bluuebunny/crossref_metadata_2025 huggingface dataset:
E-Cigarette Use Is Associated with Increased Psychological Distress among Youth: A Pooled Cross-Sectional Analysis of State-Level Data from 2019 and 2021
Authors: Cambron Christopher
Published: September 2022

A crisis of worsening youth mental health in recent years across the United States has created alarm among health professionals. As a result, health professionals have sought to improve methods of identifying youth in need of treatment services. Cigarette, cannabis, and alcohol use each consistently serve as behavioral markers of risk for youth mental health problems. Despite the recent growth of electronic cigarette (e-cigarette) use among youth, few studies have examined whether e-cigarettes follow the same associational pattern with mental health problems in the context of other substance use. Additionally, the COVID-19 pandemic may have altered the associations between youth substance use and mental health problems due to both reduced overall use and increased mental health problems after the onset of the pandemic. The current study examined associations between youth substance use and psychological distress before and after the onset of the COVID-19 pandemic using two state-representative samples of youth in grades 8, 10, and 12 from 2019 (N = 58,689) and 2021 (N = 46,823) from Utah. Pooled cross-sectional linear and negative binomial regression models clustered by grade, stratified by school district, and weighted to represent population characteristics estimated associations between recent e-cigarette, combustible cigarette, cannabis, and heavy alcohol use and two measures of psychological distress—depressive symptoms and mental health treatment needs. After controlling for sociodemographic factors and recent uses of other substances, results indicated that psychological distress increased from 2019 to 2021 and that recent e-cigarette, combustible cigarette, cannabis, and heavy alcohol use were each significantly associated with increased levels on both measures of psychological distress. Compared to other substances, e-cigarette use showed the strongest standardized associations. The association of e-cigarette use with depressive symptoms strengthened significantly from 2019 to 2021. Given the youth mental health crisis paired with the widespread adoption of e-cigarettes, health professionals should consider recent e-cigarette use an increasingly important behavioral marker for risks of mental health problems among youth. Results suggest that future research studies examining the temporal ordering of substance use and mental health among youth should include e-cigarettes.
‘Next Stop: Mum’: Evaluation of a Postpartum Depression Prevention Strategy in Poland
Authors: Chrzan-Dętkoś Magdalena , Murawska Natalia , Walczak-Kozłowska Tamara
Published: September 2022

In the article we present a mid-point evaluation of the postpartum depression (PPD) prevention strategy in Poland. As PPD is associated with potential negative consequences for the mother and infant, the need to introduce screening and treatment is vital. The project covered over 21,500 women in the first year postpartum. The average score in the Edinburgh Postnatal Depression Scale (EPDS), in a screening provided in direct contact, was 4.73 (SD = 4.14, n = 7222), and increased in 55% of women in the follow-up study. In online screening the average score in the EPDS assessment was 16.05 (SD = 5.975, n = 10,454). The ‘probable depression’ rate (EPDS > 12) in ‘direct’ contact is 7.3%, and on the online platform—77%. Additionally, 26% of possibly affected mothers assessed in ‘direct’ contact benefited from psychological consultations. The average score in the EPDS among mothers who benefitted from consultations is 16.24 (SD =4.674, n = 231). Approx. 82% of healthcare providers raised their knowledge of PPD after training sessions. Maintaining the assumptions of the program: training for medical staff, screening conducted throughout the first twelve months postpartum, online platform with the possibility of self-screening and early psychological intervention seem to be justified actions, leading to a higher number of women with risk of PPD referred.
Embodied Cognition in Meditation, Yoga, and Ethics—An Experimental Single-Case Study on the Differential Effects of Four Mind–Body Treatments
Authors: Matko Karin , Sedlmeier Peter , Bringmann Holger C.
Published: September 2022

Yoga is an embodied contemplative practice considered as a path toward long-term well-being, which fosters an integrated processing of bodily and emotional stimuli. However, little is known about how the different components of yoga contribute to these processes. This was the aim of this single-case multiple-baseline study. Herein, we explored how different yoga components affect body awareness, emotion regulation, affectivity, self-compassion, and distress tolerance. Forty-two randomly assigned participants (from initially fifty-seven) completed one of four 8-week treatments: Mantra meditation alone (MA), meditation plus physical yoga (MY), meditation plus ethical education (ME), and meditation plus yoga and ethical education (MYE). Participants had no prior regular yoga or meditation practice. Data were analyzed using visual inspection, effect size estimation, and multilevel modeling. Surprisingly, all four treatments similarly improved body awareness (Tau-UMA = 0.21 to Tau-UMY = 0.49), emotion regulation (Tau-UMYE = −0.43 to Tau-UME = −0.52), self-compassion (η2 = 0.08), and distress tolerance (η2 = 0.13). These effects were maintained until follow-up at 2 and 12 months after the study, even though home practice declined. The MA condition had the least favorable effect on affective experience (Tau-UMA = −0.14 and 0.07), while the ME condition enhanced valence the most (Tau-UME = 0.10) and the MY condition was the most effective in preventing negative affective responses. Although mantra meditation on its own negatively influenced daily affect, it can be assumed as the driving force behind the improvement in the other variables. This points to the central role of meditation in increasing interoception, self-awareness, and embodied processing.
Prevalence and Correlates of Underweight among Women of Reproductive Age in Nepal: A Cross-Sectional Study
Authors: Rana Kritika , Chimoriya Ritesh , Haque Nabila Binte , Piya Milan K. , Chimoriya Romila , Ekholuenetale Michael , Arora Amit
Published: September 2022

This study aimed to examine the prevalence of underweight and determine the sociodemographic and household environmental correlates of underweight among women of reproductive age in Nepal. This study also compared the time trends in the prevalence of underweight with the trends in the prevalence of overweight and obesity. This cross-sectional study was a secondary data analysis of the nationally representative population-based Nepal Demographic and Health Surveys (NDHSs). Firstly, the time trends of the prevalence of underweight (body mass index (BMI) < 18.5 kg/m2) among women aged 15–49 years were examined at five-year intervals, from the 1996, 2001, 2006, 2011, and 2016 NDHSs (n = 33,507). Secondly, the sociodemographic and household environmental correlates of underweight were examined from the latest NDHS 2016 (n = 6165). Univariable and multivariable logistic regression analyses were performed to examine the sociodemographic and household environmental correlates of underweight. From 1996 to 2016, the prevalence of underweight decreased from 25.3% (95% confidence interval (CI) 23.8%, 26.8%) to 16.9% (95%CI 16.0%, 17.8%), while the prevalence of overweight and obesity increased from 1.6% (95%CI 1.2%, 2.1%) to 15.6% (95%CI 14.7%, 16.5%) and 0.2% (95%CI 0.1%, 0.4%) to 4.1% (95%CI 3.6%, 4.6%), respectively. Sociodemographic factors, such as age, educational status, marital status, wealth index, and religion, were independently associated with the risk of underweight. Similarly, household environmental factors, such as province of residence, ecological zone, type of toilet facility, and household possessions, including television and mobile phone, were independently associated with the risk of underweight. Despite the declining trends, the prevalence of underweight among Nepalese women remains a public health challenge. Understanding the key sociodemographic and household environmental correlates of underweight may assist in streamlining the content of health promotion campaigns to address undernutrition and potentially mitigate adverse health outcomes.
The Potential Impact of a Public Health Approach to Improving the Physical Health of People Living with Mental Illness
Authors: Roberts Russell , Johnson Caroline , Hopwood Malcolm , Firth Joseph , Jackson Kate , Sara Grant , Allan John , Calder Rosemary , Manger Sam
Published: September 2022

With already wide disparities in physical health and life expectancy, COVID-19 presents people with mental illness with additional threats to their health: decreased access to health services, increased social isolation, and increased socio-economic disadvantage. Each of these factors has exacerbated the risk of poor health and early death for people with mental illness post-COVID-19. Unless effective primary care and preventative health responses are implemented, the physical illness epidemic for this group will increase post the COVID-19 pandemic. This perspective paper briefly reviews the literature on the impact of COVID-19 on service access, social isolation, and social disadvantage and their combined impact on physical health, particularly cancer, respiratory diseases, heart disease, smoking, and infectious diseases. The much-overlooked role of poor physical health on suicidality is also discussed. The potential impact of public health interventions is modelled based on Australian incidence data and current research on the percentage of early deaths of people living with mental illnesses that are preventable. Building on the lessons arising from services’ response to COVID-19, such as the importance of ensuring access to preventive, screening, and primary care services, priority recommendations for consideration by public health practitioners and policymakers are presented.
What Drives People to Share Misinformation on Social Media during the COVID-19 Pandemic: A Stimulus-Organism-Response Perspective
Authors: Wu Manli
Published: September 2022

(1) Background: Misinformation is prevalent on social media in the age of COVID-19, exacerbating the threat of the pandemic. Uncovering the processes underlying people’s misinformation sharing using social media assists people to cope with misinformation during the COVID-19 pandemic. This study extends the stimulus-organism-response framework to examine how individuals’ social media dependency relates to their misinformation sharing behavior, with a focus on the underlying processes. (2) Methods: A total of 393 valid questionnaires were collected using a survey method to test the proposed research model. (3) Results: The results demonstrate that informational dependency and social dependency engender both positive and negative cognitive states, namely perceived information timeliness, perceived socialization and social overload, which then invoke positive as well as negative affect. What is more, the results show that both positive affect and negative affect can engender misinformation sharing. (4) Conclusions: Theoretically, this study uncovers the processes that lead to misinformation sharing on social media during the COVID-19 pandemic. Practically, this study provides actionable guidelines on how to manage social media usage and social media content to cope with misinformation sharing during the pandemic.
Pyrite-Based Autotrophic Denitrifying Microorganisms Derived from Paddy Soils: Effects of Organic Co-Substrate Addition
Authors: Xu Baokun , Yang Xiaoxia , Li Yalong , Yang Kejun , Xiong Yujiang , Yuan Niannian
Published: September 2022

The presence of organic co-substrate in groundwater and soils is inevitable, and much remains to be learned about the roles of organic co-substrates during pyrite-based denitrification. Herein, an organic co-substrate (acetate) was added to a pyrite-based denitrification system, and the impact of the organic co-substrate on the performance and bacterial community of pyrite-based denitrification processes was evaluated. The addition of organic co-substrate at concentrations higher than 48 mg L−1 inhibited pyrite-based autotrophic denitrification, as no sulfate was produced in treatments with high organic co-substrate addition. In contrast, both competition and promotion effects on pyrite-based autotrophic denitrification occurred with organic co-substrate addition at concentrations of 24 and 48 mg L−1. The subsequent validation experiments suggested that competition had a greater influence than promotion when organic co-substrate was added, even at a low concentration. Thiobacillus, a common chemolithoautotrophic sulfur-oxidizing denitrifier, dominated the system with a relative abundance of 13.04% when pyrite served as the sole electron donor. With the addition of organic co-substrate, Pseudomonas became the dominant genus, with 60.82%, 61.34%, 70.37%, 73.44%, and 35.46% abundance at organic matter concentrations of 24, 48, 120, 240, and 480 mg L−1, respectively. These findings provide an important theoretical basis for the cultivation of pyrite-based autotrophic denitrifying microorganisms for nitrate removal in soils and groundwater.
Impact of Accessibility to Cities at Multiple Administrative Levels on Soil Conservation: A Case Study of Hunan Province
Authors: Dai Yunzhe , Li Xiangmei , Wang Dan , Wang Yayun
Published: September 2022

The development of traffic infrastructure involves massive land use changes along the transportation routes and stimulates urban sprawl at transfer nodes, leading to a degradation in ecosystem services, including soil conservation. For developing countries, especially for China, it is very important to differentiate the influences between different standards of traffic infrastructure associated with the different administrative levels of the regions where they are constructed on soil conservation. In this study, we attempt to analyze the differences in the influence of accessibility at different levels on soil conservation, for the case study area in Hunan province in China. The results indicate that: (1) traffic conditions in Hunan province have witnessed continuous improvement, and the time taken to access mega-cities, prefecture-level cities, and county-level cities from various regions has been significantly reduced. (2) The total annual soil conservation in Hunan province is maintained at approximately 2.93 × 109 t. However, the spatial heterogeneity shows severe degradation in regions with lower accessibility, and weak enhancement in regions with higher accessibility. (3) A negative spatial autocorrelationship exists between accessibility and soil conservation at all levels, with the increase of administrative rank of the destination making it more obvious and intense, along with an increased tendency for the spatial distribution to concentrate. (4) Building more railways and highways from prefecture-level cities with LH clusters nearby as transfer nodes, instead of the construction of national roads and provincial roads that diverge from these railways and highways, will help limit the massive expansion of construction land and soil erosion within prefecture-level cities, rather than spreading to towns of LH clusters. This research provides an important scientific basis for future regional planning and traffic infrastructure construction, and also a reference for traffic infrastructure development in other geographically similar regions on a synchronous development stage in the world.
Functional Therapeutic Strategies Used in Different Stages of Alzheimer’s Disease—A Systematic Review
Authors: Olczak Anna , Truszczyńska-Baszak Aleksandra , Stępień Adam , Górecki Krzysztof
Published: September 2022

As Alzheimer’s disease develops, the central nervous system is gradually damaged. It is manifested by progressive dementia and the appearance of neurological and extrapyramidal symptoms that impair everyday functioning. The aim of the study was to evaluate the influence of physical exercise on cognitive and motor functions in various stages of Alzheimer’s disease. Methods: Four databases (PubMed, Scopus, Ovid, and Cochrane Library) were searched for relevant papers published between 2012 and May 2022. The works were assessed in terms of the adopted inclusion criteria. The measures of the results were changed in the parameters assessing motor and cognitive functions. Methodological quality was assessed using the Cochrane Collaboration. This review was recorded with the Cochrane Library: CRD42022340496. The results of the database search showed 302 articles, 12 of which were included in the review. All studies have shown a significant positive effect on improving cognitive and motor functions. This systematic review revealed a beneficial effect in improving cognitive and motor functions after the application of various kinds of activities, especially in the early and mild stages of Alzheimer’s disease.
Hysteroscopic Resection Followed by Adjuvant Radiotherapy: Report of a New Therapeutic Approach to Primary Cervical Diffuse Large B-Cell Lymphoma
Authors: Stabile Guglielmo , Sancin Lara , Boschian Bailo Pierino , Ripepi Chiara , Romano Andrea , Carlucci Stefania , Ricci Giuseppe
Published: September 2022

The female genital tract can be involved as a secondary manifestation of disseminated lymphomas or leukemia but can rarely be the primary site of so-called extranodal lymphomas. Primary lymphomas of the female genital tract can affect the uterine corpus, uterine cervix, vulva, vagina or adnexa. Only about 0.008% of all cervical tumors are primary malignant lymphomas. The presenting symptoms are unspecific and also refer to much more common diseases of the female genital tract. Cervical cytology is usually negative. Preoperative diagnosis requires deep cervical biopsy. To date there is no consensus regarding optimal treatment. Radiotherapy, chemotherapy and surgery are used in different association. We report the first case reported in literature managed with an urgent hysteroscopic resection of a primary cervical diffuse large B-cell lymphoma, followed by adjuvant radiotherapy. Relevant literature was reviewed. Our conservative approach needs to be validated in the future, especially for women with pregnancy desire and for those with low performance status. To date, after 24 months from diagnosis, our patient is still disease-free.
Sensing Tourist Distributions and Their Sentiment Variations Using Social Media: Evidence from 5A Scenic Areas in China
Authors: Wang Jingbo , Xia Yu , Wu Yuting
Published: September 2022

The distribution and sentiment characteristics of tourists directly reflect the state of tourism development, and are an important reference for tourists to choose scenic areas. Sensing the tourist distributions and their sentiment variations can provide decision support for the development planning of scenic areas. In this study, we crawled tourist social media data to explore tourist distribution characteristics and the patterns of tourist sentiment variations. First, we used web crawlers to obtain social media data (tourist comment data) and the location data of China’s 5A scenic areas from the Ctrip tourism platform. Second, SnowNLP (Simplified Chinese Text Processing) was optimized and used to classify the sentiment of tourists’ comments and calculate the sentiment value. Finally, we mined the distribution characteristics of tourists in 5A scenic areas and the spatio-temporal variations in tourists’ sentiments. The results show that: (1) There is a negative correlation between the number of tourists to China’s 5A scenic areas and tourist sentiment: the number of tourists is highest in October and lowest in March, while tourist sentiment is highest in March and lowest in October. (2) The spatio-temporal distribution of tourists has obvious aggregation: temporally mainly in July, August and October, spatially mainly in the Yangtze River Delta city cluster, Beijing-Tianjin-Hebei city cluster, and Guanzhong Plain city cluster. (3) Tourist sentiment cold/hot spots vary significantly by city clusters: the Yangtze River Delta city cluster is always a sentiment hot spot; the northern city cluster has more sentiment cold spots; the central city cluster varies significantly during the year; the southwestern city cluster has more sentiment hot spots.
MSEN-GRP: A Geographic Relations Prediction Model Based on Multi-Layer Similarity Enhanced Networks for Geographic Relations Completion
Authors: Huang Zongcai , Qiu Peiyuan , Yu Li , Lu Feng
Published: September 2022

Geographic relation completion contributes greatly to improving the quality of large-scale geographic knowledge graphs (GeoKGs). However, the internal features of a GeoKG used in large-scale GeoKGs embedding are often limited by the weak connectivity between geographic entities (geo-entities). If there is no proper choice in the method of external semantic enhancement, this will often interfere with the representation and learning of the KG. Therefore, we here propose a geographic relation (geo-relation) prediction model based on multi-layer similarity enhanced networks for geo-relations completion (MSEN-GRP). The MSEN-GRP comprises three parts: enhancer, encoder, and decoder. The enhancer constructs semantic, spatial, structural, and attribute-similarity networks for geo-entities, which can explicitly and effectively enhance the implicit semantic associations between existing geo-entities. The encoder can obtain the long path relation dependency characteristics of geo-entities using a mixed-path sampling strategy and can support different optimization schemes for external semantic enhancement. Geo-relations prediction experiments show that the mean reciprocal ranking of this method is significantly higher than those of the traditional TransE DisMult and methods, and Hits@10 is improved by up to 57.57%. Furthermore, the spatial-similarity network has the most significant enhancement effect on geo-relations prediction. The proposed method provides a new way to perform relation completion in sparse GeoKGs.
The Detection of Pine Wilt Disease: A Literature Review
Authors: Li Min , Li Huan , Ding Xiaolei , Wang Lichao , Wang Xinyang , Chen Fengmao
Published: September 2022

Pine wilt disease (PWD) is a global quarantine disease of forests that mainly affects Pinaceae species. The disease spreads rapidly. Once infected, pine trees have an extremely high mortality rate. This paper provides a summary of the common techniques used to detect PWD, including morphological-, molecular-, chemical- and physical-based methods. By comprehending the complex relationship among pinewood nematodes, vectors and host pine trees and employing the available approaches for nematode detection, we can improve the implementation of intervention and control measures to effectively reduce the damage caused by PWD. Although conventional techniques allow a reliable diagnosis of the symptomatic phase, the volatile compound detection and remote sensing technology facilitate a rapid diagnosis during asymptomatic stages. Moreover, the remote sensing technology is capable of monitoring PWD over large areas. Therefore, multiple perspective evaluations based on these technologies are crucial for the rapid and effective detection of PWD.
Zygo-Albuside A: New Saponin from Zygophyllum album L. with Significant Antioxidant, Anti-Inflammatory and Antiapoptotic Effects against Methotrexate-Induced Testicular Damage
Authors: Abdelhameed Reda F. A. , Fattah Shaimaa A. , Mehanna Eman T. , Hal Dina M. , Mosaad Sarah M. , Abdel-Kader Maged S. , Ibrahim Amany K. , Ahmed Safwat A. , Badr Jihan M. , Eltamany Enas E.
Published: September 2022

Chemical investigation of the crude extract of the aerial part of Zygophyllum album L. (Z. album) led to the isolation of a new saponin, Zygo-albuside A (7), together with seven known compounds, one of them (caffeic acid, compound 4) is reported in the genus for the first time. NMR (1D and 2D) and mass spectrometric analysis, including high-resolution mass spectrometry (HRMS), were utilized to set up the chemical structures of these compounds. The present biological study aimed to investigate the protective antioxidant, anti-inflammatory, and antiapoptotic activities of the crude extract from the aerial part of Z. album and two of its isolated compounds, rutin and the new saponin zygo-albuside A, against methotrexate (MTX)-induced testicular injury, considering the role of miRNA-29a. In all groups except for the normal control group, which received a mixture of distilled water and DMSO (2:1) as vehicle orally every day for ten days, testicular damage was induced on the fifth day by intraperitoneal administration of MTX at a single dose of 20 mg/kg. Histopathological examination showed that pre-treatment with the crude extract of Z. album, zygo-albuside A, or rutin reversed the testicular damage induced by MTX. In addition, biochemical analysis in the protected groups showed a decrease in malondialdehyde (MDA), interleukin-6 (IL-6) and IL-1β, Bcl-2-associated-protein (Bax), and an increase in B-cell lymphoma 2 (Bcl-2) protein, catalase (CAT), superoxide dismutase (SOD) in the testis, along with an increase in serum testosterone levels compared with the unprotected (positive control) group. The mRNA expression levels of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), p53, and miRNA-29a were downregulated in the testicular tissues of the protected groups compared with the unprotected group. In conclusion, the study provides sufficient evidence that Z. album extract, and its isolated compounds, zygo-albuside A and rutin, could alleviate testicular damage caused by the chemotherapeutic agent MTX.
Impact of Environmental Risk Factors on Mitochondrial Dysfunction, Neuroinflammation, Protein Misfolding, and Oxidative Stress in the Etiopathogenesis of Parkinson’s Disease
Authors: Huang Minhong , Bargues-Carot Alejandra , Riaz Zainab , Wickham Hannah , Zenitsky Gary , Jin Huajun , Anantharam Vellareddy , Kanthasamy Arthi , Kanthasamy Anumantha G.
Published: September 2022

As a prevalent progressive neurodegenerative disorder, Parkinson’s disease (PD) is characterized by the neuropathological hallmark of the loss of nigrostriatal dopaminergic (DAergic) innervation and the appearance of Lewy bodies with aggregated α-synuclein. Although several familial forms of PD have been reported to be associated with several gene variants, most cases in nature are sporadic, triggered by a complex interplay of genetic and environmental risk factors. Numerous epidemiological studies during the past two decades have shown positive associations between PD and several environmental factors, including exposure to neurotoxic pesticides/herbicides and heavy metals as well as traumatic brain injury. Other environmental factors that have been implicated as potential risk factors for PD include industrial chemicals, wood pulp mills, farming, well-water consumption, and rural residence. In this review, we summarize the environmental toxicology of PD with the focus on the elaboration of chemical toxicity and the underlying pathogenic mechanisms associated with exposure to several neurotoxic chemicals, specifically 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, paraquat (PQ), dichloro-diphenyl-trichloroethane (DDT), dieldrin, manganese (Mn), and vanadium (V). Our overview of the current findings from cellular, animal, and human studies of PD provides information for possible intervention strategies aimed at halting the initiation and exacerbation of environmentally linked PD.
Ionizing Radiation from Radiopharmaceuticals and the Human Gut Microbiota: An Ex Vivo Approach
Authors: Fernandes Ana , Oliveira Ana , Guedes Carla , Fernandes Rúben , Soares Raquel , Barata Pedro
Published: September 2022

This study aimed to determine the effect of three widely used radiopharmaceuticals with intestinal excretion on selected relevant bacteria that are part of the human gut microbiota, using an ex vivo approach. Fecal samples obtained from healthy volunteers were analyzed. Each sample was divided into four smaller aliquots. One served as the non-irradiated control. The other three were homogenized with three radiopharmaceutical solutions ([131I]NaI, [99mTc]NaTcO4, and [223Ra]RaCl2). Relative quantification of each taxa was determined by the 2−ΔΔC method, using the ribosomal gene 16S as an internal control (primers 534/385). Twelve fecal samples were analysed: three controls and nine irradiated. Our experiment showed fold changes in all analyzed taxa with all radiopharmaceuticals, but results were more significant with I-131, ranging from 1.87–83.58; whereas no relevant differences were found with Tc-99m and Ra-223, ranging from 0.98–1.58 and 0.83–1.97, respectively. This study corroborates limited existing research on how ionizing radiation changes the gut microbiota composition, providing novel data regarding the ex vivo effect of radiopharmaceuticals. Our findings justify the need for future larger scale projects.
The Roles of Mitophagy and Autophagy in Ineffective Erythropoiesis in β-Thalassemia
Authors: Chaichompoo Pornthip , Svasti Saovaros , Smith Duncan R.
Published: September 2022

β-Thalassemia is one of the most common genetically inherited disorders worldwide, and it is characterized by defective β-globin chain synthesis leading to reduced or absent β-globin chains. The excess α-globin chains are the key factor leading to the death of differentiating erythroblasts in a process termed ineffective erythropoiesis, leading to anemia and associated complications in patients. The mechanism of ineffective erythropoiesis in β-thalassemia is complex and not fully understood. Autophagy is primarily known as a cell recycling mechanism in which old or dysfunctional proteins and organelles are digested to allow recycling of constituent elements. In late stage, erythropoiesis autophagy is involved in the removal of mitochondria as part of terminal differentiation. Several studies have shown that autophagy is increased in earlier erythropoiesis in β-thalassemia erythroblasts, as compared to normal erythroblasts. This review summarizes what is known about the role of autophagy in β-thalassemia erythropoiesis and shows that modulation of autophagy and its interplay with apoptosis may provide a new therapeutic route in the treatment of β-thalassemia. Literature was searched and relevant articles were collected from databases, including PubMed, Scopus, Prospero, Clinicaltrials.gov, Google Scholar, and the Google search engine. Search terms included: β-thalassemia, ineffective erythropoiesis, autophagy, novel treatment, and drugs during the initial search. Relevant titles and abstracts were screened to choose relevant articles. Further, selected full-text articles were retrieved, and then, relevant cross-references were scanned to collect further information for the present review.
5-Arylidenerhodanines as P-gp Modulators: An Interesting Effect of the Carboxyl Group on ABCB1 Function in Multidrug-Resistant Cancer Cells
Authors: Żesławska Ewa , Tejchman Waldemar , Kincses Annamária , Spengler Gabriella , Nitek Wojciech , Żuchowski Grzegorz , Szymańska Ewa
Published: September 2022

Multidrug resistance (MDR) is considered one of the major mechanisms responsible for the failure of numerous anticancer and antiviral chemotherapies. Various strategies to overcome the MDR phenomenon have been developed, and one of the most attractive research directions is focused on the inhibition of MDR transporters, membrane proteins that extrude cytotoxic drugs from living cells. Here, we report the results of our studies on a series newly synthesized of 5-arylidenerhodanines and their ability to inhibit the ABCB1 efflux pump in mouse T-lymphoma cancer cells. In the series, compounds possessing a triphenylamine moiety and the carboxyl group in their structure were of particular interest. These amphiphilic compounds showed over 17-fold stronger efflux pump inhibitory effects than verapamil. The cytotoxic and antiproliferative effects of target rhodanines on T-lymphoma cells were also investigated. A putative binding mode for 11, one of the most potent P-gp inhibitors tested here, was predicted by molecular docking studies and discussed with regard to the binding mode of verapamil.
Dietary Risk Factors and Eating Behaviors in Peripheral Arterial Disease (PAD)
Authors: Cecchini Andrea Leonardo , Biscetti Federico , Rando Maria Margherita , Nardella Elisabetta , Pecorini Giovanni , Eraso Luis H. , Dimuzio Paul J. , Gasbarrini Antonio , Massetti Massimo , Flex Andrea
Published: September 2022

Dietary risk factors play a fundamental role in the prevention and progression of atherosclerosis and PAD (Peripheral Arterial Disease). The impact of nutrition, however, defined as the process of taking in food and using it for growth, metabolism and repair, remains undefined with regard to PAD. This article describes the interplay between nutrition and the development/progression of PAD. We reviewed 688 articles, including key articles, narrative and systematic reviews, meta-analyses and clinical studies. We analyzed the interaction between nutrition and PAD predictors, and subsequently created four descriptive tables to summarize the relationship between PAD, dietary risk factors and outcomes. We comprehensively reviewed the role of well-studied diets (Mediterranean, vegetarian/vegan, low-carbohydrate ketogenic and intermittent fasting diet) and prevalent eating behaviors (emotional and binge eating, night eating and sleeping disorders, anorexia, bulimia, skipping meals, home cooking and fast/ultra-processed food consumption) on the traditional risk factors of PAD. Moreover, we analyzed the interplay between PAD and nutritional status, nutrients, dietary patterns and eating habits. Dietary patterns and eating disorders affect the development and progression of PAD, as well as its disabling complications including major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nutrition and dietary risk factor modification are important targets to reduce the risk of PAD as well as the subsequent development of MACE and MALE.
Medical Advances in Hepatitis D Therapy: Molecular Targets
Authors: Vogt Amelie , Wohlfart Sabrina , Urban Stephan , Mier Walter
Published: September 2022

An approximate number of 250 million people worldwide are chronically infected with hepatitis B virus, making them susceptible to a coinfection with hepatitis D virus. The superinfection causes the most severe form of a viral hepatitis and thus drastically worsens the course of the disease. Until recently, the only available therapy consisted of interferon-α, only eligible for a minority of patients. In July 2020, the EMA granted Hepcludex conditional marketing authorization throughout the European Union. This first-in-class entry inhibitor offers the promise to prevent the spread in order to gain control and eventually participate in curing hepatitis B and D. Hepcludex is an example of how understanding the viral lifecycle can give rise to new therapy options. Sodium taurocholate co-transporting polypeptide, the virus receptor and the target of Hepcludex, and other targets of hepatitis D therapy currently researched are reviewed in this work. Farnesyltransferase inhibitors such as Lonafarnib, targeting another essential molecule in the HDV life cycle, represent a promising target for hepatitis D therapy. Farnesyltransferase attaches a farnesyl (isoprenyl) group to proteins carrying a C-terminal Ca1a2X (C: cysteine, a: aliphatic amino acid, X: C-terminal amino acid) motif like the large hepatitis D virus antigen. This modification enables the interaction of the HBV/HDV particle and the virus envelope proteins. Lonafarnib, which prevents this envelopment, has been tested in clinical trials. Targeting the lifecycle of the hepatitis B virus needs to be considered in hepatitis D therapy in order to cure a patient from both coexisting infections. Nucleic acid polymers target the hepatitis B lifecycle in a manner that is not yet understood. Understanding the possible targets of the hepatitis D virus therapy is inevitable for the improvement and development of a sufficient therapy that HDV patients are desperately in need of.
AST-487 Inhibits RET Kinase Driven TERT Expression in Bladder Cancer
Authors: Agarwal Neeraj , Zhou Qiong , Arya Deepak , Rinaldetti Sébastien , Duex Jason , LaBarbera Daniel V. , Theodorescu Dan
Published: September 2022

Mutations in the promoter of the human Telomerase Reverse Transcriptase (hTERT) gene are common and associated with its elevated expression in bladder cancer, melanoma, and glioblastoma. Though these mutations and TERT overexpression are associated with aggressive disease and poor outcome, an incomplete understanding of mutant TERT regulation limits treatment options directed at this gene. Herein, we unravel a signaling pathway that leads to upregulated hTERT expression resulting from the −124 bp promoter mutation, the most frequent variant across human cancer. We employed engineered bladder cancer cells that harbor a GFP insertion at the TSS region on −124 hTERT promoter for high-content screening drug discovery using a focused library of ~800 kinase inhibitors. Studies using in vitro and in vivo models prioritized AST-487, an inhibitor of the wild-type, and mutant RET (rearranged during transfection) proto-oncogene as a novel drug inhibitor of both wild-type and mutant promoter-driven hTERT expression. We also identified the RET kinase pathway, targeted by AST-487, as a novel regulator of mutant hTERT promoter-driven transcription in bladder cancer cells. Collectively, our work provides new potential precision medicine approaches for cancer patients with upregulated hTERT expression, perhaps, especially those harboring mutations in both the RET gene and the hTERT promoter, such as in thyroid cancer.
Use of a Molecular Switch Probe to Activate or Inhibit GIRK1 Heteromers In Silico Reveals a Novel Gating Mechanism
Authors: Gazgalis Dimitrios , Cantwell Lucas , Xu Yu , Thakur Ganesh A. , Cui Meng , Guarnieri Frank , Logothetis Diomedes E.
Published: September 2022

G protein-gated inwardly rectifying K+ (GIRK) channels form highly active heterotetramers in the body, such as in neurons (GIRK1/GIRK2 or GIRK1/2) and heart (GIRK1/GIRK4 or GIRK1/4). Based on three-dimensional atomic resolution structures for GIRK2 homotetramers, we built heterotetrameric GIRK1/2 and GIRK1/4 models in a lipid bilayer environment. By employing a urea-based activator ML297 and its molecular switch, the inhibitor GAT1587, we captured channel gating transitions and K+ ion permeation in sub-microsecond molecular dynamics (MD) simulations. This allowed us to monitor the dynamics of the two channel gates (one transmembrane and one cytosolic) as well as their control by the required phosphatidylinositol bis 4-5-phosphate (PIP2). By comparing differences in the two trajectories, we identify three hydrophobic residues in the transmembrane domain 1 (TM1) of GIRK1, namely, F87, Y91, and W95, which form a hydrophobic wire induced by ML297 and de-induced by GAT1587 to orchestrate channel gating. This includes bending of the TM2 and alignment of a dipole of two acidic GIRK1 residues (E141 and D173) in the permeation pathway to facilitate K+ ion conduction. Moreover, the TM movements drive the movement of the Slide Helix relative to TM1 to adjust interactions of the CD-loop that controls the gating of the cytosolic gate. The simulations reveal that a key basic residue that coordinates PIP2 to stabilize the pre-open and open states of the transmembrane gate flips in the inhibited state to form a direct salt-bridge interaction with the cytosolic gate and destabilize its open state.
Mixture Effects of Tryptophan Intestinal Microbial Metabolites on Aryl Hydrocarbon Receptor Activity
Authors: Vrzalová Aneta , Pečinková Petra , Illés Peter , Gurská Soňa , Džubák Petr , Szotkowski Martin , Hajdúch Marián , Mani Sridhar , Dvořák Zdeněk
Published: September 2022

Aryl hydrocarbon receptor (AHR) plays pivotal roles in intestinal physiology and pathophysiology. Intestinal AHR is activated by numerous dietary, endogenous, and microbial ligands. Whereas the effects of individual compounds on AHR are mostly known, the effects of real physiological mixtures occurring in the intestine have not been studied. Using reporter gene assays and RT-PCR, we evaluated the combinatorial effects (3520 combinations) of 11 microbial catabolites of tryptophan (MICTs) on AHR. We robustly (n = 30) determined the potencies and relative efficacies of single MICTs. Synergistic effects of MICT binary mixtures were observed between low- or medium-efficacy agonists, in particular for combinations of indole-3-propionate and indole-3-lactate. Combinations comprising highly efficacious agonists such as indole-3-pyruvate displayed rather antagonist effects, caused by saturation of the assay response. These synergistic effects were confirmed by RT-PCR as CYP1A1 mRNA expression. We also tested mimic multicomponent and binary mixtures of MICTs, prepared based on the metabolomic analyses of human feces and colonoscopy aspirates, respectively. In this case, AHR responsiveness did not correlate with type of diet or health status, and the indole concentrations in the mixtures were determinative of gross AHR activity. Future systematic research on the synergistic activation of AHR by microbial metabolites and other ligands is needed.
Brown Adipose Tissue Sheds Extracellular Vesicles That Carry Potential Biomarkers of Metabolic and Thermogenesis Activity Which Are Affected by High Fat Diet Intervention
Authors: Camino Tamara , Lago-Baameiro Nerea , Sueiro Aurelio , Bravo Susana Belén , Couto Iván , Santos Francisco Fernando , Baltar Javier , Casanueva Felipe F. , Pardo María
Published: September 2022

Brown adipose tissue (BAT) is a key target for the development of new therapies against obesity due to its role in promoting energy expenditure; BAT secretory capacity is emerging as an important contributor to systemic effects, in which BAT extracellular vesicles (EVs) (i.e., batosomes) might be protagonists. EVs have emerged as a relevant cellular communication system and carriers of disease biomarkers. Therefore, characterization of the protein cargo of batosomes might reveal their potential as biomarkers of the metabolic activity of BAT. In this study, we are the first to isolate batosomes from lean and obese Sprague–Dawley rats, and to establish reference proteome maps. An LC-SWATH/MS analysis was also performed for comparisons with EVs secreted by white adipose tissue (subcutaneous and visceral WAT), and it showed that 60% of proteins were exclusive to BAT EVs. Precisely, batosomes of lean animals contain proteins associated with mitochondria, lipid metabolism, the electron transport chain, and the beta-oxidation pathway, and their protein cargo profile is dramatically affected by high fat diet (HFD) intervention. Thus, in obesity, batosomes are enriched with proteins involved in signal transduction, cell communication, the immune response, inflammation, thermogenesis, and potential obesity biomarkers including UCP1, Glut1, MIF, and ceruloplasmin. In conclusion, the protein cargo of BAT EVs is affected by the metabolic status and contains potential biomarkers of thermogenesis activity.
Multiple Parallel Fusion Network for Predicting Protein Subcellular Localization from Stimulated Raman Scattering (SRS) Microscopy Images in Living Cells
Authors: Wei Zhihao , Liu Wu , Yu Weiyong , Liu Xi , Yan Ruiqing , Liu Qiang , Guo Qianjin
Published: September 2022

Stimulated Raman Scattering Microscopy (SRS) is a powerful tool for label-free detailed recognition and investigation of the cellular and subcellular structures of living cells. Determining subcellular protein localization from the cell level of SRS images is one of the basic goals of cell biology, which can not only provide useful clues for their functions and biological processes but also help to determine the priority and select the appropriate target for drug development. However, the bottleneck in predicting subcellular protein locations of SRS cell imaging lies in modeling complicated relationships concealed beneath the original cell imaging data owing to the spectral overlap information from different protein molecules. In this work, a multiple parallel fusion network, MPFnetwork, is proposed to study the subcellular locations from SRS images. This model used a multiple parallel fusion model to construct feature representations and combined multiple nonlinear decomposing algorithms as the automated subcellular detection method. Our experimental results showed that the MPFnetwork could achieve over 0.93 dice correlation between estimated and true fractions on SRS lung cancer cell datasets. In addition, we applied the MPFnetwork method to cell images for label-free prediction of several different subcellular components simultaneously, rather than using several fluorescent labels. These results open up a new method for the time-resolved study of subcellular components in different cells, especially cancer cells.
Molecular Characteristics, Receptor Specificity, and Pathogenicity of Avian Influenza Viruses Isolated from Wild Ducks in Russia
Authors: Boravleva Elizaveta , Treshchalina Anastasia , Postnikova Yulia , Gambaryan Alexandra , Belyakova Alla , Sadykova Galina , Prilipov Alexey , Lomakina Natalia , Ishmukhametov Aydar
Published: September 2022

Avian influenza viruses (AIV) of wild ducks are known to be able to sporadically infect domestic birds and spread along poultry. Regular surveillance of AIV in the wild is needed to prepare for potential outbreaks. During long-year monitoring, 46 strains of AIV were isolated from gulls and mallards in Moscow ponds and completely sequenced. Amino acid positions that affect the pathogenicity of influenza viruses in different hosts were tested. The binding affinity of the virus for receptors analogs typical for different hosts and the pathogenicity of viruses for mice and chickens were investigated. Moscow isolates did not contain well-known markers of pathogenicity and/or adaptation to mammals, so as a polybasic cleavage site in HA, substitutions of 226Q and 228G amino acids in the receptor-binding region of HA, and substitutions of 627E and 701D amino acids in the PB2. The PDZ-domain ligand in the NS protein of all studied viruses contains the ESEV or ESEI sequence. Although several viruses had the N66S substitution in the PB1-F2 protein, all Moscow isolates were apathogenic for both mice and chickens. This demonstrates that the phenotypic manifestation of pathogenicity factors is not absolute but depends on the genome context.
OsHsfB4b Confers Enhanced Drought Tolerance in Transgenic Arabidopsis and Rice
Authors: Zhang Yan , Wang Chen , Wang Changyu , Yun Liu , Song Linhu , Idrees Muhammad , Liu Huiying , Zhang Qianlong , Yang Jingyu , Zheng Xu , Zhang Zhiyong , Gao Jie
Published: September 2022

Heat shock factors (Hsfs) play pivotal roles in plant stress responses and confer stress tolerance. However, the functions of several Hsfs in rice (Oryza sativa L.) are not yet known. In this study, genome-wide analysis of the Hsf gene family in rice was performed. A total of 25 OsHsf genes were identified, which could be clearly clustered into three major groups, A, B, and C, based on the characteristics of the sequences. Bioinformatics analysis showed that tandem duplication and fragment replication were two important driving forces in the process of evolution and expansion of the OsHsf family genes. Both OsHsfB4b and OsHsfB4d showed strong responses to the stress treatment. The results of subcellular localization showed that the OsHsfB4b protein was in the nucleus whereas the OsHsfB4d protein was located in both the nucleus and cytoplasm. Over-expression of the OsHsfB4b gene in Arabidopsis and rice can increase the resistance to drought stress. This study provides a basis for understanding the function and evolutionary history of the OsHsf gene family, enriching our knowledge of understanding the biological functions of OsHsfB4b and OsHsfB4d genes involved in the stress response in rice, and also reveals the potential value of OsHsfB4b in rice environmental adaptation improvement.