bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Spatial Correlations of Tourism Ecological Security in China: A Perspective from Social Network Analysis
Authors: Wang Zhaofeng , Huang Dongchun , Wang Jing
Published: February 2023

The imbalance of regional tourism ecological security (TES) is an important barrier to the sustainable development of tourism. Relying on the spatial correlation network to coordinate the regional TES is effective. Taking 31 provinces in China as examples, social network analysis (SNA) and the quadratic assignment procedure (QAP) are used to analyze the spatial network structure of TES and its influencing factors. The results show that (1) the network density and the number of network relationships increased, while the network efficiency remained at approximately 0.7, and the network hierarchy decreased from 0.376 to 0.234. (2) Jiangsu, Guangdong, Shandong, Zhejiang, and Henan were always more central than the average and dominated. Anhui, Shanghai, and Guangxi have much lower centrality degrees than the average, with little effect on other provinces. (3) The TES networks could be divided into four parts: “net spillover”, “agent”, “bidirectional spillover” and “net benefit”. (4) The differences in economic development level, tourism industry dependence, tourism load level, educational attainment, investment in environmental governance, and transportation accessibility all had a negative impact on the TES spatial network, whereas geographic proximity had a positive driving effect. In conclusion, the spatial correlation network of provincial TES in China is increasingly close, but the network structure is loose and hierarchical. The core–edge structure is obvious, and there are significant spatial autocorrelations and spatial spillover effects between provinces. The difference in regional influencing factors has a significant effect on the TES network. This paper presents a new research framework for the spatial correlation of TES and provides a Chinese solution to promote the sustainable development of tourism.
Low-Frequency Noise: Experiences from a Low-Frequency Noise Perceiving Population
Authors: Erdélyi Kristina H. , Fuermaier Anselm B. M. , Tucha Lara , Tucha Oliver , Koerts Janneke
Published: February 2023

Although low-frequency noise (LFN) is associated with various complaints, there is still much unknown about this phenomenon. This research aims to provide an extensive description of (1) LFN perceptions, (2) LFN-related complaints, and (3) the characteristics of LFN complainants. In an explorative observational cross-sectional survey study, a sample of Dutch adults reporting to experience LFN (n = 190) and a group not experiencing LFN (n = 371) completed a comprehensive questionnaire. Descriptions of LFN perceptions varied individually and were dependent on different circumstances, although some common patterns were observed. Complaints were wide-ranging and individual, with a reported high impact on daily living. Common complaints included sleeping difficulties, fatigue, or annoyance. Societal consequences were described regarding housing, work, and relationships. Attempts to stop or escape the perception were manifold but often unsuccessful. The LFN sample differed regarding sex, education level, and age from the Dutch adult population, indicating more frequent inability to work, less full-time work, and less years lived in their homes. No further differences in occupational or marital status or living circumstances were found. Although this research supports some previous findings and identifies common patterns, it also highlights the individual nature of LFN-related experiences and the heterogeneity of this group. It is advised to pay attention to the complaints of affected individuals, to inform concerned authorities, and to conduct more systematic and multidisciplinary research using standardized and validated measuring instruments.
Associations of Clusters of Cardiovascular Risk Factors with Insulin Resistance and Β-Cell Functioning in a Working-Age Diabetic-Free Population in Kazakhstan
Authors: Saruarov Yerbolat , Nuskabayeva Gulnaz , Gencer Mehmet Ziya , Sadykova Karlygash , Zhunissova Mira , Tatykayeva Ugilzhan , Iskandirova Elmira , Sarsenova Gulmira , Durmanova Aigul , Gaipov Abduzhappar , Atageldiyeva Kuralay , Sarría-Santamera Antonio
Published: February 2023

Cardiovascular risk factors aggregate in determined individuals. Patients with Type 2 diabetes mellitus (T2DM) have higher cardiovascular This study aimed to investigate insulinresistance (IR) and β-cell function using the homeostasis model assessment (HOMA) indexes in a general Kazakh population and determine the effect he effect that cardiovascular factors may have on those indexes. We conducted a cross-sectional study among employees of the Khoja Akhmet Yassawi International Kazakh-Turkish University (Turkistan, Kazakhstan) aged between 27 and 69 years. Sociodemographic variables, anthropometric measurements (body mass, height, waist circumference, hip circumference), and blood pressure were obtained. Fasting blood samples were collected to measure insulin, glucose, total cholesterol (TC), triglycerides (TG), and high- (HDL) andlow-density lipoprotein (LDL) levels. Oral glucose tolerance tests were performed. Hierarchical and K-means cluster analyses were obtained. The final sample was composed of 427 participants. Spearmen correlation analysis showed that cardiovascular parameters were statistically associated with HOMA-β (p < 0.001) and not with HOMA IR. Participants were aggregated into the three clusters where the cluster with a higher age and cardiovascular risk revealed deficient β-cell functioning, but not IR (p < 0.000 and p = 0.982). Common and easy to obtain biochemical and anthropometric measurements capturing relevant cardiovascular risk factors have been demonstrated to be associated with significant deficiency in insulin secretion. Although further longitudinal studies of the incidence of T2DM are needed, this study highlights that cardiovascular profiling has a significant role not just for risk stratification of patients for cardiovascular prevention but also for targeted vigilant glucose monitoring.
Molecular Mechanisms of Tebuconazole Affecting the Social Behavior and Reproduction of Zebrafish
Authors: Yan Wei , Li Guangyu , Lu Qiqi , Hou Jianjun , Pan Meiqi , Peng Maomin , Peng Xitian , Wan Hui , Liu Xixia , Wu Qin
Published: February 2023

The aim of this study was to explore the underlying mechanism of adverse effects caused by tebuconazole (TEB) on the reproduction of aquatic organisms In the present study, in order to explore the effects of TEB on reproduction, four-month-old zebrafish were exposed to TEB (0, DMSO, 0.4 mg/L, 0.8 mg/L, and 1.6 mg/L) for 21 days. After exposure, the accumulations of TEB in gonads were observed and the cumulative egg production was evidently decreased. The decline of fertilization rate in F1 embryos was also observed. Then the changes in sperm motility and histomorphology of gonads were discovered, evaluating that TEB had adverse effects on gonadal development. Additionally, we also found the alternations of social behavior, 17β-estradiol (E2) level, and testosterone (T) level. Furthermore, the expression levels of genes involved in the hypothalamic-pituitary-gonadal (HPG) axis and social behavior were remarkably altered. Taken together, it could be concluded that TEB affected the egg production and fertilization rate by interfering with gonadal development, sex hormone secretion, and social behavior, which were eventually attributed to the disruption of the expressions of genes associated with the HPG axis and social behavior. This study provides a new perspective to understanding the mechanism of TEB-induced reproductive toxicity.
The Predicament and Outlet of Environmental Impact Assessment Mechanism from the Perspective of Risk Society: Taking Japan’s Accident-Type Nuclear Sewage Disposal as a Cut-In
Authors: Zhang Qiang , Yang Fang , Chen Yaru
Published: February 2023

As an important yardstick of social modernization, nuclear technology not only promotes the in-depth development of the national economy but also hangs a sword of Damocles in the field of the risk society. Against the background of the unrest of the nuclear leakage disaster at the Fukushima nuclear power plant, the Japanese government has announced its unilateral decision to discharge nuclear sewage into the sea, undoubtedly putting at least the Pacific Rim countries at huge potential risks. In order to maximize risk reduction and focus on preventive construction in advance, Japan’s measures to discharge accident nuclear sewage into the sea have a legitimate basis for the application of an environmental impact assessment system. At the same time, in the process of operation, there are numerous risk dilemmas, such as lack of safety treatment standards, long follow-up disposal cycle and negative domestic supervision system, which need to be broken through one by one. The effective application of the environmental impact assessment system in the Japanese nuclear accident not only helps to reduce the environmental crisis caused by accidental nuclear effluent discharge to the sea but also has a positive and far-reaching international demonstration significance, which helps to better build a foundation of international trust and preventive guarantee system in advance for the possible accidental nuclear effluent treatment in the future.
Eldercare’s Turnover Intention and Human Resource Approach: A Systematic Review
Authors: Jurij Rahimah , Ismail Ida Rosnita , Alavi Khadijah , Alavi Rokiah
Published: February 2023

Eldercare workers’ turnover intentions have caused serious concern given their high demand and pivotal role in ensuring elderly individuals’ well-being. This systematic review examined the main factors of eldercare employees’ turnover intentions with the purpose of identifying gaps and structure a novel human resource (HR) approach framework for eldercare social enterprises through a global literature review and realistic conclusions. A total of 29 publications appeared between 2015 and 2021 were digitally extracted from six databases and are extensively discussed in this review. Resultantly, eldercare workers’ turnover intentions were positively impacted by job burnout, low job motivation, and restricted job autonomy. The findings of this study correspond to those of past literature, which highlighted the necessity of thoroughly examining eldercare worker retention practices from an organisational (HR) perspective. Furthermore, the current study outlines the factors influencing eldercare workers’ turnover intentions as well as determine proper HR approaches to mitigate employee turnover issues among eldercare workers for organisational sustainability.
Assessing the Efficacy of a Virtual Assistant in the Remote Cardiac Rehabilitation of Heart Failure and Ischemic Heart Disease Patients: Case-Control Study of Romanian Adult Patients
Authors: Lăcraru Andreea-Elena , Busnatu Ștefan-Sebastian , Pană Maria-Alexandra , Olteanu Gabriel , Șerbănoiu Liviu , Gand Kai , Schlieter Hannes , Kyriazakos Sofoklis , Ceban Octavian , Andrei Cătălina Liliana , Sinescu Crina-Julieta
Published: February 2023

Cardiovascular diseases (CVDs) are the leading cause of mortality in Europe, with potentially more than 60 million deaths per year, with an age-standardized rate of morbidity-mortality higher in men than women, exceeding deaths from cancer. Heart attacks and strokes account for more than four out of every five CVD fatalities globally. After a patient overcomes an acute cardiovascular event, they are referred for rehabilitation to help them to restore most of their normal cardiac functions. One effective way to provide this activity regimen is via virtual models or telerehabilitation, where the patient can avail themselves of the rehabilitation services from the comfort of their homes at designated timings. Under the funding of the European Union’s Horizon 2020 Research and Innovation program, grant no 769807, a virtual rehabilitation assistant has been designed for elderly patients (vCare), with the overall objective of supporting recovery and an active life at home, enhancing patients’ quality of life, lowering disease-specific risk factors, and ensuring better adherence to a home rehabilitation program. In the vCare project, the Carol Davila University of Bucharest (UMFCD) was in charge of the heart failure (HF) and ischemic heart disease (IHD) groups of patients. By creating a digital environment at patients’ homes, the vCare system’s effectiveness, use, and feasibility was evaluated. A total of 30 heart failure patients and 20 ischemic heart disease patients were included in the study. Despite the COVID-19 restrictions and a few technical difficulties, HF and IHD patients who performed cardiac rehabilitation using the vCare system had similar results compared to the ambulatory group, and better results compared to the control group.
The Influence of Hip and Knee Joint Angles on Quadriceps Muscle-Tendon Unit Properties during Maximal Voluntary Isometric Contraction
Authors: de Sousa Alessandra Martins Melo , Cavalcante Jonathan Galvão Tenório , Bottaro Martim , Vieira Denis César Leite , Babault Nicolas , Geremia Jeam Marcel , Corrigan Patrick , Silbernagel Karin Grävare , Durigan João Luiz Quaglioti , Marqueti Rita de Cássia
Published: February 2023

Determining how the quadriceps femoris musculotendinous unit functions, according to hip and knee joint angles, may help with clinical decisions when prescribing knee extension exercises. We aimed to determine the effect of hip and knee joint angles on structure and neuromuscular functioning of all constituents of the quadriceps femoris and patellar tendon properties. Twenty young males were evaluated in four positions: seated and supine in both 20° and 60° of knee flexion (SIT20, SIT60, SUP20, and SUP60). Peak knee extension torque was determined during maximal voluntary isometric contraction (MVIC). Ultrasound imaging was used at rest and during MVIC to characterize quadriceps femoris muscle and tendon aponeurosis complex stiffness. We found that peak torque and neuromuscular efficiency were higher for SUP60 and SIT60 compared to SUP20 and SIT20 position. We found higher fascicle length and lower pennation angle in positions with the knee flexed at 60°. The tendon aponeurosis complex stiffness, tendon force, stiffness, stress, and Young’s modulus seemed greater in more elongated positions (60°) than in shortened positions (20°). In conclusion, clinicians should consider positioning at 60° of knee flexion rather than 20°, regardless if seated or supine, during rehabilitation to load the musculotendinous unit enough to stimulate a cellular response.
How COVID-19 News Affect Older Adults’ Mental Health—Evidence of a Positivity Bias
Authors: Ng Zoe Ziyi , Li Grace , Flynn Suzanne , Yow W. Quin
Published: February 2023

Background: Media affects the trajectory of many individuals’ mental health—with media news, individuals experience negative bias more than positive bias. However, there is also evidence of an age-related positivity effect, with negativity bias generally fading with age. With the rise of COVID-19 cases, older adults (aged 55 years and older) who consume media frequently are at a high risk for declining mental health. To date, there has been no research on the positivity vs. negativity bias of media news on older adults. Here, we investigated whether positivity or negativity bias plays a larger role in affecting how older adults react to COVID-19 news. Methods: Sixty-nine older adults (aged 55–95) answered questions about their weekly media consumption and how closely they followed news relating to COVID-19. They also completed a general health questionnaire. They were then randomly assigned to read either positive or negative COVID-19 news (n = 35 and 34, respectively). The adults were asked if the news made them feel happy or fearful, and if they wanted to read more about the news or ignore the news. Results: An analysis revealed that the more often older adults consumed media and the more closely they followed COVID-19 news, the more they felt unhappy and depressed. Importantly, older adults who read positive news reported stronger responses than those who read negative news. Older adults appeared to have a strong positivity bias for COVID-19 news, reporting feeling happy and wanting to read about positive news. In contrast, negative COVID-19 news did not evoke similar levels of response from the older adults. Conclusions: Media consumption of COVID-19 news does negatively impact the mental well-being of older adults, but older adults appear to have a strong positivity bias and a lack of negativity bias for COVID-19 news. These findings suggest that older adults can remain hopeful and positive during periods of public health crises and intense stress, which is essential to sustaining their mental well-being during difficult times.
Systematic Review: Neurodevelopmental Benefits of Active/Passive School Exposure to Green and/or Blue Spaces in Children and Adolescents
Authors: Díaz-Martínez Francisco , Sánchez-Sauco Miguel F. , Cabrera-Rivera Laura T. , Sánchez Carlos Ojeda , Hidalgo-Albadalejo Maria D. , Claudio Luz , Ortega-García Juan A.
Published: February 2023

Today more than half of the world’s population lives in urban areas. Children spend about 40 h a week in the school environment. Knowing the influence of school exposure to green/blue spaces could improve the children’s health, creating healthier environments and preventing exposure to legal/illegal drugs. This systematic review summarized the main results of published studies on active or passive exposure to green or blue spaces in different domains of child neurodevelopment. In August 2022, five databases were searched and twenty-eight eligible studies were included in the analysis. Cognitive and/or academic performance was the most frequently studied (15/28). Most studies evaluate passive exposure to green/blue spaces (19/28) versus active exposure (9/28). Only three studies addressed the relationship between blue space and neurodevelopment. The main results point toward mixed evidence of a protective relationship between green/blue space exposure and neurodevelopment, especially in improving cognitive/academic performance, attention restoration, behavior, and impulsivity. Renaturalizing school spaces and promoting “greener” capacities for school environmental health could improve children’s neurodevelopment. There was great heterogeneity in methodologies and adjustment for confounding factors across studies. Future research should seek a standardized approach to delivering school environmental health interventions beneficial to children’s development.
Applying Nudge to Public Health Policy: Practical Examples and Tips for Designing Nudge Interventions
Authors: Murayama Hiroshi , Takagi Yusuke , Tsuda Hirokazu , Kato Yuri
Published: February 2023

Given the cost-effective nature of promoting desirable behaviors among individuals and societies, national and local governments have widely applied the nudge concept in various public policy fields. This viewpoint briefly explains the concept of nudge and presents the trend of nudge application in public health policy with illustrative examples. While most academic evidence on its effectiveness has been derived from Western countries, there is a significant accumulation of cases of nudge practices in non-Western countries, including the Western Pacific nations. This viewpoint also provides tips for designing nudge interventions. We introduce a simple, three-step procedure for this purpose: (1) identify target behavior, (2) determine friction and fuel of the behavior, and (3) design and implement a nudge—as well as the behavioral process map and the EAST framework.
Impact of Clinical Pharmacist Consultations on Postoperative Pain in Ambulatory Surgery
Authors: Barat Eric , Chenailler Catherine , Gillibert André , Pouplin Sophie , Varin Remi , Compere Vincent
Published: February 2023

Post-operative pain is a common symptom of ambulatory surgery. The objective of this study was to evaluate a pain management protocol integrating a pharmacist consultation. We conducted a quasi-experimental, single center, before-after study. The control group was recruited between 1 March and 31 May 2018 and the intervention group between 1 March and 31 May 2019. Outpatients in the intervention group received a pharmacist consultation, in addition to the usual anesthesiologist and nurse consultations. Pharmacist consultations were conducted in two steps: the first step consisted of general open-ended questions and the second step of a specific and individualized pharmaceutical interview. A total of 125 outpatients were included in each group. There were 17% (95% CI 5 to 27%, p = 0.022) fewer patients with moderate to severe pain in the pharmaceutical intervention group compared with the control group, which corresponded to a decrease in the mean pain level of 0.9/10 (95% CI −1.5/10; −0.3/10; p = 0.002). The multivariate analysis did not reveal any confounding factors, showing that only the pharmaceutical intervention could explain this result. This study demonstrates a positive impact of pharmacist consultations on postoperative pain in ambulatory surgery.
Comparison of Nutri-Score and Health Star Rating Nutrient Profiling Models Using Large Branded Foods Composition Database and Sales Data
Authors: Hafner Edvina , Pravst Igor
Published: February 2023

Front-of-package nutrition labelling (FOPNL) is known as an effective tool that can encourage healthier food choices and food reformulation. A very interesting type of FOPNL is grading schemes. Our objective was to compare two market-implemented grading schemes—European Nutri-Score (NS) and Australian Health Star Rating (HSR), using large Slovenian branded foods database. NS and HSR were used for profiling 17,226 pre-packed foods and drinks, available in Slovenian food supply dataset (2020). Alignment between models was evaluated with agreement (% of agreement and Cohen’s Kappa) and correlation (Spearman rho). The 12-month nationwide sales-data were used for sale-weighing, to address market-share differences. Study results indicated that both models have good discriminatory ability between products based on their nutritional composition. NS and HSR ranked 22% and 33% of Slovenian food supply as healthy, respectively. Agreement between NS and HSR was strong (70%, κ = 0.62) with a very strong correlation (rho = 0.87). Observed profiling models were most aligned within food categories Beverages and Bread and bakery products, while less aligned for Dairy and imitates and Edible oils and emulsions. Notable disagreements were particularly observed in subcategories of Cheese and processed cheeses (8%, κ = 0.01, rho = 0.38) and Cooking oils (27%, κ = 0.11, rho = 0.40). Further analysis showed that the main differences in Cooking oils were due to olive oil and walnut oil, which are favoured by NS and grapeseed, flaxseed and sunflower oil that are favoured by HSR. For Cheeses and cheese products, we observed that HSR graded products across the whole scale, with majority (63%) being classified as healthy (≥3.5 *), while NS mostly graded lower scores. Sale-weighting analyses showed that offer in the food supply does not always reflect the sales. Sale-weighting increased overall agreement between profiles from 70% to 81%, with notable differences between food categories. In conclusion, NS and HSR were shown as highly compliant FOPNLs with few divergences in some subcategories. Even these models do not always grade products equally high, very similar ranking trends were observed. However, the observed differences highlight the challenges of FOPNL ranking schemes, which are tailored to address somewhat different public health priorities in different countries. International harmonization can support further development of grading type nutrient profiling models for the use in FOPNL, and make those acceptable for more stake-holders, which will be crucial for their successful regulatory implementation.
Measuring Sleep Quality in the Hospital Environment with Wearable and Non-Wearable Devices in Adults with Stroke Undergoing Inpatient Rehabilitation
Authors: Pellegrini Michael , Lannin Natasha A. , Mychasiuk Richelle , Graco Marnie , Kramer Sharon Flora , Giummarra Melita J.
Published: February 2023

Sleep disturbances are common after stroke and may affect recovery and rehabilitation outcomes. Sleep monitoring in the hospital environment is not routine practice yet may offer insight into how the hospital environment influences post-stroke sleep quality while also enabling us to investigate the relationships between sleep quality and neuroplasticity, physical activity, fatigue levels, and recovery of functional independence while undergoing rehabilitation. Commonly used sleep monitoring devices can be expensive, which limits their use in clinical settings. Therefore, there is a need for low-cost methods to monitor sleep quality in hospital settings. This study compared a commonly used actigraphy sleep monitoring device with a low-cost commercial device. Eighteen adults with stroke wore the Philips Actiwatch to monitor sleep latency, sleep time, number of awakenings, time spent awake, and sleep efficiency. A sub-sample (n = 6) slept with the Withings Sleep Analyzer in situ, recording the same sleep parameters. Intraclass correlation coefficients and Bland–Altman plots indicated poor agreement between the devices. Usability issues and inconsistencies were reported between the objectively measured sleep parameters recorded by the Withings device compared with the Philips Actiwatch. While these findings suggest that low-cost devices are not suitable for use in a hospital environment, further investigations in larger cohorts of adults with stroke are needed to examine the utility and accuracy of off-the-shelf low-cost devices to monitor sleep quality in the hospital environment.
Effects of Comprehensive Rehabilitation on Pulmonary Function in Patients Recovering from COVID-19
Authors: Mińko Alicja , Turoń-Skrzypińska Agnieszka , Rył Aleksandra , Szylińska Aleksandra , Denisewicz Iwona , Rotter Iwona
Published: February 2023

The aim of this study is to evaluate the effect of inpatient rehabilitation on pulmonary function in patients recovering from COVID-19, a multifaceted disease caused by the SARS-CoV-2 virus. This aspect of recovery is crucial, as pneumonia associated with this disease can cause lung-function abnormalities with varying degrees of hypoxemia. This study involved 150 patients qualified for inpatient rehabilitation following SARS-CoV-2 infection. Functional assessment of the lungs was performed by spirometry. The mean age of patients was 64.66 (±11.93) years, and the mean body mass index (BMI) was 29.16 (±5.68). The tests showed a statistically significant improvement in spirometric parameters. The rehabilitation program based on aerobic, strength, and endurance exercises improved lung-function parameters in the long term. The improvement in spirometric parameters in patients after COVID-19 may be related to body mass index (BMI).
Cancer Survivors’ Experiences of Navigating the Australian Health Care System for Physical and Mental Health Care Needs
Authors: Gulliver Amelia , Morse Alyssa R. , Banfield Michelle
Published: February 2023

People living with cancer experience many impacts on their health and mental health, and are thus likely to require ongoing health care. The aim of the current study was to investigate the health and mental health care experiences and needs of Australian cancer survivors. A total of 131 people (119 female, 12 male) with lived experience of a cancer diagnosis (at least 12 months ago) participated in an online survey collecting qualitative and quantitative data, advertised via social media groups and paid advertising. Analysis of the written responses was conducted using inductive qualitative content analysis. The findings showed that a major issue facing cancer survivors was difficulties around access to and management of services for both their mental and physical health. There was also a strong preference for increasing access to allied health care, such as physiotherapy, psychology, and remedial massage. There appear to be some inequities in the experiences of cancer survivors, particularly in accessing care. Improving the experiences of health care for physical and mental health cancer survivors should focus on increasing access to and improving the management of services, specifically allied health, through a variety of avenues, including reducing costs, increasing transport, and providing closer and more co-located services.
Amblyopinae Mitogenomes Provide Novel Insights into the Paraphyletic Origin of Their Adaptation to Mudflat Habitats
Authors: Lü Zhenming , Liu Yantao , Zhao Shijie , Fang Jiaqi , Zhu Kehua , Liu Jing , Gong Li , Liu Liqin , Liu Bingjian
Published: February 2023

The water-to-land transition is one of the most important events in evolutionary history of vertebrates. However, the genetic basis underlying many of the adaptations during this transition remains unclear. Mud-dwelling gobies in the subfamily Amblyopinae are one of the teleosts lineages that show terrestriality and provide a useful system for clarifying the genetic changes underlying adaptations to terrestrial life. Here, we sequenced the mitogenome of six species in the subfamily Amblyopinae. Our results revealed a paraphyletic origin of Amblyopinae with respect to Oxudercinae, which are the most terrestrial fishes and lead an amphibious life in mudflats. This partly explains the terrestriality of Amblyopinae. We also detected unique tandemly repeated sequences in the mitochondrial control region in Amblyopinae, as well as in Oxudercinae, which mitigate oxidative DNA damage stemming from terrestrial environmental stress. Several genes, such as ND2, ND4, ND6 and COIII, have experienced positive selection, suggesting their important roles in enhancing the efficiency of ATP production to cope with the increased energy requirements for life in terrestrial environments. These results strongly suggest that the adaptive evolution of mitochondrial genes has played a key role in terrestrial adaptions in Amblyopinae, as well as in Oxudercinae, and provide new insights into the molecular mechanisms underlying the water-to-land transition in vertebrates.
Dual Transcriptome Analysis Reveals That ChATG8 Is Required for Fungal Development, Melanization and Pathogenicity during the Interaction between Colletotrichum higginsianum and Arabidopsis thaliana
Authors: Zhu Yiming , Duan Lingtao , Zhu Chengqi , Wang Li , He Zhenrui , Yang Mei , Zhou Erxun
Published: February 2023

Anthracnose disease of cruciferous plants caused by Colletotrichum higginsianum is a serious fungal disease that affects cruciferous crops such as Chinese cabbage, Chinese flowering cabbage, broccoli, mustard plant, as well as the model plant Arabidopsis thaliana. Dual transcriptome analysis is commonly used to identify the potential mechanisms of interaction between host and pathogen. In order to identify differentially expressed genes (DEGs) in both the pathogen and host, the conidia of wild-type (ChWT) and Chatg8 mutant (Chatg8Δ) strains were inoculated onto leaves of A. thaliana, and the infected leaves of A. thaliana at 8, 22, 40, and 60 h post-inoculation (hpi) were subjected to dual RNA-seq analysis. The results showed that comparison of gene expression between the ‘ChWT’ and ‘Chatg8Δ’ samples detected 900 DEGs (306 upregulated and 594 down-regulated) at 8 hpi, 692 DEGs (283 upregulated and 409 down-regulated) at 22 hpi, 496 DEGs (220 upregulated and 276 down-regulated) at 40 hpi, and 3159 DEGs (1544 upregulated and 1615 down-regulated) at 60 hpi. GO and KEGG analyses found that the DEGs were mainly involved in fungal development, biosynthesis of secondary metabolites, plant–fungal interactions, and phytohormone signaling. The regulatory network of key genes annotated in the Pathogen–Host Interactions database (PHI-base) and Plant Resistance Genes database (PRGdb), as well as a number of key genes highly correlated with the 8, 22, 40, and 60 hpi, were identified during the infection. Among the key genes, the most significant enrichment was in the gene encoding the trihydroxynaphthalene reductase (THR1) in the melanin biosynthesis pathway. Both Chatg8Δ and Chthr1Δ strains showed varying degrees of reduction of melanin in appressoria and colonies. The pathogenicity of the Chthr1Δ strain was lost. In addition, six DEGs from C. higginsianum and six DEGs from A. thaliana were selected for real-time quantitative PCR (RT-qPCR) to confirm the RNA-seq results. The information gathered from this study enriches the resources available for research into the role of the gene ChATG8 during the infection of A. thaliana by C. higginsianum, such as potential links between melanin biosynthesis and autophagy, and the response of A. thaliana to different fungal strains, thereby providing a theoretical basis for the breeding of cruciferous green leaf vegetable cultivars with resistance to anthracnose disease.
In Vivo Reversal of P-Glycoprotein-Mediated Drug Resistance in a Breast Cancer Xenograft and in Leukemia Models Using a Novel, Potent, and Nontoxic Epicatechin EC31
Authors: Sun Wenqin , Wong Iris L. K. , Law Helen Ka-Wai , Su Xiaochun , Chan Terry C. F. , Sun Gege , Yang Xinqing , Wang Xingkai , Chan Tak Hang , Wan Shengbiao , Chow Larry M. C.
Published: February 2023

The modulation of P-glycoprotein (P-gp, ABCB1) can reverse multidrug resistance (MDR) and potentiate the efficacy of anticancer drugs. Tea polyphenols, such as epigallocatechin gallate (EGCG), have low P-gp-modulating activity, with an EC50 over 10 μM. In this study, we optimized a series of tea polyphenol derivatives and demonstrated that epicatechin EC31 was a potent and nontoxic P-gp inhibitor. Its EC50 for reversing paclitaxel, doxorubicin, and vincristine resistance in three P-gp-overexpressing cell lines ranged from 37 to 249 nM. Mechanistic studies revealed that EC31 restored intracellular drug accumulation by inhibiting P-gp-mediated drug efflux. It did not downregulate the plasma membrane P-gp level nor inhibit P-gp ATPase. It was not a transport substrate of P-gp. A pharmacokinetic study revealed that the intraperitoneal administration of 30 mg/kg of EC31 could achieve a plasma concentration above its in vitro EC50 (94 nM) for more than 18 h. It did not affect the pharmacokinetic profile of coadministered paclitaxel. In the xenograft model of the P-gp-overexpressing LCC6MDR cell line, EC31 reversed P-gp-mediated paclitaxel resistance and inhibited tumor growth by 27.4 to 36.1% (p < 0.001). Moreover, it also increased the intratumor paclitaxel level in the LCC6MDR xenograft by 6 fold (p < 0.001). In both murine leukemia P388ADR and human leukemia K562/P-gp mice models, the cotreatment of EC31 and doxorubicin significantly prolonged the survival of the mice (p < 0.001 and p < 0.01) as compared to the doxorubicin alone group, respectively. Our results suggested that EC31 was a promising candidate for further investigation on combination therapy for treating P-gp-overexpressing cancers.
The Geomagnetic Field (GMF) Is Necessary for Black Garden Ant (Lasius niger L.) Foraging and Modulates Orientation Potentially through Aminergic Regulation and MagR Expression
Authors: Mannino Giuseppe , Casacci Luca Pietro , Bianco Dolino Giorgia , Badolato Giuseppe , Maffei Massimo Emilio , Barbero Francesca
Published: February 2023

The geomagnetic field (GMF) can affect a wide range of animal behaviors in various habitats, primarily providing orientation cues for homing or migratory events. Foraging patterns, such as those implemented by Lasius niger, are excellent models to delve into the effects of GMF on orientation abilities. In this work, we assessed the role of GMF by comparing the L. niger foraging and orientation performance, brain biogenic amine (BA) contents, and the expression of genes related to the magnetosensory complex and reactive oxygen species (ROS) of workers exposed to near-null magnetic fields (NNMF, ~40 nT) and GMF (~42 µT). NNMF affected workers’ orientation by increasing the time needed to find the food source and return to the nest. Moreover, under NNMF conditions, a general drop in BAs, but not melatonin, suggested that the lower foraging performance might be correlated to a decrease in locomotory and chemical perception abilities, potentially driven by dopaminergic and serotoninergic regulations, respectively. The variation in the regulation of genes related to the magnetosensory complex in NNMF shed light on the mechanism of ant GMF perception. Overall, our work provides evidence that the GMF, along with chemical and visual cues, is necessary for the L. niger orientation process.
Discovery-Based Proteomics Identify Skeletal Muscle Mitochondrial Alterations as an Early Metabolic Defect in a Mouse Model of β-Thalassemia
Authors: Reboucas Patricia , Fillebeen Carine , Botta Amy , Cleverdon Riley , Steele Alexandra P. , Richard Vincent , Zahedi René P. , Borchers Christoph H. , Burelle Yan , Hawke Thomas J. , Pantopoulos Kostas , Sweeney Gary
Published: February 2023

Although metabolic complications are common in thalassemia patients, there is still an unmet need to better understand underlying mechanisms. We used unbiased global proteomics to reveal molecular differences between the th3/+ mouse model of thalassemia and wild-type control animals focusing on skeletal muscles at 8 weeks of age. Our data point toward a significantly impaired mitochondrial oxidative phosphorylation. Furthermore, we observed a shift from oxidative fibre types toward more glycolytic fibre types in these animals, which was further supported by larger fibre-type cross-sectional areas in the more oxidative type fibres (type I/type IIa/type IIax hybrid). We also observed an increase in capillary density in th3/+ mice, indicative of a compensatory response. Western blotting for mitochondrial oxidative phosphorylation complex proteins and PCR analysis of mitochondrial genes indicated reduced mitochondrial content in the skeletal muscle but not the hearts of th3/+ mice. The phenotypic manifestation of these alterations was a small but significant reduction in glucose handling capacity. Overall, this study identified many important alterations in the proteome of th3/+ mice, amongst which mitochondrial defects leading to skeletal muscle remodelling and metabolic dysfunction were paramount.
Metabolomics Analysis Reveals Novel Targets of Chemosensitizing Polyphenols and Omega-3 Polyunsaturated Fatty Acids in Triple Negative Breast Cancer Cells
Authors: Rushing Blake R. , Wiggs Alleigh , Molina Sabrina , Schroder Madison , Sumner Susan
Published: February 2023

Triple negative breast cancer (TNBC) is a subtype of breast cancer with typically poorer outcomes due to its aggressive clinical behavior and lack of targeted treatment options. Currently, treatment is limited to the administration of high-dose chemotherapeutics, which results in significant toxicities and drug resistance. As such, there is a need to de-escalate chemotherapeutic doses in TNBC while also retaining/improving treatment efficacy. Dietary polyphenols and omega-3 polyunsaturated fatty acids (PUFAs) have been demonstrated to have unique properties in experimental models of TNBC, improving the efficacy of doxorubicin and reversing multi-drug resistance. However, the pleiotropic nature of these compounds has caused their mechanisms to remain elusive, preventing the development of more potent mimetics to take advantage of their properties. Using untargeted metabolomics, we identify a diverse set of metabolites/metabolic pathways that are targeted by these compounds following treatment in MDA-MB-231 cells. Furthermore, we demonstrate that these chemosensitizers do not all target the same metabolic processes, but rather organize into distinct clusters based on similarities among metabolic targets. Common themes in metabolic targets included amino acid metabolism (particularly one-carbon and glutamine metabolism) and alterations in fatty acid oxidation. Moreover, doxorubicin treatment alone generally targeted different metabolites/pathways than chemosensitizers. This information provides novel insights into chemosensitization mechanisms in TNBC.
Application of Nicotinamide to Culture Medium Improves the Efficiency of Genome Editing in Hexaploid Wheat
Authors: Wang Wanxin , Huang Peipei , Dai Wenshuang , Tang Huali , Qiu Yuliang , Chang Yanan , Han Zhiyang , Li Xi , Du Lipu , Ye Xingguo , Zou Cheng , Wang Ke
Published: February 2023

Histone acetylation is the earliest and most well-characterized of post-translation modifications. It is mediated by histone acetyltransferases (HAT) and histone deacetylases (HDAC). Histone acetylation could change the chromatin structure and status and further regulate gene transcription. In this study, nicotinamide, a histone deacetylase inhibitor (HDACi), was used to enhance the efficiency of gene editing in wheat. Transgenic immature and mature wheat embryos harboring a non-mutated GUS gene, the Cas9 and a GUS-targeting sgRNA were treated with nicotinamide in two concentrations (2.5 and 5 mM) for 2, 7, and 14 days in comparison with a no-treatment control. The nicotinamide treatment resulted in GUS mutations in up to 36% of regenerated plants, whereas no mutants were obtained from the non-treated embryos. The highest efficiency was achieved when treated with 2.5 mM nicotinamide for 14 days. To further validate the impact of nicotinamide treatment on the effectiveness of genome editing, the endogenous TaWaxy gene, which is responsible for amylose synthesis, was tested. Utilizing the aforementioned nicotinamide concentration to treat embryos containing the molecular components for editing the TaWaxy gene, the editing efficiency could be increased to 30.3% and 13.3%, respectively, for immature and mature embryos in comparison to the 0% efficiency observed in the control group. In addition, nicotinamide treatment during transformation progress could also improve the efficiency of genome editing approximately threefold in a base editing experiment. Nicotinamide, as a novel approach, may be employed to improve the editing efficacy of low-efficiency genome editing tools such as base editing and prime editing (PE) systems in wheat.
Synthesis of Bio-Based Polyester from Microbial Lipidic Residue Intended for Biomedical Application
Authors: Capêto Ana P. , Azevedo-Silva João , Sousa Sérgio , Pintado Manuela , Guimarães Ana S. , Oliveira Ana L. S.
Published: February 2023

In the last decade, selectively tuned bio-based polyesters have been increasingly used for their clinical potential in several biomedical applications, such as tissue engineering, wound healing, and drug delivery. With a biomedical application in mind, a flexible polyester was produced by melt polycondensation using the microbial oil residue collected after the distillation of β-farnesene (FDR) produced industrially by genetically modified yeast, Saccharomyces cerevisiae. After characterization, the polyester exhibited elongation up to 150% and presented Tg of −51.2 °C and Tm of 169.8 °C. In vitro degradation revealed a mass loss of about 87% after storage in PBS solution for 11 weeks under accelerated conditions (40 °C, RH = 75%). The water contact angle revealed a hydrophilic character, and biocompatibility with skin cells was demonstrated. 3D and 2D scaffolds were produced by salt-leaching, and a controlled release study at 30 °C was performed with Rhodamine B base (RBB, 3D) and curcumin (CRC, 2D), showing a diffusion-controlled mechanism with about 29.3% of RBB released after 48 h and 50.4% of CRC after 7 h. This polymer offers a sustainable and eco-friendly alternative for the potential use of the controlled release of active principles for wound dressing applications.
Tumor Vasculature as an Emerging Pharmacological Target to Promote Anti-Tumor Immunity
Authors: Tzeng Hong-Tai , Huang Yu-Jie
Published: February 2023

Tumor vasculature abnormality creates a microenvironment that is not suitable for anti-tumor immune response and thereby induces resistance to immunotherapy. Remodeling of dysfunctional tumor blood vessels by anti-angiogenic approaches, known as vascular normalization, reshapes the tumor microenvironment toward an immune-favorable one and improves the effectiveness of immunotherapy. The tumor vasculature serves as a potential pharmacological target with the capacity of promoting an anti-tumor immune response. In this review, the molecular mechanisms involved in tumor vascular microenvironment-modulated immune reactions are summarized. In addition, the evidence of pre-clinical and clinical studies for the combined targeting of pro-angiogenic signaling and immune checkpoint molecules with therapeutic potential are highlighted. The heterogeneity of endothelial cells in tumors that regulate tissue-specific immune responses is also discussed. The crosstalk between tumor endothelial cells and immune cells in individual tissues is postulated to have a unique molecular signature and may be considered as a potential target for the development of new immunotherapeutic approaches.
RF Design and Measurements of a C-Band Prototype Structure for an Ultra-High Dose-Rate Medical Linac
Authors: Giuliano Lucia , Bosco Fabio , Carillo Martina , Felici Giuseppe , Ficcadenti Luca , Mostacci Andrea , Migliorati Mauro , Palumbo Luigi , Spataro Bruno , Faillace Luigi
Published: February 2023

In this paper, we illustrate the RF design and measurements of a C-band prototype structure for an Ultra High Dose Rate medical linac. (1) Background: FLASH Radiotherapy (RT) is a revolutionary new technique for cancer cure. It releases ultra-high radiation dose rates (above 100 Gy/s) in microsecond short pulses. In order to obtain a high dose in a very short time, accelerators with high-intensity currents (the order of 100 mA peak currents) have to be developed. In this contest, Sapienza University, in collaboration with SIT-Sordina IORT Technology spa, is developing a new C-band linac to achieve the FLASH regime. (2) Methods: We performed the RF electromagnetic design of the prototype of the C band linac using CST STUDIO Suite Code and the RF low power RF test at Sapienza University of Rome. The measurements of the field in the cavity have been done with the bead-pull technique. (3) Results: This device is a nine-cell structure operating on the π/2 mode at 5.712 GHz (C-band). We report and discuss the test measurement results on a full-scale copper prototype, showing good agreement with CST RF simulations. A tuning procedure has been implemented in order to ensure proper operating frequency and to reach a field profile flatness of the order of a few percent. (4) Conclusions: The prototype of a C-band linac for FLASH applications was successfully tested with low RF power at Sapienza University. The fabrication and ad hoc tuning procedures have been optimized and discussed in the paper.