bluuebunny/crossref_metadata_2025 huggingface dataset:
Cooling Effect of Urban Blue and Green Spaces: A Case Study of Changsha, China
Authors: Qiu Xinyi , Kil Sung-Ho , Jo Hyun-Kil , Park Chan , Song Wonkyong , Choi Yun Eui
Published: February 2023

The cooling effects of blue–green spaces on the urban heat island effect are complex and different. The purpose of this study is to simulate how the cooling effect of blue–green space changes with its size and shape. The cooling effects of 53 green patches and 28 water bodies in Changsha were extracted based on Landsat images. A surface fitting model was used to quantitatively reveal the relationship between the cooling effect of blue–green space and its size and shape. The results show that the cooling effects of blue–green spaces were enhanced with the increasing size, and then would become stable after a certain range (threshold). Certain thresholds were identified between the blue and green space areas (2.98 ha and 3.15 ha, respectively) and the cooling distance, and between the blue and green space areas (4.84 ha and 4.92 ha, respectively) and the cooling magnitude. In addition, the green space with an area of 9.08 ha and landscape shape index (LSI) of 2.97 could achieve a better cooling distance (413.46 m); and the blue space with an area of 29.4 ha and LSI of 1.75 could achieve a better cooling magnitude (5.17 °C). These findings provide useful guidelines for urban planning and improving urban livability in other regions with terrain and climate conditions similar to Changsha.
Laboring Alone: Perinatal Outcomes during Childbirth without a Birth Partner or Other Companion during the COVID-19 Pandemic
Authors: Pařízek Antonín , Janků Petr , Kameníková Miloslava , Pařízková Petra , Javornická Daniela , Benešová Dana , Rogalewicz Vladimír , Laštůvka Zdeněk , Barták Miroslav
Published: February 2023

During the first wave of the COVID-19 pandemic in the spring of 2020, the government of the Czech Republic issued a nationwide ban on visitors to maternity wards. We studied whether the absence of a close person during labor due to this ban impacted perinatal indicators. This study was performed using an administrative observational questionnaire focused on absolute frequencies of events sent to maternity facilities across the Czech Republic. Completed answers were received from 33 facilities covering 4805 births during the study period in 2019 and 4514 births in 2020. The differences in individual parameters were tested using Pearson’s chi-squared homogeneity test. There were no significant differences between the two periods in spontaneous pre-term births (p = 0.522) or in the number of cesarean sections (p = 0.536). No significant changes were seen in either local or systemic analgesia. Data showed a significantly shorter (p = 0.026) first stage of labor in 2020 compared to 2019, while there was no significant difference (p = 0.673) in the second stage of labor. There was no statistically significant difference found for newborn perinatal adaptation. There were also no significant differences in intrapartum maternal injuries. Overall, we found no significant differences in basic perinatal indicators during the first wave of COVID-19 in 2020 compared to 2019. Although the absence of a close person may cause stress for the laboring women, it does not impair objective clinical outcomes.
“One and a Half Years of Things We Could Have Done”: Multi-Method Analysis of the Narratives of Adolescents with Type 1 Diabetes during the COVID-19 Pandemic
Authors: Tremolada Marta , Cusinato Maria , D’Agnillo Alessia , Negri Arianna , Righetto Elena , Moretti Carlo
Published: February 2023

Background: Public health interventions for COVID-19 forced families to adopt changes in daily routines that affected children’s and adolescents’ psychological well-being. In youth with type 1 diabetes (T1D), psychological symptoms may compromise glycemic control and outcomes; however, evidence of improved glycemic control in children and adolescents with T1D emerged early during the pandemic. This qualitative study aims to provide a more in-depth understanding of how the COVID-19 pandemic affected adolescents’ with T1D routines, experiences, T1D management, and psychological well-being. Methods: 24 adolescents, aged 15–18 years, with T1D, joined focus-group discussions during the diabetes summer camp. Word frequency analysis and thematic analysis were conducted on adolescents’ narratives. The average frequencies of use of words related to COVID-19 and to T1D were compared by t-test. Results: Word frequency analysis identified “friends”, “family”, and “home” as the most recurrent terms. Seven themes were highlighted: (1) COVID-19 and T1D; (2) emotional reactions to the COVID-19 pandemic; (3) changes in daily life; (4) feelings of loss; (5) coping with the COVID-19 pandemic; (6) the COVID-19 pandemic as opportunity; (7) return to (new) normality. COVID-19 related words were on average more frequent than words referring to T1D. Conclusions: The COVID-19 pandemic may have represented a more stressful condition for adolescents with T1D, facing additional challenges compared to their healthy peers. Findings offer directions to the diabetes care team for customized interventions while the effects of the pandemic on adolescents’ health continue.
Development of a Scale to Measure Healthy Behaviors in Spanish-Speaking University Students
Authors: Semir-González Carla , Ferrer-Urbina Rodrigo , Suazo-Navarro Carolina , Flores-Denegri Catalina , Bolados Darinka , Rosales Joaquín , Sepúlveda-Páez Geraldy
Published: February 2023

Chronic non-communicable diseases (NCDs) are a public health problem that affect the quality of life and well-being of people, especially the youth, who have been identified as a high-risk population. Physical inactivity is a key risk factor for NCDs, and an unhealthy diet is a significant driver of NCDs. On the other hand, physical exercise and healthy habits are effective methods of prevention. Although there are scales that measure different behaviors related to NCDs, most of them have been developed in another language (e.g., English) or only focus on one aspect of NCDs. The present study aimed to develop a scale to assess healthy behaviors (i.e., healthy eating and physical exercise) in Spanish-speaking university students, using an instrumental design, with a sample of 369 Chilean university students between 18 and 25 years of age. The results presented show evidence of validity through an exploratory structural equation model (ESEM), reliability estimation through McDonald’s omega and Cronbach’s alpha, evidence of invariance by sex, and evidence of validity in relation to other variables with an SEM model. It is concluded that the Healthy Behavior Scale, consisting of nine items to measure healthy eating and physical exercise, is a brief instrument with evidence of reliability and validity (CFI = 0.998; TLI = 0.995; and RMSEA = 0.063) for application in a Spanish-speaking university population, offering potential applications in research instruments, screening studies, and the development of new studies for other contexts.
Metabolic Control, Diabetic Complications and Drug Therapy in a Cohort of Patients with Type 1 and Type 2 Diabetes in Secondary and Tertiary Care between 2004 and 2019
Authors: Roth Matthias , Lehmann Thomas , Kloos Christof , Schmidt Sebastian , Kellner Christiane , Wolf Gunter , Müller Nicolle
Published: February 2023

This paper studies the features of metabolic parameters, diabetic complications and drug therapy of a single-centre cohort of patients with type 1 diabetes (T1DM) or type 2 diabetes (T2DM) in secondary care and tertiary care over a 15-year period. Methods: Retrospective cross-sectional analysis of four single-centre cohorts between 2004 and 2019. All patients with T1DM or T2DM in secondary care (n = 5571) or tertiary care (n = 2001) were included. Statistical analyses were performed using linear mixed models. Results: Diabetes duration increased in both patients with T1DM and T2DM in secondary care and tertiary care (p < 0.001). Patients in secondary care consistently showed good glycaemic control, while patients in tertiary care showed inadequate glycaemic control. All four cross-sectional cohorts showed a significant increase in the prevalence of nephropathy over time and three out of four cohorts (T1DM and T2DM in secondary care and T2DM in tertiary care) showed an increase in the prevalence of neuropathy (all p < 0.001). The incidence of severe hypoglycaemia was consistently low. The use of insulin pumps and insulin analogues in the therapy of T1DM increased significantly. Conclusions: The increased prevalence of complications is likely due to older age and longer diabetes duration. Low rates of hypoglycaemia, lower limb amputations and good glycaemic control in secondary care patients indicate a good structure of patient care.
Adverse Maternal and Infant Outcomes of Women Who Differ in Smoking Status: E-Cigarette and Tobacco Cigarette Users
Authors: Nanninga Eline K. , Weiland Stella , Berger Marjolein Y. , Feijen-de Jong Esther I. , Erwich Jan Jaap H. M. , Peters Lilian L.
Published: February 2023

The electronic cigarette (e-cigarette) became commercially available around 2004, yet the characteristics of pregnant women who use these devices and their effects on maternal and infant health remain largely unknown. This study aimed to investigate maternal characteristics and pregnancy outcomes according to maternal smoking status. We conducted a cross-sectional study of Dutch women with reported pregnancies between February 2019 and May 2022, using an online questionnaire to collect data on smoking status and demographic, lifestyle, pregnancy, and infant characteristics. Smoking status is compared among non-smokers, tobacco cigarette users, e-cigarette users, and dual users (tobacco and e-cigarette). We report descriptive statistics and calculate differences in smoking status between women with the chi-square or Fisher (Freeman–Halton) test. Of the 1937 included women, 88.1% were non-smokers, 10.8% were tobacco cigarette users, 0.5% were e-cigarette users, and 0.6% were dual users. Compared with tobacco users, e-cigarette users more often reported higher education, having a partner, primiparity, and miscarriages. Notably, women who used e-cigarettes more often had small infants for gestational age. Despite including few women in the e-cigarette subgroup, these exploratory results indicate the need for more research to examine the impact of e-cigarettes on pregnancy outcomes.
Australian Consumers’ Attitudes towards Sustainable Diet Practices Regarding Food Waste, Food Processing, and the Health Aspects of Diet: A Cross Sectional Survey
Authors: Healy Janelle D. , Dhaliwal Satvinder S. , Pollard Christina M. , Sharma Piyush , Whitton Clare , Blekkenhorst Lauren C. , Boushey Carol J. , Scott Jane A. , Kerr Deborah A.
Published: February 2023

Environmentally sustainable diets are increasingly aspired to in food-based dietary guidelines across the world. However, little is known about consumer attitudes toward these diets when making food decisions. This study aimed to identify the demographic characteristics of Australian adults based on the level of attention they paid to the healthfulness of their diet, their consideration of the level of food processing, and their concern about household food waste and sustainable packaging disposal. Adults aged from 18 to over 75 years (n = 540) were surveyed online. Thirty-seven percent were concerned about sustainable food waste, 28% considered the level of food processing when making food decisions, and 23% paid attention to the healthfulness of the food they ate. Adults who had higher educational attainment (above Year 12) were twice as likely to be concerned about food waste and sustainable packaging disposal (odds ratio (OR) = 2.10, 95% confidence interval (CI) 1.29–3.4), and processing levels (OR = 2.04, 95% CI 1.23–3.42) (controlling for age and gender). Those earning an income over AUD$100,000 were twice as likely to pay attention to the healthfulness of their food choices than those earning less than AUD$50,000 (OR = 2.19, 95% CI 1.28–3.74). Only 9% percent were concerned about or paid attention to all three of the components of healthy sustainable diets investigated, and 45% paid no attention and were not concerned about all three components. These findings suggest there is a need to educate the public to raise awareness of and concern for healthy, minimally processed, and sustainable food choices.
Health Symptoms and Proximity to Active Multi-Well Unconventional Oil and Gas Development Sites in the City and County of Broomfield, Colorado
Authors: Weisner Meagan L. , Allshouse William B. , Erjavac Benjamin W. , Valdez Andrew P. , Vahling Jason L. , McKenzie Lisa M.
Published: February 2023

City and County of Broomfield (CCOB) residents reported over 500 health concerns between January 2020 and December 2021. Our objective was to determine if CCOB residents living within 1 mile of multi-well unconventional oil and gas development (UOGD) sites reported more frequent health symptoms than residents living > 2 miles away. We invited 3993 randomly selected households to participate in a health survey. We applied linear regression to test associations between distance to UOGD and summed Likert scores for health symptom categories. After covariate adjustment, respondents living within 1 mile of one of CCOB’s UOGD sites tended to report higher frequencies of upper respiratory, lower respiratory, gastrointestinal and acute symptoms than respondents living more than 2 miles from the sites, with the largest differences for upper respiratory and acute symptoms. For upper respiratory and acute symptoms, scores differed by 0.81 (95% CI: 0.06, 2.58) and 0.75 (95% CI: 0.004, 1.99), respectively. Scores for adults most concerned about air pollution, noise and odors trended higher within 1 mile for all symptom categories, while scores among adults least concerned trended lower. Scores trended higher for lower respiratory, gastrointestinal and acute symptoms in children living within 2 miles of UOGD, after covariate adjustment. We did not observe any difference in the frequency of symptoms reported in unadjusted results. Additional study is necessary to understand relationships between proximity to UOGD and health symptoms.
Analysis of the Waiting Time in Clinic Registration of Patients with Appointments and Random Walk-Ins
Authors: Kwak Jin Kyung
Published: February 2023

Healthcare institutions generally use an appointment system. However, patients often need to receive medical services unexpectedly. If they visit a clinic without an appointment, they may have to wait for a long time, as their priority is low. In this study, we investigated whether the clinic registration system can be improved by separating the queues and resources for different types of patients. From our simulation results, we found that under a certain setup, the separation policy does not effectively reduce the walk-ins’ waiting time, nor improve the service. The study gives valuable managerial insights into the factors affecting patients’ waiting times. As the number of random walk-ins is relatively higher, the service times are longer, and the no-show rate of appointments is lower, separation may reduce the waiting time of walk-in patients.
The Relationship between Personality Traits, Work–Family Support and Job Satisfaction among Frontline Power Grid Workers
Authors: Zhou Xiao , Li Hualiang , Wang Qiru , Xiong Chaolin , Lin Aihua
Published: February 2023

Frontline power grid workers are always facing plenty of stressors such as aerial work and high job demands, which may lead them to be less satisfied with their job. Therefore, this study aims to investigate frontline power grid workers’ job satisfaction (JS) and explore how it can be improved by its relationship with personality traits and work–family support (WFS). Data from 535 frontline power grid workers were collected from two power supply bureaus in Guangdong Province, China. Structural equation modeling (SEM) was adopted to examine the structural relationship between personality traits taken as independent variables, JS as dependent variable, and WFS as mediator. The bootstrap method was used to test the significance of indirect effects. Results suggested the overall job satisfaction of our sample is 3.34 ± 0.55 on a scale ranging from 1 to 5, and significantly correlated with personality traits and WFS. Moreover, the results of SEM and bootstrap indicated that WFS partially mediates the effect of neuroticism on JS and fully mediates the effect of conscientiousness and extraversion on JS. These findings shed light on how personality traits and environmental factors jointly impact JS and highlight the important role of WFS among frontline power grid workers.
The Influence of Parental Sleep and Experiences Related to COVID-19 on Sleep in Children and Adolescents between 2020 and 2021 in Brazil
Authors: Richter Samanta Andresa , Schilling Luísa Basso , Ferraz-Rodrigues Clarissa , Camargo Nathália Fritsch , Nunes Magda Lahorgue
Published: February 2023

The study aimed to evaluate the influence of parental sleep and experiences related to COVID-19 on sleep changes in children and adolescents in the period between 2020 and 2021 in Brazil and further compare the sleep of adults with and without children. This is a longitudinal web-survey study. Participants were invited to respond to a questionnaire regarding sleep characteristics, mental health issues, and work/lifestyle modifications in two waves of the pandemic (April–July 2020 and 2021). A total of 1172 adults answered both questionnaires, and 281 were dyads (parent–child/adolescent). Parent and non-parent adult responders had similar sociodemographic data, with a predominance of the female sex and self-declared white skin color prevailing along with higher levels of education in both groups. The prevalence of sleep problems in adults varied from 20.6% to 30.2% in the parent group and from 16.9% to 30.1% in non-parents. The prevalence of sleep problems in children and adolescents raised from 2020 to 2021 (respectively, 48% and 49.5%) but differences were not statistically significant. The multivariate logistic model showed in both years that changes in children’s/adolescents’ sleep was related to parents working at home, infected family/friends, time of exposure to COVID-19, and daytime sleep dysfunction. Our data showed that parental sleep and experiences related to COVID-19 influenced sleep changes in children and adolescents. Parents had a significant difference in daytime sleepiness compared to the group without children.
Special Issue “Disaster Risk Reduction and Climate Change Adaptation: An Interdisciplinary Approach”
Authors: Ishiwatari Mikio , Sasaki Daisuke
Published: February 2023

The UN member states adopted three international agreements for the post-2015 agenda: the Sendai Framework for Disaster Risk Reduction 2015–2030, the Paris Agreement of the United Nations Framework Convention on Climate Change, and the 2030 Agenda for Sustainable Development [...]
Spatial-Temporal Genome Regulation in Stress-Response and Cell-Fate Change
Authors: Erenpreisa Jekaterina , Giuliani Alessandro , Yoshikawa Kenichi , Falk Martin , Hildenbrand Georg , Salmina Kristine , Freivalds Talivaldis , Vainshelbaum Ninel , Weidner Jonas , Sievers Aaron , Pilarczyk Götz , Hausmann Michael
Published: February 2023

Complex functioning of the genome in the cell nucleus is controlled at different levels: (a) the DNA base sequence containing all relevant inherited information; (b) epigenetic pathways consisting of protein interactions and feedback loops; (c) the genome architecture and organization activating or suppressing genetic interactions between different parts of the genome. Most research so far has shed light on the puzzle pieces at these levels. This article, however, attempts an integrative approach to genome expression regulation incorporating these different layers. Under environmental stress or during cell development, differentiation towards specialized cell types, or to dysfunctional tumor, the cell nucleus seems to react as a whole through coordinated changes at all levels of control. This implies the need for a framework in which biological, chemical, and physical manifestations can serve as a basis for a coherent theory of gene self-organization. An international symposium held at the Biomedical Research and Study Center in Riga, Latvia, on 25 July 2022 addressed novel aspects of the abovementioned topic. The present article reviews the most recent results and conclusions of the state-of-the-art research in this multidisciplinary field of science, which were delivered and discussed by scholars at the Riga symposium.
Leptin Increases: Physiological Roles in the Control of Sympathetic Nerve Activity, Energy Balance, and the Hypothalamic–Pituitary–Thyroid Axis
Authors: Martelli Davide , Brooks Virginia L.
Published: February 2023

It is well established that decreases in plasma leptin levels, as with fasting, signal starvation and elicit appropriate physiological responses, such as increasing the drive to eat and decreasing energy expenditure. These responses are mediated largely by suppression of the actions of leptin in the hypothalamus, most notably on arcuate nucleus (ArcN) orexigenic neuropeptide Y neurons and anorexic pro-opiomelanocortin neurons. However, the question addressed in this review is whether the effects of increased leptin levels are also significant on the long-term control of energy balance, despite conventional wisdom to the contrary. We focus on leptin’s actions (in both lean and obese individuals) to decrease food intake, increase sympathetic nerve activity, and support the hypothalamic–pituitary–thyroid axis, with particular attention to sex differences. We also elaborate on obesity-induced inflammation and its role in the altered actions of leptin during obesity.
FDA-Approved Monoclonal Antibodies for Unresectable Hepatocellular Carcinoma: What Do We Know So Far?
Authors: Psilopatis Iason , Damaskos Christos , Garmpi Anna , Sarantis Panagiotis , Koustas Evangelos , Antoniou Efstathios A. , Dimitroulis Dimitrios , Kouraklis Gregory , Karamouzis Michail V. , Vrettou Kleio , Marinos Georgios , Kontzoglou Konstantinos , Garmpis Nikolaos
Published: February 2023

Unresectable hepatocellular carcinoma (HCC) is an advanced primary liver malignancy with a poor prognosis. The Food and Drug Administration (FDA) has, to date, approved nivolumab, pembrolizumab, ramucirumab, nivolumab/ipilimumab, atezolizumab/bevacizumab, as well as tremelimumab/durvalumab, as first- or second-line monoclonal antibodies (mAbs) for unresectable HCC. The present review examines the current state of knowledge, and provides a useful update on the safety and efficacy of these therapeutic agents, thus attempting to define the suitability of each mAb for different patient subgroups.
Application of RSM Method for Optimization of Geraniol Transformation Process in the Presence of Garnet
Authors: Fajdek-Bieda Anna , Perec Andrzej , Radomska-Zalas Aleksandra
Published: February 2023

This paper presents the results of tests obtained for the transformation of geraniol in the presence of garnet as a catalyst by the response surface method (RSM). The method analyzed the influence of the following parameters: a temperature of 50–150 °C, a catalyst concentration (garnet) of 1.0–10.0 wt% and a reaction time of 0.25–24 h. Response functions included the conversion of geraniol (GA), selectivity for conversion to neral (NE) and selectivity for conversion to citronellol (CL). In addition, the influence of all control parameters on each of the response parameters is presented in the form of second-order polynomials. The optimal parameters of the geraniol transformation process were a temperature of 55 °C, a catalyst concentration of 5 wt% and a reaction time of 2 h, for which high values of the GA conversion function and the selectivity of conversion to NE and CL were obtained. For the GA conversion, the optimum was obtained at 94 mol% at 60 °C, a catalyst concentration of 5.0 wt% and a reaction time of 2 h. For NE selectivity, the optimum value was reached at 49 mol% at 60 °C, a catalyst concentration equal to 2.5 (5.0) wt% mole and a reaction time of almost 2 h. For CL selectivity, the optimum value of 49 mol% was obtained for control factors: a temperature equal to 20 °C, a catalyst concentration equal to 5.0 wt% and a response time equal to 2 h. The optimal set of control factors for all power factors is characterized by a temperature of 55 °C, a catalyst concentration of 5 wt% and a reaction time of 2 h.
RPLP1 Is Up-Regulated in Human Adenomyosis and Endometrial Adenocarcinoma Epithelial Cells and Is Essential for Cell Survival and Migration In Vitro
Authors: Peterson Riley , Minchella Paige , Cui Wei , Graham Amanda , Nothnick Warren B.
Published: February 2023

Adenomyosis is defined as the development of endometrial epithelial glands and stroma within the myometrial layer of the uterus. These “ectopic” lesions share many cellular characteristics with endometriotic epithelial cells as well as endometrial adenocarcinoma cells, including enhanced proliferation, migration, invasion and progesterone resistance. We recently reported that the 60S acidic ribosomal protein P1, RPLP1, is up-regulated in endometriotic epithelial cells and lesion tissue where it plays a role in cell survival. To evaluate if a similar pattern of expression and function for RPLP1 exists in adenomyosis and endometrial cancer, we examined RPLP1 expression in adenomyosis and endometrial cancer tissue specimens and assessed its function in vitro using well-characterized cell lines. A total of 12 control endometrial biopsies and 20 eutopic endometrial and matched adenomyosis biopsies as well as 103 endometrial adenocarcinoma biopsies were evaluated for RPLP1 localization by immunohistochemistry. Endometrial adenocarcinoma cell lines, Ishikawa, HEC1A, HEC1B and AN3 were evaluated for RPLP1 protein and transcript expression, while in vitro function was evaluated by knocking down RPLP1 expression and assessing cell survival and migration. RPLP1 protein was up-regulated in eutopic epithelia as well as in adenomyosis lesions compared to eutopic endometria from control subjects. RPLP1 was also significantly up-regulated in endometrial adenocarcinoma tissue. Knockdown of RPLP1 in endometrial adenocarcinoma cell lines was associated with reduced cell survival and migration. RPLP1 expression is up-regulated in eutopic and ectopic adenomyotic epithelia as well as in the epithelia of endometrial cancer specimens. In vitro studies support an essential role for RPLP1 in mediating cell survival and migration, processes which are all involved in pathophysiology associated with both diseases.
The Influence of Constraints on Gelation in a Controlling/Living Copolymerization Process
Authors: Polanowski Piotr , Sikorski Andrzej
Published: February 2023

We developed a simple model of the copolymerization process in the formation of crosslinked macromolecular systems. A living copolymerization was carried out for free chains, in bulk and in a slit, as well as for grafted chains in a slit. In addition, polymer 2D brushes were placed in a slit with initiator molecules attached to one of the confining walls. Coarse-grained chains were embedded in the vertices of a face-centered cubic lattice with the excluded volume interactions. The simulations of the copolymerization processes were performed using the Dynamic Lattice Liquid algorithm, a version of the Monte Carlo method. The influence of the initial initiator to cross-linker ratio, slit width and grafting on the polymerization and on the gelation was examined. It was also shown that the influence of a confining slit was rather small, while the grafting of chains affected the location of the gel pint significantly.
Prussian Blue Nanoparticle-Entrapped GelMA Gels Laden with Mesenchymal Stem Cells as Prospective Biomaterials for Pelvic Floor Tissue Repair
Authors: Wen Jirui , Zhao Zhiwei , Fang Fei , Xiao Jingyue , Wang Ling , Cheng Juan , Wu Jiang , Miao Yali
Published: February 2023

Pelvic organ prolapse (POP) seriously affects elderly patients’ quality of life, and new repair materials are urgently needed. To solve this problem, we synthesized methacrylated gelatin (GelMA) hydrogels and incorporated photothermally active Prussian blue nanoparticles (PBNPs) to synthesize PBNP@GelMA. Then, MSCs were encapsulated in the PBNP@GelMA and exposed to a 1.0 W/cm2 of 808 nm laser for 10 min to perform heat shock pretreatment for the implantation of mesenchymal stem cells (MSCs). Next, we tested the repair efficacy of scaffold–cell complexes both in vitro and in vivo. Our results reveal that the heat shock treatment induced by PBNP@GelMA improved the viability of MSCs, and the underlying mechanism may be related to HSP70. Furthermore, 2 weeks after implantation in the SD rat model, the collagen content increased in the MSC implantation group and PBNP@GelMA implantation group. However, the muscle regeneration at the implanting position was mostly enhanced after the implantation of the heat-shock-pretreated MSCs, which illustrates that heat shock treatment can further promote the MSC-mediated muscle regeneration. Therefore, manipulating the cell environment and providing proper heat stimulus by using PBNP@GelMA with NIR is a novel strategy to enhance the regenerative potential of MSCs and to promote pelvic tissue repair.
Exploration of Novel Scaffolds Targeting Cytochrome b of Pyricularia oryzae
Authors: Pinna Cecilia , Laurenzi Tommaso , Forlani Fabio , Palazzolo Luca , Nolan Claire Beatrice , Christodoulou Michael S. , Cortesi Paolo , Pinto Andrea , Eberini Ivano , Kunova Andrea , Dallavalle Sabrina
Published: February 2023

The fulfilment of the European “Farm to Fork” strategy requires a drastic reduction in the use of “at risk” synthetic pesticides; this exposes vulnerable agricultural sectors—among which is the European risiculture—to the lack of efficient means for the management of devastating diseases, thus endangering food security. Therefore, novel scaffolds need to be identified for the synthesis of new and more environmentally friendly fungicides. In the present work, we employed our previously developed 3D model of P. oryzae cytochrome bc1 (cyt bc1) complex to perform a high-throughput virtual screening of two commercially available compound libraries. Three chemotypes were selected, from which a small collection of differently substituted analogues was designed and synthesized. The compounds were tested as inhibitors of the cyt bc1 enzyme function and the mycelium growth of both strobilurin-sensitive (WT) and -resistant (RES) P. oryzae strains. This pipeline has permitted the identification of thirteen compounds active against the RES cyt bc1 and five compounds that inhibited the WT cyt bc1 function while inhibiting the fungal mycelia only minimally. Serendipitously, among the studied compounds we identified a new chemotype that is able to efficiently inhibit the mycelium growth of WT and RES strains by ca. 60%, without inhibiting the cyt bc1 enzymatic function, suggesting a different mechanism of action.
Genes Encoding Structurally Conserved Serpins in the Wheat Genome: Identification and Expression Profiles during Plant Development and Abiotic and Biotic Stress
Authors: Dong Chongmei , Huang Ting-Chun , Roberts Thomas H.
Published: February 2023

Serpins constitute a family of proteins with a very wide distribution in nature. Serpins have a well-conserved tertiary structure enabling irreversible protease inhibition or other specific biochemical functions. We examined the 189 putative wheat serpin genes previously identified by Benbow et al. (2019) via analysis of gene annotations (RefSeq v1.0) and combined our previous examinations of wheat ESTs and the 454 genome assembly. We found that 81 of the 189 putative serpin genes, plus two manually annotated genes, encode full-length, structurally conserved serpins. Expression of these serpin genes during wheat development and disease/abiotic stress responses was analysed using a publicly available RNAseq database. Results showed that the wheat LR serpins, homologous to Arabidopsis AtSerpin1 and barley BSZx, are ubiquitously expressed across all tissues throughout the wheat lifecycle, whereas the expression of other wheat serpin genes is tissue-specific, including expression only in the grain, only in the root, and only in the anther and microspore. Nine serpin genes were upregulated in both biotic and abiotic responses. Two genes in particular were highly expressed during disease and abiotic challenges. Our findings provide valuable information for further functional study of the wheat serpins, which in turn may lead to their application as molecular markers in wheat breeding.
A Comprehensive Analysis of Cytokine Network in Centenarians
Authors: Pinti Marcello , Gibellini Lara , Lo Tartaro Domenico , De Biasi Sara , Nasi Milena , Borella Rebecca , Fidanza Lucia , Neroni Anita , Troiano Leonarda , Franceschi Claudio , Cossarizza Andrea
Published: February 2023

Cytokines have been investigated extensively in elderly people, with conflicting results. We performed a comprehensive analysis of the plasma levels of 62 cytokines and growth factors involved in the regulation of the immune system, in healthy centenarians, and middle-aged controls. We confirmed the previously observed increase in the levels of several pro-inflammatory cytokines, such as TNF-α and IL-6, and found that several other cytokines, directly or indirectly involved in inflammation (such as IFN-α, IL-23, CCL-5), were present at higher levels in centenarians. We did not observe any increase in the levels of anti-inflammatory cytokines, with the notable exception of the Th2-shifting cytokine IL-19. No relevant difference was observed in cytokines regulating T cell immunity. Several growth factors having a role in regulating immunity, such as G-CSF, GM-CSF, EGF, and VEGF, were upregulated in centenarians, too. Principal component analysis of the cytokine dataset showed that pro and anti-inflammatory cytokines were the variables that contributed the most to the variability of the data we observed.
Natural Inhibitors of Cholinesterases: Chemistry, Structure–Activity and Methods of Their Analysis
Authors: Smyrska-Wieleba Natalia , Mroczek Tomasz
Published: February 2023

This article aims to provide an updated description and comparison of the data currently available in the literature (from the last 15 years) on the studied natural inhibitors of cholinesterases (IChEs), namely, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These data also apply to the likely impact of the structures of the compounds on the therapeutic effects of available and potential cholinesterase inhibitors. IChEs are hitherto known compounds with various structures, activities and origins. Additionally, multiple different methods of analysis are used to determine the cholinesterase inhibitor potency. This summary indicates that natural sources are still suitable for the discovery of new compounds with prominent pharmacological activity. It also emphasizes that further studies are needed regarding the mechanisms of action or the structure–activity correlation to discuss the issue of cholinesterase inhibitors and their medical application.
Dysregulation of Gene Expression of Key Signaling Mediators in PBMCs from People with Type 2 Diabetes Mellitus
Authors: Qureshi Nilofer , Desousa Julia , Siddiqui Adeela Z. , Drees Betty M. , Morrison David C. , Qureshi Asaf A.
Published: February 2023

Diabetes is currently the fifth leading cause of death by disease in the USA. The underlying mechanisms for type 2 Diabetes Mellitus (DM2) and the enhanced susceptibility of such patients to inflammatory disorders and infections remain to be fully defined. We have recently shown that peripheral blood mononuclear cells (PBMCs) from non-diabetic people upregulate expression of inflammatory genes in response to proteasome modulators, such as bacterial lipopolysaccharide (LPS) and soybean lectin (LEC); in contrast, resveratrol (RES) downregulates this response. We hypothesized that LPS and LEC will also elicit a similar upregulation of gene expression of key signaling mediators in (PBMCs) from people with type 2 diabetes (PwD2, with chronic inflammation) ex vivo. Unexpectedly, using next generation sequencing (NGS), we show for the first time, that PBMCs from PwD2 failed to elicit a robust LPS- and LEC-induced gene expression of proteasome subunit LMP7 (PSMB8) and mediators of T cell signaling that were observed in non-diabetic controls. These repressed genes included: PSMB8, PSMB9, interferon-γ, interferon-λ, signal-transducer-and-activator-of-transcription-1 (STAT1), human leukocyte antigen (HLA DQB1, HLA DQA1) molecules, interleukin 12A, tumor necrosis factor-α, transporter associated with antigen processing 1 (TAP1), and several others, which showed a markedly weak upregulation with toxins in PBMCs from PwD2, as compared to those from non-diabetics. Resveratrol (proteasome inhibitor) further downregulated the gene expression of these inflammatory mediators in PBMCs from PwD2. These results might explain why PwD2 may be susceptible to infectious disease. LPS and toxins may be leading to inflammation, insulin resistance, and thus, metabolic changes in the host cells.
Exploring AlphaFold2′s Performance on Predicting Amino Acid Side-Chain Conformations and Its Utility in Crystal Structure Determination of B318L Protein
Authors: Zhao Haifan , Zhang Heng , She Zhun , Gao Zengqiang , Wang Qi , Geng Zhi , Dong Yuhui
Published: February 2023

Recent technological breakthroughs in machine-learning-based AlphaFold2 (AF2) are pushing the prediction accuracy of protein structures to an unprecedented level that is on par with experimental structural quality. Despite its outstanding structural modeling capability, further experimental validations and performance assessments of AF2 predictions are still required, thus necessitating the development of integrative structural biology in synergy with both computational and experimental methods. Focusing on the B318L protein that plays an essential role in the African swine fever virus (ASFV) for viral replication, we experimentally demonstrate the high quality of the AF2 predicted model and its practical utility in crystal structural determination. Structural alignment implies that the AF2 model shares nearly the same atomic arrangement as the B318L crystal structure except for some flexible and disordered regions. More importantly, side-chain-based analysis at the individual residue level reveals that AF2′s performance is likely dependent on the specific amino acid type and that hydrophobic residues tend to be more accurately predicted by AF2 than hydrophilic residues. Quantitative per-residue RMSD comparisons and further molecular replacement trials suggest that AF2 has a large potential to outperform other computational modeling methods in terms of structural determination. Additionally, it is numerically confirmed that the AF2 model is accurate enough so that it may well potentially withstand experimental data quality to a large extent for structural determination. Finally, an overall structural analysis and molecular docking simulation of the B318L protein are performed. Taken together, our study not only provides new insights into AF2′s performance in predicting side-chain conformations but also sheds light upon the significance of AF2 in promoting crystal structural determination, especially when the experimental data quality of the protein crystal is poor.
Exploring the Role of GMMA Components in the Immunogenicity of a 4-Valent Vaccine against Shigella
Authors: Mancini Francesca , Alfini Renzo , Caradonna Valentina , Monaci Valentina , Carducci Martina , Gasperini Gianmarco , Piccioli Diego , Biagini Massimiliano , Giannelli Carlo , Rossi Omar , Pizza Mariagrazia , Micoli Francesca
Published: February 2023

Shigellosis is the leading cause of diarrheal disease, especially in children of low- and middle-income countries, and is often associated with anti-microbial resistance. Currently, there are no licensed vaccines widely available against Shigella, but several candidates based on the O-antigen (OAg) portion of lipopolysaccharides are in development. We have proposed Generalized Modules for Membrane Antigens (GMMA) as an innovative delivery system for OAg, and a quadrivalent vaccine candidate containing GMMA from S. sonnei and three prevalent S. flexneri serotypes (1b, 2a and 3a) is moving to a phase II clinical trial, with the aim to elicit broad protection against Shigella. GMMA are able to induce anti-OAg-specific functional IgG responses in animal models and healthy adults. We have previously demonstrated that antibodies against protein antigens are also generated upon immunization with S. sonnei GMMA. In this work, we show that a quadrivalent Shigella GMMA-based vaccine is able to promote a humoral response against OAg and proteins of all GMMA types contained in the investigational vaccine. Proteins contained in GMMA provide T cell help as GMMA elicit a stronger anti-OAg IgG response in wild type than in T cell-deficient mice. Additionally, we observed that only the trigger of Toll-like Receptor (TLR) 4 and not of TLR2 contributed to GMMA immunogenicity. In conclusion, when tested in mice, GMMA of a quadrivalent Shigella vaccine candidate combine both adjuvant and carrier activities which allow an increase in the low immunogenic properties of carbohydrate antigens.
Molecular and Biologic Effects of Platelet-Rich Plasma (PRP) in Ligament and Tendon Healing and Regeneration: A Systematic Review
Authors: Chalidis Byron , Givissis Panagiotis , Papadopoulos Pericles , Pitsilos Charalampos
Published: February 2023

Platelet-rich plasma (PRP) has been introduced and applied to a wide spectrum of acute and chronic ligament and tendon pathologic conditions. Although the biological effect of PRP has been studied thoroughly in both animal and human studies, there is no consensus so far on the exact mechanism of its action as well as the optimal timing and dosage of its application. Therefore, we conducted a systematic review aiming to evaluate the molecular effect of the administration of PRP in tendoligamentous injuries and degenerative diseases. The literature search revealed 36 in vitro and in vivo studies examining the healing and remodeling response of animal and human ligament or tendon tissues to PRP. Platelet-rich plasma added in the culture media was highly associated with increased cell proliferation, migration, viability and total collagen production of both ligament- and tendon-derived cells in in vitro studies, which was further confirmed by the upregulation of collagen gene expression. In vivo studies correlated the PRP with higher fibroblastic anabolic activity, including increased cellularity, collagen production and vascularity of ligament tissue. Similarly, greater metabolic response of tenocytes along with the acceleration of the healing process in the setting of a tendon tear were noticed after PRP application, particularly between the third and fourth week after treatment. However, some studies demonstrated that PRP had no or even negative effect on tendon and ligament regeneration. This controversy is mainly related to the variable processes and methodologies of preparation of PRP, necessitating standardized protocols for both investigation and ap-plication.
The Activation of Reticulophagy by ER Stress through the ATF4-MAP1LC3A-CCPG1 Pathway in Ovarian Granulosa Cells Is Linked to Apoptosis and Necroptosis
Authors: Li Huiduo , Jing Yanan , Qu Xiaoya , Yang Jinyi , Pan Pengge , Liu Xinrui , Gao Hui , Pei Xiuying , Zhang Cheng , Yang Yanzhou
Published: February 2023

Female infertility is caused by premature ovarian failure (POF), which is triggered by the endoplasmic reticulum (ER) stress-mediated apoptosis of granulosa cells. The ER unfolded protein response (UPRer) is initiated to promote cell survival by alleviating excessive ER stress, but cellular apoptosis is induced by persistent or strong ER stress. Recent studies have reported that reticulophagy is initiated by ER stress. Whether reticulophagy is activated in the ER stress-mediated apoptosis of granulosa cells and which pathway is initiated to activate reticulophagy during the apoptosis of granulosa cells are unknown. Therefore, the role of reticulophagy in granulosa cell death and the relationship between ER stress and reticulophagy were investigated in this work. Our results suggest that the ER stress inducer tunicamycin causes POF in mice, which is attributed to the apoptosis of granulosa cells and is accompanied by the activation of UPRer and reticulophagy. Furthermore, granulosa cells were treated with tunicamycin, and granulosa cell apoptosis was triggered and increased the expression of UPRer and reticulophagy molecules. The expression of ATF4 was then downregulated by RNAi, which decreased the levels of autophagy and the reticulophagy receptor CCGP1. Furthermore, ATF4 targets MAP1LC3A, as revealed by the ChIP sequencing results, and co-IP results demonstrated that MAP1LC3A interacts with CCPG1. Therefore, reticulophagy was activated by ER stress through the ATF4-MAP1LC3A-CCPG1 pathway to mitigate ER stress. Additionally, the role of reticulophagy in granulosa cells was investigated by the knockdown of CCPG1 with RNAi. Interestingly, only a small number of granulosa cells died by apoptosis, whereas the death of most granulosa cells occurred by necroptosis triggered by STAT1 and STAT3 to impair ER proteostasis and the ER protein quality control system UPRer. Taken together, the results indicate that the necroptosis of granulosa cells is triggered by up- and downregulating the reticulophagy receptor CCPG1 through STAT1/STAT3-(p)RIPK1-(p)RIPK3-(p)MLKL and that reticulophagy is activated by ER stress through the ATF4-MAP1LC3A-CCPG1 pathway.
The Ubiquitin–26S Proteasome Pathway and Its Role in the Ripening of Fleshy Fruits
Authors: Jia Wen , Liu Gangshuai , Zhang Peiyu , Li Hongli , Peng Zhenzhen , Wang Yunxiang , Jemrić Tomislav , Fu Daqi
Published: February 2023

The 26S proteasome is an ATP-dependent proteolytic complex in eukaryotes, which is mainly responsible for the degradation of damaged and misfolded proteins and some regulatory proteins in cells, and it is essential to maintain the balance of protein levels in the cell. The ubiquitin–26S proteasome pathway, which targets a wide range of protein substrates in plants, is an important post-translational regulatory mechanism involved in various stages of plant growth and development and in the maturation process of fleshy fruits. Fleshy fruit ripening is a complex biological process, which is the sum of a series of physiological and biochemical reactions, including the biosynthesis and signal transduction of ripening related hormones, pigment metabolism, fruit texture changes and the formation of nutritional quality. This paper reviews the structure of the 26S proteasome and the mechanism of the ubiquitin–26S proteasome pathway, and it summarizes the function of this pathway in the ripening process of fleshy fruits.