bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome Analysis of Immune Responses and Metabolic Regulations of Chinese Soft-Shelled Turtle (Pelodiscus sinensis) against Edwardsiella tarda Infection
Authors: Liang Qianrong , Zhu Ningyu , Zheng Xiaoye , Ding Xueyan , He Runzhen , Xu Hongsen , Cao Feifei , Xue Huili , Zhou Fan , Zheng Tianlun
Published: April 2022

The Chinese soft-shelled turtle (Pelodiscus sinensis) is an important aquatic species in southern China that is threatened by many serious diseases. Edwardsiella tarda is one of the highly pathogenic bacteria that cause the white abdominal shell disease. Yet, little is known about the immune and metabolic responses of the Chinese soft-shelled turtle against E. tarda infection. In the paper, gene expression profiles in the turtle liver were obtained to study the immune responses and metabolic regulations induced by E. tarda infection using RNA sequencing. A total of 3908 differentially expressed unigenes between the experimental group and the control group were obtained by transcriptome analysis, among them, were the significantly upregulated unigenes and downregulated unigenes 2065 and 1922, respectively. Further annotation and analysis revealed that the DEGs were mainly enriched in complement and coagulation cascades, phagosome, and steroid hormone biosynthesis pathways, indicating that they were mainly associated with defense mechanisms in the turtle liver against E. tarda four days post infection. For the first time, we reported on the gene profile of anti-E. tarda response in the soft-shelled turtle, and our research might provide valuable data to support further study on anti-E. tarda defense mechanisms in turtles.
The Devil Is in the Data: Can Regional Variation in Amenable Mortality Help to Understand Changes in Health System Performance in Poland?
Authors: Sagan Anna , Karanikolos Marina , Gałązka-Sobotka Małgorzata , McKee Martin , Rozkrut Monika , Kowalska-Bobko Iwona
Published: April 2022

The contribution of health systems to health is commonly assessed using levels of amenable mortality. Few such studies exist for Poland, with analyses of within-the-country patterns being particularly scarce. The aim of this paper is to analyse differences in amenable mortality levels and trends across Poland’s regions using the most recent data and to gain a more nuanced understanding of these differences and possible reasons behind them. This can inform future health policy decisions, particularly when it comes to efforts to improve health system performance. We used national and regional mortality data to construct amenable mortality rates between 2002 and 2019. We found that the initially observed decline in amenable mortality stagnated between 2014 and 2019, something not seen elsewhere in Europe. The main driver behind this trend is the change in ischemic heart disease (IHD) mortality. However, we also found that there is a systematic underreporting of IHD as a cause of death in Poland in favour of heart failure, which makes analysis of health system performance using amenable mortality as an indicator less reliable. We also found substantial geographical differences in amenable mortality levels and trends across Poland, which ranged from −3.3% to +8.1% across the regions in 2014–2019. These are much bigger than variations in total mortality trends, ranging from −1.5% to −0.2% in the same period, which suggests that quality of care across regions varies substantially, although some of this effect is also a coding artefact. This means that interpretation of health system performance indicators is not straightforward and may prevent implementation of policies that are needed to improve population health.
Health Effects of the Asthma Care Program under the Universal Coverage Scheme in Children and Young Adults in Thailand
Authors: Inmai Phatthanawilai Namuenhong , Liabsuetrakul Tippawan , Ichihara Nao , Yamamoto Hiroyuki , Thungthong Jutatip , Chongsuvivatwong Virasakdi , Miyata Hiroaki
Published: April 2022

This study aimed to evaluate the effect of the asthma care program available under the Universal Coverage Scheme (UCS) in Thailand on hospital admissions per 100,000 population, its regional and seasonal variation, readmission within 28 days, and the asthma-specific fatality rate of patients aged 0–29 years in 2009–2016 compared with those in 2007–2008. A retrospective study was conducted using data sources from the UCS register and in-patient databases from the National Health Security Office (NHSO), Thailand. Hospital admissions per 100,000 population was the highest among those aged 0–4 years, but the trends decreased from 470.8 to 288.1 per 100,000 population in 2010–2014. The hospital admission rates were high in Southern Thailand and common in rainy seasons. The readmission rates within 28 days slightly decreased in all age groups in 2016 compared to those in 2007. The case fatality rate of patients aged 20–29 years decreased from 0.40% in 2007 to 0.34% in 2016. The readmission rate within 28 days and case fatality rate were the highest in patients aged 20–29 years. In conclusion, the asthma hospital admission, readmission, and case fatality rates declined over time along with the investment in the asthma care program under the UCS in Thailand. The highest hospital admission rates in patients aged 0–4 years and the readmission and case fatality rates in patients aged 20–29 years should be given more attention. Recordings of individual service utilization data in asthma patients, including quality of care provided, should be monitored to improve the asthma care system.
Impact of Autonomy Support on the Association between Personal Control, Healthy Behaviors, and Psychological Well-Being among Patients with Hypertension and Cardiovascular Comorbidities
Authors: Yeom Hyun-E , Lee Jungmin
Published: April 2022

A sense of control and autonomy are key components in guiding health-related behaviors and quality of life in people with chronic diseases. This study investigated whether autonomy support from health professionals moderates the impact of personal control on psychological well-being through healthy behaviors in patients with hypertension and cardiovascular comorbidities. Data from 149 hypertensive patients with comorbid cardiovascular risk factors were collected via self-administered surveys. A moderated mediation effect of a hypothesized model was analyzed using the PROCESS macro bootstrapping method. Autonomy support from health professionals moderated the relationship between personal control and healthy behaviors (B = 0.16, t = 2.48, p < 0.05), showing that the effect of personal control on healthy behaviors differed by the level of autonomy support. Additionally, autonomy support moderated the mediation effect of healthy behaviors in the relationship between personal control and psychological well-being (Index = 0.15; 95% CI = 0.010, 0.335). The mediation effect existed only in patients with higher autonomy support. The findings demonstrate that autonomy support from health professionals plays a crucial role in reinforcing the positive impact of personal control on healthy behaviors and psychological well-being. Enhancing the supportive attitudes of health professionals that facilitate patients’ autonomous self-regulation is necessary for better health outcomes in people with combined cardiovascular diseases.
Cardiopulmonary Rehabilitation in Long-COVID-19 Patients with Persistent Breathlessness and Fatigue: The COVID-Rehab Study
Authors: Besnier Florent , Bérubé Béatrice , Malo Jacques , Gagnon Christine , Grégoire Catherine-Alexandra , Juneau Martin , Simard François , L’Allier Philippe , Nigam Anil , Iglésies-Grau Josep , Vincent Thomas , Talamonti Deborah , Dupuy Emma Gabrielle , Mohammadi Hânieh , Gayda Mathieu , Bherer Louis
Published: April 2022

(1) Background: Cardiopulmonary and brain functions are frequently impaired after COVID-19 infection. Exercise rehabilitation could have a major impact on the healing process of patients affected by long COVID-19. (2) Methods: The COVID-Rehab study will investigate the effectiveness of an eight-week cardiopulmonary rehabilitation program on cardiorespiratory fitness (V˙O2max) in long-COVID-19 individuals. Secondary objectives will include functional capacity, quality of life, perceived stress, sleep quality (questionnaires), respiratory capacity (spirometry test), coagulation, inflammatory and oxidative-stress profile (blood draw), cognition (neuropsychological tests), neurovascular coupling and pulsatility (fNIRS). The COVID-Rehab project was a randomised clinical trial with two intervention arms (1:1 ratio) that will be blindly evaluated. It will recruit a total of 40 individuals: (1) rehabilitation: centre-based exercise-training program (eight weeks, three times per week); (2) control: individuals will have to maintain their daily habits. (3) Conclusions: Currently, there are no specific rehabilitation guidelines for long-COVID-19 patients, but preliminary studies show encouraging results. Clinicaltrials.gov (NCT05035628).
Voice Navigation Created by VIP Improves Spatial Performance in People with Impaired Vision
Authors: Hung Yu-Hsiu , Tsai Kai-Yu , Chang Eva , Chen Rain
Published: April 2022

The difficulty associated with spatial navigation is one of the main obstacles to independent living for visually impaired people. With a lack of visual feedback, visually impaired people must identify information from the external environment through other sense organs. This study employed an observational survey to assess voice navigation version A, created by visually impaired people, and voice navigation version B, created by non-visually impaired people. Thirty-two simulated visually impaired people were assigned to conduct task assessments of voice navigation version A and version B. For mission 1, the mean completion rate is 0.988 ± 0.049 (version A); the mean error rate is 0.125 ± 0.182 (version A). For mission 2, the mean completion rate is 0.953 ± 0.148 (version A); the mean error rate is 0.094 ± 0.198 (version A). The assessment results concluded that version A has a higher completion rate (p = 0.001) and a lower error rate (p = 0.001). In the assessment of subjective satisfaction, all the indicators regarding the impression of navigation directives in version A were significantly superior to those indicators in version B. It appears that version A has a different logic of framing than version B. In future applications, a voice navigation version shall be built, according to the way visually impaired people think, because it will facilitate the direction guide when there is a lack of visual feedback.
A Single-Day Training for Managers Reduces Cognitive Stigma Regarding Mental Health Problems: A Randomized Trial
Authors: Gast Michael , Lehmann Janina , Schwarz Elena , Hirning Christian , Hoelzer Michael , Guendel Harald , Balint Elisabeth Maria
Published: April 2022

Background: Mental illnesses have received increasing attention in the work context in recent years, yet they are still often accompanied by stigma. One starting point for stigma reduction is interventions in the workplace. The present study evaluated a one-day workshop for managers in a large company. Method: Enrolled managers (n = 70) were randomly assigned to the intervention group and the waiting control group. The training included a theoretical section on mental and stress-related diseases as well as the interplay between work and health, group work on personal stress experience, theoretical input on dealing with mentally ill employees, and a group discussion on this topic along with case studies. Both groups completed the following questionnaires at baseline and three months after training: Effort–Reward Imbalance Questionnaire, Patient Health Questionnaire, Mental Health Knowledge Schedule, Social Distance Scale, and the Irritation Scale. Results: Compared to the waiting group, the intervention group showed a significant improvement in the Mental Health Knowledge Schedule (U = 417.00, p = 0.040) and an increase in the Irritation Scale (U = 371.50 p = 0.011). All other scales remained unchanged. Conclusion: The content and duration of the training were adequate to reduce cognitive stigma towards mental illness. However, the present approach was not sufficient for an improvement in the subjective stress level of the participating managers.
Incidence of Peri-Implantitis and Relationship with Different Conditions: A Retrospective Study
Authors: Astolfi Víctor , Ríos-Carrasco Blanca , Gil-Mur Francisco Javier , Ríos-Santos José Vicente , Bullón Beatriz , Herrero-Climent Mariano , Bullón Pedro
Published: April 2022

Articles on the prevalence of peri-implant diseases showed that 90% of peri-implant tissues had some form of inflammatory response and a prevalence of peri-implantitis from 28% to 51% according to various publications. Objective: To provide an overview of how risk factors can be related with peri-implantitis. Methods: A retrospective longitudinal study including 555 implants placed in 132 patients was evaluated based on the presence of peri-implantitis following the criteria of Renvert et al. 2018. Results: In total, 21 patients (15.9%) suffered peri-implantitis (PPG) and 111 patients (84.1%) did not suffer peri-implantitis (NPG). The results reveal that smokers have a high incidence of peri-implantitis (72.7%) compared to non-smokers (27.3%) (p < 0.0005). Another variable with significant results (p < 0.01) was periodontitis: 50% PPG and 23.9% NPG suffered advanced periodontitis. Systemic diseases such as arterial hypertension, diabetes mellitus, osteoporosis, and cardiovascular diseases do not show a statistically significant influence on the incidence of peri-implantitis. Patients who did not attend their maintenance therapy appointment had an incidence of peri-implantitis of 61.4%, compared to 27.3% in those who attend (p < 0.0001). From the results obtained, we can conclude that relevant factors affect peri-implantitis, such as tobacco habits, moderate and severe periodontitis, and attendance in maintenance therapy.
Match Analysis, Physical Training, Risk of Injury and Rehabilitation in Padel: Overview of the Literature
Authors: Demeco Andrea , de Sire Alessandro , Marotta Nicola , Spanò Riccardo , Lippi Lorenzo , Palumbo Arrigo , Iona Teresa , Gramigna Vera , Palermi Stefano , Leigheb Massimiliano , Invernizzi Marco , Ammendolia Antonio
Published: April 2022

Padel is a racket sport that has been gaining great popularity and scientific interest in recent years. It could be considered to be a high-intensity intermittent sport with valuable cardiovascular and neuromuscular benefits; however, the risk of injury cannot be neglected. To date, there is still a gap of knowledge in the scientific literature on this emergent sport. Therefore, the present review aims to synthetize the current knowledge on padel game dynamics to better characterize the main risk factors, the injury rate and characteristics, and the most effective rehabilitative treatment strategies. PubMed, Scopus, Cochrane, and PEDro were screened up to January 2022 to identify eligible studies focusing on padel players as participants. Out of 160 records, we included 19 studies, which were focused on match analysis, anthropometric and physical training, the risk of injury, and rehabilitative interventions. The results showed that the high action velocity and the sudden changes in direction during a padel match could represent a risk factor for injuries, especially in untrained players. However, the high heterogeneity of the studies in the literature hinders our ability to draw any strong conclusions, and the results should be carefully considered. Future research should address the lack of knowledge on injury mechanisms and type to implement a tailored rehabilitation program.
Household Tenure and Its Associations with Multiple Long-Term Conditions amongst Working-Age Adults in East London: A Cross-Sectional Analysis Using Linked Primary Care and Local Government Records
Authors: Ingram Elizabeth , Gomes Manuel , Hogarth Sue , McDonald Helen I. , Osborn David , Sheringham Jessica
Published: April 2022

Multiple long-term conditions (MLTCs) are influenced in extent and nature by social determinants of health. Few studies have explored associations between household tenure and different definitions of MLTCs. This study aimed to examine associations between household tenure and MLTCs amongst working-age adults (16 to 64 years old, inclusive). This cross-sectional study used the 2019–2020 wave of an innovative dataset that links administrative data across health and local government for residents of a deprived borough in East London. Three definitions of MLTCs were operationalised based on a list of 38 conditions. Multilevel logistic regression models were built for each outcome and adjusted for a range of health and sociodemographic factors. Compared to working-age owner-occupiers, odds of basic MLTCs were 36% higher for social housing tenants and 19% lower for private renters (OR 1.36; 95% CI 1.30–1.42; p < 0.001 and OR 0.81, 95% CI 0.77–0.84, p < 0.001, respectively). Results were consistent across different definitions of MLTCs, although associations were stronger for social housing tenants with physical-mental MLTCs. This study finds strong evidence that household tenure is associated with MLTCs, emphasising the importance of understanding household-level determinants of health. Resources to prevent and tackle MLTCs among working-age adults could be differentially targeted by tenure type.
Dermal Exposure to Hazardous Chemicals in Baby Diapers: A Re-Evaluation of the Quantitative Health Risk Assessment Conducted by The French Agency for Food, Environmental and Occupational Health and Safety (ANSES)
Authors: Bernard Alfred
Published: April 2022

In January 2019, the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) published an opinion on risks related to the presence of hazardous chemicals in infant diapers. ANSES found that health reference values were largely exceeded for polycyclic aromatic hydrocarbons (PAHs), dioxins (PCCD/Fs) and dioxin-like polychlorobiphenyls (DL-PCBs). The levels of formaldehyde and some fragrances were also considered potentially unsafe. Therefore, ANSES concluded that actions have to be taken to restrict levels of these contaminants in diapers. Under the exposure scenario deemed the most reliable by ANSES, estimates of cancer risks of the most potent PAHs detected in diapers exceeded 10−3 and hazard quotients for neurobehavioral effects attained values up to 66. Regarding dioxins and DL-PCBs, ANSES derived a hazard quotient of 12 for the risk of decreased sperm count at adult age. The aim of this study was to examine whether the exposure and risk assessment conducted by ANSES contained potential flaws that could explain such a high exceedance of health reference values. This study also put into perspective the exposure from diapers with that from breast milk whose benefits for children’s health are undisputable despite contamination by PAHs, dioxins and DL-PCBS.
Teaching Presence, Self-Regulated Learning and Learning Satisfaction on Distance Learning for Students in a Nursing Education Program
Authors: Yoo Leeho , Jung Dukyoo
Published: April 2022

The novel coronavirus pandemic has dramatically affected how nursing students are educated. Distance learning has become the norm, and an evaluation of learning achievement is needed. This is a mixed-method study of teaching presence, self-regulated learning, and learning satisfaction in distance learning to evaluate the learning achievement of students in a nursing education program. Ninety-four students for quantitative and seven students for qualitative research were sampled. All the sampled students attend the nursing education program in Seoul and Gyeonggi Province and were enrolled during the first semester of 2020. Quantitative data were analyzed using SPSS/WIN 21.0, and qualitative data were analyzed via content analysis in NVivo 12. Teaching presence and self-regulated learning were identified as the factors affecting learning satisfaction. In a focus group interview, teaching presence increased when the students received feedback and saw the faces of their professors. Self-regulated learning occurred when they had opportunities to practice self-study and leadership and when they formed relationships between professors and colleagues. These methods have also been recognized to increase learning satisfaction. Considering the results of this study, it is necessary to develop teaching methods that enhance the learning satisfaction of students in distance learning nursing education programs.
Global Trends of Nutrition in Cancer Research: A Bibliometric and Visualized Analysis Study over the Past 10 Years
Authors: Youn Bo-Young , Lee Seo-Yeon , Cho Wonje , Bae Kwang-Rok , Ko Seong-Gyu , Cheon Chunhoo
Published: April 2022

The increasing application of nutrition in cancer management has attracted a great deal of research interest in recent decades. Nutritional therapies, interventions, and assessments were known to have positive effects on reducing side effects from cancer therapy. In order to identify the global research output for nutrition in cancer research, a bibliometric analysis during the past 10 years was conducted to evaluate the current status of trends, gaps, and research directions as no bibliometric studies have been conducted regarding nutrition and cancer. After the data collection, a total of 1521 articles were chosen for this bibliometric study. The visualization analysis was performed with VOSviewer. The number of publications has grown continuously since a substantial spark was identified in 2019. The majority of the authors’ affiliations were in European countries. Four cancer types were recognized among the top 10 author keywords; they were breast cancer, head and neck cancer, colorectal cancer, and gastric cancer. The Nutrients journal was the most popular among the authors as the journal published 195 articles related to the topic. In conclusion, providing evidence-based nutritional solutions for various types of cancer is essential to nutrition and cancer research. Since it is presumed to have a growing number of cancer patients worldwide with the aging population, it is vital to continuously generate research finding effective nutrition therapies for cancer patients.
Understanding Consumers’ Food Waste Reduction Behavior—A Study Based on Extended Norm Activation Theory
Authors: Wang Jingjing , Li Mingyue , Li Sinan , Chen Kai
Published: April 2022

Based on norm activation theory, a research framework was built to explore the food waste reduction behavior when consumers eat out. The framework included behavior intentions and four psychological factors: awareness of consequence (persons understanding that actions have consequences), ascription of responsibility (duty to respond), self-efficacy (belief in own skills and capacity), personal norm (individuals’ values to act by socially accepted rules and reduce food waste as a code of conduct and moral obligation). A total of 514 samples from different regions of China were collected through an online survey platform, and the research framework was tested by applying structural equation modeling (SEM). This study found that ascription of responsibility and self-efficacy can effectively activate personal norm to reduce food waste. Personal norm and self-efficacy had a significant positive effect on behavior intentions to reduce food waste. Specifically, self-efficacy had the greatest effect on personal norm, followed by ascription of responsibility, and on behavior intentions to reduce food waste, followed by personal norm. Interestingly, while ascription of responsibility and self-efficacy had an impact on personal norm, awareness of consequence did not significantly influence personal norm to reduce food waste, suggesting that emotional factors are more likely to trigger personal norms that motivate consumers to take action to reduce food waste than cognitive factors. Based on the findings, several suggestions are provided for more effective interventions by restaurants to promote food waste reduction behavior, such as information intervention strategies, displaying information related to food consumption, and reducing the size of plates for some meals.
Sulfobutylation of Beta-Cyclodextrin Enhances the Complex Formation with Mitragynine: An NMR and Chiroptical Study
Authors: Várnai Bianka , Zsila Ferenc , Szakács Zoltán , Garádi Zsófia , Malanga Milo , Béni Szabolcs
Published: April 2022

Mitragynine (MTR), the main indole alkaloid of the well-known plant kratom (Mitragyna speciosa), is one of the most studied natural products nowadays, due to its remarkable biological effects. It is a partial agonist on the opioid receptors, and as such relieves pain without the well-known side-effects of the opioids applied in the clinical practice. MTR and its derivatives therefore became novel candidates for drug development. The poor aqueous solubility and low bioavailability of drugs are often improved by cyclodextrins (CyDs) as excipients through host-guest type complex formation. Among the wide variety of CyDs, sulfobutylether-beta-cyclodextrin (SBEβCyD) is frequently used and official in the European and U.S. Pharmacopoeia. Herein, the host-guest complexation of MTR with βCyD and SBEβCyD was studied using chiroptical and NMR spectroscopy. It was found by NMR measurements that MTR forms a rather weak (logβ11 = 0.8) 1:1 host-guest complex with βCyD, while the co-existence of the 2MTR∙SBEβCyD and MTR∙SBEβCyD species was deducted from 1H NMR titrations in the millimolar MTR concentration range. Sulfobutylation of βCyD significantly enhanced the affinity towards MTR. The structure of the formed inclusion complex was extensively studied by circular dichroism spectroscopy and 2D ROESY NMR. The insertion of the indole moiety was confirmed by both techniques.
The Evidence for Effective Inhibition of INa Produced by Mirogabalin ((1R,5S,6S)-6-(aminomethyl)-3-ethyl-bicyclo [3.2.0] hept-3-ene-6-acetic acid), a Known Blocker of CaV Channels
Authors: Wu Chao-Liang , Chuang Chao-Wei , Cho Hsin-Yen , Chuang Tzu-Hsien , Wu Sheng-Nan
Published: April 2022

Mirogabalin (MGB, Tarlige®), an inhibitor of the α2δ-1 subunit of voltage-gated Ca2+ (CaV) channels, is used as a way to alleviate peripheral neuropathic pain and diabetic neuropathy. However, to what extent MGB modifies the magnitude, gating, and/or hysteresis of various types of plasmalemmal ionic currents remains largely unexplored. In pituitary tumor (GH3) cells, we found that MGB was effective at suppressing the peak (transient, INa(T)) and sustained (late, INa(L)) components of the voltage-gated Na+ current (INa) in a concentration-dependent manner, with an effective IC50 of 19.5 and 7.3 μM, respectively, while the KD value calculated on the basis of minimum reaction scheme was 8.2 μM. The recovery of INa(T) inactivation slowed in the presence of MGB, although the overall current–voltage relation of INa(T) was unaltered; however, there was a leftward shift in the inactivation curve of the current. The magnitude of the window (INa(W)) or resurgent INa (INa(R)) evoked by the respective ascending or descending ramp pulse (Vramp) was reduced during cell exposure to MGB. MGB-induced attenuation in INa(W) or INa(R) was reversed by the further addition of tefluthrin, a pyrethroid insecticide known to stimulate INa. MGB also effectively lessened the strength of voltage-dependent hysteresis of persistent INa in response to the isosceles triangular Vramp. The cumulative inhibition of INa(T), evoked by pulse train stimulation, was enhanced in its presence. Taken together, in addition to the inhibition of CaV channels, the NaV channel attenuation produced by MGB might have an impact in its analgesic effects occurring in vivo.
The Role of Chitooligosaccharidolytic β-N-Acetylglucosamindase in the Molting and Wing Development of the Silkworm Bombyx mori
Authors: Zhang Bili , Li Chunlin , Luan Yue , Lu Yaru , Hu Hai , Liu Yanyu , Lu Kunpeng , Zhang Guizheng , Dai Fangyin , Tong Xiaoling
Published: April 2022

The insect glycoside hydrolase family 20 β-N-acetylhexosaminidases (HEXs) are key enzymes involved in chitin degradation. In this study, nine HEX genes in Bombyx mori were identified by genome-wide analysis. Bioinformatic analysis based on the transcriptome database indicated that each gene had a distinct expression pattern. qRT-PCR was performed to detect the expression pattern of the chitooligosaccharidolytic β-N-acetylglucosaminidase (BmChiNAG). BmChiNAG was highly expressed in chitin-rich tissues, such as the epidermis. In the wing disc and epidermis, BmChiNAG has the highest expression level during the wandering stage. CRISPR/Cas9-mediated BmChiNAG deletion was used to study the function. In the BmChiNAG-knockout line, 39.2% of female heterozygotes had small and curly wings. The ultrastructure of a cross-section showed that the lack of BmChiNAG affected the stratification of the wing membrane and the formation of the correct wing vein structure. The molting process of the homozygotes was severely hindered during the larva to pupa transition. Epidermal sections showed that the endocuticle of the pupa was not degraded in the mutant. These results indicate that BmChiNAG is involved in chitin catabolism and plays an important role in the molting and wing development of the silkworm, which highlights the potential of BmChiNAG as a pest control target.
Dimerization Activity of a Disordered N-Terminal Domain from Drosophila CLAMP Protein
Authors: Tikhonova Evgeniya , Mariasina Sofia , Arkova Olga , Maksimenko Oksana , Georgiev Pavel , Bonchuk Artem
Published: April 2022

In Drosophila melanogaster, CLAMP is an essential zinc-finger transcription factor that is involved in chromosome architecture and functions as an adaptor for the dosage compensation complex. Most of the known Drosophila architectural proteins have structural N-terminal homodimerization domains that facilitate distance interactions. Because CLAMP performs architectural functions, we tested its N-terminal region for the presence of a homodimerization domain. We used a yeast two-hybrid assay and biochemical studies to demonstrate that the adjacent N-terminal region between 46 and 86 amino acids is capable of forming homodimers. This region is conserved in CLAMP orthologs from most insects, except Hymenopterans. Biophysical techniques, including nuclear magnetic resonance (NMR) and small-angle X-ray scattering (SAXS), suggested that this domain lacks secondary structure and has features of intrinsically disordered regions despite the fact that the protein structure prediction algorithms suggested the presence of beta-sheets. The dimerization domain is essential for CLAMP functions in vivo because its deletion results in lethality. Thus, CLAMP is the second architectural protein after CTCF that contains an unstructured N-terminal dimerization domain.
PEDOT-Carbon Nanotube Counter Electrodes and Bipyridine Cobalt (II/III) Mediators as Universally Compatible Components in Bio-Sensitized Solar Cells Using Photosystem I and Bacteriorhodopsin
Authors: Teodor Alexandra H. , Monge Stephanie , Aguilar Dariana , Tames Alexandra , Nunez Roger , Gonzalez Elaine , Rodríguez Juan J. Montero , Bergkamp Jesse J. , Starbird Ricardo , Renugopalakrishnan Venkatesan , Bruce Barry D. , Villarreal Claudia
Published: April 2022

In nature, solar energy is captured by different types of light harvesting protein–pigment complexes. Two of these photoactivatable proteins are bacteriorhodopsin (bR), which utilizes a retinal moiety to function as a proton pump, and photosystem I (PSI), which uses a chlorophyll antenna to catalyze unidirectional electron transfer. Both PSI and bR are well characterized biochemically and have been integrated into solar photovoltaic (PV) devices built from sustainable materials. Both PSI and bR are some of the best performing photosensitizers in the bio-sensitized PV field, yet relatively little attention has been devoted to the development of more sustainable, biocompatible alternative counter electrodes and electrolytes for bio-sensitized solar cells. Careful selection of the electrolyte and counter electrode components is critical to designing bio-sensitized solar cells with more sustainable materials and improved device performance. This work explores the use of poly (3,4-ethylenedioxythiophene) (PEDOT) modified with multi-walled carbon nanotubes (PEDOT/CNT) as counter electrodes and aqueous-soluble bipyridine cobaltII/III complexes as direct redox mediators for both PSI and bR devices. We report a unique counter electrode and redox mediator system that can perform remarkably well for both bio-photosensitizers that have independently evolved over millions of years. The compatibility of disparate proteins with common mediators and counter electrodes may further the improvement of bio-sensitized PV design in a way that is more universally biocompatible for device outputs and longevity.
CsSWEET2, a Hexose Transporter from Cucumber (Cucumis sativus L.), Affects Sugar Metabolism and Improves Cold Tolerance in Arabidopsis
Authors: Hu Liping , Zhang Feng , Song Shuhui , Yu Xiaolu , Ren Yi , Zhao Xuezhi , Liu Huan , Liu Guangmin , Wang Yaqin , He Hongju
Published: April 2022

Sugars, which are critical osmotic compounds and signalling molecules in plants, and Sugars Will Eventually be Exported Transporters (SWEETs), which constitute a novel family of sugar transporters, play central roles in plant responses to multiple abiotic stresses. In the present study, a member of the SWEET gene family from cucumber (Cucumis sativus L.), CsSWEET2, was identified and characterized. Histochemical analysis of β-glucuronidase expression in transgenic Arabidopsis plants showed that CsSWEET2 is highly expressed in the leaves; subcellular localization indicated that CsSWEET2 proteins are localized in the plasma membrane and endoplasmic reticulum. Heterologous expression assays in yeast demonstrated that CsSWEET2 encodes an energy-independent hexose/H+ uniporter that can complement both glucose and fructose transport deficiencies. Compared with wild-type Arabidopsis plants, transgenic Arabidopsis plants overexpressing CsSWEET2 had much lower relative electrolyte leakage levels and were much more resistant to cold stress. Sugar content analysis showed that glucose and fructose levels in the transgenic Arabidopsis plants were significantly higher than those in the wild-type plants. Taken together, our results suggest that, by mediating sugar metabolism and compartmentation, CsSWEET2 plays a vital role in improving plant cold tolerance.
New Perspectives in Treating Acute Myeloid Leukemia: Driving towards a Patient-Tailored Strategy
Authors: Andreozzi Fabio , Massaro Fulvio , Wittnebel Sebastian , Spilleboudt Chloé , Lewalle Philippe , Salaroli Adriano
Published: April 2022

For decades, intensive chemotherapy (IC) has been considered the best therapeutic option for treating acute myeloid leukemia (AML), with no curative option available for patients who are not eligible for IC or who have had failed IC. Over the last few years, several new drugs have enriched the therapeutic arsenal of AML treatment for both fit and unfit patients, raising new opportunities but also new challenges. These include the already approved venetoclax, the IDH1/2 inhibitors enasidenib and ivosidenib, gemtuzumab ozogamicin, the liposomal daunorubicin/cytarabine formulation CPX-351, and oral azacitidine. Venetoclax, an anti BCL2-inhibitor, in combination with hypomethylating agents (HMAs), has markedly improved the management of unfit and elderly patients from the perspective of improved quality of life and better survival. Venetoclax is currently under investigation in combination with other old and new drugs in early phase trials. Recently developed drugs with different mechanisms of action and new technologies that have already been investigated in other settings (BiTE and CAR-T cells) are currently being explored in AML, and ongoing trials should determine promising agents, more synergic combinations, and better treatment strategies. Access to new drugs and inclusion in clinical trials should be strongly encouraged to provide scientific evidence and to define the future standard of treatment in AML.
Silkworm Gut Fibres from Silk Glands of Samia cynthia ricini—Potential Use as a Scaffold in Tissue Engineering
Authors: Aznar-Cervantes Salvador D. , Pagán Ana , Candel María J. , Pérez-Rigueiro José , Cenis José L.
Published: April 2022

High-performance fibroin fibres are ideal candidates for the manufacture of scaffolds with applications in tissue engineering due to the excellent mechanical properties and optimal biocompatibility of this protein. In this work, the manufacture of high-strength fibres made from the silk glands of Samia cynthia ricini is explored. The glands were subjected to soaking in aqueous dissolutions of acetic acid and stretched to manufacture the fibres. The materials produced were widely characterized, in terms of morphology, mechanical properties, crystallinity and content of secondary structures, comparing them with those produced by the standard procedure published for Bombyx mori. In addition, mechanical properties and biocompatibility of a braided scaffold produced from these fibres was evaluated. The results obtained show that the fibres from B. mori present a higher degree of crystallinity than those from S. c. ricini, which is reflected in higher values of elastic modulus and lower values of strain at break. Moreover, a decrease in the elongation values of the fibres from S. c. ricini was observed as the concentration of acetic acid was increased during the manufacture. On the other hand, the study of the braided scaffolds showed higher values of tensile strength and strain at break in the case of S. c. ricini materials and similar values of elastic modulus, compared to those of B. mori, displaying both scaffolds optimal biocompatibility using a fibroblast cell line.
Curcuminoids Inhibit Angiogenic Behaviors of Human Umbilical Vein Endothelial Cells via Endoglin/Smad1 Signaling
Authors: Chou Yi-Fan , Lan Yu-Hsuan , Hsiao Jun-Han , Chen Chiao-Yun , Chou Pei-Yu , Sheu Ming-Jyh
Published: April 2022

Background: Angiogenesis is primarily attributed to the excessive proliferation and migration of endothelial cells. Targeting the vascular endothelial growth factor (VEGF) is therefore significant in anti-angiogenic therapy. Although these treatments have not reached clinical expectations, the upregulation of alternative angiogenic pathways (endoglin/Smad1) may play a critical role in drug (VEGF-neutralizing agents) resistance. Enhanced endoglin expression following a VEGF-neutralizing therapy (semaxanib®) was noted in patients. Treatment with an endoglin-targeting antibody augmented VEGF expression in human umbilical vein endothelial cells (HUVECs). Therefore, approaches that inhibit both the androgen and VEGF pathways enhance the HUVECs cytotoxicity and reverse semaxanib resistance. The purpose of this study was to find natural-occurring compounds that inhibited the endoglin-targeting pathway. Methods: Curcuminoids targeting endoglin were recognized from two thousand compounds in the Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan) using Discovery Studio 4.5. Results: Our results, obtained using cytotoxicity, migration/invasion, and flow cytometry assays, showed that curcumin (Cur) and demethoxycurcumin (DMC) reduced angiogenesis. In addition, Cur and DMC downregulated endoglin/pSmad1 phosphorylation. Conclusions: The study first showed that Cur and DMC demonstrated antiangiogenic activity via the inhibition of endoglin/Smad1 signaling. Synergistic effects of curcuminoids (i.e., curcumin and DMC) and semaxanib on HUVECs were found. This might be attributed to endoglin/pSmad1 downregulation in HUVECs. Combination treatment with curcuminoids and a semaxanib is therefore expected to reverse semaxanib resistance.
Visualizing Cell Death in Live Retina: Using Calpain Activity Detection as a Biomarker for Retinal Degeneration
Authors: Belhadj Soumaya , Hermann Nina Sofia , Zhu Yu , Christensen Gustav , Strasser Torsten , Paquet-Durand François
Published: April 2022

Calpains are a family of calcium-activated proteases involved in numerous disorders. Notably, previous studies have shown that calpain activity was substantially increased in various models for inherited retinal degeneration (RD). In the present study, we tested the capacity of the calpain-specific substrate t-BOC-Leu-Met-CMAC to detect calpain activity in living retina, in organotypic retinal explant cultures derived from wild-type mice, as well as from rd1 and RhoP23H/+ RD-mutant mice. Test conditions were refined until the calpain substrate readily detected large numbers of cells in the photoreceptor layer of RD retina but not in wild-type retina. At the same time, the calpain substrate was not obviously toxic to photoreceptor cells. Comparison of calpain activity with immunostaining for activated calpain-2 furthermore suggested that individual calpain isoforms may be active in distinct temporal stages of photoreceptor cell death. Notably, calpain-2 activity may be a relatively short-lived event, occurring only towards the end of the cell-death process. Finally, our results support the development of calpain activity detection as a novel in vivo biomarker for RD suitable for combination with non-invasive imaging techniques.
The Cerebellar Involvement in Autism Spectrum Disorders: From the Social Brain to Mouse Models
Authors: Mapelli Lisa , Soda Teresa , D’Angelo Egidio , Prestori Francesca
Published: April 2022

Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders that include a variety of forms and clinical phenotypes. This heterogeneity complicates the clinical and experimental approaches to ASD etiology and pathophysiology. To date, a unifying theory of these diseases is still missing. Nevertheless, the intense work of researchers and clinicians in the last decades has identified some ASD hallmarks and the primary brain areas involved. Not surprisingly, the areas that are part of the so-called “social brain”, and those strictly connected to them, were found to be crucial, such as the prefrontal cortex, amygdala, hippocampus, limbic system, and dopaminergic pathways. With the recent acknowledgment of the cerebellar contribution to cognitive functions and the social brain, its involvement in ASD has become unmistakable, though its extent is still to be elucidated. In most cases, significant advances were made possible by recent technological developments in structural/functional assessment of the human brain and by using mouse models of ASD. Mouse models are an invaluable tool to get insights into the molecular and cellular counterparts of the disease, acting on the specific genetic background generating ASD-like phenotype. Given the multifaceted nature of ASD and related studies, it is often difficult to navigate the literature and limit the huge content to specific questions. This review fulfills the need for an organized, clear, and state-of-the-art perspective on cerebellar involvement in ASD, from its connections to the social brain areas (which are the primary sites of ASD impairments) to the use of monogenic mouse models.
Additive Manufacturing of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Poly(D,L-lactide-co-glycolide) Biphasic Scaffolds for Bone Tissue Regeneration
Authors: Pecorini Gianni , Braccini Simona , Parrini Gianluca , Chiellini Federica , Puppi Dario
Published: April 2022

Polyhydroxyalkanoates are biopolyesters whose biocompatibility, biodegradability, environmental sustainability, processing versatility, and mechanical properties make them unique scaffolding polymer candidates for tissue engineering. The development of innovative biomaterials suitable for advanced Additive Manufacturing (AM) offers new opportunities for the fabrication of customizable tissue engineering scaffolds. In particular, the blending of polymers represents a useful strategy to develop AM scaffolding materials tailored to bone tissue engineering. In this study, scaffolds from polymeric blends consisting of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(D,L-lactide-co-glycolide) (PLGA) were fabricated employing a solution-extrusion AM technique, referred to as Computer-Aided Wet-Spinning (CAWS). The scaffold fibers were constituted by a biphasic system composed of a continuous PHBV matrix and a dispersed PLGA phase which established a microfibrillar morphology. The influence of the blend composition on the scaffold morphological, physicochemical, and biological properties was demonstrated by means of different characterization techniques. In particular, increasing the content of PLGA in the starting solution resulted in an increase in the pore size, the wettability, and the thermal stability of the scaffolds. Overall, in vitro biological experiments indicated the suitability of the scaffolds to support murine preosteoblast cell colonization and differentiation towards an osteoblastic phenotype, highlighting higher proliferation for scaffolds richer in PLGA.
The Chromatin Architectural Protein CTCF Is Critical for Cell Survival upon Irradiation-Induced DNA Damage
Authors: Mamberti Stefania , Pabba Maruthi K. , Rapp Alexander , Cardoso M. Cristina , Scholz Michael
Published: April 2022

CTCF is a nuclear protein initially discovered for its role in enhancer-promoter insulation. It has been shown to play a role in genome architecture and in fact, its DNA binding sites are enriched at the borders of chromatin domains. Recently, we showed that depletion of CTCF impairs the DNA damage response to ionizing radiation. To investigate the relationship between chromatin domains and DNA damage repair, we present here clonogenic survival assays in different cell lines upon CTCF knockdown and ionizing irradiation. The application of a wide range of ionizing irradiation doses (0–10 Gy) allowed us to investigate the survival response through a biophysical model that accounts for the double-strand breaks’ probability distribution onto chromatin domains. We demonstrate that the radiosensitivity of different cell lines is increased upon lowering the amount of the architectural protein. Our model shows that the deficiency in the DNA repair ability is related to the changes in the size of chromatin domains that occur when different amounts of CTCF are present in the nucleus.