffer the relation of any previous ACE with EBP.
Effect of a UV-C Automatic Last-Generation Mobile Robotic System on Multi-Drug Resistant Pathogens
Authors: Russo Carla , Bartolini Desirée , Corbucci Cristina , Stabile Anna Maria , Rende Mario , Gioiello Antimo , Cruciani Gabriele , Mencacci Antonella , Galli Francesco , Pietrella Donatella
Published: December 2021

Background: Healthcare-associated infections caused by multi-drug resistant (MDR) pathogens are associated with increased mortality and morbidity among hospitalized patients. Inanimate surfaces, and in particular high-touch surfaces, have often been described as the source for outbreaks of nosocomial infections. The present work aimed to evaluate the efficacy of a last-generation mobile (robotic) irradiation UV-C light device R2S on MDR microorganisms in inanimate surfaces and its translation to hospital disinfection. Methods: The efficacy of R2S system was evaluated in environmental high-touch surfaces of two separate outpatient rooms of Perugia Hospital in Italy. The static UV-C irradiation effect was investigated on both the bacterial growth of S. aureus, MRSA, P. aeruginosa, and K. pneumoniae KPC and photoreactivation. The antimicrobial activity was also tested on different surfaces, including glass, steel, and plastic. Results: In the environmental tests, the R2S system decreased the number of bacteria, molds, and yeasts of each high-touch spot surface (HTSs) compared with manual sanitization. UV-C light irradiation significantly inhibits in vitro bacterial growth, also preventing photoreactivation. UV-C light bactericidal activity on MDR microorganisms is affected by the type of materials of inanimate surfaces. Conclusions: The last-generation mobile R2S system is a more reliable sanitizing procedure compared with its manual counterpart.
A Comparative Study of Two-Minute versus Three-Minute Passive Recovery on Sprint Skating Performance of Ice Hockey Forwards and Defensemen
Authors: Stanula Arkadiusz , Gupta Subir , Baron Jakub , Bieniec Anna , Tomik Rajmund , Gabrys Tomasz , Valach Petr , Swinarew Andrzej Szymon
Published: December 2021

The impact of two different passive recovery durations, two and three minutes, between sets of repeated sprint skating ability (RSSA) test on skating speed, speed decrement (Sdec), and heart rate (HR) response of ice hockey forwards (n = 12) and defensemen (n = 7) were determined. Six sets of 3 × 80 m sprint, with two-minute passive recovery between two consecutive sets, were performed in RSSA-2. A three-minute passive recovery period between two consecutive sets was allowed in RSSA-3. Skating speed, Sdec, and HR were measured in all tests. Subjects skated faster (p < 0.05) in most of the RSSA-3 sets than the corresponding set of RSSA-2. Defensemen were slower (p < 0.05) than forwards in most of the cases. The Sdec was higher in defensemen than in forwards, although the difference was significant occasionally. No difference in peak HR and minimum HR between forwards and defensemen was found. RSSA-3 is beneficial over RSSA-2 in both forwards and defensemen by increasing speed. Defensemen are slower and show early fatigability than forwards, and no difference in HR response was noted between forwards and defensemen. This study concludes that three-minute recovery is beneficial over two-minute recovery by increasing skating speed, although Sdec and HR response neither vary significantly between RSSA-2 and RSSA-3, nor between forwards and defensemen.
Effect of Spousal Loss on Depression in Older Adults: Impacts of Time Passing, Living Arrangement, and Spouse’s Health Status before Death
Authors: Hung Yu-Chan , Chen Yong-Hsin , Lee Meng-Chih , Yeh Chih-Jung
Published: December 2021

In addition to increasing the mortality among older adults, spousal death (SD) increases their risk of depression. This study explored the factors affecting depression among widowed older adults to provide health care strategies for successful aging. A total of 710 adults older than 60 years completed a questionnaire before and after their spouses’ deaths. The survey data included age, sex, ethnic group, education level, financial station socioeconomic status, SD (including time point), smoking status, alcohol consumption, self-rated health status, Center for Epidemiologic Studies Depression Scale score, mobility, and degree of support from relatives and friends. The proportion of participants with depression after SD was 1.7 times that of before SD (p < 0.0001). Worsened mobility (odds ratio [OR] = 1.3, p < 0.01), low self-rated health status (OR = 0.5, p < 0.01), and a high degree of support from relatives and friends (OR = 1.5, p < 0.01) had a significant positive correlation with depression after SD. The proportion of depression that occurred within 6 months after SD was 6.0 times higher than that of depression before SD. Participants who lived alone after losing their spouses who were healthy before their deaths exhibited a significantly increased proportion of depression after their spouses’ deaths. Male sex, spouse’s health, and the period of 6 months after SD are risk factors for depression in older adults. The maintenance of mobility, positive self-rated health status, and a shorter period of depression after a spouse’s death result in more favorable adaptability among women. Social workers or family members should focus on older adults whose spouses died unexpectedly or within the last 6 months. Living with family members after SD can alleviate depression in older adults.
The Relationship between Social Norms, Avoidance, Future Orientation, and Willingness to Engage in Climate Change Advocacy Communications
Authors: Latkin Carl , Dayton Lauren , Coyle Catelyn , Yi Grace , Lee Da-In , Winiker Abigail
Published: December 2021

This study examined factors associated with willingness to engage in communication behaviors related to climate change advocacy. Data were collected as part of an online, longitudinal US study beginning in March 2020. Outcomes included willingness to post materials online, contact state legislators, and talk with peers about climate change. Covariates included climate change-related social norms, avoidance of climate change information, and perceptions of the future impact of climate change. A minority of the 586 respondents (23%) reported regular conversations about climate change, while approximately half of the respondents reported willingness to discuss climate change with peers (58%), post materials online (47%), and contact state legislators (46%). Strong predictors of willingness to engage in each climate change communications behaviors included climate change social norms, not avoiding climate change information, and believing that climate change will have a negative impact on the future. Findings indicate the importance of designing programs to foster increased climate change communications in order to promote community-level climate change advocacy norms.
Charity Misconduct on Public Health Issues Impairs Willingness to Offer Help
Authors: Yin Lijun , Mao Ruzhen , Ke Zijun
Published: December 2021

Charity organizations positively impact our societies but charity misconduct impairs people’s willingness to contribute to charity and functional health systems on public health issues. This study investigates the impact of charity misconduct on people’s willingness to offer help on public health issues and possible ways of reducing the negative impact brought by charity misconduct news through four studies (Ntotal = 1269). Results showed that charity misconduct on public health issues significantly reduced individuals’ willingness to offer help via both the charity involved with the misconduct and any charity they prefer (Study 1 and 2). Furthermore, news on charity misconduct reduced people’s general willingness to help in contexts that did not involve charity (Study 3). Finally, presenting charity nonmisconduct news after charity misconduct news increases individuals’ willingness to offer help via the nonmisconduct charity (Study 4), suggesting a potential way to nudge people to provide help in the fight against the negative impact brought by charity misconduct news. The findings show the backfire of reporting charity misconduct news and have important implications for potential ways to facilitate people to offer help.
Metabolic Syndrome and Endocrine Disrupting Chemicals: An Overview of Exposure and Health Effects
Authors: Haverinen Elsi , Fernandez Mariana F. , Mustieles Vicente , Tolonen Hanna
Published: December 2021

Increasing prevalence of metabolic syndrome (MetS) is causing a significant health burden among the European population. Current knowledge supports the notion that endocrine-disrupting chemicals (EDCs) interfere with human metabolism and hormonal balance, contributing to the conventionally recognized lifestyle-related MetS risk factors. This review aims to identify epidemiological studies focusing on the association between MetS or its individual components (e.g., obesity, insulin resistance, diabetes, dyslipidemia and hypertension) and eight HBM4EU priority substances (bisphenol A (BPA), per- and polyfluoroalkyl substances (PFASs), phthalates, polycyclic aromatic hydrocarbons (PAHs), pesticides and heavy metals (cadmium, arsenic and mercury)). Thus far, human biomonitoring (HBM) studies have presented evidence supporting the role of EDC exposures on the development of individual MetS components. The strength of the association varies between the components and EDCs. Current evidence on metabolic disturbances and EDCs is still limited and heterogeneous, and mainly represent studies from North America and Asia, highlighting the need for well-conducted and harmonized HBM programmes among the European population. Rigorous and ongoing HBM in combination with health monitoring can help to identify the most concerning EDC exposures, to guide future risk assessment and policy actions.
Impact of MiFID II on Romanian Stock Market Liquidity—Comparative Analysis with a Developed Stock Market
Authors: Miloș Marius Cristian , Miloș Laura Raisa , Barna Flavia , Boțoc Claudiu
Published: December 2021

In light of previous literature that has investigated the effects of MiFID and MiFID II regulation on stock market liquidity, we investigate whether the introduction of MiFID II in Romania has had any effect on the stock market liquidity. Through our empirical analysis, we were able to estimate a meaningful reduction of liquidity in the Romanian stock market liquidity, in response to MiFID II, in line with the previous empirical literature. We find that the liquidity of the BET index constituents has decreased in the period following MiFID II. We find contradictory results in what concerns the German stock market, which could be explained by the different level of development of the stock markets and of the financial education of investors.
Estimating the Photovoltaic Potential of Building Facades and Roofs Using the Industry Foundation Classes
Authors: Lu Xiu , Li Guannan , Wang Andong , Xiong Qingqin , Lin Bingxian , Lv Guonian
Published: December 2021

Photovoltaic energy generation has gained wide attention owing to its efficiency and environmental benefits. Therefore, it has become important to accurately evaluate the photovoltaic energy generation potential of building surfaces. As the number of building floors increases, the area of the facades becomes much larger than that of the roof, providing improved potential for photovoltaic equipment installation. Conventional urban solar potential evaluation methods are usually based on light detection and ranging (LiDAR). However, LiDAR can only be used in existing buildings, and the lack of semantic information in the point cloud data generated by LiDAR makes it impossible to evaluate the photovoltaic potential of facades (including details such as windows) in detail and with accuracy. In this study, we developed a method to accurately extract facades and roofs in order to evaluate photovoltaic potential based on the Industry Foundation Classes. To verify the feasibility of this approach, we used a building from Xuzhou city, Jiangsu province, China. The simulation results indicate that, out of the total building photovoltaic installable area (8995 m2), that of the facade is 8240 m2. The photovoltaic potential of the simulated building could reach 1054.69 MWh/year. The sensitivity studies of the grid resolution, the time interval and the computation time confirmed the reasonability of the determined conditions. The method proposed offers great potential for energy planning departments and the improved utilization of buildings.
Ribosome Fate during Decoding of UGA-Sec Codons
Authors: Copeland Paul R. , Howard Michael T.
Published: December 2021

Decoding of genetic information into polypeptides occurs during translation, generally following the codon assignment rules of the organism’s genetic code. However, recoding signals in certain mRNAs can overwrite the normal rules of translation. An exquisite example of this occurs during translation of selenoprotein mRNAs, wherein UGA codons are reassigned to encode for the 21st proteogenic amino acid, selenocysteine. In this review, we will examine what is known about the mechanisms of UGA recoding and discuss the fate of ribosomes that fail to incorporate selenocysteine.
Influence of Injection Application on the Sol–Gel Phase Transition Conditions of Polysaccharide-Based Hydrogels
Authors: Rył Anna , Owczarz Piotr
Published: December 2021

Polysaccharide matrices formed via thermoinduced sol–gel phase transition are promising systems used as drug carriers and minimally invasiveness scaffolds in tissue engineering. The strong shear field generated during injection may lead to changes in the conformation of polymer molecules and, consequently, affect the gelation conditions that have not been studied so far. Chitosan (CS) and hydroxypropyl cellulose (HPC) sols were injected through injection needles (14 G–25 G) or sheared directly in the rheometer measuring system. Then the sol–gel phase transition conditions were determined at 37 °C using rheometric, turbidimetric, and rheo-optical techniques. It was found that the use of low, respecting injection, shear rates accelerate the gelation, its increase extends the gelation time; applying the highest shear rates may significantly slow down (HPC) or accelerate gelation (CS) depending on thixotropic properties. From a practical point of view, the conducted research indicates that the use of thin needles without preliminary tests may lead to an extension of the gelation time and consequently the spilling of the polymeric carrier before gelation. Finally, an interpretation of the influence of an intensive shear field on the conformation of the molecules on a molecular scale was proposed.
Biological and Corrosion Evaluation of In Situ Alloyed NiTi Fabricated through Laser Powder Bed Fusion (LPBF)
Authors: Chmielewska Agnieszka , Dobkowska Anna , Kijeńska-Gawrońska Ewa , Jakubczak Michał , Krawczyńska Agnieszka , Choińska Emilia , Jastrzębska Agnieszka , Dean David , Wysocki Bartłomiej , Święszkowski Wojciech
Published: December 2021

In this work, NiTi alloy parts were fabricated using laser powder bed fusion (LBPF) from pre-alloyed NiTi powder and in situ alloyed pure Ni and Ti powders. Comparative research on the corrosive and biological properties of both studied materials was performed. Electrochemical corrosion tests were carried out in phosphate buffered saline at 37 °C, and the degradation rate of the materials was described based on Ni ion release measurements. Cytotoxicity, bacterial growth, and adhesion to the surface of the fabricated coupons were evaluated using L929 cells and spherical Escherichia coli (E. coli) bacteria, respectively. The in situ alloyed NiTi parts exhibit slightly lower corrosion resistance in phosphate buffered saline solution than pre-alloyed NiTi. Moreover, the passive layer formed on in situ alloyed NiTi is weaker than the one formed on the NiTi fabricated from pre-alloyed NiTi powder. Furthermore, in situ alloyed NiTi and NiTi made from pre-alloyed powders have comparable cytotoxicity and biological properties. Overall, the research has shown that nitinol sintered using in situ alloyed pure Ni and Ti is potentially useful for biomedical applications.
Transcriptomic Crosstalk between Gliomas and Telencephalic Neural Stem and Progenitor Cells for Defining Heterogeneity and Targeted Signaling Pathways
Authors: Deleanu Roxana , Ceafalan Laura Cristina , Dricu Anica
Published: December 2021

Recent studies have begun to reveal surprising levels of cell diversity in the human brain, both in adults and during development. Distinctive cellular phenotypes point to complex molecular profiles, cellular hierarchies and signaling pathways in neural stem cells, progenitor cells, neuronal and glial cells. Several recent reports have suggested that neural stem and progenitor cell types found in the developing and adult brain share several properties and phenotypes with cells from brain primary tumors, such as gliomas. This transcriptomic crosstalk may help us to better understand the cell hierarchies and signaling pathways in both gliomas and the normal brain, and, by clarifying the phenotypes of cells at the origin of the tumor, to therapeutically address their most relevant signaling pathways.
Systems Biology Approaches to Decipher the Underlying Molecular Mechanisms of Glioblastoma Multiforme
Authors: Kaynar Ali , Altay Ozlem , Li Xiangyu , Zhang Cheng , Turkez Hasan , Uhlén Mathias , Shoaie Saeed , Mardinoglu Adil
Published: December 2021

Glioblastoma multiforme (GBM) is one of the most malignant central nervous system tumors, showing a poor prognosis and low survival rate. Therefore, deciphering the underlying molecular mechanisms involved in the progression of the GBM and identifying the key driver genes responsible for the disease progression is crucial for discovering potential diagnostic markers and therapeutic targets. In this context, access to various biological data, development of new methodologies, and generation of biological networks for the integration of multi-omics data are necessary for gaining insights into the appearance and progression of GBM. Systems biology approaches have become indispensable in analyzing heterogeneous high-throughput omics data, extracting essential information, and generating new hypotheses from biomedical data. This review provides current knowledge regarding GBM and discusses the multi-omics data and recent systems analysis in GBM to identify key biological functions and genes. This knowledge can be used to develop efficient diagnostic and treatment strategies and can also be used to achieve personalized medicine for GBM.
A Conserved Allosteric Site on Drug-Metabolizing CYPs: A Systematic Computational Assessment
Authors: Fischer André , Smieško Martin
Published: December 2021

Cytochrome P450 enzymes (CYPs) are the largest group of enzymes involved in human drug metabolism. Ligand tunnels connect their active site buried at the core of the membrane-anchored protein to the surrounding solvent environment. Recently, evidence of a superficial allosteric site, here denoted as hotspot 1 (H1), involved in the regulation of ligand access in a soluble prokaryotic CYP emerged. Here, we applied multi-scale computational modeling techniques to study the conservation and functionality of this allosteric site in the nine most relevant mammalian CYPs responsible for approximately 70% of drug metabolism. In total, we systematically analyzed over 44 μs of trajectories from conventional MD, cosolvent MD, and metadynamics simulations. Our bioinformatic analysis and simulations with organic probe molecules revealed the site to be well conserved in the CYP2 family with the exception of CYP2E1. In the presence of a ligand bound to the H1 site, we could observe an enlargement of a ligand tunnel in several members of the CYP2 family. Further, we could detect the facilitation of ligand translocation by H1 interactions with statistical significance in CYP2C8 and CYP2D6, even though all other enzymes except for CYP2C19, CYP2E1, and CYP3A4 presented a similar trend. As the detailed comprehension of ligand access and egress phenomena remains one of the most relevant challenges in the field, this work contributes to its elucidation and ultimately helps in estimating the selectivity of metabolic transformations using computational techniques.
Profiling Glioblastoma Cases with an Expression of DCX, OLIG2 and NES
Authors: Odrzywolski Adrian , Jarosz Bożena , Kiełbus Michał , Telejko Ilona , Ziemianek Dominik , Knaga Sebastian , Rola Radosław
Published: December 2021

Glioblastoma (GBM) remains the leading cause of cancer-related deaths with the lowest five-year survival rates among all of the human cancers. Multiple factors contribute to its poor outcome, including intratumor heterogeneity, along with migratory and invasive capacities of tumour cells. Over the last several years Doublecortin (DCX) has been one of the debatable factors influencing GBM cells’ migration. To resolve DCX’s ambiguous role in GBM cells’ migration, we set to analyse the expression patterns of DCX along with Nestin (NES) and Oligodendrocyte lineage transcription factor 2 (OLIG2) in 17 cases of GBM, using immunohistochemistry, followed by an analysis of single-cell RNA-seq data. Our results showed that only a small subset of DCX positive (DCX+) cells was present in the tumour. Moreover, no particular pattern emerged when analysing DCX+ cells relative position to the tumour margin. By looking into single-cell RNA-seq data, the majority of DCX+ cells were classified as non-cancerous, with a small subset of cells that could be regarded as glioma stem cells. In conclusion, our findings support the notion that glioma cells express DCX; however, there is no clear evidence to prove that DCX participates in GBM cell migration.
The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease
Authors: Filipovic Branka , Lukic Snezana , Mijac Dragana , Marjanovic-Haljilji Marija , Vojnovic Marko , Bogdanovic Jelena , Glisic Tijana , Filipovic Natasa , Al Kiswani Jamal , Djokovic Aleksandra , Kapor Suncica , Kapor Slobodan , Bukumiric Zoran , Starcevic Ana
Published: December 2021

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut microbiota, and interaction between the brain-liver-axis and the regulation of hepatic lipid metabolism. The new therapeutic approaches in the treatment of NAFLD are targeting some of these milestones along the pathophysiological pathway and include drugs like agonists of peroxisome proliferator-activated receptors (PPARs), glucagon-like peptide-1 (GLP-1) agonists, sodium/glucose transport protein 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists, probiotics, and symbiotics. Further efforts in biomedical sciences should focus on the investigation of the relationship between the microbiome, liver metabolism, and response to inflammation, systemic consequences of metabolic syndrome.
Novel Strategy of Proxalutamide for the Treatment of Prostate Cancer through Coordinated Blockade of Lipogenesis and Androgen Receptor Axis
Authors: Gu Yue , Xue Mengxia , Wang Qizhi , Hong Xiaodan , Wang Xinyu , Zhou Fang , Sun Jianguo , Wang Guangji , Peng Ying
Published: December 2021

Objective: Prostate cancer (PCa) is the most common malignant tumor diagnosed in men in developed countries. In developing countries, the PCa morbidity and mortality rates are also increasing rapidly. Since androgen receptor (AR) is a key driver and plays a critical role in the regulation of PCa development, AR-targeted agents provide a key component of current therapy regimens. However, even new-generation AR antagonists are prone to drug resistance, and there is currently no effective strategy for overcoming advanced PCa aggressiveness, including drug-resistance progression. The aim of this study was to evaluate the potential efficacy and novel therapy strategy of proxalutamide (a newly developed AR antagonist) in PCa. Methods: Four PCa cell lines with various biological heterogeneities were utilized in this study, namely, androgen-sensitive/-insensitive with/without AR expression. Proliferation, migration and apoptosis assays in PCa cells were used to evaluate the effective therapeutic activity of proxalutamide. The changes in lipid droplet accumulation and lipidomic profiles were analyzed to determine the influence of proxalutamide on lipogenesis in PCa cells. The molecular basis of the effects of proxalutamide on lipogenesis and the AR axis was then further investigated. Results: Proxalutamide significantly inhibited the proliferation and migration of PCa cells, and its inhibitory effect was superior to that of enzalutamide (Enz, second-generation AR antagonist). Proxalutamide induced the caspase-dependent apoptosis of PCa cells. Proxalutamide significantly diminished the level of lipid droplets in PCa cells, changed the lipid profile of PCa cells and reduced the content of most lipids (especially triglycerides) in PCa cells. Proxalutamide attenuated de novo lipogenesis by inhibiting the expression of ATP citrate lyase (ACL), acetyl CoA carboxylase (ACC), fatty acid synthase (FASN) and sterol regulatory element-binding protein-1 (SREBP-1). Moreover, proxalutamide also decreased AR expression in PCa cells, and its inhibitory effect on lipogenesis did not depend on its ability to down-regulate AR expression. However, Enz had no effect on AR expression, lipid accumulation or lipid de novo synthesis in PCa cells. Conclusions: By co-targeting the AR axis and endogenous adipogenesis, a novel and promising strategy was established for proxalutamide to combat the progress of PCa. The unique effect of proxalutamide on the metabolic reprogramming of PCa provides a potential solution to overcome the resistance of current AR-targeted therapy, which will help to effectively prolong its clinical service life.
NLRP3 Inflammasome in Diabetic Cardiomyopathy and Exercise Intervention
Authors: Sun Yi , Ding Shuzhe
Published: December 2021

Diabetic cardiomyopathy (DCM), as a common complication of diabetes, is characterized by chronic low-grade inflammation. The NLRP3 inflammasome is a key sensor mediating innate immune and inflammatory responses. However, the mechanisms initiating and promoting NLRP3 inflammasome activation in DCM is largely unexplored. The aim of the present review is to describe the link between NLRP3 inflammasome and DCM, and to provide evidence highlighting the importance of exercise training in DCM intervention. Collectively, this evidence suggests that DCM is an inflammatory disease aggravated by NLRP3 inflammasome-mediated release of IL-1β and IL-18. In addition, chronic exercise intervention is an effective preventive and therapeutic method to alleviate DCM via modulating the NLRP3 inflammasome.
Organelle Comparative Genome Analysis Reveals Novel Alloplasmic Male Sterility with orf112 in Brassica oleracea L.
Authors: Chen Li , Ren Wenjing , Zhang Bin , Chen Wendi , Fang Zhiyuan , Yang Limei , Zhuang Mu , Lv Honghao , Wang Yong , Ji Jialei , Zhang Yangyong
Published: December 2021

B. oleracea Ogura CMS is an alloplasmic male-sterile line introduced from radish by interspecific hybridization and protoplast fusion. The introduction of alien cytoplasm resulted in many undesirable traits, which affected the yield of hybrids. Therefore, it is necessary to identify the composition and reduce the content of alien cytoplasm in B. oleracea Ogura CMS. In the present study, we sequenced, assembled, and compared the organelle genomes of Ogura CMS cabbage and its maintainer line. The chloroplast genome of Ogura-type cabbage was completely derived from normal-type cabbage, whereas the mitochondrial genome was recombined from normal-type cabbage and Ogura-type radish. Nine unique regions derived from radish were identified in the mitochondrial genome of Ogura-type cabbage, and the total length of these nine regions was 35,618 bp, accounting for 13.84% of the mitochondrial genome. Using 32 alloplasmic markers designed according to the sequences of these nine regions, one novel sterile source with less alien cytoplasm was discovered among 305 materials and named Bel CMS. The size of the alien cytoplasm in Bel CMS was 21,587 bp, accounting for 8.93% of its mtDNA, which was much less than that in Ogura CMS. Most importantly, the sterility gene orf138 was replaced by orf112, which had a 78-bp deletion, in Bel CMS. Interestingly, Bel CMS cabbage also maintained 100% sterility, although orf112 had 26 fewer amino acids than orf138. Field phenotypic observation showed that Bel CMS was an excellent sterile source with stable 100% sterility and no withered buds at the early flowering stage, which could replace Ogura CMS in cabbage heterosis utilization.
Live-Cell Imaging of Single Neurotrophin Receptor Molecules on Human Neurons in Alzheimer’s Disease
Authors: Barabás Klaudia , Kobolák Julianna , Godó Soma , Kovács Tamás , Ernszt Dávid , Kecskés Miklós , Varga Csaba , Jánosi Tibor Z. , Fujiwara Takahiro , Kusumi Akihiro , Téglási Annamária , Dinnyés András , Ábrahám István M.
Published: December 2021

Neurotrophin receptors such as the tropomyosin receptor kinase A receptor (TrkA) and the low-affinity binding p75 neurotrophin receptor p75NTR play a critical role in neuronal survival and their functions are altered in Alzheimer’s disease (AD). Changes in the dynamics of receptors on the plasma membrane are essential to receptor function. However, whether receptor dynamics are affected in different pathophysiological conditions is unexplored. Using live-cell single-molecule imaging, we examined the surface trafficking of TrkA and p75NTR molecules on live neurons that were derived from human-induced pluripotent stem cells (hiPSCs) of presenilin 1 (PSEN1) mutant familial AD (fAD) patients and non-demented control subjects. Our results show that the surface movement of TrkA and p75NTR and the activation of TrkA- and p75NTR-related phosphoinositide-3-kinase (PI3K)/serine/threonine-protein kinase (AKT) signaling pathways are altered in neurons that are derived from patients suffering from fAD compared to controls. These results provide evidence for altered surface movement of receptors in AD and highlight the importance of investigating receptor dynamics in disease conditions. Uncovering these mechanisms might enable novel therapies for AD.
Insecticidal Triterpenes in Meliaceae: Plant Species, Molecules and Activities: Part Ⅰ (Aphanamixis-Chukrasia)
Authors: Lin Meihong , Yang Sifan , Huang Jiguang , Zhou Lijuan
Published: December 2021

Plant-originated triterpenes are important insecticidal molecules. The research on insecticidal activity of molecules from Meliaceae plants has always received attention due to the molecules from this family showing a variety of insecticidal activities with diverse mechanisms of action. In this paper, we discuss 102 triterpenoid molecules with insecticidal activity of plants of eight genera (Aglaia, Aphanamixis, Azadirachta, Cabralea, Carapa, Cedrela, Chisocheton, and Chukrasia) in Meliaceae. In total, 19 insecticidal plant species are presented. Among these species, Azadirachta indica A. Juss is the most well-known insecticidal plant and azadirachtin is the active molecule most widely recognized and highly effective botanical insecticide. However, it is noteworthy that six species from Cedrela were reported to show insecticidal activity and deserve future study. In this paper, a total of 102 insecticidal molecules are summarized, including 96 nortriterpenes, 4 tetracyclic triterpenes, and 2 pentacyclic triterpenes. Results showed antifeedant activity, growth inhibition activity, poisonous activity, or other activities. Among them, 43 molecules from 15 plant species showed antifeedant activity against 16 insect species, 49 molecules from 14 plant species exhibited poisonous activity on 10 insect species, and 19 molecules from 11 plant species possessed growth regulatory activity on 12 insect species. Among these molecules, azadirachtins were found to be the most successful botanical insecticides. Still, other molecules possessed more than one type of obvious activity, including 7-deacetylgedunin, salannin, gedunin, azadirone, salannol, azadiradione, and methyl angolensate. Most of these molecules are only in the primary stage of study activity; their mechanism of action and structure–activity relationship warrant further study.
Identification of an ATP-Binding Cassette Transporter Implicated in Aluminum Tolerance in Wild Soybean (Glycine soja)
Authors: Wen Ke , Pan Huanting , Li Xingang , Huang Rong , Ma Qibin , Nian Hai
Published: December 2021

The toxicity of aluminum (Al) in acidic soil limits global crop yield. The ATP-binding cassette (ABC) transporter-like gene superfamily has functions and structures related to transportation, so it responds to aluminum stress in plants. In this study, one half-size ABC transporter gene was isolated from wild soybeans (Glycine soja) and designated GsABCI1. By real-time qPCR, GsABCI1 was identified as not specifically expressed in tissues. Phenotype identification of the overexpressed transgenic lines showed increased tolerance to aluminum. Furthermore, GsABCI1 transgenic plants exhibited some resistance to aluminum treatment by ion translocation or changing root components. This work on the GsABCI1 identified the molecular function, which provided useful information for understanding the gene function of the ABC family and the development of new aluminum-tolerant soybean germplasm.
Nano-Sized Extracellular Matrix Particles Lead to Therapeutic Improvement for Cutaneous Wound and Hindlimb Ischemia
Authors: Ha Sang Su , Kim Jung-Hyun , Savitri Cininta , Choi Donghoon , Park Kwideok
Published: December 2021

Cell-derived matrix (CDM) has proven its therapeutic potential and been utilized as a promising resource in tissue regeneration. In this study, we prepared a human fibroblast-derived matrix (FDM) by decellularization of in vitro cultured cells and transformed the FDM into a nano-sized suspended formulation (sFDM) using ultrasonication. The sFDM was then homogeneously mixed with Pluronic F127 and hyaluronic acid (HA), to effectively administer sFDM into target sites. Both sFDM and sFDM containing hydrogel (PH/sFDM) were characterized via immunofluorescence, sol–gel transition, rheological analysis, and biochemical factors array. We found that PH/sFDM hydrogel has biocompatible, mechanically stable, injectable properties and can be easily administered into the external and internal target regions. sFDM itself holds diverse bioactive molecules. Interestingly, sFDM-containing serum-free media helped maintain the metabolic activity of endothelial cells significantly better than those in serum-free condition. PH/sFDM also promoted vascular endothelial growth factor (VEGF) secretion from monocytes in vitro. Moreover, when we evaluated therapeutic effects of PH/sFDM via the murine full-thickness skin wound model, regenerative potential of PH/sFDM was supported by epidermal thickness, significantly more neovessel formation, and enhanced mature collagen deposition. The hindlimb ischemia model also found some therapeutic improvements, as assessed by accelerated blood reperfusion and substantially diminished necrosis and fibrosis in the gastrocnemius and tibialis muscles. Together, based on sFDM holding a strong therapeutic potential, our engineered hydrogel (PH/sFDM) should be a promising candidate in tissue engineering and regenerative medicine.
Proteomic Studies of Blood and Vascular Wall in Atherosclerosis
Authors: Stakhneva Ekaterina Mikhailovna , Striukova Evgeniia Vitalievna , Ragino Yulia Igorevna
Published: December 2021

The review is devoted to the analysis of literature data related to the role of proteomic studies in the study of atherosclerotic cardiovascular diseases. Diagnosis of patients with atherosclerotic plaques before clinical manifestations is an arduous task. The review presents the results of research on the new proteomic potential biomarkers of coronary heart disease, coronary atherosclerosis, acute coronary syndrome, myocardial infarction, carotid artery atherosclerosis. Also, the analysis of literature data on proteomic studies of the vascular wall was carried out. To assess the involvement of proteins in the pathological process of atherosclerosis, it is important to investigate the specific relationships between proteins in the arteries, expression and concentration of proteins. The development of proteomic technologies has made it possible to analyse the number of proteins associated with the development of the disease. Analysis of the proteomic profile of the vascular wall in atherosclerosis can help to detect possible diagnostically significant protein structures or potential biomarkers of the disease and develop novel approaches to the diagnosis of atherosclerosis and its complications.
Depth of the Steroid Core Location Determines the Mode of Na,K-ATPase Inhibition by Cardiotonic Steroids
Authors: Tverskoi Artem M. , Poluektov Yuri M. , Klimanova Elizaveta A. , Mitkevich Vladimir A. , Makarov Alexander A. , Orlov Sergei N. , Petrushanko Irina Yu. , Lopina Olga D.
Published: December 2021

Cardiotonic steroids (CTSs) are specific inhibitors of Na,K-ATPase (NKA). They induce diverse physiological effects and were investigated as potential drugs in heart diseases, hypertension, neuroinflammation, antiviral and cancer therapy. Here, we compared the inhibition mode and binding of CTSs, such as ouabain, digoxin and marinobufagenin to NKA from pig and rat kidneys, containing CTSs-sensitive (α1S) and -resistant (α1R) α1-subunit, respectively. Marinobufagenin in contrast to ouabain and digoxin interacted with α1S-NKA reversibly, and its binding constant was reduced due to the decrease in the deepening in the CTSs-binding site and a lower number of contacts between the site and the inhibitor. The formation of a hydrogen bond between Arg111 and Asp122 in α1R-NKA induced the reduction in CTSs’ steroid core deepening that led to the reversible inhibition of α1R-NKA by ouabain and digoxin and the absence of marinobufagenin’s effect on α1R-NKA activity. Our results elucidate that the difference in signaling, and cytotoxic effects of CTSs may be due to the distinction in the deepening of CTSs into the binding side that, in turn, is a result of a bent-in inhibitor steroid core (marinobufagenin in α1S-NKA) or the change of the width of CTSs-binding cavity (all CTSs in α1R-NKA).
Injectable Human Hair Keratin–Fibrinogen Hydrogels for Engineering 3D Microenvironments to Accelerate Oral Tissue Regeneration
Authors: Kang Hyeon Jeong , Ko Nare , Oh Seung Jun , An Seong Yeong , Hwang Yu-Shik , Kim So Yeon
Published: December 2021

Traumatic injury of the oral cavity is atypical and often accompanied by uncontrolled bleeding and inflammation. Injectable hydrogels have been considered to be promising candidates for the treatment of oral injuries because of their simple formulation, minimally invasive application technique, and site-specific delivery. Fibrinogen-based hydrogels have been widely explored as effective materials for wound healing in tissue engineering due to their uniqueness. Recently, an injectable foam has taken the spotlight. However, the fibrin component of this biomaterial is relatively stiff. To address these challenges, we created keratin-conjugated fibrinogen (KRT-FIB). This study aimed to develop a novel keratin biomaterial and assess cell–biomaterial interactions. Consequently, a novel injectable KRT-FIB hydrogel was optimized through rheological measurements, and its injection performance, swelling behavior, and surface morphology were investigated. We observed an excellent cell viability, proliferation, and migration/cell–cell interaction, indicating that the novel KRT-FIB-injectable hydrogel is a promising platform for oral tissue regeneration with a high clinical applicability.
Sequestosome 1 Is Part of the Interaction Network of VAPB
Authors: James Christina , Lenz Christof , Urlaub Henning , Kehlenbach Ralph H.
Published: December 2021

VAPB (Vesicle-Associated-membrane Protein-associated protein B) is a tail-anchored membrane protein of the endoplasmic reticulum that can also be detected at the inner nuclear membrane. As a component of many contact sites between the endoplasmic reticulum and other organelles, VAPB is engaged in multiple protein interactions with a plethora of binding partners. A mutant version of VAPB, P56S-VAPB, which results from a single point mutation, is involved in a familial form of amyotrophic lateral sclerosis (ALS8). We performed RAPIDS (rapamycin- and APEX-dependent identification of proteins by SILAC) to identify proteins that interact with or are in close proximity to P56S-VAPB. The mutation abrogates the interaction of VAPB with many known binding partners. Here, we identify Sequestosome 1 (SQSTM1), a well-known autophagic adapter protein, as a major interaction/proximity partner of P56S-VAPB. Remarkably, not only the mutant protein, but also wild-type VAPB interacts with SQSTM1, as shown by proximity ligation assays and co-immunoprecipiation experiments.
Immune Signaling Kinases in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD)
Authors: García-García Raquel , Martín-Herrero Laura , Blanca-Pariente Laura , Pérez-Cabello Jesús , Roodveldt Cintia
Published: December 2021

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disorder of motor neurons in adults, with a median survival of 3–5 years after appearance of symptoms, and with no curative treatment currently available. Frontotemporal dementia (FTD) is also an adult-onset neurodegenerative disease, displaying not only clinical overlap with ALS, but also significant similarities at genetic and pathologic levels. Apart from the progressive loss of neurons and the accumulation of protein inclusions in certain cells and tissues, both disorders are characterized by chronic inflammation mediated by activated microglia and astrocytes, with an early and critical impact of neurodegeneration along the disease course. Despite the progress made in the last two decades in our knowledge around these disorders, the underlying molecular mechanisms of such non-cell autonomous neuronal loss still need to be clarified. In particular, immune signaling kinases are currently thought to have a key role in determining the neuroprotective or neurodegenerative nature of the central and peripheral immune states in health and disease. This review provides a comprehensive and updated view of the proposed mechanisms, therapeutic potential, and ongoing clinical trials of immune-related kinases that have been linked to ALS and/or FTD, by covering the more established TBK1, RIPK1/3, RACK I, and EPHA4 kinases, as well as other emerging players in ALS and FTD immune signaling.