bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Maternal Blood Glucose Levels during Pregnancy and Birth Outcomes: A Birth Cohort Study
Authors: Zhao Doudou , Liu Danmeng , Shi Wenhao , Shan Li , Yue Wentao , Qu Pengfei , Yin Chenghong , Mi Yang
Published: January 2023

Objective: This study aimed to investigate the relationship between maternal blood glucose levels during pregnancy and neonatal birth outcomes in Northwest China. Methods: This population-based cohort study included 10,010 first-trimester pregnant women who joined the birth cohort of the Northwest Women’s and Children’s Hospital from July 2018 to July 2020. Basic demographic characteristics, lifestyle and behavior patterns were collected. Oral glucose tolerance test (OGTT) results during the second trimester and pregnancy outcomes after childbirth were also collected. A generalized linear model was constructed to analyze the effects of blood glucose levels on neonatal birth outcomes. Results: We found that every 1 mmol/L increase in fasting plasma glucose (FPG) was associated with an increase in birth weight (β = 100.22 g, 95% confidence interval (95%CI): 81.91, 118.52), birth weight Z score (β = 0.23, 95%CI: 0.19, 0.27) and birth weight Z centile (β = 6.72%, 95%CI: 5.51, 7.94). Moreover, the risk of macrosomia, premature birth and being born large for gestational age (LGA) increased by 2.01 (95%CI: 1.67, 2.43), 1.35 (95%CI: 1.09, 1.66) and 1.80 (95%CI: 1.57, 2.07) times, respectively. Additionally, for every 1 mmol/L increase in FPG associated with a decrease in gestational age (β = −0.12 weeks, 95%CI: −0.19, −0.06), the risk of SGA decreased by 0.70 (OR = 0.70, 95%CI: 0.55, 0.89) times. Every 1 mmol/L increase in 1/2-h PG had similar outcomes as FPG, besides premature birth and SGA. Conclusions: Higher blood glucose in pregnant women may increase neonatal birth weight, decrease gestational age and lead to a higher risk of macrosomia, premature birth and LGA. Mothers should actively prevent and control hyperglycemia to promote maternal and infant health.
A Cross-Sectional Survey of Different Types of School Bullying before and during COVID-19 in Shantou City, China
Authors: Xie Linlin , Da Qingchen , Huang Jingyu , Peng Zhekuan , Li Liping
Published: January 2023

Background: Since the end of 2019, the COVID-19 pandemic has had serious wide-ranging effects on academic, occupational and other daily activities. Like other types of institutions, schools are facing unprecedented challenges. Students may face a variety of adverse consequences, including sleep disturbances and school bullying, if they are unable to adjust to the current learning and living environment. This study explored the effects of the COVID-19 pandemic on school bullying. Methods: A total of 5782 middle school students were enrolled in this multi-stage, cross-sectional study (3071 before and 2711 during the pandemic). The pre-pandemic group had a mean age of 14.9 ± 1.73, the pandemic group of 14.75 ± 1.47. Three models were set up using binary logistic regression to adjust for confounding variables (gender, school type, alcohol consumption, smoking, playing violent video games). Results: All types of bullying victimization and perpetration (physical, verbal, social and property bullying) were more common during the pandemic than before the pandemic. In terms of bullying victimization, property bullying victimization (crude odds ratio [OR]: 2.398, 95% CI: 2.014–2.854, p < 0.001; model 2 adjusted OR: 2.344, 95% CI: 1.966–2.795, p < 0.001; model 3 adjusted OR: 2.818, 95% CI: 2.292–3.464, p < 0.001) increased the most. In terms of bullying perpetration, verbal bullying perpetration (crude OR: 3.007, 95% CI: 2.448–3.693, p <0.001; model 2 adjusted OR: 2.954, 95% CI: 2.399–3.637, p < 0.001; model 3 adjusted OR:3.345, 95% CI: 2.703–4.139, p < 0.001) increased the most. Conclusion: This study corroborate the significance of the pandemic on traditional school bullying and suggests that we should further consider other types of bullying and establish and improve the response and prevention mechanisms during public health emergencies such as the COVID-19 pandemic.
Challenges to Promote Sustainability in Urban Agriculture Models: A Review
Authors: Bennedetti Luiza Vigne , de Almeida Sinisgalli Paulo Antônio , Ferreira Maurício Lamano , Lemes de Oliveira Fabiano
Published: January 2023

Urban agriculture (UA) can be used as an action to promote sustainability in cities and inform public health policies for urban populations. Despite this growing recognition, its implementation still presents challenges in countries in the Global North and Global South. Background: In this context, this systematic review aims to identify the development of frameworks for the implementation of UA as a sustainable action and its main opportunities and shortcomings in meeting urban socio-environmental demands. Methods: In this review, using the PRISMA protocol, we evaluated 26 studies on the interplay between UA and sustainability surveyed on the Web of Science to provide an overview of the state of the art. Conclusions: In summary, it was possible to identify many key challenges in UA adoption, which regard air and soil contamination, availability of green areas, layout of urban infrastructure, food distribution, among others. Due to numerous socio-economic and environmental contextual factors in cities, especially when comparing realities of the Global North and Global South, there is a need to develop a model that can be adaptable to these different contexts. Thus, it is recognized that the concept of sustainability does not present a universal understanding and that in its search it could be argued that one of the most important gaps is still to address social issues in relation to environmental ones.
Green Economy and Waste Management as Determinants of Modeling Green Capital of Districts in Poland in 2010–2020
Authors: Misztal Piotr , Dziekański Paweł
Published: January 2023

Waste management must comply with the principle of sustainable development. A green economy is one of the paths to sustainable development and response to environmental problems. Waste should be a raw material that can be reused, processed, or turned into energy. The aim of the article is to assess the relationship and present the concept of zero waste and green economy, and to show selected framework conditions for their development in the county. To study the formation of phenomena depending on the location of a given object in the socio-economic space, a synthetic measure, the similarity matrix, the Gini coefficient was used. The analysis took into account features describing the condition of the natural environment, links between the natural environment, economy and society, the quality of life of the population, economic policy, and instruments influencing the economy, society and the environment. Empirical data were obtained from the local database of the Central Statistical Office for the years 2010–2020. The obtained results indicate the existence of dependencies in the development of a green economy and waste management in the region. The synthetic measure of waste management is from 0.43 to 0.61 in 2010, from 0.39 to 0.55 in 2020; green economy from 0.42 to 0.55 in 2010 and from 0.43 to 0.56 in 2020. Waste management is based on multidimensional waste management, taking into account economic, ecological and social aspects. Economic activity is related to the degradation of the natural environment. The green economy should assume the elimination of waste and environmental threats and the preservation of their value. The green economy is becoming a factor inducing structural changes in the economy and social life, helping in the most effective, sustainable and efficient use of limited resources. In the literature on the subject, this type of research is carried out at the level of regions or voivodeships. The authors use their own sets of indicators or their own indicators aggregated according to the available data at the poviat level. The obtained results can be an important source of information for local government authorities about disproportions between units.
Mother-Child Bond through Feeding: A Prospective Study including Neuroticism, Pregnancy Worries and Post-Traumatic Symptomatology
Authors: Gutiérrez Hermoso Lorena , Catalá Mesón Patricia , Écija Gallardo Carmen , Marín Morales Dolores , Peñacoba Puente Cecilia
Published: January 2023

Post-traumatic stress disorder (PTSD) is a common postpartum problem and influences maternal bonding with the infant. However, the relationship between this disorder, maternal personality, and the infant’s emotional state during feeding is not clear. The aim of the present study was to explore the contribution of neuroticism on the infant’s emotional state during feeding, by attending to the mediating role of postpartum PTSD (P-PTSD) symptoms and the moderating role of worries during pregnancy. A prospective design study was developed with 120 women with a low pregnancy risk. They responded to a questionnaire assessing maternal personality (first trimester), worries during pregnancy (third trimester), P-PTSD symptoms, and mother-baby bonding (4 months postpartum). The results showed a positive association among neuroticism, infant irritability during feeding, and P-PTSD symptoms, suggesting the latter plays a mediating role in the relationship between neuroticism and infant irritability (B = 0.102, standard error (SE) = 0.03, 95% coefficient interval (CI) [0.038, 0.176]). Excessive worries, related to coping with infant care, played a moderating role between neuroticism and P-PTSD symptoms (B = 0.413, SE = 0.084, p = 0.006, 95% CI [0.245, 0.581]). This relationship was interfered with by depressive symptoms in the first trimester (covariate) (B = 1.820, SE = 0.420, p = 0.016, ci [2.314, 0.251]). This study contributes to a better understanding of the role of neuroticism as an influential factor in the occurrence of P-PTSD symptoms, and in the impairment of infant bonding during feeding. Paying attention to these factors may favor the development of psychological support programs for mothers, with the aim of strengthening the bond with their child.
Well-Being and Perceived Competence in School Children from 1 to 9 Class
Authors: Sigmundsson Hermundur , Ingebrigtsen Jan , Dybendal Benjamin
Published: January 2023

Motivational aspects in reading, math, science and physical education are often studied on whole samples and not grouped into different classes. In our study we wish to investigate cross-sectional data across classes. Our research question wishes to investigate what class differences are there in school subject-based well-being and perceived competence? A total of 378 Icelandic pupils in classes 1–9 did answer a survey with nine items, focusing on how are you feeling at school, how do you like and how are you doing in reading, math, science and physical education. There were 163 girls (43%), and 202 boys (53%) ranging from 6 to 15 years of age (M = 10.86, SD = 2.57). The findings, for the whole sample, indicate that girls tend to like reading more than boys do. Additionally, girls feel that they are better in science compared to boys, while boys like physical education more than girls. In terms of classes, multiple items, including reading, math and science, indicated class differences, where higher classes (i.e., eighth and ninth class) tend to have lower average scores in how much they liked a certain topic, and how competent they felt. It is also of great interest that the correlation between ‘how do you like’ and ‘how are you doing’ are 0.53, 0.71, 0.66 and 0.66 for reading, math, science and physical activity, respectively. Well-being and perceived competence in all subjects correlate with each other, and well-being at school. This shows the importance of seeing the school as a holistic system, where experiences related to individual subjects coincide with the overall experience (and vice versa). The results are discussed in relation to self-perception, motivation and practice.
How to Achieve Carbon Neutrality in Cities? Evidence from China’s Low-Carbon Cities Development
Authors: Wang Huaxing , Chen Chuan , Xiong Zhiqiao , Li Dandan
Published: January 2023

Low-carbon city pilots (LCCP) is a key policy for realizing emission peak and carbon neutrality in China, using China’s samples from 280 towns from 2006 to 2016. The article utilizes PSM-DID, mediated effects, and moderating effects approach for validating a CO2 reduction effect, mechanisms, and synergistic elements of LCCP. The regression outcomes suggest that (1) LCCP significantly decreases CO2 emissions levels and average annual carbon emissions in LCCP fall by 2.6 percent. (2) LCCP focus on reducing carbon emissions by increasing R&D investment, the efficiency of energy, and decreasing the high CO2 emissions industry. Among them, the reduction of the high carbon emission industry is mainly FDI, while the reduction of local industry is not obvious. (3) LCCP’s carbon reduction effects suggest a reversed U-shape relationship with city size. Digitalization and marketization of LCCP are crucial to the carbon reduction effect. Carbon reduction and pollution reduction have a strong synergistic effect.
The Impact of Various Methods of Obesity Treatment on the Quality of Life and Mental Health—A Narrative Review
Authors: Hachuła Marcin , Kosowski Michał , Zielańska Kaja , Basiak Marcin , Okopień Bogusław
Published: January 2023

Obesity, defined as body mass index (BMI) ≥ 30 kg/m2, is one of the most important public health problems. Over one billion people are obese, including 650 million adults, which is 13% of the worldwide population, according to the World Health Organization (WHO). Similar to obesity, mental disorders such as depression and anxiety are huge social problems with serious health implications. There are numerous studies proving a strong link between the prevalence of obesity and depressive disorders, and being overweight is also associated with decreased health-related quality of life (HRQoL). Due to the broad negative impact of obesity on a patient’s health, proper treatment is crucial. Currently, the literature describes many methods of treatment such as dietary treatment, pharmacotherapy using glucagon-like peptide-1 (GLP-1) analogs, orlistat, naltrexone/bupropion (NB), or finally bariatric surgery. The most commonly used methods of obesity treatment significantly improve the patient’s quality of life and reduce the symptoms of depression and anxiety. The aim of our study was to summarize the knowledge about the impact of known and commonly used methods of obesity treatment (e.g., dietary treatment, bariatric surgery, and pharmacological treatment) on mental health and quality of life. For this purpose, we will try to review the current scientific data, originating from international reports.
Civic Engagement and Personality: Associations with the Big Five and the Dark Triad
Authors: Rico-Bordera Pilar , Piqueras José A. , Soto-Sanz Victoria , Rodríguez-Jiménez Tíscar , Marzo Juan-Carlos , Galán Manuel , Pineda David
Published: January 2023

Several studies have analyzed the relationship between general personality traits and attitudes and behaviors, indicating that a person is more committed to the community. After raising the question of whether malevolent traits might also be related, the aim was to analyze the relationship between civic engagement and personality, delving into the contribution of the Dark Triad (narcissism, Machiavellianism, and psychopathy) and controlling for the association with the Big Five. The Civic Engagement Questionnaire, the Short Dark Triad, and the Big Five Inventory-10 were administered to 1175 Spanish students (convenience sampling). After performing statistical analyses using SPSS statistical software, it was obtained that the three Dark Triad traits explained 11% of the total explained variance of civic engagement, while 19% was reached when the Big Five were included. Narcissism and openness were the factors most strongly associated with engagement. The positive relationship between narcissism and general personality traits could explain why narcissistic people have more favorable attitudes. Furthermore, people with narcissistic traits may display these attitudes for their own benefit. This study provides further evidence of how the narcissistic personality trait differs from the other two malevolent traits. Given that these traits are also associated with maladaptive behaviors, knowing all their characteristics could facilitate the design of prevention programs aimed at reducing such maladaptive behaviors.
Mercury Exposure from the Consumption of Dietary Supplements Containing Vegetable, Cod Liver, and Shark Liver Oils
Authors: Brodziak-Dopierała Barbara , Fischer Agnieszka , Chrzanowska Martyna , Ahnert Bożena
Published: January 2023

Vegetable and fish oils constitute a significant part of all dietary supplements. Due to increasing environmental pollution, the raw materials used for their production may be contaminated with toxic substances, including metals. The aim of the present study was to determine the mercury (Hg) content in vegetable oils, shark liver oils, and cod liver oils. The tests conducted were to help determine the level of mercury contamination of the tested preparations and the related potential threat to human health. The amount of Hg in the tested dietary supplements was compared, and the amount of the metal consumed at various times of use was determined. A total of 36 preparations of dietary supplements available on the Polish market were used for the study. The method of atomic absorption spectrometry using the amalgamation technique was used for the determinations (AMA 254, Altec, Czech Republic). Among the sample of all of the tested preparations, the Hg concentration ranged from 0.023 to 0.427 µg/kg, with an average of 0.165 µg/kg. Differences in Hg content in the various tested preparations (shark liver oil, cod liver oil, and vegetable oils) were statistically significant. The average concentration of Hg in the vegetable oils (0.218 µg/kg) was more than twice that of the cod liver oils (0.106 µg/kg) and shark liver oils (0.065 µg/kg). In none of the tested preparations did the amount of Hg exceed the acceptable standard for dietary supplements (0.10 mg/kg). The analysis showed that the Hg content in vegetable oils, shark liver oils, and fish oils from the Polish market is at a low level, guaranteeing the safety of their use, and as such, they do not pose a threat to health.
The Effects of Winter Parks in Cold Regions on Cognition Recovery and Emotion Improvement of Older Adults: An Empirical Study of Changchun Parks
Authors: Yan Tianjiao , Leng Hong , Yuan Qing
Published: January 2023

Urban parks are one of the primary settings for older adults to exercise, and their health benefits have been confirmed by a large number of studies. However, with the increased social attention to mental health, there is not enough research on the short-term mental health recovery of older adults in parks. Meanwhile, the health recovery effects of winter parks in special climate areas have not been well explored. This study aimed to explore the effects of winter parks in cold regions on the short-term mental health recovery of older adults and the potential predictors of these effects, including individual status, park characteristics, and behavioral characteristics. This study divided short-term mental health recovery into cognitive recovery and emotional improvement, and selected the digit span test and 10 kinds of emotional expression as the experimental methods, recruited 92 older adults from 6 parks in Changchun, and compared the pre-test and post-test results for evaluation. The results showed that winter parks in cold cities still had short-term cognitive recovery and emotional improvement effects on older adults. The main park characteristic factors affecting the overall cognitive recovery were the evergreen vegetation area and the existence of structures, and that which affected the overall emotional improvement was the main pathway length. Furthermore, individual conditions, including gender, age, physical health, living and customary conditions, and park characteristics, including park type, park area, main pathway length, square area, equipment area, evergreen vegetation area, the presence of water, and structures, all related to short-term mental health recovery effects. Among behavioral characteristics, stay time in parks and MVPA (Moderate and Vigorous Physical Activity) times were also related to certain effects, but behavior type was not.
SARS-CoV-2 Infection in San Patrignano, the Largest European Drug Rehabilitation Community
Authors: Sala Isabella , Jarach Carlotta Micaela , Bagnardi Vincenzo , Cattaruzza Maria Sofia , Morri Michela , Ottogalli Paolo , Zagà Vincenzo , Gallus Silvano , Boschini Antonio
Published: January 2023

Background: Studies on SARS-CoV-2 conducted in confined settings for prolonged times allow researchers to assess how the coronavirus spreads. San Patrignano (SP), Italy, is the largest European drug rehabilitation facility. Methods: Between 15 October and 31 December 2020, all SP residents were tested for SARS-CoV-2. We analyzed the relationships between individual characteristics and being SARS-CoV-2-positive. Three selected predictive models were used to calculate the number of expected hospitalizations. For each model, we summed the estimated individual risks to obtain the expected number of hospitalizations in our sample, and we tested whether the observed and expected numbers differed. Results: Of 807 residents, 529 (65.6%) were SARS-CoV-2-positive. Of these 323 (61.1%) were symptomatic. A strong relationship was found between being positive and living connections (p-value < 0.001). No statistically significant relationship was found with age, sex, smoking history, or comorbidities. Although 9 to 17 hospitalizations were expected, no hospitalizations were observed (p-value < 0.001). No one died of COVID-19. Conclusions: The peculiar characteristics of SP residents or the SP environment might at least partially explain the null hospitalization rates. Despite the extreme uniqueness of our population and despite the protected environment and all precautions that were taken, the fact that the virus was able to circulate and infect a large portion of the population highlights the fundamental role of social interactions in the spread of the disease.
“We Just Don’t Know Where They Are”: The Geographical Distribution of Exercise Classes for Older People, Including Those Living with Dementia in the East Midlands
Authors: Long Annabelle , Timmons Stephen , Di Lorito Claudio , Booth Vicky , Logan Pip
Published: January 2023

Older people living with dementia are advised to exercise to remain independent. Although several exercise classes for older people take place across the UK, there is limited information about the geographical distribution of these classes. This study identified the location and explored the population characteristics of the classes in a UK region, to aid improved access to exercise. Using a geographical information system, data were collected on population characteristics, including size and age, socio-economic status, and rurality of the exercise classes in one area of the UK (East Midlands, population 5 million). The relationship between data sets was explored and a visual representation of these patterns was provided. A systematic internet search identified 520 exercise classes, evenly spread across the region and areas of socio-economic deprivation: 471 (90%) were in urban areas; 428 (80%) were in areas where less than 20% of the population was over 65 years of age; and 13 (2%) stated that they were suitable for people with dementia. People living with dementia are less likely than older people without dementia to have access to exercise classes.
Unconscious Processing of Greenery in the Tourism Context: A Breaking Continuous Flash Suppression Experiment
Authors: Huang Xiang , Jiang Hao , Lv Ming
Published: January 2023

Both tourism and nature have been proven to contribute to people’s physical and mental health. Most studies have discussed their positive effects at the conscious level, but the unconscious mechanisms underlying these effects remain under-investigated, especially in the tourism context. Using a psychological experimental paradigm called breaking continuous flash suppression (b-CFS), this study tested how the proportion of greenery in an environment influences people’s perceptions of tourism sites and compared the effects of different proportions of greenery on participants’ unconscious responses to tourism sites. The results suggest that the presence of greenery improves the participants’ unconscious perceptions, and that this effect is due to greenery as an element of the natural world, rather than to green as a color. These findings enhance the understanding of the role that the unconscious response plays in the effect of nature on human health and may have managerial implications for the tourism industry.
Examining the Correlates of HIV Testing for Venezuelan Migrants in Trinidad
Authors: Lyons Nyla , Bhagwandeen Brendon , Edwards Jeffrey
Published: January 2023

An important preventive measure in the fight against the HIV epidemic is the adoption of HIV testing. The government of the Republic of Trinidad and Tobago conducted a registration exercise in 2019 for undocumented migrants and refugees from Venezuela residing in the country. These migrants were allowed access to the public health system. In this study, we observed the correlates of HIV testing in Venezuelan migrants residing in Trinidad. A convenience sample of n = 250 migrants was collected via telephone survey from September through December 2020. Variables of interest included social factors, health needs, and uptake of HIV testing. Pearson χ2 tests examined the associations between study variables, and multivariable logistic regression with backward elimination produced the odds of taking an HIV test. In our study, 40.8% of migrants reported having received an HIV test since arriving in Trinidad. Persons who migrated with family or friends had greater odds of getting an HIV test relative to persons who arrived alone (OR = 2.912, 95% CI: 1.002–8.466), and migrants who knew where to get an HIV test also greater odds of getting a test relative to person who did not know where to get a test (OR = 3.173, 95% CI: 1.683–5.982). Migrants with known physical health problems had greater odds of getting an HIV test relative to migrants without these health problems (OR = 1.856, 95% CI: 1.032–3.337). Persons who arrived with family or friends had greater odds of experiencing difficulties accessing public health care relative to persons who arrived alone (OR = 3.572, 95% CI: 1.352–9.442). Migrants earning between $1000 and $2999 TT per month had greater odds of experiencing trouble accessing public health services relative to persons who had monthly earnings of less than $1000 TT (OR = 2.567, 95% CI: 1.252–5.264). This was the first quantitative study on HIV testing among Venezuelan migrants in Trinidad. Migrants still experience difficulties accessing healthcare, which, in turn influences national HIV prevention and control efforts. The results gathered may help in developing HIV prevention plans that are led by a national health policy that takes migrant communities’ needs into account.
Current Role of Delta Radiomics in Head and Neck Oncology
Authors: Marcu David C. , Grava Cristian , Marcu Loredana G.
Published: January 2023

The latest developments in the management of head and neck cancer show an increasing trend in the implementation of novel approaches using artificial intelligence for better patient stratification and treatment-related risk evaluation. Radiomics, or the extraction of data from various imaging modalities, is a tool often used to evaluate specific features related to the tumour or normal tissue that are not identifiable by the naked eye and which can add value to existing clinical data. Furthermore, the assessment of feature variations from one time point to another based on subsequent images, known as delta radiomics, was shown to have even higher value for treatment-outcome prediction or patient stratification into risk categories. The information gathered from delta radiomics can, further, be used for decision making regarding treatment adaptation or other interventions found to be beneficial to the patient. The aim of this work is to collate the existing studies on delta radiomics in head and neck cancer and evaluate its role in tumour response and normal-tissue toxicity predictions alike. Moreover, this work also highlights the role of holomics, which brings under the same umbrella clinical and radiomic features, for a more complex patient characterization and treatment optimisation.
Myeloma Microenvironmental TIMP1 Induces the Invasive Phenotype in Fibroblasts to Modulate Disease Progression
Authors: Ishihara Rei , Oda Tsukasa , Murakami Yuki , Matsumura Ikuko , Watanabe Saki , Asao Yuta , Masuda Yuta , Gotoh Nanami , Kasamatsu Tetsuhiro , Takei Hisashi , Kobayashi Nobuhiko , Sasaki Nobuo , Saitoh Takayuki , Murakami Hirokazu , Handa Hiroshi
Published: January 2023

Tissue inhibitors of metalloproteinases (TIMPs) are endogenous matrix metalloproteinase inhibitors. TIMP1 is produced by cancer cells and has pleiotropic activities. However, its role and source in multiple myeloma (MM) are unclear. Here, we evaluated TIMP1 protein and mRNA levels in bone marrow (BM) plasma cells and assessed the effects of TIMP1 expression on fibroblast invasive capacity using three-dimensional spheroid cell invasion assays. TIMP1 mRNA and protein levels were elevated when patients progressed from monoclonal gammopathy of undetermined significance or smouldering myeloma to MM. Furthermore, TIMP1 levels decreased at complete response and TIMP1 protein levels increased with higher international staging. TIMP1 mRNA levels were markedly higher in extramedullary plasmacytoma and MM with t(4;14). Overall survival and post-progression survival were significantly lower in MM patients with high TIMP1 protein. Recombinant TIMP1 did not directly affect MM cells but enhanced the invasive capacity of fibroblasts; this effect was suppressed by treatment with anti-TIMP1 antibodies. Fibroblasts supported myeloma cell invasion and expansion in extracellular matrix. Overall, these results suggested that MM-derived TIMP1 induces the invasive phenotype in fibroblasts and is involved in disease progression. Further studies are required to elucidate the specific roles of TIMP1 in MM and facilitate the development of novel therapies targeting the TIMP1 pathway.
Biodrug Delivery Systems: Do mRNA Lipid Nanoparticles Come of Age?
Authors: Puccetti Matteo , Schoubben Aurelie , Giovagnoli Stefano , Ricci Maurizio
Published: January 2023

As an appealing alternative to treat and prevent diseases ranging from cancer to COVID-19, mRNA has demonstrated significant clinical effects. Nanotechnology facilitates the successful implementation of the systemic delivery of mRNA for safe human consumption. In this manuscript, we provide an overview of current mRNA therapeutic applications and discuss key biological barriers to delivery and recent advances in the development of nonviral systems. The relevant challenges that LNPs face in achieving cost-effective and widespread clinical implementation when delivering mRNA are likewise discussed.
Conjugates of Tacrine and Salicylic Acid Derivatives as New Promising Multitarget Agents for Alzheimer’s Disease
Authors: Makhaeva Galina F. , Kovaleva Nadezhda V. , Rudakova Elena V. , Boltneva Natalia P. , Grishchenko Maria V. , Lushchekina Sofya V. , Astakhova Tatiana Y. , Serebryakova Olga G. , Timokhina Elena N. , Zhilina Ekaterina F. , Shchegolkov Evgeny V. , Ulitko Mariya V. , Radchenko Eugene V. , Palyulin Vladimir A. , Burgart Yanina V. , Saloutin Victor I. , Bachurin Sergey O. , Richardson Rudy J.
Published: January 2023

A series of previously synthesized conjugates of tacrine and salicylamide was extended by varying the structure of the salicylamide fragment and using salicylic aldehyde to synthesize salicylimine derivatives. The hybrids exhibited broad-spectrum biological activity. All new conjugates were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity toward BChE. The structure of the salicylamide moiety exerted little effect on anticholinesterase activity, but AChE inhibition increased with spacer elongation. The most active conjugates were salicylimine derivatives: IC50 values of the lead compound 10c were 0.0826 µM (AChE) and 0.0156 µM (BChE), with weak inhibition of the off-target carboxylesterase. The hybrids were mixed-type reversible inhibitors of both cholinesterases and displayed dual binding to the catalytic and peripheral anionic sites of AChE in molecular docking, which, along with experimental results on propidium iodide displacement, suggested their potential to block AChE-induced β-amyloid aggregation. All conjugates inhibited Aβ42 self-aggregation in the thioflavin test, and inhibition increased with spacer elongation. Salicylimine 10c and salicylamide 5c with (CH2)8 spacers were the lead compounds for inhibiting Aβ42 self-aggregation, which was corroborated by molecular docking to Aβ42. ABTS•+-scavenging activity was highest for salicylamides 5a–c, intermediate for salicylimines 10a–c, low for F-containing salicylamides 7, and non-existent for methoxybenzoylamides 6 and difluoromethoxybenzoylamides 8. In the FRAP antioxidant (AO) assay, the test compounds displayed little or no activity. Quantum chemical analysis and molecular dynamics (MD) simulations with QM/MM potentials explained the AO structure–activity relationships. All conjugates were effective chelators of Cu2+, Fe2+, and Zn2+, with molar compound/metal (Cu2+) ratios of 2:1 (5b) and ~1:1 (10b). Conjugates exerted comparable or lower cytotoxicity than tacrine on mouse hepatocytes and had favorable predicted intestinal absorption and blood-brain barrier permeability. The overall results indicate that the synthesized conjugates are promising new multifunctional agents for the potential treatment of AD.
Zebrafish Cancer Avatars: A Translational Platform for Analyzing Tumor Heterogeneity and Predicting Patient Outcomes
Authors: Al-Hamaly Majd A. , Turner Logan T. , Rivera-Martinez Angelica , Rodriguez Analiz , Blackburn Jessica S.
Published: January 2023

The increasing number of available anti-cancer drugs presents a challenge for oncologists, who must choose the most effective treatment for the patient. Precision cancer medicine relies on matching a drug with a tumor’s molecular profile to optimize the therapeutic benefit. However, current precision medicine approaches do not fully account for intra-tumoral heterogeneity. Different mutation profiles and cell behaviors within a single heterogeneous tumor can significantly impact therapy response and patient outcomes. Patient-derived avatar models recapitulate a patient’s tumor in an animal or dish and provide the means to functionally assess heterogeneity’s impact on drug response. Mouse xenograft and organoid avatars are well-established, but the time required to generate these models is not practical for clinical decision-making. Zebrafish are emerging as a time-efficient and cost-effective cancer avatar model. In this review, we highlight recent developments in zebrafish cancer avatar models and discuss the unique features of zebrafish that make them ideal for the interrogation of cancer heterogeneity and as part of precision cancer medicine pipelines.
miRNA-124 Prevents Rat Diabetic Retinopathy by Inhibiting the Microglial Inflammatory Response
Authors: Chen Ying , Schlotterer Andrea , Kurowski Luke , Li Lin , Dannehl Marcus , Hammes Hans-Peter , Lin Jihong
Published: January 2023

Diabetic retinopathy (DR) is characterized by vasoregression and glial activation. miRNA-124 (miR-124) reduces retinal microglial activation and alleviates vasoregression in a neurodegenerative rat model. Our aim was to determine whether miR-124 affects vascular and neural damage in the early diabetic retina. Diabetes was induced in 8-week-old Wistar rats by streptozotocin (STZ) injection. At 16 and 20 weeks, the diabetic rats were intravitreally injected with miR-124 mimic, and retinae were analyzed at 24 weeks. Microvascular damage was identified by evaluating pericyte loss and acellular capillary (AC) formation. Müller glial activation was assessed by glial fibrillary acidic protein (GFAP) immunofluorescence staining. Microglial activation was determined by immunofluorescent staining of ionized calcium-binding adaptor molecule 1 (Iba1) in whole mount retinae. The neuroretinal function was assessed by electroretinography. The expression of inflammation-associated genes was evaluated by qRT-PCR. A wound healing assay was performed to quantitate the mobility of microglial cells. The results showed that miR-124 treatment alleviated diabetic vasoregression by reducing AC formation and pericyte loss. miR-124 blunted Müller glial- and microglial activation in diabetic retinae and ameliorated neuroretinal function. The retinal expression of inflammatory factors including Tnf-α, Il-1β, Cd74, Ccl2, Ccl3, Vcam1, Tgf-β1, Arg1, and Il-10 was reduced by miR-124 administration. The elevated mobility of microglia upon high glucose exposure was normalized by miR-124. The expression of the transcription factor PU.1 and lipid raft protein Flot1 was downregulated by miR-124. In rat DR, miR-124 prevents vasoregression and glial activation, improves neuroretinal function, and modulates microglial activation and inflammatory responses.
The Gold(I) Complex with Plant Hormone Kinetin Shows Promising In Vitro Anticancer and PPARγ Properties
Authors: Trávníček Zdeněk , Vančo Ján , Belza Jan , Hošek Jan , Dvořák Zdeněk , Lenobel René , Popa Igor , Šmejkal Karel , Uhrin Pavel
Published: January 2023

Motivated by the clinical success of gold(I) metallotherapeutic Auranofin in the effective treatment of both inflammatory and cancer diseases, we decided to prepare, characterize, and further study the [Au(kin)(PPh3)] complex (1), where Hkin = kinetin, 6-furfuryladenine, for its in vitro anti-cancer and anti-inflammatory activities. The results revealed that the complex (1) had significant in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, and THP-1), with IC50 ≈ 1–5 μM, which was even significantly better than that for the conventional platinum-based drug Cisplatin while comparable with Auranofin. Although its ability to inhibit transcription factor NF-κB activity did not exceed the comparative drug Auranofin, it has been found that it is able to positively influence peroxisome-proliferator-activated receptor-gamma (PPARγ), and as a consequence of this to have the impact of moderating/reducing inflammation. The cellular effects of the complex (1) in A2780 cancer cells were also investigated by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential, and shotgun proteomic analysis. Proteomic analysis of R2780 cells treated with complex (1) and starting compounds revealed possible different places of the effect of the studied compounds. Moreover, the time-dependent cellular accumulation of copper was studied by means of the mass spectrometry study with the aim of exploring the possible mechanisms responsible for its biological effects.
GUS Reporter-Aided Promoter Deletion Analysis of A. thaliana POLYAMINE OXIDASE 3
Authors: Podia Varvara , Chatzopoulos Dimitris , Milioni Dimitra , Stravopodis Dimitrios J. , Dervisi Irene , Roussis Andreas , Roubelakis-Angelakis Kalliopi A. , Haralampidis Kosmas
Published: January 2023

Polyamine oxidases (PAOs) have been correlated with numerous physiological and developmental processes, as well as responses to biotic and abiotic stress conditions. Their transcriptional regulation is driven by signals generated by various developmental and environmental cues, including phytohormones. However, the inductive mechanism(s) of the corresponding genes remains elusive. Out of the five previously characterized Arabidopsis PAO genes, none of their regulatory sequences have been analyzed to date. In this study, a GUS reporter-aided promoter deletion approach was used to investigate the transcriptional regulation of AtPAO3 during normal growth and development as well as under various inductive environments. AtPAO3 contains an upstream open reading frame (uORF) and a short inter-cistronic sequence, while the integrity of both appears to be crucial for the proper regulation of gene expression. The full-length promoter contains several cis-acting elements that regulate the tissue-specific expression of AtPAO3 during normal growth and development. Furthermore, a number of TFBS that are involved in gene induction under various abiotic stress conditions display an additive effect on gene expression. Taken together, our data indicate that the transcription of AtPAO3 is regulated by multiple environmental factors, which probably work alongside hormonal signals and shed light on the fine-tuning mechanisms of PAO regulation.
High Temperature CO2 Capture Performance and Kinetic Analysis of Novel Potassium Stannate
Authors: Baird Ross , Chang Ribooga , Cheung Ocean , Sanna Aimaro
Published: January 2023

For the first time, the use of stannate-based sorbents was investigated as high temperature CO2 sorption to evaluate their potential to contribute towards reducing carbon emissions. The sorption capacity and kinetics of commercial tin oxide, sodium, potassium and calcium stannates and lab synthesised potassium stannates were tested using thermogravimetric analysis. Commercial K2SnO3 was found to possess the largest CO2 uptake capacity (2.77 mmol CO2/g or 12.2 wt%) at 700 °C, which is among the highest for potassium sorbents, but the CO2 desorption was not successful. On the contrary, the in-house synthesised K-stannate (K-B) using facile solid-state synthesis outperformed the other sorbents, resulting in a CO2 uptake of 7.3 wt% after 5 min, an adsorption rate (0.016 mg/s) one order of magnitude higher than the other stannates, and stability after 40 cycles. The XRD and XPS analyses showed that K-B contains a mixture of K2SnO3 (76%) and K4SnO4 (21%), while the Scherrer crystal sizes confirmed good resistance to sintering for the potassium stannates. Among the apparent kinetic model tested, the pseudo-second order model was the most suitable to predict the CO2 sorption process of K-B, indicating that chemical adsorption is dominant, while film-diffusion resistance and intra-particle diffusion resistance governed the sorption process in K-B. In summary, this work shows that solid-state synthesised potassium stannate could be an effective sorbent for high temperature separation, and additional work is required to further elucidate its potential.
The Roles of CDPKs as a Convergence Point of Different Signaling Pathways in Maize Adaptation to Abiotic Stress
Authors: Du Hanwei , Chen Jiajia , Zhan Haiying , Li Shen , Wang Yusheng , Wang Wei , Hu Xiuli
Published: January 2023

The calcium ion (Ca2+), as a well-known second messenger, plays an important role in multiple processes of growth, development, and stress adaptation in plants. As central Ca2+ sensor proteins and a multifunctional kinase family, calcium-dependent protein kinases (CDPKs) are widely present in plants. In maize, the signal transduction processes involved in ZmCDPKs’ responses to abiotic stresses have also been well elucidated. In addition to Ca2+ signaling, maize ZmCDPKs are also regulated by a variety of abiotic stresses, and they transmit signals to downstream target molecules, such as transport proteins, transcription factors, molecular chaperones, and other protein kinases, through protein interaction or phosphorylation, etc., thus changing their activity, triggering a series of cascade reactions, and being involved in hormone and reactive oxygen signaling regulation. As such, ZmCDPKs play an indispensable role in regulating maize growth, development, and stress responses. In this review, we summarize the roles of ZmCDPKs as a convergence point of different signaling pathways in regulating maize response to abiotic stress, which will promote an understanding of the molecular mechanisms of ZmCDPKs in maize tolerance to abiotic stress and open new opportunities for agricultural applications.
Characterization of the 1-Deoxy-D-xylulose 5-Phosphate synthase Genes in Toona ciliata Suggests Their Role in Insect Defense
Authors: Wang Yueyang , Li Yue , Song Huiyun , Wang Zhi , Li Pei
Published: January 2023

The first enzyme, 1-Deoxy-D-xylulose-5-phosphate synthase (DXS), in the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway for isoprenoid precursor biosynthesis has been reported to function differently according to species. However, the current state of knowledge about this gene family in Toona ciliata is limited. The TcDXS gene family was identified from the whole genome of T. ciliata by firstly using bioinformatics analysis. Then, the phylogenetic tree was built and the promoter cis-elements were predicted. Six DXS genes were identified and divided into three groups, which had similar domains and gene structure. They are located on five different chromosomes and encode products that do not vary much in size. An analysis of the cis-acting elements revealed that TcDXS genes possessed light, abiotic stress, and hormone responsive elements. Ultimately, TcDXS1/2/5 was cloned for an in-depth analysis of their subcellular localization and expression patterns. The subcellular localization results of TcDXS1/2/5 showed that they were located in the chloroplast envelope membranes. Based on tissue-specific analyses, TcDXS1/2/5 had the highest expression in mature leaves. Under Hypsipyla robusta stress, their different expressions indicated that these genes may have insect-resistance functions. This research provides a theoretical basis for further functional verification of TcDXSs in the future, and a new concept for breeding pest-resistant T. ciliata.
CARs and Drugs: Pharmacological Ways of Boosting CAR-T-Cell Therapy
Authors: Harrer Dennis Christoph , Dörrie Jan , Schaft Niels
Published: January 2023

The development of chimeric antigen receptor T cells (CAR-T cells) has marked a new era in cancer immunotherapy. Based on a multitude of durable complete remissions in patients with hematological malignancies, FDA and EMA approval was issued to several CAR products targeting lymphoid leukemias and lymphomas. Nevertheless, about 50% of patients treated with these approved CAR products experience relapse or refractory disease necessitating salvage strategies. Moreover, in the vast majority of patients suffering from solid tumors, CAR-T-cell infusions could not induce durable complete remissions so far. Crucial obstacles to CAR-T-cell therapy resulting in a priori CAR-T-cell refractory disease or relapse after initially successful CAR-T-cell therapy encompass antigen shutdown and CAR-T-cell dysfunctionality. Antigen shutdown predominately rationalizes disease relapse in hematological malignancies, and CAR-T-cell dysfunctionality is characterized by insufficient CAR-T-cell proliferation and cytotoxicity frequently observed in patients with solid tumors. Thus, strategies to surmount those obstacles are being developed with high urgency. In this review, we want to highlight different approaches to combine CAR-T cells with drugs, such as small molecules and antibodies, to pharmacologically boost CAR-T-cell therapy. In particular, we discuss how certain drugs may help to counteract antigen shutdown and CAR-T-cell dysfunctionality in both hematological malignancies and solid tumors.